A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Efficacy of Risdiplam (RO7034067) in Type 2 and 3 Spinal Muscular Atrophy (SMA) Participants (SUNFISH)

• ClinicalTrials.gov Identifier: NCT02908685
• Recruitment Status: Completed
• First Posted: September 21, 2016
• Results First Posted: June 15, 2021
• Last Update Posted: April 24, 2024
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Sequential Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Muscular Atrophy, Spinal
• Interventions: Drug: Placebo; Drug: Risdiplam
• Enrollment: 231

Participant Flow

Recruitment Details	Study Part 1 was conducted at 5 investigational sites across 4 countries, and Part 2 was conducted at 42 investigational sites across 14 countries. Screening in both Part 1 and 2 was up to 30 days prior to first dose.
Pre-assignment Details	In Part 1 participants were initially enrolled by age and in a dose-escalating design; each group included participants on active and placebo treatment in a 2:1 ratio. After Part 2 dose selection the study enrolled additional participants in a 2:1 ratio in Part 2.

Arm/Group Title	Part 1 Group A Cohort 1: Adolescents and Adults (3 mg Risdiplam)	Part 1 Group A Cohort 2: Adolescents and Adults (5 mg Risdiplam)	Part 1 Group A Cohort 1: Adolescents and Adults (Placebo)	Part 1 Group A Cohort 2: Adolescents and Adults (Placebo)	Part 1 Group B Cohort 1: Children (0.02 mg/kg Risdiplam)	Part 1 Group B Cohort 2: Children (0.05 mg/kg Risdiplam)	Part 1 Group B Cohort 3: Children (0.25 mg/kg Risdiplam)	Part 1 Group B Cohort 1: Children (Placebo)	Part 1 Group B Cohort 2: Children (Placebo)	Part 1 Group B Cohort 3: Children (Placebo)	Part 1 Group A: OLE	Part 1 Group B: OLE	Part 2: Risdiplam	Part 2: Placebo
Arm/Group Description	Adolescent and adult participants aged 12-25 years received risdiplam for at least 12 weeks. Once the placebo-controlled period was completed and Part 2 dose was selected, participants switched to Part 2 dose and were treated in an open-label phase.	Adolescent and adult participants aged 12-25 years received risdiplam for at least 12 weeks. Once the placebo-controlled period was completed and Part 2 dose was selected, participants switched to Part 2 dose and were treated in an open-label phase.	Adolescent and adult participants aged 12-25 years received placebo matching to risdiplam for at least 12 weeks. Once the placebo-controlled period was completed, participants first switched to their cohort risdiplam dose (i.e. 3 mg). After the Part 2 dose was selected, participants switched to Part 2 dose and were treated in an open-label phase.	Adolescent and adult participants aged 12-25 years received placebo matching to risdiplam for at least 12 weeks. Once the placebo-controlled period was completed, participants first switched to their cohort risdiplam dose (i.e. 5 mg). After the Part 2 dose was selected, participants switched to Part 2 dose and were treated in an open-label phase.	Children aged 2-11 years received risdiplam for at least 12 weeks. During the placebo-controlled period, participants escalated to 0.05 mg/kg and then to 0.15 mg/kg in two steps. Once the placebo-controlled period was completed, and after Part 2 dose was selected, participants switched to Part 2 dose and were treated in an open-label phase.	Children aged 2-11 years received risdiplam for at least 12 weeks. During the placebo-controlled period, participants escalated to 0.15 mg/kg in one step. Once the placebo-controlled period was completed, and after Part 2 dose was selected, participants switched to Part 2 dose and were treated in an open-label phase.	Children aged 2-11 years received risdiplam for at least 12 weeks. Once the placebo-controlled period was completed, and after Part 2 dose was selected, participants switched to Part 2 dose and were treated in an open-label phase.	Children aged 2-11 years received placebo matching to risdiplam for at least 12 weeks. Once the placebo-controlled period was completed, participants first switched to the final 0.15 mg/kg cohort risdiplam dose. After the Part 2 dose was selected, participants switched to Part 2 dose and were treated in an open-label phase.	Children aged 2-11 years received placebo matching to risdiplam for at least 12 weeks. Once the placebo-controlled period was completed, participants first switched to the final 0.15 mg/kg cohort risdiplam dose. After the Part 2 dose was selected, participants switched to Part 2 dose and were treated in an open-label phase.	Children aged 2-11 years received placebo matching to risdiplam for at least 12 weeks. Once the placebo-controlled period was completed, and after Part 2 dose was selected, participants switched to Part 2 dose and were treated in an open-label phase.	Once the placebo-controlled period was completed and Part 2 dose was selected, adolescents and adults switched to Part 2 dose and were treated in an open-label extension (OLE) phase.	Once the placebo-controlled period was completed and Part 2 dose was selected, children switched to Part 2 dose and were treated in an open-label extension (OLE) phase.	Participants aged 2-25 years received risdiplam at the dose of 5 mg once daily for participants with a body weight (BW) >/=20kg or 0.25 mg/kg for participants with a BW <20 kg for 12 months. Once the Part 2 placebo-controlled period was completed participants received risdiplam at the same dose level for another 12 months (Month 12-24) in the open-label treatment (OLT) phase. After Month 24 participants entered the Part 2 OLE phase and continued to receive risdiplam at the same dose level.	Participants aged 2-25 years received placebo matching to risdiplam for 12 months. After 12 months of treatment with placebo, participants switched to risdiplam (5 mg once daily for participants with a body weight (BW) >/=20kg or 0.25 mg/kg for participants with a BW <20) in a blinded manner in the OLT phase. After Month 24 participants entered the Part 2 OLE phase and continued to receive risdiplam at the same dose level.
Period Title: Part 1 Placebo-Controlled
Started	7	7	3	3	7	7	7	3	4	3	0	0	0	0
Completed	7	7	3	3	7	7	7	3	4	3	0	0	0	0
Not Completed	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Period Title: Part 1 OLE
Started	0	0	0	0	0	0	0	0	0	0	20	31	0	0
Completed	0	0	0	0	0	0	0	0	0	0	18	30	0	0
Not Completed	0	0	0	0	0	0	0	0	0	0	2	1	0	0
Reason Not Completed
Withdrawal by Subject	0	0	0	0	0	0	0	0	0	0	2	1	0	0
Period Title: Part 2 Placebo-Controlled: Month 1-12
Started	0	0	0	0	0	0	0	0	0	0	0	0	120	60
Completed	0	0	0	0	0	0	0	0	0	0	0	0	117	59
Not Completed	0	0	0	0	0	0	0	0	0	0	0	0	3	1
Reason Not Completed
Changed to Spinraza	0	0	0	0	0	0	0	0	0	0	0	0	2	1
Changed to other treatment	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Period Title: Part 2 OLT: Month 12-24
Started	0	0	0	0	0	0	0	0	0	0	0	0	117	59
Completed	0	0	0	0	0	0	0	0	0	0	0	0	116	59
Not Completed	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Reason Not Completed
Withdrawal by Subject	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Period Title: Part 2 OLE: > Month 24
Started	0	0	0	0	0	0	0	0	0	0	0	0	116	59
Completed	0	0	0	0	0	0	0	0	0	0	0	0	103	53
Not Completed	0	0	0	0	0	0	0	0	0	0	0	0	13	6
Reason Not Completed
Death	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Reason not specified	0	0	0	0	0	0	0	0	0	0	0	0	2	1
Withdrawal by Subject	0	0	0	0	0	0	0	0	0	0	0	0	10	5

Baseline Characteristics

Arm/Group Title		Part 1 Group A Cohort 1: Adolescents and Adults (3 mg Risdiplam)	Part 1 Group A Cohort 2: Adolescents and Adults (5 mg Risdiplam)	Part 1 Group A Cohort 1: Adolescents and Adults (Placebo)	Part 1 Group A Cohort 2: Adolescents and Adults (Placebo)	Part 1 Group B Cohort 1: Children (0.02 mg/kg Risdiplam)	Part 1 Group B Cohort 2: Children (0.05 mg/kg Risdiplam)	Part 1 Group B Cohort 3: Children (0.25 mg/kg Risdiplam)	Part 1 Group B Cohort 1: Children (Placebo)	Part 1 Group B Cohort 2: Children (Placebo)	Part 1 Group B Cohort 3: Children (Placebo)	Part 2: Risdiplam	Part 2: Placebo	Total
Arm/Group Description		Adolescent and adult participants aged 12-25 years received risdiplam for at least 12 weeks. Once the placebo-controlled period was completed and Part 2 dose was selected, participants switched to Part 2 dose and were treated in an open-label phase.	Adolescent and adult participants aged 12-25 years received risdiplam for at least 12 weeks. Once the placebo-controlled period was completed and Part 2 dose was selected, participants switched to Part 2 dose and were treated in an open-label phase.	Adolescent and adult participants aged 12-25 years received placebo matching to risdiplam for at least 12 weeks. Once the placebo-controlled period was completed, participants first switched to their cohort risdiplam dose (i.e. 3 mg). After the Part 2 dose was selected, participants switched to Part 2 dose and were treated in an open-label phase.	Adolescent and adult participants aged 12-25 years received placebo matching to risdiplam for at least 12 weeks. Once the placebo-controlled period was completed, participants first switched to their cohort risdiplam dose (i.e. 5 mg). After the Part 2 dose was selected, participants switched to Part 2 dose and were treated in an open-label phase.	Children aged 2-11 years received risdiplam for at least 12 weeks. During the placebo-controlled period, participants escalated to 0.05 mg/kg and then to 0.15 mg/kg in two steps. Once the placebo-controlled period was completed, and after Part 2 dose was selected, participants switched to Part 2 dose and were treated in an open-label phase.	Children aged 2-11 years received risdiplam for at least 12 weeks. During the placebo-controlled period, participants escalated to 0.15 mg/kg in one step. Once the placebo-controlled period was completed, and after Part 2 dose was selected, participants switched to Part 2 dose and were treated in an open-label phase.	Children aged 2-11 years received risdiplam for at least 12 weeks. Once the placebo-controlled period was completed, and after Part 2 dose was selected, participants switched to Part 2 dose and were treated in an open-label phase.	Children aged 2-11 years received placebo matching to risdiplam for at least 12 weeks. Once the placebo-controlled period was completed, participants first switched to the final 0.15 mg/kg cohort risdiplam dose. After the Part 2 dose was selected, participants switched to Part 2 dose and were treated in an open-label phase.	Children aged 2-11 years received placebo matching to risdiplam for at least 12 weeks. Once the placebo-controlled period was completed, participants first switched to the final 0.15 mg/kg cohort risdiplam dose. After the Part 2 dose was selected, participants switched to Part 2 dose and were treated in an open-label phase.	Children aged 2-11 years received placebo matching to risdiplam for at least 12 weeks. Once the placebo-controlled period was completed, and after Part 2 dose was selected, participants switched to Part 2 dose and were treated in an open-label phase.	Participants aged 2-25 years received risdiplam at the dose of 5 mg once daily for participants with a body weight (BW) >/=20kg or 0.25 mg/kg for participants with a BW <20 kg for 12 months.	Participants aged 2-25 years received placebo matching to risdiplam for 12 months. After 12 months of treatment with placebo, participants switched to risdiplam (5 mg once daily for participants with a body weight (BW) >/=20kg or 0.25 mg/kg for participants with a BW <20) in a blinded manner and participants will continue with treatment and observations.	Total of all reporting groups
Overall Number of Baseline Participants		7	7	3	3	7	7	7	3	4	3	120	60	231
Baseline Analysis Population Description		[Not Specified]
Age, Continuous [1]; Mean (Standard Deviation); Unit of measure: Years
Part 1	Number Analyzed	7 participants	7 participants	3 participants	3 participants	7 participants	7 participants	7 participants	3 participants	4 participants	3 participants	0 participants	0 participants	51 participants
		13.3 (1.1)	18.1 (4.6)	14.7 (1.5)	17.3 (5.1)	6.1 (2.9)	4.3 (1.7)	6.0 (2.7)	5.3 (2.1)	3.5 (0.6)	5.3 (2.9)			9.4 (6.0)
Part 2	Number Analyzed	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	120 participants	60 participants	180 participants
												9.9 (5.8)	10.3 (6.0)	10.0 (5.8)
		[1] Measure Analysis Population Description: Intent-to-Treat (ITT) population: Part 1 and Part 2 were analyzed separately and population results are provided for each part in the study.
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	7 participants	7 participants	3 participants	3 participants	7 participants	7 participants	7 participants	3 participants	4 participants	3 participants	120 participants	60 participants	231 participants
	Female	5 71.4%	5 71.4%	1 33.3%	2 66.7%	5 71.4%	3 42.9%	4 57.1%	0 0.0%	2 50.0%	0 0.0%	61 50.8%	30 50.0%	118 51.1%
	Male	2 28.6%	2 28.6%	2 66.7%	1 33.3%	2 28.6%	4 57.1%	3 42.9%	3 100.0%	2 50.0%	3 100.0%	59 49.2%	30 50.0%	113 48.9%
Race/Ethnicity, Customized; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	7 participants	7 participants	3 participants	3 participants	7 participants	7 participants	7 participants	3 participants	4 participants	3 participants	120 participants	60 participants	231 participants
	Asian	0 0.0%	0 0.0%	0 0.0%	0 0.0%	1 14.3%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	23 19.2%	12 20.0%	36 15.6%
	White	7 100.0%	7 100.0%	3 100.0%	3 100.0%	6 85.7%	6 85.7%	7 100.0%	3 100.0%	3 75.0%	3 100.0%	80 66.7%	41 68.3%	169 73.2%
	Multiple	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	1 14.3%	0 0.0%	0 0.0%	1 25.0%	0 0.0%	1 0.8%	0 0.0%	3 1.3%
	Black or African American	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	2 1.7%	0 0.0%	2 0.9%
	Unknown	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	14 11.7%	7 11.7%	21 9.1%
Race/Ethnicity, Customized; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	7 participants	7 participants	3 participants	3 participants	7 participants	7 participants	7 participants	3 participants	4 participants	3 participants	120 participants	60 participants	231 participants
	Hispanic or Latino	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	5 4.2%	2 3.3%	7 3.0%
	Not Hispanic or Latino	7 100.0%	7 100.0%	3 100.0%	3 100.0%	6 85.7%	7 100.0%	7 100.0%	3 100.0%	4 100.0%	3 100.0%	114 95.0%	57 95.0%	221 95.7%
	Not Stated	0 0.0%	0 0.0%	0 0.0%	0 0.0%	1 14.3%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	1 1.7%	2 0.9%
	Unknown	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	1 0.8%	0 0.0%	1 0.4%

Outcome Measures

1. Primary Outcome

Title	Part 1: Selected Part 2 Dose of Risdiplam for Participants With a Body Weight (BW) of >/=20kg
Description	The Internal Monitoring Committee (IMC) was responsible for selecting the dose for Part 2 of the study (pivotal dose). An external Independent Data Monitoring Committee (iDMC) reviewed data from Part 1 and confirmed the dose-selection decision of the IMC. The dose for Part 2 selected by the IMC was a dose that: 1.Was judged to be safe and well-tolerated, based on all available safety data from Part 1 and as confirmed by the iDMC; 2. Resulted in an exposure at steady-state below the exposure cap (mean value) of AUC0-24h,ss 2000 ng*h/mL (adjusted for free-fraction, if required); 3. Resulted in an SMN protein increase that was expected to be clinically relevant.
Time Frame	Day 1 up to at least 4 weeks on study (Up to CCOD of 25 July 2017)

Outcome Measure Data

Analysis Population Description

All participants in Part 1.

Arm/Group Title	Part 1: All Risdiplam
Arm/Group Description:	Children aged 2-11 years and adolescent and adult participants aged 12-25 years received risdiplam or risdiplam matching placebo.
Overall Number of Participants Analyzed	51
Measure Type: Number; Unit of Measure: milligram (mg)
	5

2. Primary Outcome

Title	Part 1: Selected Part 2 Dose of Risdiplam for Participants With BW of <20kg
Description	The Internal Monitoring Committee (IMC) was responsible for selecting the dose for Part 2 of the study (pivotal dose). An external Independent Data Monitoring Committee (iDMC) reviewed data from Part 1 and confirmed the dose-selection decision of the IMC. The dose for Part 2 selected by the IMC was a dose that: 1.Was judged to be safe and well-tolerated, based on all available safety data from Part 1 and as confirmed by the iDMC; 2. Resulted in an exposure at steady-state below the exposure cap (mean value) of AUC0-24h,ss 2000 ng*h/mL (adjusted for free-fraction, if required); 3. Resulted in an SMN protein increase that was expected to be clinically relevant.
Time Frame	Day 1 up to at least 4 weeks on study (Up to CCOD of 25 July 2017)

Outcome Measure Data

Analysis Population Description

All participants in Part 1.

Arm/Group Title	Part 1: All Risdiplam
Arm/Group Description:	Children aged 2-11 years and adolescent and adult participants aged 12-25 years received risdiplam or risdiplam matching placebo.
Overall Number of Participants Analyzed	51
Measure Type: Number; Unit of Measure: milligram/kilogram (mg/kg)
	0.25

3. Primary Outcome

Title	Part 2: Change From Baseline in the Total Motor Function Measure 32 (MFM-32) Total Score at Month 12
Description	The Motor Function Measure 32 (MFM32) is a scale constructed for use in neuromuscular disorders. It comprises 32 items that evaluate physical function in three dimensions: D1 function related to standing and transfer; D2 axial and proximal function; D3 distal motor function. Tasks are scored with a 4-point Likert scale: 0 - cannot initiate the task or maintain the starting position; 1 - performs the task partially; 2 - performs the task incompletely or imperfectly; 3 - performs the task fully and "normally". The 32 scores are summed and expressed on a 0-100 scale for the MFM32 total score. Higher scores indicate increased motor function. A positive change from Baseline indicates improvement. MMRM analysis was performed based on primary efficacy hypothetical estimand, which included participants data assuming no prohibited medication intended for treatment of SMA was received and participants continued on their randomized treatment until the analysis time point at Month 12.
Time Frame	Baseline (Day-1) and Month 12

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) population defined as all randomized participants in Part 2. Participants with missing MFM32 total score at Baseline were not included in the analysis.

Arm/Group Title	Part 2: Risdiplam	Part 2: Placebo
Arm/Group Description:	Participants aged 2-25 years received risdiplam at the dose of 5 mg once daily for participants with a body weight (BW) >/=20kg or 0.25 mg/kg for participants with a BW <20 kg for 12 months.	Participants aged 2-25 years received placebo matching to risdiplam for 12 months. After 12 months of treatment with placebo, participants switched to risdiplam (5 mg once daily for participants with a body weight (BW) >/=20kg or 0.25 mg/kg for participants with a BW <20) in a blinded manner and participants will continue with treatment and observations.
Overall Number of Participants Analyzed	115	59
Least Squares Mean (95% Confidence Interval); Unit of Measure: Scores on a Scale
	1.36; (0.61 to 2.11)	-0.19; (-1.22 to 0.84)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 2: Risdiplam, Part 2: Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	This is the first end point and first family tested in the hierarchical testing. The variables included in the MMRM model are: baseline total score, treatment, age group, visit, treatment-by-visit and baseline score-by-visit interaction.
Statistical Test of Hypothesis	P-Value	0.0156
	Comments	[Not Specified]
	Method	Mixed Model Repeated Measure Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least Square Mean Difference
	Estimated Value	1.55
	Confidence Interval	(2-Sided) 95%; 0.30 to 2.81
	Estimation Comments	[Not Specified]

4. Secondary Outcome

Title	Part 2: Percentage of Participants With Marked Improvement (Defined as >= 3) in the Total Motor Function Measure (MFM32) Score at Month 12
Description	The MFM32 comprises 32 items that evaluate physical function. The scoring of each task uses a 4-point Likert scale: 0 - cannot initiate the task or maintain the starting position; 1 - performs the task partially; 2 - performs the task incompletely or imperfectly; 3 - performs the task fully and "normally". The 32 scores are summed and expressed on a 0-100 scale for the MFM32 total score. A change in MFM32 total score of threshold >/=3 represents marked improvement in this measure. Logistic regression analysis was performed based on efficacy hypothetical estimand, which included participants data assuming no prohibited medication intended for treatment of SMA was received and participants continued on their randomized treatment until the analysis time point at Month 12.
Time Frame	At Month 12

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) population defined as all randomized participants in Part 2. Participants with missing MFM32 total score at Baseline were not included in the analysis. Missing results at Month 12 are considered as non-responders.

Arm/Group Title	Part 2: Risdiplam	Part 2: Placebo
Arm/Group Description:	Participants aged 2-25 years received risdiplam at the dose of 5 mg once daily for participants with a body weight (BW) >/=20kg or 0.25 mg/kg for participants with a BW <20 kg for 12 months.	Participants aged 2-25 years received placebo matching to risdiplam for 12 months. After 12 months of treatment with placebo, participants switched to risdiplam (5 mg once daily for participants with a body weight (BW) >/=20kg or 0.25 mg/kg for participants with a BW <20) in a blinded manner and participants will continue with treatment and observations.
Overall Number of Participants Analyzed	115	59
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of Participants
	38.3; (28.94 to 47.58)	23.7; (12.03 to 35.43)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 2: Risdiplam, Part 2: Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	This is the second end point and second family tested in the hierarchical testing. Logistic Regression Model.The variables included in the logistic regression are: baseline total score, treatment and age group.
Statistical Test of Hypothesis	P-Value	0.0469
	Comments	Adjusted p-Value The adjusted p-values were derived based on all the p-values from end points in order of the hierarchical testing up to the current endpoint.
	Method	Wald test
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.35
	Confidence Interval	(2-Sided) 95%; 1.01 to 5.44
	Estimation Comments	[Not Specified]

5. Secondary Outcome

Title	Part 2: Change From Baseline in the Total Score of the Revised Upper Limb Module (RULM) at Month 12
Description	The RULM is a 20 items scale that assesses the proximal and distal motor functions of the arm. There is an entry item and the remaining 18 items are scored on the 3 point scale of: 0: cannot complete task independently; 1: modified method but can complete task independently; 2: completes task without any assistance, and with 1 item scored on a 2 point scale of as a can/cannot score with 1 as the highest score. The RULM total score is the sum of 19 items scores with range of 0-37, and the entry item does not contribute to the total score. Higher scores indicate greater upper limb function. A positive change from Baseline indicates improvement. MMRM analysis was performed based on the efficacy hypothetical estimand, which included participants data assuming no prohibited medication intended for treatment of SMA was received and participants continued on their randomized treatment until the analysis time point at Month 12.
Time Frame	Baseline (Day-1) and Month 12

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) population defined as all randomized participants in Part 2. Participants with missing RULM total score at Baseline were not included in the analysis.

Arm/Group Title	Part 2: Risdiplam	Part 2: Placebo
Arm/Group Description:	Participants aged 2-25 years received risdiplam at the dose of 5 mg once daily for participants with a body weight (BW) >/=20kg or 0.25 mg/kg for participants with a BW <20 kg for 12 months.	Participants aged 2-25 years received placebo matching to risdiplam for 12 months. After 12 months of treatment with placebo, participants switched to risdiplam (5 mg once daily for participants with a body weight (BW) >/=20kg or 0.25 mg/kg for participants with a BW <20) in a blinded manner and participants will continue with treatment and observations.
Overall Number of Participants Analyzed	119	58
Least Squares Mean (95% Confidence Interval); Unit of Measure: Scores on a Scale
	1.61; (1.00 to 2.22)	0.02; (-0.83 to 0.87)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 2: Risdiplam, Part 2: Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	This is the third end point and third family tested in the hierarchical testing. The variables included in the MMRM model are: baseline total score, treatment, age group, visit, treatment-by-visit and baseline score-by-visit interaction.
Statistical Test of Hypothesis	P-Value	0.0469
	Comments	Adjusted p-Value The adjusted p-values were derived based on all the p-values from end points in order of the hierarchical testing up to the current endpoint.
	Method	Mixed Model Repeated Measure Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least Square Mean Difference
	Estimated Value	1.59
	Confidence Interval	(2-Sided) 95%; 0.55 to 2.62
	Estimation Comments	[Not Specified]

6. Secondary Outcome

Title	Part 2: Change From Baseline in Total Score of Hammersmith Functional Motor Scale Expanded (HFMSE) at Month 12
Description	The HFMSE scale contains 33 items, which are scored on a 3-point Likert-type scale (0-2) and summed to derive the total score, with lower scores indicating greater impairment. The HFMSE contains a series of assessments designed to assess important functional abilities, including standing, transfers, ambulation, and proximal and axial function. The overall score is the sum of the scores for all activities with a maximum achievable score of 66. Higher scores indicate greater motor function. A positive change from Baseline indicates improvement. MMRM analysis was performed based on the efficacy hypothetical estimand, which included participants data assuming no prohibited medication intended for treatment of SMA was received and participants continued on their randomized treatment until the analysis time point at Month 12.
Time Frame	Baseline (Day-1) and Month 12

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) population defined as all randomized participants in Part 2.

Arm/Group Title	Part 2: Risdiplam	Part 2: Placebo
Arm/Group Description:	Participants aged 2-25 years received risdiplam at the dose of 5 mg once daily for participants with a body weight (BW) >/=20kg or 0.25 mg/kg for participants with a BW <20 kg for 12 months.	Participants aged 2-25 years received placebo matching to risdiplam for 12 months. After 12 months of treatment with placebo, participants switched to risdiplam (5 mg once daily for participants with a body weight (BW) >/=20kg or 0.25 mg/kg for participants with a BW <20) in a blinded manner and participants will continue with treatment and observations.
Overall Number of Participants Analyzed	120	60
Least Squares Mean (95% Confidence Interval); Unit of Measure: Scores on a Scale
	0.95; (0.29 to 1.61)	0.37; (-0.54 to 1.28)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 2: Risdiplam, Part 2: Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	This is one of the two end points in family four in the hierarchical testing. The variables included in the MMRM model are: baseline total score, treatment, age group, visit, treatment-by-visit and baseline score-by-visit interaction.
Statistical Test of Hypothesis	P-Value	0.3902
	Comments	Adjusted p-Value The adjusted p-values were derived based on all the p-values from end points in order of the hierarchical testing up to the current endpoint.
	Method	Mixed Model Repeated Measure Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least Square Mean Difference
	Estimated Value	0.58
	Confidence Interval	(2-Sided) 95%; -0.53 to 1.69
	Estimation Comments	[Not Specified]

7. Secondary Outcome

Title	Part 2: Change From Baseline in Forced Vital Capacity (FVC) at Month 12 in Participants Aged 6-25 Years
Description	Spirometry is a pulmonary function test that assesses how the lungs work by measuring how much air moves through the airways. Spirometry was performed by all participants aged 6 or older. Forced vital capacity (FVC) is the total volume that can be exhaled after inhaling maximally. The best % predicted value out of all attempts were used for the analysis. MMRM analysis was performed based on the efficacy hypothetical estimand, which included participants data assuming no prohibited medication intended for treatment of SMA was received and participants continued on their randomized treatment until the analysis time point at Month 12.
Time Frame	Baseline (Day-1) and Month 12

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) population defined as all randomized participants in Part 2. Participants with missing FVC data at Baseline were not included in the analysis.

Arm/Group Title	Part 2: Risdiplam	Part 2: Placebo
Arm/Group Description:	Participants aged 2-25 years received risdiplam at the dose of 5 mg once daily for participants with a body weight (BW) >/=20kg or 0.25 mg/kg for participants with a BW <20 kg for 12 months.	Participants aged 2-25 years received placebo matching to risdiplam for 12 months. After 12 months of treatment with placebo, participants switched to risdiplam (5 mg once daily for participants with a body weight (BW) >/=20kg or 0.25 mg/kg for participants with a BW <20) in a blinded manner and participants will continue with treatment and observations.
Overall Number of Participants Analyzed	83	40
Least Squares Mean (95% Confidence Interval); Unit of Measure: Percentage Predicted
	-5.16; (-7.93 to -2.39)	-3.11; (-6.59 to 0.74)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 2: Risdiplam, Part 2: Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	This is one of the two end points in family four in the hierarchical testing. The variables included in the MMRM model are: baseline total score, treatment, age group, visit, treatment-by-visit and baseline score-by-visit interaction.
Statistical Test of Hypothesis	P-Value	0.3902
	Comments	Adjusted p-Value The adjusted p-values were derived based on all the p-values from end points in order of the hierarchical testing up to the current endpoint.
	Method	Mixed Model Repeated Measure Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least Square Mean Difference
	Estimated Value	-2.05
	Confidence Interval	(2-Sided) 95%; -6.67 to 2.56
	Estimation Comments	[Not Specified]

8. Secondary Outcome

Title	Part 2: Change From Baseline in the Caregiver-Reported SMA Independence Scale (SMAIS) Total Score at Month 12
Description	The SMA Independence Scale (SMAIS) was developed specifically for SMA participants in order to assess function-related independence. The SMAIS contains 29 items, assessing the amount of assistance required from another individual to perform daily activities such as eating, or bathing. Each item is scored on a 0-4 scale (with an additional option to indicate that an item is non-applicable). The SMAIS total score ranging from 0-44 is obtained based on 22 items with each item on the 0-2 scale. Lower scores indicate greater dependence on another individual. The SMAIS was completed by participants aged 12 years or older and caregivers of participants aged 2-25 years. MMRM analysis was performed based on efficacy hypothetical estimand, which included participants data assuming no prohibited medication intended for treatment of SMA was received and participants continued on their randomized treatment until the analysis time point at Month 12.
Time Frame	Baseline (Day-1) and Month 12

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) population defined as all randomized participants in Part 2. Participants with missing SMAIS total score at Baseline were not included in the analysis.

Arm/Group Title	Part 2: Risdiplam	Part 2: Placebo
Arm/Group Description:	Participants aged 2-25 years received risdiplam at the dose of 5 mg once daily for participants with a body weight (BW) >/=20kg or 0.25 mg/kg for participants with a BW <20 kg for 12 months.	Participants aged 2-25 years received placebo matching to risdiplam for 12 months. After 12 months of treatment with placebo, participants switched to risdiplam (5 mg once daily for participants with a body weight (BW) >/=20kg or 0.25 mg/kg for participants with a BW <20) in a blinded manner and participants will continue with treatment and observations.
Overall Number of Participants Analyzed	116	60
Least Squares Mean (95% Confidence Interval); Unit of Measure: Scores on a Scale
	1.65; (0.66 to 2.63)	-0.91; (-2.23 to 0.42)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 2: Risdiplam, Part 2: Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	This is the sixth endpoint and the fifth family tested in the hierarchical testing. The variables included in the MMRM model are: baseline total score, treatment, age group, visit, treatment-by-visit and baseline score-by-visit interaction.
Statistical Test of Hypothesis	P-Value	0.3902
	Comments	Adjusted p-Value The adjusted p-values were derived based on all the p-values from end points in order of the hierarchical testing up to the current endpoint.
	Method	Mixed Model Repeated Measure Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least Square Mean Difference
	Estimated Value	2.55
	Confidence Interval	(2-Sided) 95%; 0.93 to 4.17
	Estimation Comments	[Not Specified]

9. Secondary Outcome

Title	Part 2: Percentage of Participants Rated by Clinicians as Improved in the Clinical Global Impression of Change (CGI-C) Scale Ratings at Month 12
Description	The Clinical Global Impression of Change (CGI-C) is used to score a clinician's impression of a participant's change in global health. The CGI-C is a single item measure of change in global health, using seven response options: "very much improved", "much improved", "minimally improved", "no change", "minimally worse", "much worse", and "very much worse". Participants considered as "improved" included responses of "very much improved, "much improved" and "minimally improved". Logistic regression analysis was performed based on efficacy hypothetical estimand, which included participants data assuming no prohibited medication intended for treatment of SMA was received and participants continued on their randomized treatment until the analysis time point at Month 12.
Time Frame	At Month 12

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) population defined as all randomized participants in Part 2. Missing results at Month 12 are considered as non-responders.

Arm/Group Title	Part 2: Risdiplam	Part 2: Placebo
Arm/Group Description:	Participants aged 2-25 years received risdiplam at the dose of 5 mg once daily for participants with a body weight (BW) >/=20kg or 0.25 mg/kg for participants with a BW <20 kg for 12 months.	Participants aged 2-25 years received placebo matching to risdiplam for 12 months. After 12 months of treatment with placebo, participants switched to risdiplam (5 mg once daily for participants with a body weight (BW) >/=20kg or 0.25 mg/kg for participants with a BW <20) in a blinded manner and participants will continue with treatment and observations.
Overall Number of Participants Analyzed	120	60
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of Participants
	47.5; (38.15 to 56.86)	40.0; (26.77 to 53.23)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 2: Risdiplam, Part 2: Placebo
	Comments	CGI Improved
	Type of Statistical Test	Superiority
	Comments	This is the seventh endpoint and the sixth family tested in the hierarchical testing. Logistic Regression Model. The variables included in the logistic regression are: baseline total score, treatment and age group.
Statistical Test of Hypothesis	P-Value	0.3902
	Comments	Adjusted p-Value The adjusted p-values were derived based on all the p-values from end points in order of the hierarchical testing up to the current endpoint.
	Method	Wald-test
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.38
	Confidence Interval	(2-Sided) 95%; 0.70 to 2.74
	Estimation Comments	[Not Specified]

10. Secondary Outcome

Title	Part 2: Percentage of Participants Who Achieve Stabilization or Improvement (Defined as >= 0) in the Total Motor Function Measure (MFM-32) Score at Month 12
Description	The MFM32 comprises 32 items that evaluate physical function in three dimensions: D1 function related to standing and transfer; D2 axial and proximal function; D3 distal motor function. Tasks are scored with a 4-point Likert scale: 0 - cannot initiate the task or maintain the starting position; 1 - performs the task partially; 2 - performs the task incompletely or imperfectly; 3 - performs the task fully and "normally". The 32 scores are summed and expressed on a 0-100 scale for the MFM32 total score. Higher scores indicate increased motor function. Logistic regression analysis was performed based on efficacy hypothetical estimand, which included participants data assuming no prohibited medication intended for treatment of SMA was received and participants continued on their randomized treatment until the analysis time point at Month 12.
Time Frame	At Month 12

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) population defined as all randomized participants in Part 2. Participants with missing MFM32 total score at Baseline were not included in the analysis. Missing results at Month 12 are considered as non-responders.

Arm/Group Title	Part 2: Risdiplam	Part 2: Placebo
Arm/Group Description:	Participants aged 2-25 years received risdiplam at the dose of 5 mg once daily for participants with a body weight (BW) >/=20kg or 0.25 mg/kg for participants with a BW <20 kg for 12 months.	Participants aged 2-25 years received placebo matching to risdiplam for 12 months. After 12 months of treatment with placebo, participants switched to risdiplam (5 mg once daily for participants with a body weight (BW) >/=20kg or 0.25 mg/kg for participants with a BW <20) in a blinded manner and participants will continue with treatment and observations.
Overall Number of Participants Analyzed	115	59
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of Participants
	69.6; (60.72 to 78.41)	54.2; (40.68 to 67.80)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 2: Risdiplam, Part 2: Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	Logistic Regression Model. The variables included in the logistic regression are: baseline total score, treatment and age group.
Statistical Test of Hypothesis	P-Value	0.0430
	Comments	[Not Specified]
	Method	Wald test
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.00
	Confidence Interval	(2-Sided) 95%; 1.02 to 3.93
	Estimation Comments	[Not Specified]

11. Secondary Outcome

Title	Part 2: Percentage of Participants Who Achieve an Improvement of at Least One Standard Error of Measurement on the Total MFM-32 Score at Month 12
Description	The MFM32 comprises 32 items that evaluate physical function in three dimensions: D1 standing and transfer; D2 axial and proximal function; D3 distal motor function. Tasks are scored with a 4-point Likert scale: 0-cannot initiate the task or maintain the starting position; 1-performs the task partially; 2-performs the task incompletely or imperfectly; 3-performs the task fully and "normally". The 32 scores are summed and expressed on a 0-100 scale for the total score. Higher scores indicate increased motor function. Standard error of measurement (SEM) is derived using 32 items scores and total scores at baseline. Change from baseline > = one SEM is equivalent to a change >= 4. Logistic regression analysis was performed based on efficacy hypothetical estimand included participants data assuming no prohibited medication intended for treatment of SMA was received and participants continued on their randomized treatment until the analysis time point at Month 12.
Time Frame	At Month 12

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) population defined as all randomized participants in Part 2. Participants with missing MFM32 total score at Baseline were not included in the analysis.

Arm/Group Title	Part 2: Risdiplam	Part 2: Placebo
Arm/Group Description:	Participants aged 2-25 years received risdiplam at the dose of 5 mg once daily for participants with a body weight (BW) >/=20kg or 0.25 mg/kg for participants with a BW <20 kg for 12 months.	Participants aged 2-25 years received placebo matching to risdiplam for 12 months. After 12 months of treatment with placebo, participants switched to risdiplam (5 mg once daily for participants with a body weight (BW) >/=20kg or 0.25 mg/kg for participants with a BW <20) in a blinded manner and participants will continue with treatment and observations.
Overall Number of Participants Analyzed	115	59
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of Participants
	28.7; (20.65 to 37.88)	16.9; (8.44 to 28.97)

12. Secondary Outcome

Title	Part 2: Change From Baseline in the MFM-32 Domain 1 (D1) Score at Month 12
Description	The MFM32 comprises 32 items that evaluate physical function in three dimensions: D1 function related to standing and transfer; D2 axial and proximal function; D3 distal motor function. Tasks are scored with a 4-point Likert scale: 0 - cannot initiate the task or maintain the starting position; 1 - performs the task partially; 2 - performs the task incompletely or imperfectly; 3 - performs the task fully and "normally". The D1 items score are summed and expressed on 0-100 scale for the MFM D1 total score. Higher scores indicate increased motor function. A positive change from Baseline indicates improvement. MMRM analysis was performed based on efficacy hypothetical estimand, which included participants data assuming no prohibited medication intended for treatment of SMA was received and participants continued on their randomized treatment until the analysis time point at Month 12.
Time Frame	Baseline (Day-1) and Month 12

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) population defined as all randomized participants in Part 2. Participants with missing MFM32 D1 score at Baseline were not included in the analysis.

Arm/Group Title	Part 2: Risdiplam	Part 2: Placebo
Arm/Group Description:	Participants aged 2-25 years received risdiplam at the dose of 5 mg once daily for participants with a body weight (BW) >/=20kg or 0.25 mg/kg for participants with a BW <20 kg for 12 months.	Participants aged 2-25 years received placebo matching to risdiplam for 12 months. After 12 months of treatment with placebo, participants switched to risdiplam (5 mg once daily for participants with a body weight (BW) >/=20kg or 0.25 mg/kg for participants with a BW <20) in a blinded manner and participants will continue with treatment and observations.
Overall Number of Participants Analyzed	118	60
Least Squares Mean (95% Confidence Interval); Unit of Measure: Scores on a Scale
	0.37; (-0.12 to 0.87)	-0.26; (-0.94 to 0.42)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 2: Risdiplam, Part 2: Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	The variables included in the MMRM model are: baseline total score, treatment, age group, visit, treatment-by-visit and baseline score-by-visit interaction.
Statistical Test of Hypothesis	P-Value	0.1328
	Comments	[Not Specified]
	Method	Mixed Model Repeated Measure Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least Square Mean Difference
	Estimated Value	0.64
	Confidence Interval	(2-Sided) 95%; -0.20 to 1.47
	Estimation Comments	[Not Specified]

13. Secondary Outcome

Title	Part 2: Change From Baseline in the MFM-32 Domain 2 (D2) Score at Month 12
Description	The MFM32 comprises 32 items that evaluate physical function in three dimensions: D1 function related to standing and transfer; D2 axial and proximal function; D3 distal motor function. Tasks are scored with a 4-point Likert scale: 0 - cannot initiate the task or maintain the starting position; 1 - performs the task partially; 2 - performs the task incompletely or imperfectly; 3 - performs the task fully and "normally". The D2 items score are summed and expressed on 0-100 scale for the MFM D2 total score. Higher scores indicate increased motor function. A positive change from Baseline indicates improvement. MMRM analysis was performed based on efficacy hypothetical estimand, which included participants data assuming no prohibited medication intended for treatment of SMA was received and participants continued on their randomized treatment until the analysis time point at Month 12.
Time Frame	Baseline (Day-1) and Month 12

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) population defined as all randomized participants in Part 2. Participants with missing MFM32 D2 score at Baseline were not included in the analysis.

Arm/Group Title	Part 2: Risdiplam	Part 2: Placebo
Arm/Group Description:	Participants aged 2-25 years received risdiplam at the dose of 5 mg once daily for participants with a body weight (BW) >/=20kg or 0.25 mg/kg for participants with a BW <20 kg for 12 months.	Participants aged 2-25 years received placebo matching to risdiplam for 12 months. After 12 months of treatment with placebo, participants switched to risdiplam (5 mg once daily for participants with a body weight (BW) >/=20kg or 0.25 mg/kg for participants with a BW <20) in a blinded manner and participants will continue with treatment and observations.
Overall Number of Participants Analyzed	118	60
Least Squares Mean (95% Confidence Interval); Unit of Measure: Scores on a Scale
	1.04; (-0.38 to 2.46)	-0.93; (-2.87 to 1.02)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 2: Risdiplam, Part 2: Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	The variables included in the MMRM model are: baseline total score, treatment, age group, visit, treatment-by-visit and baseline score-by-visit interaction.
Statistical Test of Hypothesis	P-Value	0.1030
	Comments	[Not Specified]
	Method	Mixed Model Repeated Measure Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least Square Mean Difference
	Estimated Value	1.97
	Confidence Interval	(2-Sided) 95%; -0.40 to 4.34
	Estimation Comments	[Not Specified]

14. Secondary Outcome

Title	Part 2: Change From Baseline in the MFM-32 Domain 3 (D3) Score at Month 12
Description	The MFM32 comprises 32 items that evaluate physical function in three dimensions: D1 function related to standing and transfer; D2 axial and proximal function; D3 distal motor function. Tasks are scored with a 4-point Likert scale: 0 - cannot initiate the task or maintain the starting position; 1 - performs the task partially; 2 - performs the task incompletely or imperfectly; 3 - performs the task fully and "normally". The D3 items score are summed and expressed on 0-100 scale for the MFM D3 total score. Higher scores indicate increased motor function. A positive change from Baseline indicates improvement. MMRM analysis was performed based on efficacy hypothetical estimand, which included participants data assuming no prohibited medication intended for treatment of SMA was received and participants continued on their randomized treatment until the analysis time point at Month 12.
Time Frame	Baseline (Day-1) and Month 12

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) population defined as all randomized participants in Part 2. Participants with missing MFM32 D3 score at Baseline were not included in the analysis.

Arm/Group Title	Part 2: Risdiplam	Part 2: Placebo
Arm/Group Description:	Participants aged 2-25 years received risdiplam at the dose of 5 mg once daily for participants with a body weight (BW) >/=20kg or 0.25 mg/kg for participants with a BW <20 kg for 12 months.	Participants aged 2-25 years received placebo matching to risdiplam for 12 months. After 12 months of treatment with placebo, participants switched to risdiplam (5 mg once daily for participants with a body weight (BW) >/=20kg or 0.25 mg/kg for participants with a BW <20) in a blinded manner and participants will continue with treatment and observations.
Overall Number of Participants Analyzed	115	59
Least Squares Mean (95% Confidence Interval); Unit of Measure: Scores on a Scale
	3.68; (2.31 to 5.04)	1.34; (-0.54 to 3.22)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 2: Risdiplam, Part 2: Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	The variables included in the MMRM model are: baseline total score, treatment, age group, visit, treatment-by-visit and baseline score-by-visit interaction.
Statistical Test of Hypothesis	P-Value	0.0451
	Comments	[Not Specified]
	Method	Mixed Model Repeated Measure Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least Square Mean Difference
	Estimated Value	2.34
	Confidence Interval	(2-Sided) 95%; 0.05 to 4.62
	Estimation Comments	[Not Specified]

15. Secondary Outcome

Title	Part 2: Change From Baseline in the Total Combined Scores of MFM-32 Domains 1 and 2 at Month 12
Description	The MFM32 comprises 32 items that evaluate physical function in three dimensions: D1 function related to standing and transfer; D2 axial and proximal function; D3 distal motor function. Tasks are scored with a 4-point Likert scale: 0 - cannot initiate the task or maintain the starting position; 1 - performs the task partially; 2 - performs the task incompletely or imperfectly; 3 - performs the task fully and "normally". The D1+D2 items score are summed and expressed on 0-100 scale for the MFM D1+D2 total score. Higher scores indicate increased motor function. A positive change from Baseline indicates improvement. MMRM analysis was performed based on efficacy hypothetical estimand, which included participants data assuming no prohibited medication intended for treatment of SMA was received and participants continued on their randomized treatment until the analysis time point at Month 12.
Time Frame	Baseline (Day-1) and Month 12

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) population defined as all randomized participants in Part 2. Participants with missing MFM32 D1+D2 scores at Baseline were not included in the analysis.

Arm/Group Title	Part 2: Risdiplam	Part 2: Placebo
Arm/Group Description:	Participants aged 2-25 years received risdiplam at the dose of 5 mg once daily for participants with a body weight (BW) >/=20kg or 0.25 mg/kg for participants with a BW <20 kg for 12 months.	Participants aged 2-25 years received placebo matching to risdiplam for 12 months. After 12 months of treatment with placebo, participants switched to risdiplam (5 mg once daily for participants with a body weight (BW) >/=20kg or 0.25 mg/kg for participants with a BW <20) in a blinded manner and participants will continue with treatment and observations.
Overall Number of Participants Analyzed	118	60
Least Squares Mean (95% Confidence Interval); Unit of Measure: Scores on a Scale
	0.69; (-0.07 to 1.45)	-0.59; (-1.64 to 0.45)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 2: Risdiplam, Part 2: Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	The variables included in the MMRM model are: baseline total score, treatment, age group, visit, treatment-by-visit and baseline score-by-visit interaction.
Statistical Test of Hypothesis	P-Value	0.0489
	Comments	[Not Specified]
	Method	Mixed Model Repeated Measure Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least Square Mean Difference
	Estimated Value	1.28
	Confidence Interval	(2-Sided) 95%; 0.01 to 2.56
	Estimation Comments	[Not Specified]

16. Secondary Outcome

Title	Part 2: Change From Baseline in the Total Combined Scores of MFM-32 Domains 2 and 3 at Month 12
Description	The MFM32 comprises 32 items that evaluate physical function in three dimensions: D1 function related to standing and transfer; D2 axial and proximal function; D3 distal motor function. Tasks are scored with a 4-point Likert scale: 0 - cannot initiate the task or maintain the starting position; 1 - performs the task partially; 2 - performs the task incompletely or imperfectly; 3 - performs the task fully and "normally". The D2+D3 items score are summed and expressed on 0-100 scale for the MFM D2+D3 total score. Higher scores indicate increased motor function. A positive change from Baseline indicates improvement. MMRM analysis was performed based on efficacy hypothetical estimand, which included participants data assuming no prohibited medication intended for treatment of SMA was received and participants continued on their randomized treatment until the analysis time point at Month 12.
Time Frame	Baseline (Day-1) and Month 12

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) population defined as all randomized participants in Part 2. Participants with missing MFM32 D2+D3 scores at Baseline were not included in the analysis.

Arm/Group Title	Part 2: Risdiplam	Part 2: Placebo
Arm/Group Description:	Participants aged 2-25 years received risdiplam at the dose of 5 mg once daily for participants with a body weight (BW) >/=20kg or 0.25 mg/kg for participants with a BW <20 kg for 12 months.	Participants aged 2-25 years received placebo matching to risdiplam for 12 months. After 12 months of treatment with placebo, participants switched to risdiplam (5 mg once daily for participants with a body weight (BW) >/=20kg or 0.25 mg/kg for participants with a BW <20) in a blinded manner and participants will continue with treatment and observations.
Overall Number of Participants Analyzed	115	59
Least Squares Mean (95% Confidence Interval); Unit of Measure: Scores on a Scale
	2.02; (0.84 to 3.20)	-0.14; (-1.76 to 1.48)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 2: Risdiplam, Part 2: Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	The variables included in the MMRM model are: baseline total score, treatment, age group, visit, treatment-by-visit and baseline score-by-visit interaction.
Statistical Test of Hypothesis	P-Value	0.0326
	Comments	[Not Specified]
	Method	Mixed Model Repeated Measure Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least Square Mean Difference
	Estimated Value	2.16
	Confidence Interval	(2-Sided) 95%; 0.18 to 4.14
	Estimation Comments	[Not Specified]

17. Secondary Outcome

Title	Part 2: Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Month 12 in Participants Aged 6-25 Years
Description	Spirometry is a pulmonary function test that assesses how the lungs work by measuring how much air moves through the airways. Spirometry was performed by all participants aged 6 or older. Forced expiratory volume (FEV1) is the volume forcefully exhaled in the first second of the forced vital capacity test. The best % predicted value out of all attempts were used for the analysis. MMRM analysis was performed based on efficacy hypothetical estimand, which included participants data assuming no prohibited medication intended for treatment of SMA was received and participants continued on their randomized treatment until the analysis time point at Month 12.
Time Frame	Baseline (Day-1) and Month 12

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) population defined as all randomized participants in Part 2. Participants with missing FEV1 data at Baseline were not included in the analysis.

Arm/Group Title	Part 2: Risdiplam	Part 2: Placebo
Arm/Group Description:	Participants aged 2-25 years received risdiplam at the dose of 5 mg once daily for participants with a body weight (BW) >/=20kg or 0.25 mg/kg for participants with a BW <20 kg for 12 months.	Participants aged 2-25 years received placebo matching to risdiplam for 12 months. After 12 months of treatment with placebo, participants switched to risdiplam (5 mg once daily for participants with a body weight (BW) >/=20kg or 0.25 mg/kg for participants with a BW <20) in a blinded manner and participants will continue with treatment and observations.
Overall Number of Participants Analyzed	83	40
Least Squares Mean (95% Confidence Interval); Unit of Measure: Percentage Predicted
	-4.22; (-7.49 to -0.96)	-1.35; (-5.91 to 3.20)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 2: Risdiplam, Part 2: Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	The variables included in the MMRM model are: baseline total score, treatment, age group, visit, treatment-by-visit and baseline score-by-visit interaction.
Statistical Test of Hypothesis	P-Value	0.3029
	Comments	[Not Specified]
	Method	Mixed Model Repeated Measure Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least Square Mean Difference
	Estimated Value	-2.87
	Confidence Interval	(2-Sided) 95%; -8.36 to 2.62
	Estimation Comments	[Not Specified]

18. Secondary Outcome

Title	Part 2: Change From Baseline in the Peak Cough Flow (PCF) at Month 12 in Participants Aged 6-25 Years
Description	Spirometry is a pulmonary function test that assesses how the lungs work by measuring how much air moves through the airways. Spirometry was performed by all participants aged 6 or older. Peak cough flow (PCF) is an assessment of cough strength. The best % predicted value out of all attempts were used for the analysis MMRM analysis was performed based on efficacy hypothetical estimand, which included participants data assuming no prohibited medication intended for treatment of SMA was received and participants continued on their randomized treatment until the analysis time point at Month 12.
Time Frame	Baseline (Day-1) and Month 12

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) population defined as all randomized participants in Part 2. Participants with missing PCF data at Baseline were not included in the analysis.

Arm/Group Title	Part 2: Risdiplam	Part 2: Placebo
Arm/Group Description:	Participants aged 2-25 years received risdiplam at the dose of 5 mg once daily for participants with a body weight (BW) >/=20kg or 0.25 mg/kg for participants with a BW <20 kg for 12 months.	Participants aged 2-25 years received placebo matching to risdiplam for 12 months. After 12 months of treatment with placebo, participants switched to risdiplam (5 mg once daily for participants with a body weight (BW) >/=20kg or 0.25 mg/kg for participants with a BW <20) in a blinded manner and participants will continue with treatment and observations.
Overall Number of Participants Analyzed	83	42
Least Squares Mean (95% Confidence Interval); Unit of Measure: Percent Predicted
	1.06; (-1.18 to 3.31)	-0.22; (-3.27 to 2.83)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 2: Risdiplam, Part 2: Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	The variables included in the MMRM model are: baseline total score, treatment, age group, visit, treatment-by-visit and baseline score-by-visit interaction.
Statistical Test of Hypothesis	P-Value	0.4937
	Comments	[Not Specified]
	Method	Mixed Model Repeated Measure Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least Square Mean Difference
	Estimated Value	1.28
	Confidence Interval	(2-Sided) 95%; -2.42 to 4.99
	Estimation Comments	[Not Specified]

19. Secondary Outcome

Title	Part 2: Change From Baseline in the Best Sniff Nasal Inspiratory Pressure (SNIP) at Month 12
Description	The Sniff Nasal Inspiratory Pressure (SNIP) is a volitional, non-invasive test of inspiratory muscle strength that has been successfully applied to children > 2 years of age. Advantages include the simplicity of the maneuver and the absence of a mouthpiece, which is particularly helpful for participants with SMA, who may have bulbar weakness. SNIP also has the advantage of measuring inspiratory pressure during a natural maneuver that is easily performed even by young children with neuromuscular disorders. The best % predicted value out of all attempts were used for the analysis. MMRM analysis was performed based on efficacy hypothetical estimand, which included participants data assuming no prohibited medication intended for treatment of SMA was received and participants continued on their randomized treatment until the analysis time point at Month 12.
Time Frame	Baseline (Day-1) and Month 12

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) population defined as all randomized participants in Part 2. Participants with missing SNIP data at Baseline were not included in the analysis.

Arm/Group Title	Part 2: Risdiplam	Part 2: Placebo
Arm/Group Description:	Participants aged 2-25 years received risdiplam at the dose of 5 mg once daily for participants with a body weight (BW) >/=20kg or 0.25 mg/kg for participants with a BW <20 kg for 12 months.	Participants aged 2-25 years received placebo matching to risdiplam for 12 months. After 12 months of treatment with placebo, participants switched to risdiplam (5 mg once daily for participants with a body weight (BW) >/=20kg or 0.25 mg/kg for participants with a BW <20) in a blinded manner and participants will continue with treatment and observations.
Overall Number of Participants Analyzed	118	59
Least Squares Mean (95% Confidence Interval); Unit of Measure: Percentage Predicted
	3.42; (0.22 to 6.62)	1.07; (-3.42 to 5.57)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 2: Risdiplam, Part 2: Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	The variables included in the MMRM model are: baseline total score, treatment, age group, visit, treatment-by-visit and baseline score-by-visit interaction.
Statistical Test of Hypothesis	P-Value	0.3967
	Comments	[Not Specified]
	Method	Mixed Model Repeated Measure Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least Square Mean Difference
	Estimated Value	2.35
	Confidence Interval	(2-Sided) 95%; -3.11 to 7.80
	Estimation Comments	[Not Specified]

20. Secondary Outcome

Title	Part 2: Change From Baseline in Maximal Inspiratory Pressure (MIP) at Month 12 in Participants Aged 6-25 Years
Description	The maximal inspiratory pressure (MIP) is a non-invasive test of muscle strength, which measures the maximum strength of the diaphragm and other inspiratory muscles. MIP was measured in participants aged 6 or older. Participants were asked to perform a forceful inspiration against an occluded mouth piece. The best % predicted value out of all attempts were used for the analysis. MMRM analysis was performed based on efficacy hypothetical estimand, which included participants data assuming no prohibited medication intended for treatment of SMA was received and participants continued on their randomized treatment until the analysis time point at Month 12.
Time Frame	Baseline (Day-1) and Month 12

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) population defined as all randomized participants in Part 2. Participants with missing MIP data at Baseline were not included in the analysis.

Arm/Group Title	Part 2: Risdiplam	Part 2: Placebo
Arm/Group Description:	Participants aged 2-25 years received risdiplam at the dose of 5 mg once daily for participants with a body weight (BW) >/=20kg or 0.25 mg/kg for participants with a BW <20 kg for 12 months.	Participants aged 2-25 years received placebo matching to risdiplam for 12 months. After 12 months of treatment with placebo, participants switched to risdiplam (5 mg once daily for participants with a body weight (BW) >/=20kg or 0.25 mg/kg for participants with a BW <20) in a blinded manner and participants will continue with treatment and observations.
Overall Number of Participants Analyzed	81	40
Least Squares Mean (95% Confidence Interval); Unit of Measure: Percentage Predicted
	1.99; (-6.13 to 10.11)	-0.97; (-12.33 to 10.38)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 2: Risdiplam, Part 2: Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	The variables included in the MMRM model are: baseline total score, treatment, age group, visit, treatment-by-visit and baseline score-by-visit interaction.
Statistical Test of Hypothesis	P-Value	0.6704
	Comments	[Not Specified]
	Method	Mixed Model Repeated Measure Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least Square Mean Difference
	Estimated Value	2.96
	Confidence Interval	(2-Sided) 95%; -10.78 to 16.70
	Estimation Comments	[Not Specified]

21. Secondary Outcome

Title	Part 2: Change From Baseline in Maximal Expiratory Pressure (MEP) at Month 12 in Participants Aged 6-25 Years
Description	The maximal expiratory pressure (MEP) is a non-invasive test of muscle strength, which measures the maximum strength of the abdominal muscles and other expiratory muscles. MEP was measured in participants aged 6 or older. Participants were asked to perform a forceful inspiration against an occluded mouth piece. The best % predicted value out of all attempts were used for the analysis. MMRM analysis was performed based on efficacy hypothetical estimand, which included participants data assuming no prohibited medication intended for treatment of SMA was received and participants continued on their randomized treatment until the analysis time point at Month 12.
Time Frame	Baseline (Day-1) and Month 12

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) population defined as all randomized participants in Part 2. Participants with missing MEP data at Baseline were not included in the analysis.

Arm/Group Title	Part 2: Risdiplam	Part 2: Placebo
Arm/Group Description:	Participants aged 2-25 years received risdiplam at the dose of 5 mg once daily for participants with a body weight (BW) >/=20kg or 0.25 mg/kg for participants with a BW <20 kg for 12 months.	Participants aged 2-25 years received placebo matching to risdiplam for 12 months. After 12 months of treatment with placebo, participants switched to risdiplam (5 mg once daily for participants with a body weight (BW) >/=20kg or 0.25 mg/kg for participants with a BW <20) in a blinded manner and participants will continue with treatment and observations.
Overall Number of Participants Analyzed	83	41
Least Squares Mean (95% Confidence Interval); Unit of Measure: Percentage Predicted
	-2.75; (-6.22 to 0.72)	-2.33; (-7.21 to 2.56)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 2: Risdiplam, Part 2: Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	The variables included in the MMRM model are: baseline total score, treatment, age group, visit, treatment-by-visit and baseline score-by-visit interaction.
Statistical Test of Hypothesis	P-Value	0.8856
	Comments	[Not Specified]
	Method	Mixed Model Repeated Measure Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least Square Mean Difference
	Estimated Value	-0.43
	Confidence Interval	(2-Sided) 95%; -6.30 to 5.45
	Estimation Comments	[Not Specified]

22. Secondary Outcome

Title	Part 2: Change From Baseline in the Participant-Reported SMA Independence Scale (SMAIS) Total Score at Month 12
Description	The SMAIS was developed specifically for SMA participants in order to assess function-related independence. It contains 29 items, assessing the amount of assistance required from another individual to perform daily activities such as eating, or bathing. Each item is scored on a 0-4 scale (with an additional option to indicate that an item is non-applicable). The SMAIS total score ranging from 0-44 is obtained based on 22 items with each item on the 0-2 scale. Lower scores indicate greater dependence on another individual. The SMAIS was completed by participants aged 12 years or older and caregivers of participants aged 2-25 years. MMRM analysis was performed based on efficacy hypothetical estimand, which included participants data assuming no prohibited medication intended for treatment of SMA was received and participants continued on their randomized treatment until the analysis time point at Month 12.
Time Frame	Baseline (Day-1) and Month 12

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) population defined as all randomized participants in Part 2. Participants with missing SMAIS total score at Baseline were not included in the analysis.

Arm/Group Title	Part 2: Risdiplam	Part 2: Placebo
Arm/Group Description:	Participants aged 2-25 years received risdiplam at the dose of 5 mg once daily for participants with a body weight (BW) >/=20kg or 0.25 mg/kg for participants with a BW <20 kg for 12 months.	Participants aged 2-25 years received placebo matching to risdiplam for 12 months. After 12 months of treatment with placebo, participants switched to risdiplam (5 mg once daily for participants with a body weight (BW) >/=20kg or 0.25 mg/kg for participants with a BW <20) in a blinded manner and participants will continue with treatment and observations.
Overall Number of Participants Analyzed	43	23
Least Squares Mean (95% Confidence Interval); Unit of Measure: Scores on a Scale
	1.04; (-0.26 to 2.35)	-0.40; (-2.13 to 1.32)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 2: Risdiplam, Part 2: Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	The variables included in the MMRM model are: baseline total score, treatment, age group, visit, treatment-by-visit and baseline score-by-visit interaction.
Statistical Test of Hypothesis	P-Value	0.1778
	Comments	[Not Specified]
	Method	Mixed Model Repeated Measure Analysis
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Least Square Mean Difference
	Estimated Value	1.45
	Confidence Interval	(2-Sided) 95%; -0.68 to 3.57
	Estimation Comments	[Not Specified]

23. Secondary Outcome

Title	Part 2: Percentage of Participants Rated by Clinicians as No Change or Improved in the Clinical Global Impression of Change (CGI-C) Scale Ratings at Month 12
Description	The CGI-C is used to score a clinician's impression of a participant's change in global health. It is a single item measure of change in global health, using seven response options: "very much improved", "much improved", "minimally improved", "no change", "minimally worse", "much worse", and "very much worse". Participants considered as "no change or improved" included responses of "no change", "very much improved", "much improved" and "minimally improved". Logistic regression analysis was performed based on efficacy hypothetical estimand, which included participants data assuming no prohibited medication intended for treatment of SMA was received and participants continued on their randomized treatment until the analysis time point at Month 12.
Time Frame	At Month 12

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) population defined as all randomized participants in Part 2. Missing results at Month 12 are considered as non-responders.

Arm/Group Title	Part 2: Risdiplam	Part 2: Placebo
Arm/Group Description:	Participants aged 2-25 years received risdiplam at the dose of 5 mg once daily for participants with a body weight (BW) >/=20kg or 0.25 mg/kg for participants with a BW <20 kg for 12 months.	Participants aged 2-25 years received placebo matching to risdiplam for 12 months. After 12 months of treatment with placebo, participants switched to risdiplam (5 mg once daily for participants with a body weight (BW) >/=20kg or 0.25 mg/kg for participants with a BW <20) in a blinded manner and participants will continue with treatment and observations.
Overall Number of Participants Analyzed	120	60
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of Participants
	85.8; (79.18 to 92.49)	83.3; (73.07 to 93.60)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 2: Risdiplam, Part 2: Placebo
	Comments	CGI No Change or Improved
	Type of Statistical Test	Superiority
	Comments	Logistic Regression Model. The variables included in the logistic regression are: baseline total score, treatment and age group.
Statistical Test of Hypothesis	P-Value	0.6636
	Comments	[Not Specified]
	Method	Wald-test
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.21
	Confidence Interval	(2-Sided) 95%; 0.52 to 2.83
	Estimation Comments	[Not Specified]

24. Secondary Outcome

Title	Part 2: Percentage of Participants Who Experience at Least One Disease-Related Adverse Event at Month 12
Description	Disease-related adverse events (AEs) were identified by applying two different types of baskets to the AE dataset: Narrow prospectively defined baskets of MedDRA lowest level terms. This basket was defined based on a group of CDC terms selected from an age and gender matched case control study comparing CDC code rates observed in participants with and without SMA using commercially available insurance claim data (CLAIMS and Market scan data). The lowest level terms included in each basket, coded using the latest version of MedDRA; Broad prospectively defined basket with events selected at preferred term level from all AEs reported in ongoing clinical trials up to January 2019, i.e., prior to unblinding of Part 2 of Study BP39055.
Time Frame	Baseline up to Month 12 (Week 52; up to CCOD of 06 September 2019)

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) population defined as all randomized participants in Part 2.

Arm/Group Title	Part 2: Risdiplam	Part 2: Placebo
Arm/Group Description:	Participants aged 2-25 years received risdiplam at the dose of 5 mg once daily for participants with a body weight (BW) >/=20kg or 0.25 mg/kg for participants with a BW <20 kg for 12 months.	Participants aged 2-25 years received placebo matching to risdiplam for 12 months. After 12 months of treatment with placebo, participants switched to risdiplam (5 mg once daily for participants with a body weight (BW) >/=20kg or 0.25 mg/kg for participants with a BW <20) in a blinded manner and participants will continue with treatment and observations.
Overall Number of Participants Analyzed	120	60
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of Participants
Narrow Basket AEs	46.7; (37.51 to 55.99)	53.3; (40.00 to 66.33)
Broad Basket AEs	65.0; (55.76 to 73.48)	60.0; (46.54 to 72.44)

25. Secondary Outcome

Title	Part 2: Number of Disease-related Adverse Events Per Patient-years at Month 12
Description	Disease-related AEs were collected through the AE reporting of the study, and the disease-related AE rate was adjusted for patient years (AE rate per 100 patient-years). They were identified by applying two different types of baskets to the AE dataset: Narrow prospectively defined baskets of MedDRA lowest level terms and Broad prospectively defined basket with events selected at preferred term level from all AEs reported in ongoing clinical trials up to January 2019, i.e., prior to unblinding of Part 2 of Study BP39055.
Time Frame	Baseline up to Month 12 (Week 52; up to CCOD of 06 September 2019)

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) population defined as all randomized participants in Part 2.

Arm/Group Title	Part 2: Risdiplam	Part 2: Placebo
Arm/Group Description:	Participants aged 2-25 years received risdiplam at the dose of 5 mg once daily for participants with a body weight (BW) >/=20kg or 0.25 mg/kg for participants with a BW <20 kg for 12 months.	Participants aged 2-25 years received placebo matching to risdiplam for 12 months. After 12 months of treatment with placebo, participants switched to risdiplam (5 mg once daily for participants with a body weight (BW) >/=20kg or 0.25 mg/kg for participants with a BW <20) in a blinded manner and participants will continue with treatment and observations.
Overall Number of Participants Analyzed	120	60
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Number of Events per 100 Patient-Years
Narrow Basket AEs	101.51; (84.23 to 121.29)	119.77; (93.71 to 150.82)
Broad Basket AEs	217.29; (191.63 to 245.42)	199.61; (165.50 to 238.68)

26. Secondary Outcome

Title	Part 2: Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) in the Placebo-Controlled Period
Description	An adverse event (AE) is any untoward medical occurrence in a subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.
Time Frame	Day 1 up to 12 months of the placebo-controlled period

Outcome Measure Data

Analysis Population Description

All participants in Part 2 who receive at least one dose of study medication (risdiplam or placebo) were included in the safety population.

Arm/Group Title	Part 2: Risdiplam	Part 2: Placebo
Arm/Group Description:	Participants aged 2-25 years received risdiplam at the dose of 5 mg once daily for participants with a body weight (BW) >/=20kg or 0.25 mg/kg for participants with a BW <20 kg for 12 months.	Participants aged 2-25 years received placebo matching to risdiplam for 12 months. After 12 months of treatment with placebo, participants switched to risdiplam (5 mg once daily for participants with a body weight (BW) >/=20kg or 0.25 mg/kg for participants with a BW <20) in a blinded manner and participants will continue with treatment and observations.
Overall Number of Participants Analyzed	120	60
Measure Type: Number; Unit of Measure: Percentage of Participants
With at Least One AE	92.5	91.7
With at Least One SAE	20.0	18.3

27. Secondary Outcome

Title	Part 2: Percentage of Participants With Treatment Discontinuation Due to Adverse Events (AEs) and Serious Adverse Events (SAEs) in the Placebo-Controlled Period
Description	An adverse event (AE) is any untoward medical occurrence in a subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.
Time Frame	Day 1 up to 12 months of the placebo-controlled period

Outcome Measure Data

Analysis Population Description

All participants in Part 2 who received at least one dose of study medication (risdiplam or placebo) were included in the safety population.

Arm/Group Title	Part 2: Risdiplam	Part 2: Placebo
Arm/Group Description:	Participants aged 2-25 years received risdiplam at the dose of 5 mg once daily for participants with a body weight (BW) >/=20kg or 0.25 mg/kg for participants with a BW <20 kg for 12 months.	Participants aged 2-25 years received placebo matching to risdiplam for 12 months. After 12 months of treatment with placebo, participants switched to risdiplam (5 mg once daily for participants with a body weight (BW) >/=20kg or 0.25 mg/kg for participants with a BW <20) in a blinded manner and participants will continue with treatment and observations.
Overall Number of Participants Analyzed	120	60
Measure Type: Number; Unit of Measure: Percentage of Participants
Due to AE	0.0	0.0
Due to SAE	0.0	0.0

28. Secondary Outcome

Title	Part 2: Number of Participants Aged 6-25 Years With Suicidal Ideation Based on Columbia-Suicide Severity Rating Scale (C-SSRS) in the Placebo-Controlled Period
Description	The Columbia Suicide Severity Rating Scale (C-SSRS) is used to assess the lifetime suicidality of a participant (C-SSRS baseline) as well as any new instances of suicidality (C-SSRS since last visit). The structured interview prompts recollection of suicidal ideation, including the intensity of the ideation, behavior, and attempts with actual/potential lethality. The C-SSRS assessments results were collected for participants aged 6 years and older.
Time Frame	Day 1 up to 12 months of the placebo-controlled period

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) population defined as all randomized participants in Part 2. Data was collected for participants aged 6-25 years.

Arm/Group Title	Part 2: Risdiplam	Part 2: Placebo
Arm/Group Description:	Participants aged 2-25 years received risdiplam at the dose of 5 mg once daily for participants with a body weight (BW) >/=20kg or 0.25 mg/kg for participants with a BW <20 kg for 12 months.	Participants aged 2-25 years received placebo matching to risdiplam for 12 months. After 12 months of treatment with placebo, participants switched to risdiplam (5 mg once daily for participants with a body weight (BW) >/=20kg or 0.25 mg/kg for participants with a BW <20) in a blinded manner and participants will continue with treatment and observations.
Overall Number of Participants Analyzed	83	42
Measure Type: Number; Unit of Measure: Number of Participants
Wish to be Dead	1	1
Non-specific Active Suicidal Thoughts	1	1
Ideation with Any Methods, No Intent to Act	1	1
Ideation with Some Intent to Act, No Plan	0	1
Ideation with Specific Plan and Intent	0	1

29. Secondary Outcome

Title	Part 2: Number of Participants Aged 6-25 Years With Suicidal Behavior Based on Columbia-Suicide Severity Rating Scale (C-SSRS) in the Placebo-Controlled Period
Description	The Columbia Suicide Severity Rating Scale (C-SSRS) is used to assess the lifetime suicidality of a participant (C-SSRS baseline) as well as any new instances of suicidality (C-SSRS since last visit). The structured interview prompts recollection of suicidal ideation, including the intensity of the ideation, behavior, and attempts with actual/potential lethality. The C-SSRS assessments results were collected for participants aged 6 years and older.
Time Frame	Day 1 up to 12 months of the placebo-controlled period

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) population defined as all randomized participants in Part 2. Data was collected for participants aged 6-25 years.

Arm/Group Title	Part 2: Risdiplam	Part 2: Placebo
Arm/Group Description:	Participants aged 2-25 years received risdiplam at the dose of 5 mg once daily for participants with a body weight (BW) >/=20kg or 0.25 mg/kg for participants with a BW <20 kg for 12 months.	Participants aged 2-25 years received placebo matching to risdiplam for 12 months. After 12 months of treatment with placebo, participants switched to risdiplam (5 mg once daily for participants with a body weight (BW) >/=20kg or 0.25 mg/kg for participants with a BW <20) in a blinded manner and participants will continue with treatment and observations.
Overall Number of Participants Analyzed	83	42
Measure Type: Number; Unit of Measure: Number of Participants
Preparatory Acts or Behavior	0	0
Aborted Attempt	0	0
Interrupted Attempt	0	0
Actual Attempt (non-fatal)	0	0
Completed Suicide	0	0

30. Secondary Outcome

Title	Median Fold Change From Baseline in Survival of Motor Neuron (SMN) Protein Levels in Blood
Description	[Not Specified]
Time Frame	Part 1: Day -1, pre-dose of Weeks 1, 2 (>/= 12 years only), 17, 35 and 104, and at 4h post-dose of Weeks 4 and 52. Part 2: Day -1, pre-dose of Weeks 1, 17, 35 and 104, and at 4h post-dose of Weeks 4 and 52.

Outcome Measure Data

Analysis Population Description

All participants with at least one time point with a protein measurement were included in the pharmacodynamic (PD) analysis data set.

Arm/Group Title	Part 1: All Risdiplam	Part 2: All Risdiplam
Arm/Group Description:	Children aged 2-11 years and adolescent and adult participants aged 12-25 years received risdiplam or risdiplam matching placebo.	Children aged 2-11 years and adolescent and adult participants aged 12-25 years received risdiplam or risdiplam matching placebo.
Overall Number of Participants Analyzed	51	169
Median (Full Range); Unit of Measure: unitless
	2.91; (2.14 to 4.18)	1.96; (0.2 to 4.48)

31. Secondary Outcome

Title	Part 1 and 2: Maximum Plasma Concentration (Cmax) of Risdiplam at Year 5
Description	Reported here is the maximum observed concentration throughout the observation period.
Time Frame	Day 1: 1, 2, 4, 6 h postdose, Weeks 4, 8 (Part 1 only), 52, 87: pre-dose, 1, 2, 4, 6 h post-dose and Weeks 1 (Day 7), 2, 8 (Part 2 only) 17, 35, 70, 104: predose

Outcome Measure Data

Analysis Population Description

All participants with at least one time point with a risdiplam concentration measurement were included in the pharmacokinetic (PK) analysis data set.

Arm/Group Title	Part 1: All Risdiplam	Part 2: All Risdiplam
Arm/Group Description:	Children aged 2-11 years and adolescent and adult participants aged 12-25 years received risdiplam or risdiplam matching placebo.	Children aged 2-11 years and adolescent and adult participants aged 12-25 years received risdiplam or risdiplam matching placebo.
Overall Number of Participants Analyzed	51	179
Median (Full Range); Unit of Measure: nanograms/milliliter (ng/mL)
	137; (58.2 to 242)	140; (42.7 to 313)

32. Secondary Outcome

Title	Part 1 and 2: Area Under the Curve (AUC) From 0 to 24 Hours of Risdiplam at Year 5 Visit
Description	[Not Specified]
Time Frame	Year 5 visit pre-dose, 1, 2, 4, 6, 24 hours post-dose

Outcome Measure Data

Analysis Population Description

All participants with at least one time point with a risdiplam concentration measurement were included in the PK analysis data set.

Arm/Group Title	Part 1: All Risdiplam	Part 2: All Risdiplam
Arm/Group Description:	Children aged 2-11 years and adolescent and adult participants aged 12-25 years received risdiplam or risdiplam matching placebo.	Children aged 2-11 years and adolescent and adult participants aged 12-25 years received risdiplam or risdiplam matching placebo.
Overall Number of Participants Analyzed	49	160
Median (Full Range); Unit of Measure: ng*h/mL
	1700; (1160 to 2590)	1880; (1200 to 2890)

33. Secondary Outcome

Title	Part 1 and 2: Concentration at the End of a Dosing Interval (Ctrough) of Risdiplam at Year 5
Description	[Not Specified]
Time Frame	The last predose sample collected from each participant who had at least 1400 days of risdiplam treatment duration.

Outcome Measure Data

Analysis Population Description

All participants with at least one time point with a risdiplam concentration measurement were included in the PK analysis data set.

Arm/Group Title	Part 1: All Risdiplam	Part 2: All Risdiplam
Arm/Group Description:	Children aged 2-11 years and adolescent and adult participants aged 12-25 years received risdiplam or risdiplam matching placebo.	Children aged 2-11 years and adolescent and adult participants aged 12-25 years received risdiplam or risdiplam matching placebo.
Overall Number of Participants Analyzed	49	107
Median (Full Range); Unit of Measure: ng/mL
	54.1; (21.3 to 108)	57.2; (4.50 to 229)

Adverse Events

Time Frame	Part 1 and Part 2: Up to approximately 5 years
Adverse Event Reporting Description	The safety population included all participants who received at least one dose of study medication (risdiplam or placebo) whether prematurely withdrawn or not.
Arm/Group Title	Part 1 Group A: Adolescents and Adults (3 mg Risdiplam)		Part 1 Group A: Adolescents and Adults (5 mg Risdiplam)		Part 1 Group A: Adolescents and Adults (Placebo-Control Period Pooled)		Part 1 Group B: Children (0.02 mg/kg Risdiplam)		Part 1 Group B: Children (0.05 mg/kg Risdiplam)		Part 1 Group B: Children (0.15 mg/kg Risdiplam)		Part 1 Group B: Children (0.25 mg/kg Risdiplam)		Part 1 Group B: Children (Placebo-Control Period Pooled)		Part 1 Group A: OLE		Part 1 Group B: OLE		Part 2 Placebo-Controlled: Risdiplam		Part 2 Placebo-Controlled: Placebo		Part 2 OLT: Risdiplam/Risdiplam		Part 2 OLT: Placebo/Risdiplam		Part 2 OLE: Risdiplam
Arm/Group Description	Adolescent and adult participants aged 12-25 years received risdiplam for at least 12 weeks during the placebo-controlled period.		Adolescent and adult participants aged 12-25 years received risdiplam for at least 12 weeks during the placebo-controlled period.		Adolescent and adult participants aged 12-25 years received placebo matching to risdiplam for at least 12 weeks during the placebo-controlled period.		Children aged 2-11 years received risdiplam for at least 12 weeks during the placebo-controlled period.		Children aged 2-11 years received risdiplam for at least 12 weeks during the placebo-controlled period.		Children aged 2-11 years received risdiplam for at least 12 weeks during the placebo-controlled period.		Children aged 2-11 years received risdiplam for at least 12 weeks during the placebo-controlled period.		Children aged 2-11 years received placebo matching to risdiplam for at least 12 weeks during the placebo-controlled period.		Once the placebo-controlled period was completed and Part 2 dose was selected, adolescents and adults switched to Part 2 dose and were treated in an open-label extension (OLE) phase.		Once the placebo-controlled period was completed and Part 2 dose was selected, children switched to Part 2 dose and were treated in an open-label extension (OLE) phase.		Participants aged 2-25 years received risdiplam at the dose of 5 mg once daily for participants with a body weight (BW) >/=20kg or 0.25 mg/kg for participants with a BW <20 kg for 12 months during the placebo-controlled period..		Participants aged 2-25 years received placebo matching to risdiplam for 12 months during the placebo-controlled period.		Once the Part 2 placebo-controlled period was completed participants received risdiplam at the dose of 5 mg once daily for participants with a body weight (BW) >/=20kg or 0.25 mg/kg for participants with a BW <20 kg for another 12 months (Month 12-24) in the open-label treatment (OLT) phase.		Once the Part 2 placebo-controlled period was completed participants switched to risdiplam at the dose of 5 mg once daily for participants with a body weight (BW) >/=20kg or 0.25 mg/kg for participants with a BW <20 kg for 12 months (Month 12-24) in the open-label treatment (OLT) phase.		Once the Part 2 OLT period ended participants entered the open-label extension period and continued to receive risdiplam at the dose of 5 mg once daily for participants with a body weight (BW) >/=20kg or 0.25 mg/kg for participants with a BW <20 kg.
All-Cause Mortality
	Part 1 Group A: Adolescents and Adults (3 mg Risdiplam)		Part 1 Group A: Adolescents and Adults (5 mg Risdiplam)		Part 1 Group A: Adolescents and Adults (Placebo-Control Period Pooled)		Part 1 Group B: Children (0.02 mg/kg Risdiplam)		Part 1 Group B: Children (0.05 mg/kg Risdiplam)		Part 1 Group B: Children (0.15 mg/kg Risdiplam)		Part 1 Group B: Children (0.25 mg/kg Risdiplam)		Part 1 Group B: Children (Placebo-Control Period Pooled)		Part 1 Group A: OLE		Part 1 Group B: OLE		Part 2 Placebo-Controlled: Risdiplam		Part 2 Placebo-Controlled: Placebo		Part 2 OLT: Risdiplam/Risdiplam		Part 2 OLT: Placebo/Risdiplam		Part 2 OLE: Risdiplam
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	0/10 (0.00%)		0/10 (0.00%)		0/6 (0.00%)		0/7 (0.00%)		0/14 (0.00%)		0/21 (0.00%)		0/7 (0.00%)		0/10 (0.00%)		0/20 (0.00%)		0/31 (0.00%)		0/120 (0.00%)		0/60 (0.00%)		0/117 (0.00%)		0/59 (0.00%)		1/175 (0.57%)
Serious Adverse Events
	Part 1 Group A: Adolescents and Adults (3 mg Risdiplam)		Part 1 Group A: Adolescents and Adults (5 mg Risdiplam)		Part 1 Group A: Adolescents and Adults (Placebo-Control Period Pooled)		Part 1 Group B: Children (0.02 mg/kg Risdiplam)		Part 1 Group B: Children (0.05 mg/kg Risdiplam)		Part 1 Group B: Children (0.15 mg/kg Risdiplam)		Part 1 Group B: Children (0.25 mg/kg Risdiplam)		Part 1 Group B: Children (Placebo-Control Period Pooled)		Part 1 Group A: OLE		Part 1 Group B: OLE		Part 2 Placebo-Controlled: Risdiplam		Part 2 Placebo-Controlled: Placebo		Part 2 OLT: Risdiplam/Risdiplam		Part 2 OLT: Placebo/Risdiplam		Part 2 OLE: Risdiplam
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/10 (10.00%)		0/10 (0.00%)		0/6 (0.00%)		0/7 (0.00%)		0/14 (0.00%)		0/21 (0.00%)		0/7 (0.00%)		1/10 (10.00%)		5/20 (25.00%)		9/31 (29.03%)		24/120 (20.00%)		11/60 (18.33%)		25/117 (21.37%)		4/59 (6.78%)		34/175 (19.43%)
Blood and lymphatic system disorders
Spontaneous haematoma † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/31 (0.00%)	0	0/120 (0.00%)	0	0/60 (0.00%)	0	0/117 (0.00%)	0	0/59 (0.00%)	0	1/175 (0.57%)	1
Congenital, familial and genetic disorders
Cryptorchism † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/31 (0.00%)	0	0/120 (0.00%)	0	0/60 (0.00%)	0	0/117 (0.00%)	0	0/59 (0.00%)	0	1/175 (0.57%)	1
Gastrointestinal disorders
Abdominal pain † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	1/20 (5.00%)	1	0/31 (0.00%)	0	0/120 (0.00%)	0	0/60 (0.00%)	0	0/117 (0.00%)	0	0/59 (0.00%)	0	0/175 (0.00%)	0
Oesophagitis † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	1/20 (5.00%)	1	0/31 (0.00%)	0	0/120 (0.00%)	0	0/60 (0.00%)	0	0/117 (0.00%)	0	0/59 (0.00%)	0	0/175 (0.00%)	0
Vomiting † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	1/10 (10.00%)	1	0/20 (0.00%)	0	0/31 (0.00%)	0	0/120 (0.00%)	0	0/60 (0.00%)	0	1/117 (0.85%)	1	0/59 (0.00%)	0	1/175 (0.57%)	4
Colitis † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/31 (0.00%)	0	0/120 (0.00%)	0	0/60 (0.00%)	0	0/117 (0.00%)	0	0/59 (0.00%)	0	1/175 (0.57%)	1
Constipation † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/31 (0.00%)	0	1/120 (0.83%)	1	0/60 (0.00%)	0	0/117 (0.00%)	0	0/59 (0.00%)	0	1/175 (0.57%)	1
Dental caries † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/31 (0.00%)	0	0/120 (0.00%)	0	0/60 (0.00%)	0	0/117 (0.00%)	0	0/59 (0.00%)	0	1/175 (0.57%)	1
Duodenal obstruction † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/31 (0.00%)	0	0/120 (0.00%)	0	0/60 (0.00%)	0	0/117 (0.00%)	0	0/59 (0.00%)	0	1/175 (0.57%)	1
Gastritis † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/31 (0.00%)	0	0/120 (0.00%)	0	0/60 (0.00%)	0	2/117 (1.71%)	4	0/59 (0.00%)	0	1/175 (0.57%)	1
Gastrointestinal haemorrhage † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/31 (0.00%)	0	0/120 (0.00%)	0	0/60 (0.00%)	0	0/117 (0.00%)	0	0/59 (0.00%)	0	1/175 (0.57%)	1
Gastrooesophageal reflux disease † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/31 (0.00%)	0	0/120 (0.00%)	0	0/60 (0.00%)	0	0/117 (0.00%)	0	0/59 (0.00%)	0	1/175 (0.57%)	1
Malpositioned teeth † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/31 (0.00%)	0	0/120 (0.00%)	0	0/60 (0.00%)	0	0/117 (0.00%)	0	0/59 (0.00%)	0	1/175 (0.57%)	1
General disorders
Ill-defined disorder † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/31 (0.00%)	0	0/120 (0.00%)	0	0/60 (0.00%)	0	0/117 (0.00%)	0	0/59 (0.00%)	0	1/175 (0.57%)	1
Medical device pain † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/31 (0.00%)	0	1/120 (0.83%)	1	0/60 (0.00%)	0	0/117 (0.00%)	0	0/59 (0.00%)	0	0/175 (0.00%)	0
Pyrexia † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/31 (0.00%)	0	2/120 (1.67%)	2	0/60 (0.00%)	0	0/117 (0.00%)	0	1/59 (1.69%)	1	2/175 (1.14%)	2
Hepatobiliary disorders
Hypertransaminasaemia † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/31 (0.00%)	0	0/120 (0.00%)	0	0/60 (0.00%)	0	0/117 (0.00%)	0	0/59 (0.00%)	0	1/175 (0.57%)	1
Infections and infestations
Appendicitis † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	1/20 (5.00%)	1	0/31 (0.00%)	0	0/120 (0.00%)	0	1/60 (1.67%)	1	0/117 (0.00%)	0	0/59 (0.00%)	0	0/175 (0.00%)	0
Gastroenteritis † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	1/31 (3.23%)	1	2/120 (1.67%)	3	2/60 (3.33%)	2	0/117 (0.00%)	0	0/59 (0.00%)	0	2/175 (1.14%)	4
Influenza † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	1/31 (3.23%)	1	2/120 (1.67%)	2	0/60 (0.00%)	0	1/117 (0.85%)	1	0/59 (0.00%)	0	1/175 (0.57%)	1
Pneumonia † 1	1/10 (10.00%)	1	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	2/20 (10.00%)	3	1/31 (3.23%)	1	10/120 (8.33%)	12	2/60 (3.33%)	2	8/117 (6.84%)	10	0/59 (0.00%)	0	8/175 (4.57%)	12
Pneumonia mycoplasmal † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	1/31 (3.23%)	1	0/120 (0.00%)	0	0/60 (0.00%)	0	1/117 (0.85%)	1	0/59 (0.00%)	0	0/175 (0.00%)	0
Respiratory tract infection † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	1/20 (5.00%)	1	0/31 (0.00%)	0	0/120 (0.00%)	0	0/60 (0.00%)	0	1/117 (0.85%)	1	1/59 (1.69%)	1	0/175 (0.00%)	0
Upper respiratory tract infection † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	1/31 (3.23%)	1	1/120 (0.83%)	1	0/60 (0.00%)	0	1/117 (0.85%)	1	1/59 (1.69%)	1	2/175 (1.14%)	2
Adenovirus infection † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/31 (0.00%)	0	0/120 (0.00%)	0	0/60 (0.00%)	0	0/117 (0.00%)	0	0/59 (0.00%)	0	1/175 (0.57%)	1
Bacteraemia † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/31 (0.00%)	0	2/120 (1.67%)	2	0/60 (0.00%)	0	0/117 (0.00%)	0	0/59 (0.00%)	0	0/175 (0.00%)	0
Bronchitis † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/31 (0.00%)	0	1/120 (0.83%)	1	0/60 (0.00%)	0	0/117 (0.00%)	0	0/59 (0.00%)	0	1/175 (0.57%)	4
COVID-19 † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/31 (0.00%)	0	0/120 (0.00%)	0	0/60 (0.00%)	0	0/117 (0.00%)	0	0/59 (0.00%)	0	2/175 (1.14%)	2
COVID-19 pneumonia † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/31 (0.00%)	0	0/120 (0.00%)	0	0/60 (0.00%)	0	0/117 (0.00%)	0	0/59 (0.00%)	0	1/175 (0.57%)	1
Device related infection † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/31 (0.00%)	0	0/120 (0.00%)	0	0/60 (0.00%)	0	1/117 (0.85%)	1	0/59 (0.00%)	0	0/175 (0.00%)	0
Encephalitis † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/31 (0.00%)	0	0/120 (0.00%)	0	0/60 (0.00%)	0	1/117 (0.85%)	1	0/59 (0.00%)	0	0/175 (0.00%)	0
Gastrointestinal infection † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/31 (0.00%)	0	0/120 (0.00%)	0	0/60 (0.00%)	0	0/117 (0.00%)	0	1/59 (1.69%)	1	0/175 (0.00%)	0
Helicobacter infection † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/31 (0.00%)	0	0/120 (0.00%)	0	0/60 (0.00%)	0	0/117 (0.00%)	0	0/59 (0.00%)	0	1/175 (0.57%)	1
Herpes zoster † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/31 (0.00%)	0	0/120 (0.00%)	0	0/60 (0.00%)	0	1/117 (0.85%)	1	0/59 (0.00%)	0	0/175 (0.00%)	0
Infective thrombosis † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/31 (0.00%)	0	0/120 (0.00%)	0	0/60 (0.00%)	0	1/117 (0.85%)	1	0/59 (0.00%)	0	0/175 (0.00%)	0
Laryngitis † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/31 (0.00%)	0	1/120 (0.83%)	1	0/60 (0.00%)	0	0/117 (0.00%)	0	0/59 (0.00%)	0	0/175 (0.00%)	0
Lower respiratory tract infection † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/31 (0.00%)	0	0/120 (0.00%)	0	1/60 (1.67%)	1	0/117 (0.00%)	0	0/59 (0.00%)	0	2/175 (1.14%)	2
Lower respiratory tract infection viral † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/31 (0.00%)	0	1/120 (0.83%)	1	1/60 (1.67%)	1	0/117 (0.00%)	0	0/59 (0.00%)	0	1/175 (0.57%)	1
Lymph gland infection † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/31 (0.00%)	0	0/120 (0.00%)	0	1/60 (1.67%)	1	0/117 (0.00%)	0	0/59 (0.00%)	0	0/175 (0.00%)	0
Pneumonia aspiration † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/31 (0.00%)	0	1/120 (0.83%)	1	0/60 (0.00%)	0	0/117 (0.00%)	0	0/59 (0.00%)	0	1/175 (0.57%)	1
Pneumonia bacterial † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/31 (0.00%)	0	1/120 (0.83%)	1	0/60 (0.00%)	0	0/117 (0.00%)	0	0/59 (0.00%)	0	0/175 (0.00%)	0
Post procedural infection † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/31 (0.00%)	0	0/120 (0.00%)	0	0/60 (0.00%)	0	1/117 (0.85%)	1	0/59 (0.00%)	0	0/175 (0.00%)	0
Postoperative wound infection † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/31 (0.00%)	0	0/120 (0.00%)	0	0/60 (0.00%)	0	0/117 (0.00%)	0	1/59 (1.69%)	1	0/175 (0.00%)	0
Pyelonephritis † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/31 (0.00%)	0	0/120 (0.00%)	0	0/60 (0.00%)	0	1/117 (0.85%)	2	0/59 (0.00%)	0	0/175 (0.00%)	0
Respiratory tract infection viral † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/31 (0.00%)	0	0/120 (0.00%)	0	0/60 (0.00%)	0	0/117 (0.00%)	0	0/59 (0.00%)	0	1/175 (0.57%)	1
Skin infection † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/31 (0.00%)	0	0/120 (0.00%)	0	0/60 (0.00%)	0	0/117 (0.00%)	0	0/59 (0.00%)	0	1/175 (0.57%)	1
Tonsillitis † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/31 (0.00%)	0	0/120 (0.00%)	0	0/60 (0.00%)	0	1/117 (0.85%)	1	0/59 (0.00%)	0	0/175 (0.00%)	0
Viral upper respiratory tract infection † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/31 (0.00%)	0	1/120 (0.83%)	1	0/60 (0.00%)	0	1/117 (0.85%)	1	0/59 (0.00%)	0	0/175 (0.00%)	0
Wound infection † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/31 (0.00%)	0	0/120 (0.00%)	0	0/60 (0.00%)	0	0/117 (0.00%)	0	0/59 (0.00%)	0	1/175 (0.57%)	1
Injury, poisoning and procedural complications
Concussion † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	1/31 (3.23%)	1	0/120 (0.00%)	0	0/60 (0.00%)	0	0/117 (0.00%)	0	0/59 (0.00%)	0	0/175 (0.00%)	0
Femur fracture † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	2/31 (6.45%)	2	1/120 (0.83%)	1	1/60 (1.67%)	1	0/117 (0.00%)	0	0/59 (0.00%)	0	3/175 (1.71%)	4
Near drowning † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	1/31 (3.23%)	1	0/120 (0.00%)	0	0/60 (0.00%)	0	0/117 (0.00%)	0	0/59 (0.00%)	0	0/175 (0.00%)	0
Brain contusion † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/31 (0.00%)	0	0/120 (0.00%)	0	0/60 (0.00%)	0	1/117 (0.85%)	1	0/59 (0.00%)	0	0/175 (0.00%)	0
Fall † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/31 (0.00%)	0	1/120 (0.83%)	1	0/60 (0.00%)	0	0/117 (0.00%)	0	0/59 (0.00%)	0	0/175 (0.00%)	0
Humerus fracture † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/31 (0.00%)	0	0/120 (0.00%)	0	0/60 (0.00%)	0	0/117 (0.00%)	0	0/59 (0.00%)	0	1/175 (0.57%)	1
Musculoskeletal procedural complication † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/31 (0.00%)	0	0/120 (0.00%)	0	0/60 (0.00%)	0	0/117 (0.00%)	0	0/59 (0.00%)	0	1/175 (0.57%)	1
Toxicity to various agents † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/31 (0.00%)	0	0/120 (0.00%)	0	0/60 (0.00%)	0	0/117 (0.00%)	0	0/59 (0.00%)	0	1/175 (0.57%)	1
Wound dehiscence † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/31 (0.00%)	0	0/120 (0.00%)	0	0/60 (0.00%)	0	0/117 (0.00%)	0	0/59 (0.00%)	0	1/175 (0.57%)	1
Investigations
Oxygen saturation decreased † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/31 (0.00%)	0	0/120 (0.00%)	0	1/60 (1.67%)	1	0/117 (0.00%)	0	0/59 (0.00%)	0	0/175 (0.00%)	0
Metabolism and nutrition disorders
Decreased appetite † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	1/31 (3.23%)	1	0/120 (0.00%)	0	0/60 (0.00%)	0	0/117 (0.00%)	0	0/59 (0.00%)	0	0/175 (0.00%)	0
Dehydration † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	1/31 (3.23%)	1	0/120 (0.00%)	0	1/60 (1.67%)	1	1/117 (0.85%)	1	0/59 (0.00%)	0	1/175 (0.57%)	1
Hypoglycaemia † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/31 (0.00%)	0	0/120 (0.00%)	0	0/60 (0.00%)	0	0/117 (0.00%)	0	0/59 (0.00%)	0	1/175 (0.57%)	2
Hypokalaemia † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/31 (0.00%)	0	0/120 (0.00%)	0	0/60 (0.00%)	0	0/117 (0.00%)	0	0/59 (0.00%)	0	1/175 (0.57%)	1
Metabolic acidosis † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/31 (0.00%)	0	0/120 (0.00%)	0	0/60 (0.00%)	0	0/117 (0.00%)	0	0/59 (0.00%)	0	1/175 (0.57%)	1
Musculoskeletal and connective tissue disorders
Arthralgia † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/31 (0.00%)	0	0/120 (0.00%)	0	0/60 (0.00%)	0	0/117 (0.00%)	0	1/59 (1.69%)	1	0/175 (0.00%)	0
Back pain † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/31 (0.00%)	0	0/120 (0.00%)	0	0/60 (0.00%)	0	1/117 (0.85%)	1	1/59 (1.69%)	1	1/175 (0.57%)	1
Nervous system disorders
Febrile convulsion † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/31 (0.00%)	0	1/120 (0.83%)	1	0/60 (0.00%)	0	0/117 (0.00%)	0	0/59 (0.00%)	0	0/175 (0.00%)	0
Partial seizures † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/31 (0.00%)	0	0/120 (0.00%)	0	0/60 (0.00%)	0	1/117 (0.85%)	1	0/59 (0.00%)	0	1/175 (0.57%)	1
Syncope † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/31 (0.00%)	0	0/120 (0.00%)	0	0/60 (0.00%)	0	0/117 (0.00%)	0	0/59 (0.00%)	0	1/175 (0.57%)	1
Product Issues
Device breakage † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/31 (0.00%)	0	0/120 (0.00%)	0	0/60 (0.00%)	0	0/117 (0.00%)	0	0/59 (0.00%)	0	1/175 (0.57%)	2
Psychiatric disorders
Affective disorder † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/31 (0.00%)	0	0/120 (0.00%)	0	0/60 (0.00%)	0	0/117 (0.00%)	0	0/59 (0.00%)	0	1/175 (0.57%)	2
Encopresis † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/31 (0.00%)	0	0/120 (0.00%)	0	0/60 (0.00%)	0	0/117 (0.00%)	0	0/59 (0.00%)	0	1/175 (0.57%)	1
Renal and urinary disorders
Haematuria † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/31 (0.00%)	0	0/120 (0.00%)	0	0/60 (0.00%)	0	1/117 (0.85%)	1	0/59 (0.00%)	0	0/175 (0.00%)	0
Hydronephrosis † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/31 (0.00%)	0	1/120 (0.83%)	1	0/60 (0.00%)	0	0/117 (0.00%)	0	0/59 (0.00%)	0	0/175 (0.00%)	0
Nephrolithiasis † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/31 (0.00%)	0	1/120 (0.83%)	1	1/60 (1.67%)	1	1/117 (0.85%)	1	0/59 (0.00%)	0	1/175 (0.57%)	1
Renal colic † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/31 (0.00%)	0	0/120 (0.00%)	0	0/60 (0.00%)	0	0/117 (0.00%)	0	0/59 (0.00%)	0	1/175 (0.57%)	3
Respiratory, thoracic and mediastinal disorders
Chronic respiratory failure † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	1/31 (3.23%)	1	0/120 (0.00%)	0	0/60 (0.00%)	0	0/117 (0.00%)	0	0/59 (0.00%)	0	0/175 (0.00%)	0
Acute respiratory failure † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/31 (0.00%)	0	0/120 (0.00%)	0	0/60 (0.00%)	0	0/117 (0.00%)	0	0/59 (0.00%)	0	1/175 (0.57%)	1
Aspiration † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/31 (0.00%)	0	1/120 (0.83%)	1	0/60 (0.00%)	0	0/117 (0.00%)	0	0/59 (0.00%)	0	0/175 (0.00%)	0
Asthma † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/31 (0.00%)	0	1/120 (0.83%)	1	0/60 (0.00%)	0	0/117 (0.00%)	0	0/59 (0.00%)	0	1/175 (0.57%)	4
Atelectasis † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/31 (0.00%)	0	0/120 (0.00%)	0	0/60 (0.00%)	0	1/117 (0.85%)	1	0/59 (0.00%)	0	1/175 (0.57%)	1
Obstructive sleep apnoea syndrome † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/31 (0.00%)	0	0/120 (0.00%)	0	1/60 (1.67%)	1	0/117 (0.00%)	0	0/59 (0.00%)	0	0/175 (0.00%)	0
Pleural effusion † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/31 (0.00%)	0	0/120 (0.00%)	0	0/60 (0.00%)	0	0/117 (0.00%)	0	0/59 (0.00%)	0	1/175 (0.57%)	1
Pneumonitis aspiration † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/31 (0.00%)	0	0/120 (0.00%)	0	0/60 (0.00%)	0	1/117 (0.85%)	1	0/59 (0.00%)	0	0/175 (0.00%)	0
Pneumothorax † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/31 (0.00%)	0	0/120 (0.00%)	0	0/60 (0.00%)	0	1/117 (0.85%)	1	0/59 (0.00%)	0	0/175 (0.00%)	0
Respiratory disorder † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/31 (0.00%)	0	0/120 (0.00%)	0	0/60 (0.00%)	0	0/117 (0.00%)	0	1/59 (1.69%)	1	1/175 (0.57%)	1
Respiratory failure † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/31 (0.00%)	0	0/120 (0.00%)	0	1/60 (1.67%)	1	0/117 (0.00%)	0	0/59 (0.00%)	0	1/175 (0.57%)	1
Vascular disorders
Haematoma † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/31 (0.00%)	0	0/120 (0.00%)	0	0/60 (0.00%)	0	0/117 (0.00%)	0	0/59 (0.00%)	0	1/175 (0.57%)	1
Superficial vein thrombosis † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/31 (0.00%)	0	0/120 (0.00%)	0	0/60 (0.00%)	0	0/117 (0.00%)	0	0/59 (0.00%)	0	1/175 (0.57%)	1
1 Term from vocabulary, MedDRA 26.1; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Part 1 Group A: Adolescents and Adults (3 mg Risdiplam)		Part 1 Group A: Adolescents and Adults (5 mg Risdiplam)		Part 1 Group A: Adolescents and Adults (Placebo-Control Period Pooled)		Part 1 Group B: Children (0.02 mg/kg Risdiplam)		Part 1 Group B: Children (0.05 mg/kg Risdiplam)		Part 1 Group B: Children (0.15 mg/kg Risdiplam)		Part 1 Group B: Children (0.25 mg/kg Risdiplam)		Part 1 Group B: Children (Placebo-Control Period Pooled)		Part 1 Group A: OLE		Part 1 Group B: OLE		Part 2 Placebo-Controlled: Risdiplam		Part 2 Placebo-Controlled: Placebo		Part 2 OLT: Risdiplam/Risdiplam		Part 2 OLT: Placebo/Risdiplam		Part 2 OLE: Risdiplam
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/10 (90.00%)		8/10 (80.00%)		4/6 (66.67%)		6/7 (85.71%)		12/14 (85.71%)		18/21 (85.71%)		6/7 (85.71%)		9/10 (90.00%)		17/20 (85.00%)		28/31 (90.32%)		101/120 (84.17%)		50/60 (83.33%)		88/117 (75.21%)		40/59 (67.80%)		140/175 (80.00%)
Blood and lymphatic system disorders
Iron deficiency anaemia † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	1/20 (5.00%)	1	0/31 (0.00%)	0	1/120 (0.83%)	1	0/60 (0.00%)	0	0/117 (0.00%)	0	1/59 (1.69%)	1	0/175 (0.00%)	0
Neutropenia † 1	1/10 (10.00%)	1	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/31 (0.00%)	0	1/120 (0.83%)	1	1/60 (1.67%)	1	0/117 (0.00%)	0	0/59 (0.00%)	0	2/175 (1.14%)	2
Cardiac disorders
Palpitations † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	1/20 (5.00%)	1	0/31 (0.00%)	0	1/120 (0.83%)	2	0/60 (0.00%)	0	0/117 (0.00%)	0	1/59 (1.69%)	1	1/175 (0.57%)	1
Sinus tachycardia † 1	0/0	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	1/20 (5.00%)	1	0/31 (0.00%)	0	0/120 (0.00%)	0	0/60 (0.00%)	0	0/117 (0.00%)	0	0/59 (0.00%)	0	0/175 (0.00%)	0
Supraventricular tachycardia † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	1/20 (5.00%)	1	0/31 (0.00%)	0	0/120 (0.00%)	0	0/60 (0.00%)	0	0/117 (0.00%)	0	0/59 (0.00%)	0	0/175 (0.00%)	0
Tachycardia † 1	3/10 (30.00%)	3	0/10 (0.00%)	0	1/6 (16.67%)	1	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	1/31 (3.23%)	2	0/120 (0.00%)	0	0/60 (0.00%)	0	1/117 (0.85%)	1	1/59 (1.69%)	1	2/175 (1.14%)	2
Ear and labyrinth disorders
Ear pain † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	1/20 (5.00%)	1	4/31 (12.90%)	5	3/120 (2.50%)	4	2/60 (3.33%)	2	5/117 (4.27%)	5	2/59 (3.39%)	2	3/175 (1.71%)	4
Motion sickness † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	1/10 (10.00%)	2	0/20 (0.00%)	0	0/31 (0.00%)	0	2/120 (1.67%)	2	0/60 (0.00%)	0	0/117 (0.00%)	0	1/59 (1.69%)	1	0/175 (0.00%)	0
Vertigo † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	1/20 (5.00%)	1	0/31 (0.00%)	0	0/120 (0.00%)	0	0/60 (0.00%)	0	0/117 (0.00%)	0	0/59 (0.00%)	0	0/175 (0.00%)	0
Eye disorders
Conjunctival hyperaemia † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	1/10 (10.00%)	1	0/20 (0.00%)	0	0/31 (0.00%)	0	0/120 (0.00%)	0	0/60 (0.00%)	0	0/117 (0.00%)	0	0/59 (0.00%)	0	0/175 (0.00%)	0
Corneal infiltrates † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	1/20 (5.00%)	1	0/31 (0.00%)	0	0/120 (0.00%)	0	0/60 (0.00%)	0	0/117 (0.00%)	0	0/59 (0.00%)	0	0/175 (0.00%)	0
Eczema eyelids † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	1/7 (14.29%)	1	1/14 (7.14%)	1	1/21 (4.76%)	1	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	1/31 (3.23%)	1	0/120 (0.00%)	0	0/60 (0.00%)	0	0/117 (0.00%)	0	0/59 (0.00%)	0	0/175 (0.00%)	0
Ocular hyperaemia † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	1/20 (5.00%)	1	1/31 (3.23%)	1	1/120 (0.83%)	1	0/60 (0.00%)	0	1/117 (0.85%)	1	0/59 (0.00%)	0	2/175 (1.14%)	2
Retinal dystrophy † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	1/20 (5.00%)	1	0/31 (0.00%)	0	0/120 (0.00%)	0	0/60 (0.00%)	0	0/117 (0.00%)	0	0/59 (0.00%)	0	0/175 (0.00%)	0
Vision blurred † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	1/7 (14.29%)	1	1/14 (7.14%)	1	1/21 (4.76%)	1	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/31 (0.00%)	0	1/120 (0.83%)	1	0/60 (0.00%)	0	0/117 (0.00%)	0	0/59 (0.00%)	0	0/175 (0.00%)	0
Gastrointestinal disorders
Abdominal pain † 1	1/10 (10.00%)	1	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	1/21 (4.76%)	2	1/7 (14.29%)	2	1/10 (10.00%)	1	2/20 (10.00%)	2	4/31 (12.90%)	6	8/120 (6.67%)	10	5/60 (8.33%)	6	7/117 (5.98%)	10	4/59 (6.78%)	5	7/175 (4.00%)	15
Abdominal pain upper † 1	0/10 (0.00%)	0	1/10 (10.00%)	1	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	1/10 (10.00%)	1	3/20 (15.00%)	4	3/31 (9.68%)	5	7/120 (5.83%)	7	2/60 (3.33%)	3	1/117 (0.85%)	1	1/59 (1.69%)	1	9/175 (5.14%)	10
Aphthous ulcer † 1	1/10 (10.00%)	1	1/10 (10.00%)	1	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/31 (0.00%)	0	3/120 (2.50%)	4	0/60 (0.00%)	0	1/117 (0.85%)	1	0/59 (0.00%)	0	1/175 (0.57%)	2
Constipation † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	1/10 (10.00%)	1	0/20 (0.00%)	0	4/31 (12.90%)	12	9/120 (7.50%)	10	3/60 (5.00%)	3	4/117 (3.42%)	4	2/59 (3.39%)	4	8/175 (4.57%)	9
Diarrhoea † 1	0/10 (0.00%)	0	1/10 (10.00%)	1	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	1/21 (4.76%)	1	1/7 (14.29%)	1	0/10 (0.00%)	0	0/20 (0.00%)	0	3/31 (9.68%)	14	21/120 (17.50%)	27	5/60 (8.33%)	5	10/117 (8.55%)	12	6/59 (10.17%)	8	17/175 (9.71%)	26
Faecaloma † 1	1/10 (10.00%)	1	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/31 (0.00%)	0	1/120 (0.83%)	1	0/60 (0.00%)	0	0/117 (0.00%)	0	0/59 (0.00%)	0	1/175 (0.57%)	1
Gastrointestinal disorder † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	1/20 (5.00%)	2	0/31 (0.00%)	0	0/120 (0.00%)	0	0/60 (0.00%)	0	0/117 (0.00%)	0	0/59 (0.00%)	0	0/175 (0.00%)	0
Lip pruritus † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	1/7 (14.29%)	1	1/14 (7.14%)	1	1/21 (4.76%)	1	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/31 (0.00%)	0	0/120 (0.00%)	0	0/60 (0.00%)	0	0/117 (0.00%)	0	0/59 (0.00%)	0	0/175 (0.00%)	0
Nausea † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	1/7 (14.29%)	1	1/14 (7.14%)	1	2/21 (9.52%)	2	1/7 (14.29%)	1	1/10 (10.00%)	1	2/20 (10.00%)	3	3/31 (9.68%)	4	11/120 (9.17%)	13	3/60 (5.00%)	4	4/117 (3.42%)	5	3/59 (5.08%)	6	8/175 (4.57%)	10
Oral mucosal erythema † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	1/14 (7.14%)	1	1/21 (4.76%)	1	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	2/31 (6.45%)	2	0/120 (0.00%)	0	1/60 (1.67%)	1	0/117 (0.00%)	0	0/59 (0.00%)	0	0/175 (0.00%)	0
Swollen tongue † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	1/20 (5.00%)	2	0/31 (0.00%)	0	0/120 (0.00%)	0	0/60 (0.00%)	0	0/117 (0.00%)	0	0/59 (0.00%)	0	0/175 (0.00%)	0
Tongue oedema † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	1/20 (5.00%)	1	0/31 (0.00%)	0	0/120 (0.00%)	0	0/60 (0.00%)	0	0/117 (0.00%)	0	0/59 (0.00%)	0	0/175 (0.00%)	0
Toothache † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	1/20 (5.00%)	4	0/31 (0.00%)	0	1/120 (0.83%)	1	0/60 (0.00%)	0	0/117 (0.00%)	0	2/59 (3.39%)	2	1/175 (0.57%)	1
Vomiting † 1	0/10 (0.00%)	0	1/10 (10.00%)	1	0/6 (0.00%)	0	2/7 (28.57%)	4	4/14 (28.57%)	6	5/21 (23.81%)	7	1/7 (14.29%)	1	1/10 (10.00%)	1	4/20 (20.00%)	6	10/31 (32.26%)	27	17/120 (14.17%)	35	14/60 (23.33%)	22	15/117 (12.82%)	31	9/59 (15.25%)	13	20/175 (11.43%)	43
General disorders
Asthenia † 1	1/10 (10.00%)	1	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	2/20 (10.00%)	3	0/31 (0.00%)	0	0/120 (0.00%)	0	0/60 (0.00%)	0	1/117 (0.85%)	1	0/59 (0.00%)	0	0/175 (0.00%)	0
Catheter site extravasation † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	1/14 (7.14%)	1	1/21 (4.76%)	1	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/31 (0.00%)	0	0/120 (0.00%)	0	0/60 (0.00%)	0	0/117 (0.00%)	0	0/59 (0.00%)	0	0/175 (0.00%)	0
Fatigue † 1	2/10 (20.00%)	2	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	1/21 (4.76%)	1	1/7 (14.29%)	1	0/10 (0.00%)	0	0/20 (0.00%)	0	3/31 (9.68%)	5	1/120 (0.83%)	1	1/60 (1.67%)	1	0/117 (0.00%)	0	0/59 (0.00%)	0	4/175 (2.29%)	4
Granuloma † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	1/14 (7.14%)	1	1/21 (4.76%)	1	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/31 (0.00%)	0	0/120 (0.00%)	0	0/60 (0.00%)	0	0/117 (0.00%)	0	0/59 (0.00%)	0	0/175 (0.00%)	0
Hyperpyrexia † 1	1/10 (10.00%)	1	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	1/10 (10.00%)	2	1/20 (5.00%)	1	0/31 (0.00%)	0	1/120 (0.83%)	1	0/60 (0.00%)	0	0/117 (0.00%)	0	0/59 (0.00%)	0	1/175 (0.57%)	1
Hyperthermia † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	1/10 (10.00%)	1	0/20 (0.00%)	0	0/31 (0.00%)	0	0/120 (0.00%)	0	0/60 (0.00%)	0	0/117 (0.00%)	0	0/59 (0.00%)	0	1/175 (0.57%)	1
Influenza like illness † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	1/20 (5.00%)	1	0/31 (0.00%)	0	0/120 (0.00%)	0	0/60 (0.00%)	0	3/117 (2.56%)	3	0/59 (0.00%)	0	6/175 (3.43%)	6
Oedema † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	1/14 (7.14%)	2	1/21 (4.76%)	2	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/31 (0.00%)	0	0/120 (0.00%)	0	0/60 (0.00%)	0	0/117 (0.00%)	0	0/59 (0.00%)	0	0/175 (0.00%)	0
Pain † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	1/20 (5.00%)	1	0/31 (0.00%)	0	0/120 (0.00%)	0	0/60 (0.00%)	0	0/117 (0.00%)	0	0/59 (0.00%)	0	2/175 (1.14%)	2
Pyrexia † 1	2/10 (20.00%)	4	1/10 (10.00%)	2	0/6 (0.00%)	0	2/7 (28.57%)	2	3/14 (21.43%)	4	4/21 (19.05%)	5	1/7 (14.29%)	1	3/10 (30.00%)	5	9/20 (45.00%)	19	18/31 (58.06%)	52	25/120 (20.83%)	41	10/60 (16.67%)	20	15/117 (12.82%)	22	6/59 (10.17%)	7	30/175 (17.14%)	38
Immune system disorders
Hypersensitivity † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	2/20 (10.00%)	3	2/31 (6.45%)	2	1/120 (0.83%)	1	1/60 (1.67%)	1	1/117 (0.85%)	1	0/59 (0.00%)	0	4/175 (2.29%)	4
Infections and infestations
Bronchitis † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	1/10 (10.00%)	1	0/20 (0.00%)	0	7/31 (22.58%)	15	7/120 (5.83%)	9	10/60 (16.67%)	12	6/117 (5.13%)	7	4/59 (6.78%)	4	9/175 (5.14%)	11
COVID-19 † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	3/20 (15.00%)	3	9/31 (29.03%)	12	0/120 (0.00%)	0	0/60 (0.00%)	0	0/117 (0.00%)	0	1/59 (1.69%)	1	55/175 (31.43%)	60
Conjunctivitis † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	3/31 (9.68%)	3	4/120 (3.33%)	6	3/60 (5.00%)	3	1/117 (0.85%)	1	2/59 (3.39%)	3	0/175 (0.00%)	0
Cystitis † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	1/20 (5.00%)	2	1/31 (3.23%)	1	3/120 (2.50%)	5	0/60 (0.00%)	0	1/117 (0.85%)	2	1/59 (1.69%)	1	1/175 (0.57%)	3
Ear infection † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	1/14 (7.14%)	1	1/21 (4.76%)	1	0/7 (0.00%)	0	1/10 (10.00%)	1	2/20 (10.00%)	2	3/31 (9.68%)	3	2/120 (1.67%)	2	2/60 (3.33%)	2	3/117 (2.56%)	3	1/59 (1.69%)	1	3/175 (1.71%)	3
Ear infection fungal † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	1/14 (7.14%)	2	1/21 (4.76%)	2	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/31 (0.00%)	0	0/120 (0.00%)	0	0/60 (0.00%)	0	0/117 (0.00%)	0	0/59 (0.00%)	0	0/175 (0.00%)	0
Gastroenteritis † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	1/21 (4.76%)	2	1/7 (14.29%)	2	1/10 (10.00%)	1	4/20 (20.00%)	7	9/31 (29.03%)	11	7/120 (5.83%)	10	5/60 (8.33%)	6	9/117 (7.69%)	9	5/59 (8.47%)	7	12/175 (6.86%)	18
Gastroenteritis viral † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	1/20 (5.00%)	1	0/31 (0.00%)	0	4/120 (3.33%)	4	1/60 (1.67%)	1	0/117 (0.00%)	0	0/59 (0.00%)	0	3/175 (1.71%)	5
Gastrointestinal infection † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	1/21 (4.76%)	1	1/7 (14.29%)	1	0/10 (0.00%)	0	0/20 (0.00%)	0	0/31 (0.00%)	0	0/120 (0.00%)	0	1/60 (1.67%)	1	2/117 (1.71%)	2	0/59 (0.00%)	0	3/175 (1.71%)	3
Groin infection † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	1/14 (7.14%)	1	1/21 (4.76%)	1	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/31 (0.00%)	0	0/120 (0.00%)	0	1/60 (1.67%)	1	1/117 (0.85%)	1	0/59 (0.00%)	0	0/175 (0.00%)	0
Influenza † 1	1/10 (10.00%)	1	1/10 (10.00%)	1	1/6 (16.67%)	1	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	4/20 (20.00%)	12	6/31 (19.35%)	8	3/120 (2.50%)	3	3/60 (5.00%)	4	3/117 (2.56%)	3	2/59 (3.39%)	2	8/175 (4.57%)	8
Laryngitis † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	1/7 (14.29%)	1	1/14 (7.14%)	1	1/21 (4.76%)	1	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/31 (0.00%)	0	0/120 (0.00%)	0	1/60 (1.67%)	1	0/117 (0.00%)	0	0/59 (0.00%)	0	1/175 (0.57%)	1
Laryngitis viral † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	1/10 (10.00%)	1	0/20 (0.00%)	0	0/31 (0.00%)	0	0/120 (0.00%)	0	0/60 (0.00%)	0	0/117 (0.00%)	0	0/59 (0.00%)	0	0/175 (0.00%)	0
Nasopharyngitis † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	1/14 (7.14%)	1	2/21 (9.52%)	2	1/7 (14.29%)	1	1/10 (10.00%)	1	3/20 (15.00%)	7	12/31 (38.71%)	23	31/120 (25.83%)	54	15/60 (25.00%)	21	26/117 (22.22%)	34	6/59 (10.17%)	7	34/175 (19.43%)	48
Pharyngitis † 1	1/10 (10.00%)	1	0/10 (0.00%)	0	0/6 (0.00%)	0	2/7 (28.57%)	2	2/14 (14.29%)	2	2/21 (9.52%)	2	0/7 (0.00%)	0	0/10 (0.00%)	0	1/20 (5.00%)	3	4/31 (12.90%)	4	6/120 (5.00%)	8	3/60 (5.00%)	3	6/117 (5.13%)	6	4/59 (6.78%)	4	7/175 (4.00%)	7
Pneumonia † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	1/10 (10.00%)	1	1/20 (5.00%)	1	0/31 (0.00%)	0	5/120 (4.17%)	6	3/60 (5.00%)	3	2/117 (1.71%)	2	0/59 (0.00%)	0	12/175 (6.86%)	16
Respiratory tract infection † 1	0/10 (0.00%)	0	2/10 (20.00%)	2	1/6 (16.67%)	1	1/7 (14.29%)	1	1/14 (7.14%)	1	3/21 (14.29%)	3	2/7 (28.57%)	2	0/10 (0.00%)	0	1/20 (5.00%)	1	2/31 (6.45%)	3	8/120 (6.67%)	10	6/60 (10.00%)	9	7/117 (5.98%)	8	1/59 (1.69%)	1	5/175 (2.86%)	5
Rhinitis † 1	1/10 (10.00%)	1	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	1/10 (10.00%)	1	1/20 (5.00%)	1	3/31 (9.68%)	3	5/120 (4.17%)	10	3/60 (5.00%)	4	1/117 (0.85%)	1	3/59 (5.08%)	3	7/175 (4.00%)	7
Scarlet fever † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	2/31 (6.45%)	2	0/120 (0.00%)	0	0/60 (0.00%)	0	1/117 (0.85%)	1	1/59 (1.69%)	1	0/175 (0.00%)	0
Skin infection † 1	0/10 (0.00%)	0	1/10 (10.00%)	1	1/6 (16.67%)	1	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/31 (0.00%)	0	0/120 (0.00%)	0	0/60 (0.00%)	0	0/117 (0.00%)	0	0/59 (0.00%)	0	2/175 (1.14%)	2
Tonsillitis † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	1/14 (7.14%)	1	1/21 (4.76%)	1	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	3/31 (9.68%)	4	3/120 (2.50%)	4	2/60 (3.33%)	4	1/117 (0.85%)	1	2/59 (3.39%)	2	5/175 (2.86%)	10
Tooth abscess † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	1/20 (5.00%)	2	1/31 (3.23%)	1	0/120 (0.00%)	0	0/60 (0.00%)	0	0/117 (0.00%)	0	0/59 (0.00%)	0	0/175 (0.00%)	0
Upper respiratory tract infection † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	2/14 (14.29%)	2	4/21 (19.05%)	5	2/7 (28.57%)	3	0/10 (0.00%)	0	3/20 (15.00%)	10	14/31 (45.16%)	47	38/120 (31.67%)	54	18/60 (30.00%)	27	18/117 (15.38%)	24	10/59 (16.95%)	18	49/175 (28.00%)	99
Urinary tract infection † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	2/20 (10.00%)	2	2/31 (6.45%)	7	6/120 (5.00%)	7	0/60 (0.00%)	0	2/117 (1.71%)	3	2/59 (3.39%)	2	12/175 (6.86%)	21
Viral infection † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	1/20 (5.00%)	1	3/31 (9.68%)	3	1/120 (0.83%)	1	0/60 (0.00%)	0	0/117 (0.00%)	0	0/59 (0.00%)	0	4/175 (2.29%)	4
Sinusitis † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/31 (0.00%)	0	4/120 (3.33%)	5	2/60 (3.33%)	4	2/117 (1.71%)	2	5/59 (8.47%)	6	5/175 (2.86%)	5
Varicella † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	1/31 (3.23%)	1	3/120 (2.50%)	3	3/60 (5.00%)	3	0/117 (0.00%)	0	2/59 (3.39%)	2	3/175 (1.71%)	3
Injury, poisoning and procedural complications
Arthropod bite † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	2/14 (14.29%)	3	2/21 (9.52%)	3	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	1/31 (3.23%)	1	3/120 (2.50%)	3	1/60 (1.67%)	2	2/117 (1.71%)	2	1/59 (1.69%)	1	2/175 (1.14%)	2
Contusion † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	1/14 (7.14%)	1	1/21 (4.76%)	1	0/7 (0.00%)	0	1/10 (10.00%)	1	0/20 (0.00%)	0	1/31 (3.23%)	1	5/120 (4.17%)	5	0/60 (0.00%)	0	2/117 (1.71%)	2	1/59 (1.69%)	1	1/175 (0.57%)	1
Face injury † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	2/31 (6.45%)	2	0/120 (0.00%)	0	0/60 (0.00%)	0	0/117 (0.00%)	0	0/59 (0.00%)	0	0/175 (0.00%)	0
Fall † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	1/14 (7.14%)	1	1/21 (4.76%)	1	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	3/31 (9.68%)	4	2/120 (1.67%)	4	0/60 (0.00%)	0	0/117 (0.00%)	0	0/59 (0.00%)	0	4/175 (2.29%)	4
Femur fracture † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	3/31 (9.68%)	3	1/120 (0.83%)	1	0/60 (0.00%)	0	0/117 (0.00%)	0	0/59 (0.00%)	0	3/175 (1.71%)	3
Foot fracture † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	1/20 (5.00%)	1	0/31 (0.00%)	0	0/120 (0.00%)	0	0/60 (0.00%)	0	0/117 (0.00%)	0	0/59 (0.00%)	0	1/175 (0.57%)	1
Ligament sprain † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	1/21 (4.76%)	1	1/7 (14.29%)	1	0/10 (0.00%)	0	0/20 (0.00%)	0	1/31 (3.23%)	2	2/120 (1.67%)	2	0/60 (0.00%)	0	0/117 (0.00%)	0	1/59 (1.69%)	1	1/175 (0.57%)	1
Limb injury † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	1/20 (5.00%)	1	1/31 (3.23%)	2	1/120 (0.83%)	1	0/60 (0.00%)	0	3/117 (2.56%)	3	1/59 (1.69%)	1	0/175 (0.00%)	0
Tooth dislocation † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	1/14 (7.14%)	1	1/21 (4.76%)	1	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/31 (0.00%)	0	0/120 (0.00%)	0	0/60 (0.00%)	0	0/117 (0.00%)	0	0/59 (0.00%)	0	0/175 (0.00%)	0
Investigations
Gastric pH decreased † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	1/20 (5.00%)	1	0/31 (0.00%)	0	0/120 (0.00%)	0	0/60 (0.00%)	0	0/117 (0.00%)	0	0/59 (0.00%)	0	0/175 (0.00%)	0
Hepatic enzyme increased † 1	1/10 (10.00%)	1	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	1/20 (5.00%)	1	0/31 (0.00%)	0	0/120 (0.00%)	0	0/60 (0.00%)	0	0/117 (0.00%)	0	0/59 (0.00%)	0	0/175 (0.00%)	0
Metabolism and nutrition disorders
Decreased appetite † 1	1/10 (10.00%)	2	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/31 (0.00%)	0	2/120 (1.67%)	2	0/60 (0.00%)	0	2/117 (1.71%)	2	0/59 (0.00%)	0	2/175 (1.14%)	2
Iron deficiency † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	1/20 (5.00%)	1	0/31 (0.00%)	0	0/120 (0.00%)	0	0/60 (0.00%)	0	0/117 (0.00%)	0	0/59 (0.00%)	0	0/175 (0.00%)	0
Vitamin D deficiency † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	1/20 (5.00%)	1	0/31 (0.00%)	0	0/120 (0.00%)	0	0/60 (0.00%)	0	0/117 (0.00%)	0	0/59 (0.00%)	0	1/175 (0.57%)	1
Musculoskeletal and connective tissue disorders
Arthralgia † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	1/10 (10.00%)	2	1/20 (5.00%)	1	5/31 (16.13%)	6	6/120 (5.00%)	9	0/60 (0.00%)	0	3/117 (2.56%)	3	2/59 (3.39%)	2	13/175 (7.43%)	21
Back pain † 1	0/10 (0.00%)	0	1/10 (10.00%)	1	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	4/20 (20.00%)	14	2/31 (6.45%)	3	3/120 (2.50%)	4	2/60 (3.33%)	4	3/117 (2.56%)	3	1/59 (1.69%)	1	11/175 (6.29%)	13
Myalgia † 1	1/10 (10.00%)	1	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	1/20 (5.00%)	1	1/31 (3.23%)	1	3/120 (2.50%)	3	0/60 (0.00%)	0	0/117 (0.00%)	0	1/59 (1.69%)	1	3/175 (1.71%)	3
Neck pain † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	1/20 (5.00%)	13	1/31 (3.23%)	1	1/120 (0.83%)	1	0/60 (0.00%)	0	1/117 (0.85%)	1	0/59 (0.00%)	0	1/175 (0.57%)	1
Osteoporosis † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	2/31 (6.45%)	2	0/120 (0.00%)	0	0/60 (0.00%)	0	0/117 (0.00%)	0	0/59 (0.00%)	0	2/175 (1.14%)	2
Pain in extremity † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	1/14 (7.14%)	1	1/21 (4.76%)	1	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	4/31 (12.90%)	6	4/120 (3.33%)	4	1/60 (1.67%)	3	2/117 (1.71%)	2	3/59 (5.08%)	3	10/175 (5.71%)	12
Nervous system disorders
Dizziness † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	1/21 (4.76%)	1	1/7 (14.29%)	1	0/10 (0.00%)	0	0/20 (0.00%)	0	0/31 (0.00%)	0	0/120 (0.00%)	0	2/60 (3.33%)	2	1/117 (0.85%)	1	0/59 (0.00%)	0	7/175 (4.00%)	7
Headache † 1	1/10 (10.00%)	3	1/10 (10.00%)	3	0/6 (0.00%)	0	1/7 (14.29%)	18	1/14 (7.14%)	18	2/21 (9.52%)	20	1/7 (14.29%)	2	0/10 (0.00%)	0	3/20 (15.00%)	60	6/31 (19.35%)	47	24/120 (20.00%)	88	10/60 (16.67%)	23	12/117 (10.26%)	76	11/59 (18.64%)	32	20/175 (11.43%)	84
Psychiatric disorders
Depression † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	1/20 (5.00%)	1	0/31 (0.00%)	0	0/120 (0.00%)	0	0/60 (0.00%)	0	0/117 (0.00%)	0	0/59 (0.00%)	0	3/175 (1.71%)	3
Initial insomnia † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	1/20 (5.00%)	1	0/31 (0.00%)	0	0/120 (0.00%)	0	0/60 (0.00%)	0	0/117 (0.00%)	0	0/59 (0.00%)	0	0/175 (0.00%)	0
Renal and urinary disorders
Urinary tract pain † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	1/10 (10.00%)	1	0/20 (0.00%)	0	0/31 (0.00%)	0	0/120 (0.00%)	0	0/60 (0.00%)	0	0/117 (0.00%)	0	0/59 (0.00%)	0	0/175 (0.00%)	0
Reproductive system and breast disorders
Amenorrhoea † 1	1/10 (10.00%)	1	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/31 (0.00%)	0	0/120 (0.00%)	0	0/60 (0.00%)	0	1/117 (0.85%)	1	0/59 (0.00%)	0	1/175 (0.57%)	1
Dysmenorrhoea † 1	1/10 (10.00%)	1	2/10 (20.00%)	7	1/6 (16.67%)	3	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	4/20 (20.00%)	27	0/31 (0.00%)	0	2/120 (1.67%)	2	0/60 (0.00%)	0	1/117 (0.85%)	1	1/59 (1.69%)	2	1/175 (0.57%)	1
Heavy menstrual bleeding † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	1/20 (5.00%)	1	0/31 (0.00%)	0	0/120 (0.00%)	0	1/60 (1.67%)	1	0/117 (0.00%)	0	0/59 (0.00%)	0	1/175 (0.57%)	1
Premenstrual pain † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	1/20 (5.00%)	1	0/31 (0.00%)	0	0/120 (0.00%)	0	0/60 (0.00%)	0	0/117 (0.00%)	0	0/59 (0.00%)	0	0/175 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Cough † 1	1/10 (10.00%)	1	0/10 (0.00%)	0	0/6 (0.00%)	0	1/7 (14.29%)	1	2/14 (14.29%)	2	3/21 (14.29%)	4	1/7 (14.29%)	2	2/10 (20.00%)	4	4/20 (20.00%)	5	11/31 (35.48%)	31	17/120 (14.17%)	27	12/60 (20.00%)	19	12/117 (10.26%)	16	5/59 (8.47%)	7	14/175 (8.00%)	19
Dyspnoea † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	1/20 (5.00%)	1	0/31 (0.00%)	0	1/120 (0.83%)	1	0/60 (0.00%)	0	0/117 (0.00%)	0	0/59 (0.00%)	0	1/175 (0.57%)	2
Lower respiratory tract inflammation † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	1/20 (5.00%)	1	0/31 (0.00%)	0	0/120 (0.00%)	0	0/60 (0.00%)	0	0/117 (0.00%)	0	0/59 (0.00%)	0	0/175 (0.00%)	0
Nasal congestion † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	2/31 (6.45%)	2	1/120 (0.83%)	1	1/60 (1.67%)	1	1/117 (0.85%)	1	0/59 (0.00%)	0	1/175 (0.57%)	1
Oropharyngeal pain † 1	2/10 (20.00%)	2	3/10 (30.00%)	4	1/6 (16.67%)	1	1/7 (14.29%)	2	1/14 (7.14%)	2	1/21 (4.76%)	2	0/7 (0.00%)	0	1/10 (10.00%)	2	3/20 (15.00%)	6	6/31 (19.35%)	8	6/120 (5.00%)	6	7/60 (11.67%)	8	4/117 (3.42%)	4	1/59 (1.69%)	1	11/175 (6.29%)	16
Pleurisy † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	1/20 (5.00%)	1	0/31 (0.00%)	0	0/120 (0.00%)	0	0/60 (0.00%)	0	0/117 (0.00%)	0	0/59 (0.00%)	0	0/175 (0.00%)	0
Respiratory tract inflammation † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	3/31 (9.68%)	4	0/120 (0.00%)	0	0/60 (0.00%)	0	0/117 (0.00%)	0	0/59 (0.00%)	0	0/175 (0.00%)	0
Rhinitis allergic † 1	1/10 (10.00%)	1	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	2/20 (10.00%)	6	1/31 (3.23%)	1	1/120 (0.83%)	1	2/60 (3.33%)	3	1/117 (0.85%)	1	1/59 (1.69%)	1	3/175 (1.71%)	3
Rhinorrhoea † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	1/21 (4.76%)	1	1/7 (14.29%)	1	0/10 (0.00%)	0	0/20 (0.00%)	0	3/31 (9.68%)	7	6/120 (5.00%)	6	3/60 (5.00%)	3	3/117 (2.56%)	4	1/59 (1.69%)	1	10/175 (5.71%)	12
Upper respiratory tract inflammation † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	1/21 (4.76%)	1	1/7 (14.29%)	1	2/10 (20.00%)	2	3/20 (15.00%)	5	4/31 (12.90%)	6	0/120 (0.00%)	0	1/60 (1.67%)	1	0/117 (0.00%)	0	0/59 (0.00%)	0	0/175 (0.00%)	0
Asthma † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	1/7 (14.29%)	1	1/14 (7.14%)	1	1/21 (4.76%)	1	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/31 (0.00%)	0	0/120 (0.00%)	0	1/60 (1.67%)	1	1/117 (0.85%)	1	0/59 (0.00%)	0	1/175 (0.57%)	2
Epistaxis † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	1/31 (3.23%)	2	3/120 (2.50%)	4	3/60 (5.00%)	5	1/117 (0.85%)	1	3/59 (5.08%)	4	1/175 (0.57%)	1
Productive cough † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/31 (0.00%)	0	0/120 (0.00%)	0	3/60 (5.00%)	3	1/117 (0.85%)	1	0/59 (0.00%)	0	1/175 (0.57%)	1
Skin and subcutaneous tissue disorders
Acne † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	1/20 (5.00%)	1	0/31 (0.00%)	0	3/120 (2.50%)	3	0/60 (0.00%)	0	1/117 (0.85%)	1	1/59 (1.69%)	1	5/175 (2.86%)	6
Alopecia † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	1/20 (5.00%)	1	0/31 (0.00%)	0	0/120 (0.00%)	0	0/60 (0.00%)	0	1/117 (0.85%)	1	0/59 (0.00%)	0	2/175 (1.14%)	2
Blister † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	1/14 (7.14%)	1	1/21 (4.76%)	1	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/31 (0.00%)	0	1/120 (0.83%)	1	0/60 (0.00%)	0	1/117 (0.85%)	1	0/59 (0.00%)	0	2/175 (1.14%)	5
Dermatitis † 1	1/10 (10.00%)	1	0/10 (0.00%)	0	1/6 (16.67%)	1	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/31 (0.00%)	0	0/120 (0.00%)	0	0/60 (0.00%)	0	1/117 (0.85%)	1	1/59 (1.69%)	1	2/175 (1.14%)	2
Dermatitis diaper † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	1/10 (10.00%)	1	0/20 (0.00%)	0	0/31 (0.00%)	0	0/120 (0.00%)	0	0/60 (0.00%)	0	0/117 (0.00%)	0	0/59 (0.00%)	0	0/175 (0.00%)	0
Dry skin † 1	2/10 (20.00%)	2	0/10 (0.00%)	0	1/6 (16.67%)	1	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	1/31 (3.23%)	1	2/120 (1.67%)	2	0/60 (0.00%)	0	2/117 (1.71%)	2	1/59 (1.69%)	1	1/175 (0.57%)	1
Eczema † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	3/31 (9.68%)	3	5/120 (4.17%)	5	1/60 (1.67%)	1	3/117 (2.56%)	3	1/59 (1.69%)	1	5/175 (2.86%)	6
Hyperkeratosis † 1	1/10 (10.00%)	1	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/31 (0.00%)	0	0/120 (0.00%)	0	0/60 (0.00%)	0	0/117 (0.00%)	0	0/59 (0.00%)	0	0/175 (0.00%)	0
Palmar erythema † 1	1/10 (10.00%)	1	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	1/31 (3.23%)	1	0/120 (0.00%)	0	0/60 (0.00%)	0	0/117 (0.00%)	0	0/59 (0.00%)	0	0/175 (0.00%)	0
Pruritus † 1	1/10 (10.00%)	3	0/10 (0.00%)	0	1/6 (16.67%)	3	1/7 (14.29%)	1	1/14 (7.14%)	1	1/21 (4.76%)	1	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/31 (0.00%)	0	1/120 (0.83%)	1	0/60 (0.00%)	0	2/117 (1.71%)	2	0/59 (0.00%)	0	0/175 (0.00%)	0
Rash † 1	0/10 (0.00%)	0	1/10 (10.00%)	1	0/6 (0.00%)	0	1/7 (14.29%)	1	2/14 (14.29%)	2	3/21 (14.29%)	3	1/7 (14.29%)	1	0/10 (0.00%)	0	0/20 (0.00%)	0	3/31 (9.68%)	3	9/120 (7.50%)	11	1/60 (1.67%)	1	6/117 (5.13%)	6	0/59 (0.00%)	0	7/175 (4.00%)	10
Rash papular † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	1/14 (7.14%)	1	1/21 (4.76%)	1	0/7 (0.00%)	0	1/10 (10.00%)	1	0/20 (0.00%)	0	0/31 (0.00%)	0	1/120 (0.83%)	1	0/60 (0.00%)	0	0/117 (0.00%)	0	0/59 (0.00%)	0	0/175 (0.00%)	0
Seborrhoeic dermatitis † 1	1/10 (10.00%)	1	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/31 (0.00%)	0	1/120 (0.83%)	2	0/60 (0.00%)	0	1/117 (0.85%)	1	0/59 (0.00%)	0	2/175 (1.14%)	2
Skin induration † 1	1/10 (10.00%)	1	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/31 (0.00%)	0	0/120 (0.00%)	0	0/60 (0.00%)	0	0/117 (0.00%)	0	0/59 (0.00%)	0	0/175 (0.00%)	0
Erythema † 1	0/10 (0.00%)	0	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	1/10 (10.00%)	1	1/20 (5.00%)	1	3/31 (9.68%)	5	3/120 (2.50%)	4	0/60 (0.00%)	0	2/117 (1.71%)	2	0/59 (0.00%)	0	1/175 (0.57%)	1
Vascular disorders
Hypertension † 1	1/10 (10.00%)	1	0/10 (0.00%)	0	0/6 (0.00%)	0	0/7 (0.00%)	0	0/14 (0.00%)	0	0/21 (0.00%)	0	0/7 (0.00%)	0	0/10 (0.00%)	0	0/20 (0.00%)	0	0/31 (0.00%)	0	0/120 (0.00%)	0	0/60 (0.00%)	0	0/117 (0.00%)	0	0/59 (0.00%)	0	0/175 (0.00%)	0
1 Term from vocabulary, MedDRA 26.1; † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.

Results Point of Contact

• Name/Title: Medical Communications
• Organization: Hoffmann-La Roche
• Phone: 800 821-8590
• EMail: genentech@druginfo.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Mercuri E, Deconinck N, Mazzone ES, Nascimento A, Oskoui M, Saito K, Vuillerot C, Baranello G, Boespflug-Tanguy O, Goemans N, Kirschner J, Kostera-Pruszczyk A, Servais L, Gerber M, Gorni K, Khwaja O, Kletzl H, Scalco RS, Staunton H, Yeung WY, Martin C, Fontoura P, Day JW; SUNFISH Study Group. Safety and efficacy of once-daily risdiplam in type 2 and non-ambulant type 3 spinal muscular atrophy (SUNFISH part 2): a phase 3, double-blind, randomised, placebo-controlled trial. Lancet Neurol. 2022 Jan;21(1):42-52. doi: 10.1016/S1474-4422(21)00367-7. Erratum In: Lancet Neurol. 2022 Feb;21(2):e2. Lancet Neurol. 2022 Mar;21(3):e3. Lancet Neurol. 2022 May;21(5):e5.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT02908685
• Other Study ID Numbers: BP39055; 2016-000750-35 ( EudraCT Number )
• First Submitted: September 19, 2016
• First Posted: September 21, 2016
• Results First Submitted: August 27, 2020
• Results First Posted: June 15, 2021
• Last Update Posted: April 24, 2024