RTA 408 Capsules in Patients With Friedreich's Ataxia - MOXIe

• ClinicalTrials.gov Identifier: NCT02255435
• Recruitment Status: Active, not recruiting
• First Posted: October 2, 2014
• Results First Posted: November 29, 2022
• Last Update Posted: February 5, 2024
• Sponsor: Reata, a wholly owned subsidiary of Biogen
• Collaborators: AbbVie; Friedreich's Ataxia Research Alliance
• Information provided by (Responsible Party): Biogen ( Reata, a wholly owned subsidiary of Biogen )

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Friedreich Ataxia
• Interventions: Drug: Omaveloxolone Capsules, 2.5 mg; Drug: Omaveloxolone Capsules, 5 mg; Drug: Omaveloxolone Capsules, 10 mg; Drug: Placebo; Drug: Omaveloxolone Capsules, 20 mg; Drug: Omaveloxolone Capsules, 40 mg; Drug: Omaveloxolone Capsules, 80 mg; Drug: Omaveloxolone Capsules, 160 mg; Drug: Omaveloxolone Capsules, 300 mg; Drug: Omaveloxolone Capsules, 150 mg
• Enrollment: 172

Participant Flow

Recruitment Details	MOXIe Part 1 and Part 2 were conducted under the same protocol. Participants enrolled in Part 1 were not allowed to enroll in Part 2. Patients with pes cavus were not to comprise more than 20% of all patients enrolled in Part 2.
Pre-assignment Details

Arm/Group Title	Part 1 Omaveloxolone Capsules 2.5 and 5 mg	Part 1 Omaveloxolone Capsules 10 mg	Part 1 Omaveloxolone Capsules 20 mg	Part 1 Omaveloxolone Capsules 40 mg	Part 1 Omaveloxolone Capsules 80 mg	Part 1 Omaveloxolone Capsules 160 mg	Part 1 Omaveloxolone Capsules 300 mg	Part 1 Placebo Capsules	Part 2 Placebo Capsules	Part 2 Omaveloxolone Capsules 150 mg
Arm/Group Description	Omaveloxolone (RTA 408) Capsules, 2.5 mg administered orally one daily for 2 weeks, then 5 mg administered orally once daily for 10 weeks Omaveloxolone Capsules, 2.5 mg Omaveloxolone Capsules, 5 mg	Omaveloxolone (RTA 408) Capsules, 10 mg administered orally once daily for 12 weeks Omaveloxolone Capsules, 10 mg	Omaveloxolone (RTA 408) Capsules, 20 mg administered orally once daily for 12 weeks Omaveloxolone Capsules, 20 mg	Omaveloxolone (RTA 408) Capsules, 40 mg administered orally once daily for 12 weeks Omaveloxolone Capsules, 40 mg	Omaveloxolone (RTA 408) Capsules, 80 mg administered orally once daily for 12 weeks Omaveloxolone Capsules, 80 mg	Omaveloxolone (RTA 408) Capsules, 160 mg administered orally once daily for 12 weeks Omaveloxolone Capsules, 160 mg	Omaveloxolone (RTA 408) Capsules, 300 mg administered orally once daily for 12 weeks Omaveloxolone Capsules, 300 mg	Placebo capsules administered orally once daily for 12 weeks Placebo	Placebo capsules administered orally once daily for 48 weeks Placebo	Omaveloxolone (RTA 408) Capsules, 150 mg administered orally once daily for 48 weeks Omaveloxolone Capsules, 150 mg
Period Title: Overall Study
Started	6	6	6	6	6	12	10	17	52	51
Number of Participants With Pes Cavus	2	2	3	2	2	8	3	10	10	10
Completed	6	6	6	6	6	12	10	16	51	45
Not Completed	0	0	0	0	0	0	0	1	1	6
Reason Not Completed
Patient's Limited Time Availability	0	0	0	0	0	0	0	1	0	0
Withdrawal by Subject	0	0	0	0	0	0	0	0	1	4
Administrative reasons	0	0	0	0	0	0	0	0	0	2

Baseline Characteristics

Arm/Group Title		Part 1 Omaveloxolone Capsules 2.5 and 5 mg	Part 1 Omaveloxolone Capsules 10 mg	Part 1 Omaveloxolone Capsules 20 mg	Part 1 Omaveloxolone Capsules 40 mg	Part 1 Omaveloxolone Capsules 80 mg	Part 1 Omaveloxolone Capsules 160 mg	Part 1 Omaveloxolone Capsules 300 mg	Part 1 Placebo Capsules	Part 2 Placebo Capsules	Part 2 Omaveloxolone Capsules 150 mg	Total
Arm/Group Description		Omaveloxolone (RTA 408) Capsules, 2.5 mg administered orally one daily for 2 weeks, then 5 mg administered orally once daily for 10 weeks Omaveloxolone Capsules, 2.5 mg Omaveloxolone Capsules, 5 mg	Omaveloxolone (RTA 408) Capsules, 10 mg administered orally once daily for 12 weeks Omaveloxolone Capsules, 10 mg	Omaveloxolone (RTA 408) Capsules, 20 mg administered orally once daily for 12 weeks Omaveloxolone Capsules, 20 mg	Omaveloxolone (RTA 408) Capsules, 40 mg administered orally once daily for 12 weeks Omaveloxolone Capsules, 40 mg	Omaveloxolone (RTA 408) Capsules, 80 mg administered orally once daily for 12 weeks Omaveloxolone Capsules, 80 mg	Omaveloxolone (RTA 408) Capsules, 160 mg administered orally once daily for 12 weeks Omaveloxolone Capsules, 160 mg	Omaveloxolone (RTA 408) Capsules, 300 mg administered orally once daily for 12 weeks Omaveloxolone Capsules, 300 mg	Placebo capsules administered orally once daily for 12 weeks Placebo	Placebo capsules administered orally once daily for 48 weeks Placebo	Omaveloxolone (RTA 408) Capsules, 150 mg administered orally once daily for 48 weeks Omaveloxolone Capsules, 150 mg	Total of all reporting groups
Overall Number of Baseline Participants		6	6	6	6	6	12	10	17	52	51	172
Baseline Analysis Population Description		All randomized patients, whether or not they received study drug
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	6 participants	6 participants	6 participants	6 participants	6 participants	12 participants	10 participants	17 participants	52 participants	51 participants	172 participants
		25.8 (5.98)	25.5 (7.4)	28.3 (6.8)	27.7 (7.53)	24.3 (4.8)	25.3 (6.51)	25.6 (7.24)	24.4 (6.74)	24.1 (7.85)	23.4 (6.08)	24.5 (6.84)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	6 participants	6 participants	6 participants	6 participants	6 participants	12 participants	10 participants	17 participants	52 participants	51 participants	172 participants
	Female	4 66.7%	4 66.7%	5 83.3%	1 16.7%	3 50.0%	5 41.7%	5 50.0%	10 58.8%	17 32.7%	31 60.8%	85 49.4%
	Male	2 33.3%	2 33.3%	1 16.7%	5 83.3%	3 50.0%	7 58.3%	5 50.0%	7 41.2%	35 67.3%	20 39.2%	87 50.6%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	6 participants	6 participants	6 participants	6 participants	6 participants	12 participants	10 participants	17 participants	52 participants	51 participants	172 participants
	Hispanic or Latino	0 0.0%	1 16.7%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	1 5.9%	3 5.8%	2 3.9%	7 4.1%
	Not Hispanic or Latino	6 100.0%	5 83.3%	6 100.0%	6 100.0%	6 100.0%	12 100.0%	10 100.0%	16 94.1%	49 94.2%	49 96.1%	165 95.9%
	Unknown or Not Reported	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%	0 0.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	6 participants	6 participants	6 participants	6 participants	6 participants	12 participants	10 participants	17 participants	52 participants	51 participants	172 participants
	American Indian or Alaska Native	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%	0 0.0%
	Asian	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%	0 0.0%
	Native Hawaiian or Other Pacific Islander	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%	0 0.0%
	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%	0 0.0%
	White	6 100.0%	6 100.0%	6 100.0%	6 100.0%	6 100.0%	11 91.7%	10 100.0%	16 94.1%	50 96.2%	50 98.0%	167 97.1%
	More than one race	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%	0 0.0%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	1 8.3%	0 0.0%	1 5.9%	2 3.8%	1 2.0%	5 2.9%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants	Number Analyzed	6 participants	6 participants	6 participants	6 participants	6 participants	12 participants	10 participants	17 participants	52 participants	51 participants	172 participants
Austria		0	0	0	0	0	3	2	0	6	3	14
United States		6	6	6	6	5	8	7	16	35	36	131
United Kingdom		0	0	0	0	0	0	0	0	3	5	8
Italy		0	0	0	0	0	0	0	0	5	2	7
Australia		0	0	0	0	1	1	1	1	3	5	12
Peak Work [1]; Mean (Standard Deviation); Unit of measure: W/kg
	Number Analyzed	6 participants	6 participants	6 participants	6 participants	6 participants	12 participants	10 participants	17 participants	52 participants	51 participants	172 participants
		1.2 (0.696)	0.78 (0.677)	1.25 (0.838)	0.72 (0.565)	1.6 (0.556)	1.18 (0.646)	0.88 (0.521)	0.99 (0.637)	1.23 (0.622)	1.09 (0.576)	1.12 (0.621)
		[1] Measure Description: Peak work attained during maximal exercise testing. Cycle ergometry using a recumbent stationary bicycle was used, and workload was increased incrementally. Peak work is defined as the workload at which patients reach maximal volition (defined as an inability to continue to exercise due to exhaustion).

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Peak Work (in Watts/kg) During Exercise Testing at Week 12 in Part 1
Description	Peak work attained during maximal exercise testing. Cycle ergometry using a recumbent stationary bicycle was used, and workload was increased incrementally. Peak work is defined as the workload at which patients reach maximal volition (defined as an inability to continue to exercise due to exhaustion).
Time Frame	Baseline through 12 weeks after participant receives the first dose in Part 1.

Outcome Measure Data

Analysis Population Description

All randomized patients in Part 1, whether or not they received study drug

Arm/Group Title	Part 1 Omaveloxolone Capsules 2.5 and 5 mg	Part 1 Omaveloxolone Capsules 10 mg	Part 1 Omaveloxolone Capsules 20 mg	Part 1 Omaveloxolone Capsules 40 mg	Part 1 Omaveloxolone Capsules 80 mg	Part 1 Omaveloxolone Capsules 160 mg	Part 1 Omaveloxolone Capsules 300 mg	Part 1 Placebo Capsules
Arm/Group Description:	Omaveloxolone (RTA 408) Capsules, 2.5 mg administered orally one daily for 2 weeks, then 5 mg administered orally once daily for 10 weeks Omaveloxolone Capsules, 2.5 mg Omaveloxolone Capsules, 5 mg	Omaveloxolone (RTA 408) Capsules, 10 mg administered orally once daily for 12 weeks Omaveloxolone Capsules, 10 mg	Omaveloxolone (RTA 408) Capsules, 20 mg administered orally once daily for 12 weeks Omaveloxolone Capsules, 20 mg	Omaveloxolone (RTA 408) Capsules, 40 mg administered orally once daily for 12 weeks Omaveloxolone Capsules, 40 mg	Omaveloxolone (RTA 408) Capsules, 80 mg administered orally once daily for 12 weeks Omaveloxolone Capsules, 80 mg	Omaveloxolone (RTA 408) Capsules, 160 mg administered orally once daily for 12 weeks Omaveloxolone Capsules, 160 mg	Omaveloxolone (RTA 408) Capsules, 300 mg administered orally once daily for 12 weeks Omaveloxolone Capsules, 300 mg	Placebo capsules administered orally once daily for 12 weeks Placebo
Overall Number of Participants Analyzed	6	6	6	6	6	12	10	17
Least Squares Mean (95% Confidence Interval); Unit of Measure: W/kg
	0.14; (0.02 to 0.26)	0.07; (-0.05 to 0.18)	-0.09; (-0.20 to 0.03)	0.06; (-0.06 to 0.18)	0; (-0.11 to 0.12)	0.02; (-0.06 to 0.10)	0.07; (-0.02 to 0.17)	0.04; (-0.03 to 0.11)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 1 Omaveloxolone Capsules 2.5 and 5 mg, Part 1 Placebo Capsules
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.1524
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	Treatment group, time, and the interaction between treatment and time were used as fixed factors.
Method of Estimation	Estimation Parameter	LS Mean difference (Net)
	Estimated Value	0.10
	Confidence Interval	(2-Sided) 95%; -0.04 to 0.23
	Estimation Comments	Difference is omaveloxolone - placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Part 1 Omaveloxolone Capsules 10 mg, Part 1 Placebo Capsules
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.7086
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	Treatment group, time, and the interaction between treatment and time were used as fixed factors.
Method of Estimation	Estimation Parameter	LS Mean difference (Net)
	Estimated Value	0.03
	Confidence Interval	(2-Sided) 95%; -0.11 to 0.16
	Estimation Comments	Difference is omaveloxolone - placebo

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Part 1 Omaveloxolone Capsules 20 mg, Part 1 Placebo Capsules
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0651
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	Treatment group, time, and the interaction between treatment and time were used as fixed factors.
Method of Estimation	Estimation Parameter	LS Mean difference (Net)
	Estimated Value	-0.13
	Confidence Interval	(2-Sided) 95%; -0.26 to 0.01
	Estimation Comments	Difference is omaveloxolone - placebo

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Part 1 Omaveloxolone Capsules 40 mg, Part 1 Placebo Capsules
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.7937
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	Treatment group, time, and the interaction between treatment and time were used as fixed factors.
Method of Estimation	Estimation Parameter	LS Mean difference (Net)
	Estimated Value	0.02
	Confidence Interval	(2-Sided) 95%; -0.12 to 0.15
	Estimation Comments	Difference is omaveloxolone - placebo

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Part 1 Omaveloxolone Capsules 80 mg, Part 1 Placebo Capsules
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.5587
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	Treatment group, time, and the interaction between treatment and time were used as fixed factors.
Method of Estimation	Estimation Parameter	LS Mean difference (Net)
	Estimated Value	-0.04
	Confidence Interval	(2-Sided) 95%; -0.18 to 0.10
	Estimation Comments	Difference is omaveloxolone - placebo

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Part 1 Omaveloxolone Capsules 160 mg, Part 1 Placebo Capsules
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.7285
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	Treatment group, time, and the interaction between treatment and time were used as fixed factors.
Method of Estimation	Estimation Parameter	LS Mean difference (Net)
	Estimated Value	-0.02
	Confidence Interval	(2-Sided) 95%; -0.13 to 0.09
	Estimation Comments	Difference is omaveloxolone - placebo

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Part 1 Omaveloxolone Capsules 300 mg, Part 1 Placebo Capsules
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.5802
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	Treatment group, time, and the interaction between treatment and time were used as fixed factors.
Method of Estimation	Estimation Parameter	LS Mean difference (Net)
	Estimated Value	0.03
	Confidence Interval	(2-Sided) 95%; -0.09 to 0.15
	Estimation Comments	Difference is omaveloxolone - placebo

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Part 1 Omaveloxolone Capsules 2.5 and 5 mg, Part 1 Omaveloxolone Capsules 10 mg, Part 1 Omaveloxolone Capsules 20 mg, Part 1 Omaveloxolone Capsules 40 mg, Part 1 Omaveloxolone Capsules 80 mg, Part 1 Omaveloxolone Capsules 160 mg, Part 1 Omaveloxolone Capsules 300 mg, Part 1 Placebo Capsules
	Comments	Comparison of Omaveloxolone capsules pooled with Placebo capsules
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.9698
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	Treatment group, time, and the interaction between treatment and time were used as fixed factors.
Method of Estimation	Estimation Parameter	LS Mean difference (Net)
	Estimated Value	-0.00
	Confidence Interval	(2-Sided) 95%; -0.08 to 0.08
	Estimation Comments	Difference is omaveloxolone - placebo

2. Primary Outcome

Title	Change in the Modified Friedreich's Ataxia Rating Scale (mFARS) at Week 48 in Part 2
Description	The mFARS includes 4 of the 5 sections of the Friedreich's Ataxia Rating Scale (FARS): bulbar (score 0 to 11), upper limb coordination (score 0 to 36), lower limb coordination (score 0 to 16), and upright stability (score 0 to 36). The minimum score is 0 and the maximum score is 99. A lower score indicates better neurological function.
Time Frame	48 weeks after participant receives the first dose in Part 2

Outcome Measure Data

Analysis Population Description

Full analysis set (all patients in Part 2 randomized without pes cavus who have at least one post-baseline measurement)

Arm/Group Title	Part 2 Placebo Capsules	Part 2 Omaveloxolone Capsules 150 mg
Arm/Group Description:	Placebo capsules administered orally once daily for 48 weeks Placebo	Omaveloxolone (RTA 408) Capsules, 150 mg administered orally once daily for 48 weeks Omaveloxolone Capsules, 150 mg
Overall Number of Participants Analyzed	42	40
Least Squares Mean (Standard Error); Unit of Measure: score on a scale
	0.85 (0.640)	-1.55 (0.689)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 2 Placebo Capsules, Part 2 Omaveloxolone Capsules 150 mg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0141
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	Fixed factors: treatment group, time, interaction between treatment and time, interaction between baseline and time; covariates: site, baseline mFARS
Method of Estimation	Estimation Parameter	LS Mean difference (Net)
	Estimated Value	-2.40
	Confidence Interval	(2-Sided) 95%; -4.31 to -0.50
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.956
	Estimation Comments	Difference is omaveloxolone - placebo.

3. Secondary Outcome

Title	Change in the Modified Friedreich's Ataxia Rating Scale (mFARS) at Week 12 in Part 1
Description	The mFARS includes 4 of the 5 sections of the Friedreich's Ataxia Rating Scale (FARS): bulbar (score 0 to 11), upper limb coordination (score 0 to 36), lower limb coordination (score 0 to 16), and upright stability (score 0 to 36). The minimum score is 0 and the maximum score is 99. A lower score indicates better neurological function.
Time Frame	12 weeks after participant receives the first dose in Part 1

Outcome Measure Data

Analysis Population Description

All randomized patients in Part 1, whether or not they received study drug

Arm/Group Title	Part 1 Omaveloxolone Capsules 2.5 and 5 mg	Part 1 Omaveloxolone Capsules 10 mg	Part 1 Omaveloxolone Capsules 20 mg	Part 1 Omaveloxolone Capsules 40 mg	Part 1 Omaveloxolone Capsules 80 mg	Part 1 Omaveloxolone Capsules 160 mg	Part 1 Omaveloxolone Capsules 300 mg	Part 1 Placebo Capsules
Arm/Group Description:	Omaveloxolone (RTA 408) Capsules, 2.5 mg administered orally one daily for 2 weeks, then 5 mg administered orally once daily for 10 weeks Omaveloxolone Capsules, 2.5 mg Omaveloxolone Capsules, 5 mg	Omaveloxolone (RTA 408) Capsules, 10 mg administered orally once daily for 12 weeks Omaveloxolone Capsules, 10 mg	Omaveloxolone (RTA 408) Capsules, 20 mg administered orally once daily for 12 weeks Omaveloxolone Capsules, 20 mg	Omaveloxolone (RTA 408) Capsules, 40 mg administered orally once daily for 12 weeks Omaveloxolone Capsules, 40 mg	Omaveloxolone (RTA 408) Capsules, 80 mg administered orally once daily for 12 weeks Omaveloxolone Capsules, 80 mg	Omaveloxolone (RTA 408) Capsules, 160 mg administered orally once daily for 12 weeks Omaveloxolone Capsules, 160 mg	Omaveloxolone (RTA 408) Capsules, 300 mg administered orally once daily for 12 weeks Omaveloxolone Capsules, 300 mg	Placebo capsules administered orally once daily for 12 weeks Placebo
Overall Number of Participants Analyzed	6	6	6	6	6	12	10	17
Least Squares Mean (95% Confidence Interval); Unit of Measure: score on a scale
	-3.26; (-5.82 to -0.70)	-1.97; (-4.53 to 0.59)	-2.44; (-5.00 to 0.12)	-2.4; (-4.96 to 0.16)	-2.88; (-5.44 to -0.31)	-3.75; (-5.56 to -1.94)	-0.88; (-2.86 to 1.11)	-1.43; (-2.97 to 0.11)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 1 Omaveloxolone Capsules 2.5 and 5 mg, Part 1 Placebo Capsules
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.2310
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	Treatment group, time, and the interaction between treatment and time were used as fixed factors.
Method of Estimation	Estimation Parameter	LS Mean difference (Net)
	Estimated Value	-1.81
	Confidence Interval	(2-Sided) 95%; -4.80 to 1.18
	Estimation Comments	Difference is omaveloxolone - placebo.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Part 1 Omaveloxolone Capsules 10 mg, Part 1 Placebo Capsules
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.7298
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	Treatment group, time, and the interaction between treatment and time were used as fixed factors.
Method of Estimation	Estimation Parameter	LS Mean difference (Net)
	Estimated Value	-0.52
	Confidence Interval	(2-Sided) 95%; -3.51 to 2.47
	Estimation Comments	Difference is omaveloxolone - placebo.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Part 1 Omaveloxolone Capsules 20 mg, Part 1 Placebo Capsules
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.5102
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	Treatment group, time, and the interaction between treatment and time were used as fixed factors.
Method of Estimation	Estimation Parameter	LS Mean difference (Net)
	Estimated Value	-0.99
	Confidence Interval	(2-Sided) 95%; -3.99 to 2.00
	Estimation Comments	Difference is omaveloxolone - placebo.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Part 1 Omaveloxolone Capsules 40 mg, Part 1 Placebo Capsules
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.5281
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	Treatment group, time, and the interaction between treatment and time were used as fixed factors.
Method of Estimation	Estimation Parameter	LS Mean difference (Net)
	Estimated Value	-0.95
	Confidence Interval	(2-Sided) 95%; -3.94 to 2.04
	Estimation Comments	Difference is omaveloxolone - placebo.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Part 1 Omaveloxolone Capsules 80 mg, Part 1 Placebo Capsules
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.3458
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	Treatment group, time, and the interaction between treatment and time were used as fixed factors.
Method of Estimation	Estimation Parameter	LS Mean difference (Net)
	Estimated Value	-1.42
	Confidence Interval	(2-Sided) 95%; -4.42 to 1.57
	Estimation Comments	Difference is omaveloxolone - placebo.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Part 1 Omaveloxolone Capsules 160 mg, Part 1 Placebo Capsules
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0587
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	Treatment group, time, and the interaction between treatment and time were used as fixed factors.
Method of Estimation	Estimation Parameter	LS Mean difference (Net)
	Estimated Value	-2.30
	Confidence Interval	(2-Sided) 95%; -4.68 to 0.09
	Estimation Comments	Difference is omaveloxolone - placebo.

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Part 1 Omaveloxolone Capsules 300 mg, Part 1 Placebo Capsules
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.6480
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	Treatment group, time, and the interaction between treatment and time were used as fixed factors.
Method of Estimation	Estimation Parameter	LS Mean difference (Net)
	Estimated Value	0.58
	Confidence Interval	(2-Sided) 95%; -1.94 to 3.10
	Estimation Comments	Difference is omaveloxolone - placebo.

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Part 1 Omaveloxolone Capsules 2.5 and 5 mg, Part 1 Omaveloxolone Capsules 10 mg, Part 1 Omaveloxolone Capsules 20 mg, Part 1 Omaveloxolone Capsules 40 mg, Part 1 Omaveloxolone Capsules 80 mg, Part 1 Omaveloxolone Capsules 160 mg, Part 1 Omaveloxolone Capsules 300 mg, Part 1 Placebo Capsules
	Comments	Comparison of Omaveloxolone capsules pooled with Placebo capsules
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.2174
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	Treatment group, time, and the interaction between treatment and time were used as fixed factors.
Method of Estimation	Estimation Parameter	LS Mean difference (Net)
	Estimated Value	-1.10
	Confidence Interval	(2-Sided) 95%; -2.87 to 0.66
	Estimation Comments	Difference is omaveloxolone - placebo.

Adverse Events

Time Frame	16 weeks for Part 1 and 52 weeks for Part 2
Adverse Event Reporting Description	After the first dose, documentation of adverse events was to continue until 30 days following administration of the final dose of study medication, regardless of their relationship to study drug or their clinical significance.
Arm/Group Title	Part 1 Omaveloxolone Capsules 2.5 and 5 mg		Part 1 Omaveloxolone Capsules 10 mg		Part 1 Omaveloxolone Capsules 20 mg		Part 1 Omaveloxolone Capsules 40 mg		Part 1 Omaveloxolone Capsules 80 mg		Part 1 Omaveloxolone Capsules 160 mg		Part 1 Omaveloxolone Capsules 300 mg		Part 1 Placebo Capsules		Part 2 Placebo Capsules		Part 2 Omaveloxolone Capsules 150 mg
Arm/Group Description	Omaveloxolone (RTA 408) Capsules, 2.5 mg administered orally one daily for 2 weeks, then 5 mg administered orally once daily for 10 weeks Omaveloxolone Capsules, 2.5 mg Omaveloxolone Capsules, 5 mg		Omaveloxolone (RTA 408) Capsules, 10 mg administered orally once daily for 12 weeks Omaveloxolone Capsules, 10 mg		Omaveloxolone (RTA 408) Capsules, 20 mg administered orally once daily for 12 weeks Omaveloxolone Capsules, 20 mg		Omaveloxolone (RTA 408) Capsules, 40 mg administered orally once daily for 12 weeks Omaveloxolone Capsules, 40 mg		Omaveloxolone (RTA 408) Capsules, 80 mg administered orally once daily for 12 weeks Omaveloxolone Capsules, 80 mg		Omaveloxolone (RTA 408) Capsules, 160 mg administered orally once daily for 12 weeks Omaveloxolone Capsules, 160 mg		Omaveloxolone (RTA 408) Capsules, 300 mg administered orally once daily for 12 weeks Omaveloxolone Capsules, 300 mg		Placebo capsules administered orally once daily for 12 weeks Placebo		Placebo capsules administered orally once daily for 48 weeks Placebo		Omaveloxolone (RTA 408) Capsules, 150 mg administered orally once daily for 48 weeks Omaveloxolone Capsules, 150 mg
All-Cause Mortality
	Part 1 Omaveloxolone Capsules 2.5 and 5 mg		Part 1 Omaveloxolone Capsules 10 mg		Part 1 Omaveloxolone Capsules 20 mg		Part 1 Omaveloxolone Capsules 40 mg		Part 1 Omaveloxolone Capsules 80 mg		Part 1 Omaveloxolone Capsules 160 mg		Part 1 Omaveloxolone Capsules 300 mg		Part 1 Placebo Capsules		Part 2 Placebo Capsules		Part 2 Omaveloxolone Capsules 150 mg
	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	0/6 (0.00%)		0/6 (0.00%)		0/6 (0.00%)		0/6 (0.00%)		0/6 (0.00%)		0/12 (0.00%)		0/10 (0.00%)		0/17 (0.00%)		0/52 (0.00%)		0/51 (0.00%)
Serious Adverse Events
	Part 1 Omaveloxolone Capsules 2.5 and 5 mg		Part 1 Omaveloxolone Capsules 10 mg		Part 1 Omaveloxolone Capsules 20 mg		Part 1 Omaveloxolone Capsules 40 mg		Part 1 Omaveloxolone Capsules 80 mg		Part 1 Omaveloxolone Capsules 160 mg		Part 1 Omaveloxolone Capsules 300 mg		Part 1 Placebo Capsules		Part 2 Placebo Capsules		Part 2 Omaveloxolone Capsules 150 mg
	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	0/6 (0.00%)		0/6 (0.00%)		0/6 (0.00%)		0/6 (0.00%)		0/6 (0.00%)		0/12 (0.00%)		0/10 (0.00%)		2/17 (11.76%)		3/52 (5.77%)		5/51 (9.80%)
Blood and lymphatic system disorders
Anaemia † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/12 (0.00%)	0	0/10 (0.00%)	0	0/17 (0.00%)	0	0/52 (0.00%)	0	1/51 (1.96%)	1
Cardiac disorders
Atrial fibrillation † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/12 (0.00%)	0	0/10 (0.00%)	0	0/17 (0.00%)	0	1/52 (1.92%)	1	1/51 (1.96%)	1
Palpitations † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/12 (0.00%)	0	0/10 (0.00%)	0	0/17 (0.00%)	0	0/52 (0.00%)	0	1/51 (1.96%)	2
Sinus tachycardia † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/12 (0.00%)	0	0/10 (0.00%)	0	0/17 (0.00%)	0	0/52 (0.00%)	0	1/51 (1.96%)	1
Ventricular tachycardia † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/12 (0.00%)	0	0/10 (0.00%)	0	0/17 (0.00%)	0	0/52 (0.00%)	0	1/51 (1.96%)	1
General disorders
Drug withdrawal syndrome † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/12 (0.00%)	0	0/10 (0.00%)	0	1/17 (5.88%)	1	0/52 (0.00%)	0	0/51 (0.00%)	0
Non-cardiac chest pain † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/12 (0.00%)	0	0/10 (0.00%)	0	0/17 (0.00%)	0	0/52 (0.00%)	0	1/51 (1.96%)	1
Hepatobiliary disorders
Gallbladder disorder † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/12 (0.00%)	0	0/10 (0.00%)	0	0/17 (0.00%)	0	1/52 (1.92%)	1	0/51 (0.00%)	0
Infections and infestations
Laryngitis † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/12 (0.00%)	0	0/10 (0.00%)	0	0/17 (0.00%)	0	0/52 (0.00%)	0	1/51 (1.96%)	1
Viral upper respiratory tract infection † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/12 (0.00%)	0	0/10 (0.00%)	0	0/17 (0.00%)	0	0/52 (0.00%)	0	1/51 (1.96%)	1
Injury, poisoning and procedural complications
Ankle fracture † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/12 (0.00%)	0	0/10 (0.00%)	0	0/17 (0.00%)	0	1/52 (1.92%)	1	0/51 (0.00%)	0
Burns third degree † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/12 (0.00%)	0	0/10 (0.00%)	0	1/17 (5.88%)	1	0/52 (0.00%)	0	0/51 (0.00%)	0
Craniocerebral injury † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/12 (0.00%)	0	0/10 (0.00%)	0	0/17 (0.00%)	0	0/52 (0.00%)	0	1/51 (1.96%)	1
1 Term from vocabulary, MedDRA (14.1); † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	2%
	Part 1 Omaveloxolone Capsules 2.5 and 5 mg		Part 1 Omaveloxolone Capsules 10 mg		Part 1 Omaveloxolone Capsules 20 mg		Part 1 Omaveloxolone Capsules 40 mg		Part 1 Omaveloxolone Capsules 80 mg		Part 1 Omaveloxolone Capsules 160 mg		Part 1 Omaveloxolone Capsules 300 mg		Part 1 Placebo Capsules		Part 2 Placebo Capsules		Part 2 Omaveloxolone Capsules 150 mg
	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	6/6 (100.00%)		5/6 (83.33%)		5/6 (83.33%)		6/6 (100.00%)		6/6 (100.00%)		11/12 (91.67%)		10/10 (100.00%)		16/17 (94.12%)		52/52 (100.00%)		51/51 (100.00%)
Blood and lymphatic system disorders
Lymphadenopathy † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/12 (0.00%)	0	0/10 (0.00%)	0	1/17 (5.88%)	1	0/52 (0.00%)	0	1/51 (1.96%)	1
Cardiac disorders
Palpitations † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	1/12 (8.33%)	1	0/10 (0.00%)	0	0/17 (0.00%)	0	2/52 (3.85%)	2	1/51 (1.96%)	4
Tachycardia † 1	0/6 (0.00%)	0	1/6 (16.67%)	1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	1/12 (8.33%)	1	0/10 (0.00%)	0	0/17 (0.00%)	0	1/52 (1.92%)	1	0/51 (0.00%)	0
Ventricular extrasystoles † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/12 (0.00%)	0	0/10 (0.00%)	0	0/17 (0.00%)	0	2/52 (3.85%)	2	0/51 (0.00%)	0
Congenital, familial and genetic disorders
Friedreich's ataxia † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/12 (0.00%)	0	0/10 (0.00%)	0	1/17 (5.88%)	1	0/52 (0.00%)	0	0/51 (0.00%)	0
Eye disorders
Conjunctivitis † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/12 (0.00%)	0	0/10 (0.00%)	0	0/17 (0.00%)	0	0/52 (0.00%)	0	2/51 (3.92%)	2
Ocular hyperaemia † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	1/12 (8.33%)	1	0/10 (0.00%)	0	1/17 (5.88%)	1	0/52 (0.00%)	0	0/51 (0.00%)	0
Gastrointestinal disorders
Abdominal discomfort † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/12 (0.00%)	0	0/10 (0.00%)	0	0/17 (0.00%)	0	0/52 (0.00%)	0	3/51 (5.88%)	3
Abdominal distension † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/12 (0.00%)	0	0/10 (0.00%)	0	1/17 (5.88%)	1	0/52 (0.00%)	0	2/51 (3.92%)	2
Abdominal pain † 1	1/6 (16.67%)	2	1/6 (16.67%)	2	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	1/12 (8.33%)	1	0/10 (0.00%)	0	1/17 (5.88%)	2	3/52 (5.77%)	3	11/51 (21.57%)	21
Abdominal pain upper † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	1/12 (8.33%)	1	0/10 (0.00%)	0	3/17 (17.65%)	3	0/52 (0.00%)	0	0/51 (0.00%)	0
Abnormal faeces † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/12 (0.00%)	0	1/10 (10.00%)	1	0/17 (0.00%)	0	0/52 (0.00%)	0	0/51 (0.00%)	0
Constipation † 1	1/6 (16.67%)	1	0/6 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1	0/6 (0.00%)	0	0/12 (0.00%)	0	0/10 (0.00%)	0	2/17 (11.76%)	2	0/52 (0.00%)	0	2/51 (3.92%)	2
Diarrhoea † 1	0/6 (0.00%)	0	1/6 (16.67%)	2	0/6 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1	3/12 (25.00%)	3	1/10 (10.00%)	1	1/17 (5.88%)	1	5/52 (9.62%)	6	10/51 (19.61%)	12
Dry mouth † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1	1/12 (8.33%)	1	0/10 (0.00%)	0	0/17 (0.00%)	0	0/52 (0.00%)	0	0/51 (0.00%)	0
Dyspepsia † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/12 (0.00%)	0	0/10 (0.00%)	0	1/17 (5.88%)	1	1/52 (1.92%)	1	2/51 (3.92%)	2
Flatulence † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/12 (0.00%)	0	0/10 (0.00%)	0	0/17 (0.00%)	0	2/52 (3.85%)	2	0/51 (0.00%)	0
Gastrooesophageal reflux disease † 1	1/6 (16.67%)	1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/12 (0.00%)	0	0/10 (0.00%)	0	0/17 (0.00%)	0	0/52 (0.00%)	0	2/51 (3.92%)	2
Haematochezia † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/12 (0.00%)	0	0/10 (0.00%)	0	1/17 (5.88%)	1	0/52 (0.00%)	0	0/51 (0.00%)	0
Haemorrhoids † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/12 (0.00%)	0	1/10 (10.00%)	1	0/17 (0.00%)	0	0/52 (0.00%)	0	1/51 (1.96%)	1
Nausea † 1	0/6 (0.00%)	0	1/6 (16.67%)	1	0/6 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1	1/12 (8.33%)	2	2/10 (20.00%)	3	1/17 (5.88%)	1	7/52 (13.46%)	8	17/51 (33.33%)	22
Vomiting † 1	1/6 (16.67%)	1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/12 (0.00%)	0	1/10 (10.00%)	1	0/17 (0.00%)	0	6/52 (11.54%)	6	8/51 (15.69%)	9
General disorders
Chills † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	1/12 (8.33%)	1	0/10 (0.00%)	0	0/17 (0.00%)	0	1/52 (1.92%)	1	1/51 (1.96%)	1
Energy increased † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	1/12 (8.33%)	1	0/10 (0.00%)	0	0/17 (0.00%)	0	0/52 (0.00%)	0	0/51 (0.00%)	0
Fatigue † 1	3/6 (50.00%)	3	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	2/6 (33.33%)	2	1/12 (8.33%)	1	0/10 (0.00%)	0	2/17 (11.76%)	2	7/52 (13.46%)	7	11/51 (21.57%)	11
Gait disturbance † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/12 (0.00%)	0	0/10 (0.00%)	0	0/17 (0.00%)	0	3/52 (5.77%)	3	2/51 (3.92%)	2
Influenza like illness † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	2/6 (33.33%)	2	0/6 (0.00%)	0	0/12 (0.00%)	0	0/10 (0.00%)	0	1/17 (5.88%)	1	1/52 (1.92%)	1	3/51 (5.88%)	3
Non-cardiac chest pain † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/12 (0.00%)	0	0/10 (0.00%)	0	0/17 (0.00%)	0	2/52 (3.85%)	2	1/51 (1.96%)	1
Pain † 1	0/6 (0.00%)	0	1/6 (16.67%)	1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/12 (0.00%)	0	0/10 (0.00%)	0	0/17 (0.00%)	0	0/52 (0.00%)	0	0/51 (0.00%)	0
Pyrexia † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/12 (0.00%)	0	0/10 (0.00%)	0	0/17 (0.00%)	0	4/52 (7.69%)	6	2/51 (3.92%)	2
Immune system disorders
Seasonal allergy † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/12 (0.00%)	0	0/10 (0.00%)	0	0/17 (0.00%)	0	2/52 (3.85%)	11	0/51 (0.00%)	0
Infections and infestations
Abscess † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/12 (0.00%)	0	1/10 (10.00%)	1	0/17 (0.00%)	0	0/52 (0.00%)	0	0/51 (0.00%)	0
Gastroenteritis † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1	1/12 (8.33%)	1	0/10 (0.00%)	0	0/17 (0.00%)	0	0/52 (0.00%)	0	0/51 (0.00%)	0
Gastroenteritis viral † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/12 (0.00%)	0	0/10 (0.00%)	0	0/17 (0.00%)	0	0/52 (0.00%)	0	0/51 (0.00%)	0
Gastrointestinal infection † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/12 (0.00%)	0	0/10 (0.00%)	0	0/17 (0.00%)	0	2/52 (3.85%)	2	3/51 (5.88%)	4
Gastrointestinal viral infection † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/12 (0.00%)	0	0/10 (0.00%)	0	0/17 (0.00%)	0	0/52 (0.00%)	0	0/51 (0.00%)	0
Influenza † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/12 (0.00%)	0	0/10 (0.00%)	0	0/17 (0.00%)	0	2/52 (3.85%)	2	5/51 (9.80%)	8
Nasopharyngitis † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1	1/6 (16.67%)	1	3/12 (25.00%)	3	3/10 (30.00%)	3	0/17 (0.00%)	0	9/52 (17.31%)	13	7/51 (13.73%)	7
Pharyngitis † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/12 (0.00%)	0	0/10 (0.00%)	0	0/17 (0.00%)	0	2/52 (3.85%)	2	1/51 (1.96%)	1
Pharyngitis streptococcal † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/12 (0.00%)	0	0/10 (0.00%)	0	1/17 (5.88%)	1	0/52 (0.00%)	0	0/51 (0.00%)	0
Respiratory tract infection viral † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/12 (0.00%)	0	0/10 (0.00%)	0	0/17 (0.00%)	0	2/52 (3.85%)	3	0/51 (0.00%)	0
Rhinitis † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/12 (0.00%)	0	1/10 (10.00%)	1	0/17 (0.00%)	0	2/52 (3.85%)	2	0/51 (0.00%)	0
Sinusitis † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1	0/6 (0.00%)	0	0/12 (0.00%)	0	0/10 (0.00%)	0	0/17 (0.00%)	0	2/52 (3.85%)	2	1/51 (1.96%)	2
Upper respiratory tract infection † 1	2/6 (33.33%)	4	1/6 (16.67%)	1	5/6 (83.33%)	5	2/6 (33.33%)	2	2/6 (33.33%)	3	4/12 (33.33%)	4	6/10 (60.00%)	10	1/17 (5.88%)	1	15/52 (28.85%)	29	14/51 (27.45%)	20
Urinary tract infection † 1	0/6 (0.00%)	0	1/6 (16.67%)	2	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/12 (0.00%)	0	0/10 (0.00%)	0	0/17 (0.00%)	0	0/52 (0.00%)	0	4/51 (7.84%)	5
Viral infection † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	1/12 (8.33%)	2	0/10 (0.00%)	0	0/17 (0.00%)	0	3/52 (5.77%)	3	0/51 (0.00%)	0
Viral upper respiratory tract infection † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/12 (0.00%)	0	0/10 (0.00%)	0	1/17 (5.88%)	1	1/52 (1.92%)	1	1/51 (1.96%)	2
Injury, poisoning and procedural complications
Burns second degree † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/12 (0.00%)	0	0/10 (0.00%)	0	0/17 (0.00%)	0	2/52 (3.85%)	3	0/51 (0.00%)	0
Burns third degree † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/12 (0.00%)	0	0/10 (0.00%)	0	1/17 (5.88%)	1	0/52 (0.00%)	0	0/51 (0.00%)	0
Concussion † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/12 (0.00%)	0	0/10 (0.00%)	0	0/17 (0.00%)	0	1/52 (1.92%)	1	2/51 (3.92%)	2
Contusion † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	1/12 (8.33%)	1	1/10 (10.00%)	1	0/17 (0.00%)	0	19/52 (36.54%)	43	17/51 (33.33%)	29
Excoriation † 1	1/6 (16.67%)	1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1	0/12 (0.00%)	0	0/10 (0.00%)	0	1/17 (5.88%)	1	12/52 (23.08%)	21	13/51 (25.49%)	18
Face injury † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	1/12 (8.33%)	1	0/10 (0.00%)	0	0/17 (0.00%)	0	0/52 (0.00%)	0	0/51 (0.00%)	0
Fall † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1	0/12 (0.00%)	0	0/10 (0.00%)	0	1/17 (5.88%)	1	0/52 (0.00%)	0	0/51 (0.00%)	0
Foot fracture † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1	0/6 (0.00%)	0	0/12 (0.00%)	0	0/10 (0.00%)	0	0/17 (0.00%)	0	1/52 (1.92%)	1	2/51 (3.92%)	2
Head injury † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/12 (0.00%)	0	1/10 (10.00%)	1	1/17 (5.88%)	1	2/52 (3.85%)	2	1/51 (1.96%)	1
Joint dislocation † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/12 (0.00%)	0	0/10 (0.00%)	0	1/17 (5.88%)	1	1/52 (1.92%)	1	0/51 (0.00%)	0
Joint injury † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/12 (0.00%)	0	0/10 (0.00%)	0	0/17 (0.00%)	0	3/52 (5.77%)	3	4/51 (7.84%)	4
Laceration † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	1/12 (8.33%)	1	0/10 (0.00%)	0	0/17 (0.00%)	0	8/52 (15.38%)	10	8/51 (15.69%)	16
Ligament sprain † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	1/12 (8.33%)	1	0/10 (0.00%)	0	3/17 (17.65%)	3	8/52 (15.38%)	12	5/51 (9.80%)	7
Limb injury † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/12 (0.00%)	0	0/10 (0.00%)	0	0/17 (0.00%)	0	1/52 (1.92%)	1	5/51 (9.80%)	5
Muscle strain † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	1/12 (8.33%)	1	0/10 (0.00%)	0	0/17 (0.00%)	0	2/52 (3.85%)	3	3/51 (5.88%)	3
Periorbital haematoma † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	1/12 (8.33%)	1	0/10 (0.00%)	0	0/17 (0.00%)	0	1/52 (1.92%)	1	0/51 (0.00%)	0
Procedural pain † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1	0/12 (0.00%)	0	0/10 (0.00%)	0	0/17 (0.00%)	0	1/52 (1.92%)	1	0/51 (0.00%)	0
Sunburn † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	1/12 (8.33%)	1	0/10 (0.00%)	0	0/17 (0.00%)	0	0/52 (0.00%)	0	0/51 (0.00%)	0
Thermal burn † 1	1/6 (16.67%)	1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1	0/12 (0.00%)	0	0/10 (0.00%)	0	1/17 (5.88%)	1	1/52 (1.92%)	1	0/51 (0.00%)	0
Investigations
Alanine aminotransferase increased † 1	1/6 (16.67%)	1	0/6 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1	0/6 (0.00%)	0	2/12 (16.67%)	2	2/10 (20.00%)	2	0/17 (0.00%)	0	1/52 (1.92%)	1	19/51 (37.25%)	20
Aspartate aminotransferase increased † 1	1/6 (16.67%)	1	0/6 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1	0/6 (0.00%)	0	2/12 (16.67%)	2	2/10 (20.00%)	2	0/17 (0.00%)	0	1/52 (1.92%)	1	11/51 (21.57%)	12
Blood creatine phosphokinase increased † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/12 (0.00%)	0	1/10 (10.00%)	1	0/17 (0.00%)	0	2/52 (3.85%)	3	3/51 (5.88%)	4
Blood pressure increased † 1	1/6 (16.67%)	1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/12 (0.00%)	0	0/10 (0.00%)	0	0/17 (0.00%)	0	0/52 (0.00%)	0	1/51 (1.96%)	1
Brain natriuretic peptide increased † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/12 (0.00%)	0	0/10 (0.00%)	0	1/17 (5.88%)	1	0/52 (0.00%)	0	0/51 (0.00%)	0
Gamma-glutamyltransferase increased † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1	0/6 (0.00%)	0	1/12 (8.33%)	1	2/10 (20.00%)	3	0/17 (0.00%)	0	0/52 (0.00%)	0	3/51 (5.88%)	4
Glucose urine present † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/12 (0.00%)	0	0/10 (0.00%)	0	1/17 (5.88%)	1	0/52 (0.00%)	0	0/51 (0.00%)	0
Hepatic enzyme increased † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1	0/6 (0.00%)	0	0/12 (0.00%)	0	0/10 (0.00%)	0	0/17 (0.00%)	0	0/52 (0.00%)	0	0/51 (0.00%)	0
Liver function test abnormal † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1	0/12 (0.00%)	0	0/10 (0.00%)	0	0/17 (0.00%)	0	0/52 (0.00%)	0	0/51 (0.00%)	0
Very low density lipoprotein increased † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/12 (0.00%)	0	0/10 (0.00%)	0	0/17 (0.00%)	0	0/52 (0.00%)	0	2/51 (3.92%)	2
Metabolism and nutrition disorders
Decreased appetite † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/12 (0.00%)	0	0/10 (0.00%)	0	0/17 (0.00%)	0	2/52 (3.85%)	2	6/51 (11.76%)	6
Hypertriglyceridaemia † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	1/12 (8.33%)	1	0/10 (0.00%)	0	0/17 (0.00%)	0	0/52 (0.00%)	0	2/51 (3.92%)	2
Increased appetite † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/12 (0.00%)	0	0/10 (0.00%)	0	1/17 (5.88%)	1	0/52 (0.00%)	0	0/51 (0.00%)	0
Musculoskeletal and connective tissue disorders
Arthralgia † 1	1/6 (16.67%)	1	1/6 (16.67%)	1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	1/12 (8.33%)	1	2/10 (20.00%)	2	0/17 (0.00%)	0	10/52 (19.23%)	13	9/51 (17.65%)	10
Back pain † 1	1/6 (16.67%)	1	0/6 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1	0/6 (0.00%)	0	2/12 (16.67%)	2	0/10 (0.00%)	0	0/17 (0.00%)	0	4/52 (7.69%)	6	7/51 (13.73%)	9
Exostosis † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/12 (0.00%)	0	0/10 (0.00%)	0	1/17 (5.88%)	1	0/52 (0.00%)	0	0/51 (0.00%)	0
Muscle spasms † 1	1/6 (16.67%)	2	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	1/12 (8.33%)	1	0/10 (0.00%)	0	1/17 (5.88%)	1	3/52 (5.77%)	3	8/51 (15.69%)	13
Muscle twitching † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	1/12 (8.33%)	1	0/10 (0.00%)	0	0/17 (0.00%)	0	0/52 (0.00%)	0	0/51 (0.00%)	0
Muscular weakness † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	1/12 (8.33%)	1	0/10 (0.00%)	0	0/17 (0.00%)	0	0/52 (0.00%)	0	0/51 (0.00%)	0
Musculoskeletal chest pain † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1	1/12 (8.33%)	1	0/10 (0.00%)	0	0/17 (0.00%)	0	0/52 (0.00%)	0	2/51 (3.92%)	2
Musculoskeletal pain † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1	0/6 (0.00%)	0	1/12 (8.33%)	1	0/10 (0.00%)	0	2/17 (11.76%)	2	3/52 (5.77%)	4	1/51 (1.96%)	1
Musculoskeletal stiffness † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/12 (0.00%)	0	0/10 (0.00%)	0	1/17 (5.88%)	1	1/52 (1.92%)	1	0/51 (0.00%)	0
Myalgia † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/12 (0.00%)	0	0/10 (0.00%)	0	1/17 (5.88%)	1	2/52 (3.85%)	2	2/51 (3.92%)	2
Neck pain † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	1/12 (8.33%)	1	0/10 (0.00%)	0	1/17 (5.88%)	1	3/52 (5.77%)	3	0/51 (0.00%)	0
Pain in extremity † 1	1/6 (16.67%)	1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	3/12 (25.00%)	3	0/10 (0.00%)	0	1/17 (5.88%)	3	4/52 (7.69%)	4	1/51 (1.96%)	1
Pain in jaw † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/12 (0.00%)	0	0/10 (0.00%)	0	0/17 (0.00%)	0	0/52 (0.00%)	0	2/51 (3.92%)	2
Nervous system disorders
Autonomic nervous system imbalance † 1	0/6 (0.00%)	0	1/6 (16.67%)	1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/12 (0.00%)	0	0/10 (0.00%)	0	0/17 (0.00%)	0	0/52 (0.00%)	0	0/51 (0.00%)	0
Dizziness † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/12 (0.00%)	0	0/10 (0.00%)	0	0/17 (0.00%)	0	6/52 (11.54%)	6	3/51 (5.88%)	3
Headache † 1	1/6 (16.67%)	1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	2/6 (33.33%)	2	4/12 (33.33%)	4	2/10 (20.00%)	2	3/17 (17.65%)	3	13/52 (25.00%)	35	19/51 (37.25%)	30
Hypoaesthesia † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/12 (0.00%)	0	0/10 (0.00%)	0	0/17 (0.00%)	0	3/52 (5.77%)	3	0/51 (0.00%)	0
Migraine † 1	0/6 (0.00%)	0	1/6 (16.67%)	1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/12 (0.00%)	0	0/10 (0.00%)	0	0/17 (0.00%)	0	2/52 (3.85%)	2	1/51 (1.96%)	1
Muscle spasticity † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/12 (0.00%)	0	0/10 (0.00%)	0	0/17 (0.00%)	0	0/52 (0.00%)	0	2/51 (3.92%)	2
Paraesthesia † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/12 (0.00%)	0	0/10 (0.00%)	0	0/17 (0.00%)	0	0/52 (0.00%)	0	1/51 (1.96%)	1
Psychomotor hyperactivity † 1	0/6 (0.00%)	0	1/6 (16.67%)	1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/12 (0.00%)	0	0/10 (0.00%)	0	0/17 (0.00%)	0	0/52 (0.00%)	0	0/51 (0.00%)	0
Somnolence † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/12 (0.00%)	0	0/10 (0.00%)	0	0/17 (0.00%)	0	0/52 (0.00%)	0	2/51 (3.92%)	2
Tremor † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/12 (0.00%)	0	0/10 (0.00%)	0	0/17 (0.00%)	0	2/52 (3.85%)	2	0/51 (0.00%)	0
Psychiatric disorders
Anxiety † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/12 (0.00%)	0	0/10 (0.00%)	0	1/17 (5.88%)	1	2/52 (3.85%)	2	1/51 (1.96%)	1
Depression † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/12 (0.00%)	0	0/10 (0.00%)	0	0/17 (0.00%)	0	3/52 (5.77%)	3	1/51 (1.96%)	1
Euphoric mood † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1	0/6 (0.00%)	0	0/12 (0.00%)	0	0/10 (0.00%)	0	0/17 (0.00%)	0	0/52 (0.00%)	0	0/51 (0.00%)	0
Insomnia † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/12 (0.00%)	0	0/10 (0.00%)	0	1/17 (5.88%)	1	3/52 (5.77%)	4	3/51 (5.88%)	3
Renal and urinary disorders
Micturition urgency † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/12 (0.00%)	0	0/10 (0.00%)	0	0/17 (0.00%)	0	2/52 (3.85%)	2	1/51 (1.96%)	1
Pollakiuria † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1	1/6 (16.67%)	1	1/12 (8.33%)	1	0/10 (0.00%)	0	0/17 (0.00%)	0	0/52 (0.00%)	0	1/51 (1.96%)	1
Reproductive system and breast disorders
Dysmenorrhoea † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1	0/12 (0.00%)	0	1/10 (10.00%)	1	0/17 (0.00%)	0	0/52 (0.00%)	0	3/51 (5.88%)	7
Ovarian cyst † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/12 (0.00%)	0	0/10 (0.00%)	0	0/17 (0.00%)	0	0/52 (0.00%)	0	2/51 (3.92%)	2
Respiratory, thoracic and mediastinal disorders
Choking † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/12 (0.00%)	0	0/10 (0.00%)	0	1/17 (5.88%)	1	0/52 (0.00%)	0	0/51 (0.00%)	0
Cough † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1	0/6 (0.00%)	0	1/6 (16.67%)	1	1/12 (8.33%)	1	1/10 (10.00%)	1	1/17 (5.88%)	1	4/52 (7.69%)	4	6/51 (11.76%)	6
Dyspnoea † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	1/12 (8.33%)	1	0/10 (0.00%)	0	0/17 (0.00%)	0	0/52 (0.00%)	0	1/51 (1.96%)	1
Epistaxis † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	3/12 (25.00%)	6	0/10 (0.00%)	0	2/17 (11.76%)	2	2/52 (3.85%)	2	2/51 (3.92%)	2
Nasal congestion † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/12 (0.00%)	0	0/10 (0.00%)	0	1/17 (5.88%)	1	3/52 (5.77%)	4	2/51 (3.92%)	2
Oropharyngeal pain † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1	0/6 (0.00%)	0	0/12 (0.00%)	0	0/10 (0.00%)	0	1/17 (5.88%)	1	3/52 (5.77%)	3	9/51 (17.65%)	10
Paranasal sinus hypersecretion † 1	0/6 (0.00%)	0	1/6 (16.67%)	1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/12 (0.00%)	0	0/10 (0.00%)	0	0/17 (0.00%)	0	0/52 (0.00%)	0	0/51 (0.00%)	0
Pulmonary congestion † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/12 (0.00%)	0	1/10 (10.00%)	1	0/17 (0.00%)	0	1/52 (1.92%)	1	0/51 (0.00%)	0
Rhinitis allergic † 1	0/6 (0.00%)	0	1/6 (16.67%)	1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/12 (0.00%)	0	0/10 (0.00%)	0	0/17 (0.00%)	0	1/52 (1.92%)	1	0/51 (0.00%)	0
Rhinorrhoea † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/12 (0.00%)	0	0/10 (0.00%)	0	0/17 (0.00%)	0	0/52 (0.00%)	0	2/51 (3.92%)	4
Skin and subcutaneous tissue disorders
Alopecia † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/12 (0.00%)	0	0/10 (0.00%)	0	0/17 (0.00%)	0	0/52 (0.00%)	0	1/51 (1.96%)	1
Dermatitis † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1	0/12 (0.00%)	0	0/10 (0.00%)	0	0/17 (0.00%)	0	0/52 (0.00%)	0	0/51 (0.00%)	0
Dry skin † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/12 (0.00%)	0	0/10 (0.00%)	0	1/17 (5.88%)	1	0/52 (0.00%)	0	0/51 (0.00%)	0
Hyperhidrosis † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/12 (0.00%)	0	0/10 (0.00%)	0	0/17 (0.00%)	0	1/52 (1.92%)	1	2/51 (3.92%)	2
Petechiae † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/12 (0.00%)	0	0/10 (0.00%)	0	0/17 (0.00%)	0	0/52 (0.00%)	0	2/51 (3.92%)	2
Pruritus † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/12 (0.00%)	0	0/10 (0.00%)	0	0/17 (0.00%)	0	2/52 (3.85%)	2	0/51 (0.00%)	0
Rash † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	1/12 (8.33%)	1	0/10 (0.00%)	0	0/17 (0.00%)	0	1/52 (1.92%)	1	1/51 (1.96%)	3
Rash generalised † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	1/6 (16.67%)	1	0/6 (0.00%)	0	0/12 (0.00%)	0	0/10 (0.00%)	0	0/17 (0.00%)	0	0/52 (0.00%)	0	0/51 (0.00%)	0
Rash macular † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/12 (0.00%)	0	0/10 (0.00%)	0	0/17 (0.00%)	0	0/52 (0.00%)	0	2/51 (3.92%)	2
Skin exfoliation † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/12 (0.00%)	0	0/10 (0.00%)	0	1/17 (5.88%)	1	0/52 (0.00%)	0	0/51 (0.00%)	0
Vascular disorders
Haematoma † 1	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/12 (0.00%)	0	0/10 (0.00%)	0	0/17 (0.00%)	0	3/52 (5.77%)	5	0/51 (0.00%)	0
Hot flush † 1	0/6 (0.00%)	0	1/6 (16.67%)	2	0/6 (0.00%)	0	0/6 (0.00%)	0	0/6 (0.00%)	0	0/12 (0.00%)	0	0/10 (0.00%)	0	0/17 (0.00%)	0	0/52 (0.00%)	0	0/51 (0.00%)	0
1 Term from vocabulary, MedDRA (14.1); † 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.

Our agreement is subject to confidentiality but generally the PI can publish, for noncommercial purposes only, results and methods of the trial, but no other Sponsor Confidential Information. PI must give Sponsor no less than 60 days to review any manuscript for a proposed publication and must delay publication for up to an additional 90 days thereafter if Sponsor needs to file any patent application to protect any of Sponsor's intellectual property contained in the proposed publication.

Results Point of Contact

• Name/Title: US Biogen Clinical Trial Center
• Organization: Biogen
• Phone: 866-633-4636
• EMail: clinicaltrials@biogen.com

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

Lynch DR, Chin MP, Delatycki MB, Subramony SH, Corti M, Hoyle JC, Boesch S, Nachbauer W, Mariotti C, Mathews KD, Giunti P, Wilmot G, Zesiewicz T, Perlman S, Goldsberry A, O'Grady M, Meyer CJ. Safety and Efficacy of Omaveloxolone in Friedreich Ataxia (MOXIe Study). Ann Neurol. 2021 Feb;89(2):212-225. doi: 10.1002/ana.25934. Epub 2020 Nov 5. Erratum In: Ann Neurol. 2023 Dec;94(6):1190.

Lynch DR, Farmer J, Hauser L, Blair IA, Wang QQ, Mesaros C, Snyder N, Boesch S, Chin M, Delatycki MB, Giunti P, Goldsberry A, Hoyle C, McBride MG, Nachbauer W, O'Grady M, Perlman S, Subramony SH, Wilmot GR, Zesiewicz T, Meyer C. Safety, pharmacodynamics, and potential benefit of omaveloxolone in Friedreich ataxia. Ann Clin Transl Neurol. 2018 Nov 10;6(1):15-26. doi: 10.1002/acn3.660. eCollection 2019 Jan.

• Responsible Party: Biogen ( Reata, a wholly owned subsidiary of Biogen )
• ClinicalTrials.gov Identifier: NCT02255435
• Other Study ID Numbers: RTA 408-C-1402
• First Submitted: September 30, 2014
• First Posted: October 2, 2014
• Results First Submitted: September 30, 2022
• Results First Posted: November 29, 2022
• Last Update Posted: February 5, 2024