A Study to Assess Safety/Tolerability, pk, Effects on Histology, Clinical Parameters of Givinostat in Children With DMD

• ClinicalTrials.gov Identifier: NCT01761292
• Recruitment Status: Completed
• First Posted: January 4, 2013
• Results First Posted: June 23, 2020
• Last Update Posted: November 7, 2023
• Sponsor: Italfarmaco
• Information provided by (Responsible Party): Italfarmaco

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Duchenne Muscular Dystrophy (DMD)
• Intervention: Drug: Givinostat
• Enrollment: 20

Participant Flow

Recruitment Details
Pre-assignment Details	This is a single arm study and not a parallel group study. Patient enrollment occurred sequentially, until 20 patients were treated (part 1). For the entire design please refer to "detailed study description". Only demographics are reported by 3 Givinostat dose levels, while AEs and outcomes results are reported for the whole Givinostat population.

Arm/Group Title	Givinostat
Arm/Group Description	Givinostat will be administered as 2 oral doses daily while the child is in fed state. Givinostat: Givinostat, oral suspension 10 mg/mL or oral capsules 50 mg, administered orally under fed conditions at the dose of 25 mg BID, 37.5 mg BID, and 50 mg BID during Part 1 and 25 mg BID and 37.5 mg BID during Part 2. Givinostat, oral suspension 10 mg/mL, administered orally under fed conditions at the dose of 25 mg BID or 37.5 mg BID during Extension 1, and modified as per patient's weight during Extensions 2 and 3.
Period Title: Part 1
Started	20
Patients Receiving Drug in Part 1	19 [1]
Completed	18
Not Completed	2
Reason Not Completed
Adverse Event	1
not receiving treatment in Part 1	1
[1] One patient was enrolled in Part 1 and started treatment in Part 2.
Period Title: Part 2
Started	19 [1]
Completed	19
Not Completed	0
[1] 1 pt was enrolled in Part 1 but started the treatment in Part 2. So 19 pts started Part 2.
Period Title: Extension 1
Started	19
Completed	18
Not Completed	1
Reason Not Completed
Withdrawal by Subject	1
Period Title: Extension 2
Started	18
Completed	18
Not Completed	0
Period Title: Extension 3
Started	18
Completed	18
Not Completed	0

Baseline Characteristics

Arm/Group Title		ITF2357 25 mg BID	ITF2357 50 mg BID	ITF2357 37.5 mg BID	Total
Arm/Group Description		Givinostat, oral suspension 10 mg/mL, administered orally under fed conditions at the dose of 25 mg BID, during Part 1 and 25 mg BID during Part 2 and during Extension 1. The dosage was modified as per patient's weight during Extensions 2 and 3.	Givinostat oral capsules 50 mg, administered orally under fed conditions at the dose of 50 mg BID during Part 1. The dosage was modified as per patient's weight during Extensions 2 and 3.	Givinostat, oral suspension 10 mg/mL, administered orally under fed conditions at the dose of 37.5 mg BID during Part 1 and 37.5 mg BID during Part 2 and during Extension 1. The dosage was modified as per patient's weight during Extensions 2 and 3.	Total of all reporting groups
Overall Number of Baseline Participants		4	8	8	20
Baseline Analysis Population Description		The ITT population included all children who were enrolled in the Part 1 portion or entered the Part 2 portion of the study. Patients were analyzed according to the dose level to which they were allocated. Twenty patients were included in the ITT population.
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	4 participants	8 participants	8 participants	20 participants
	<=18 years	4 100.0%	8 100.0%	8 100.0%	20 100.0%
	Between 18 and 65 years	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	>=65 years	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	4 participants	8 participants	8 participants	20 participants
		7.8 (0.96)	8.8 (1.16)	7.9 (1.13)	8.2 (1.15)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	4 participants	8 participants	8 participants	20 participants
	Female	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Male	4 100.0%	8 100.0%	8 100.0%	20 100.0%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
Italy	Number Analyzed	4 participants	8 participants	8 participants	20 participants
		4	8	8	20

Outcome Measures

1. Primary Outcome

Title	Change From Baseline to Part 2 in the Value of Muscle Fiber Area (MFA) % Comparing the Histology Biopsies Before and After 12 Months of Treatment With Givinostat.
Description	The primary endpoint was the change in histology comparing the brachial biceps biopsies before and after ≥12 months of treatment with Givinostat. Muscle biopsies: A first brachial biceps biopsy (baseline) was taken prior to the first dose of study drug. A second brachial biceps biopsy was taken at Visit 10 (12 months) from the opposite arm. The muscle biopsy samples from the biceps muscle were collected by open biopsy. The minimum amount of muscle tissue required was a piece of muscle of at least 0.5 × 0.5 × 0.5 cm.
Time Frame	After12 months of treatment

Outcome Measure Data

Analysis Population Description

Evaluable population:all patients who received givinostat of at least 80% dose in Part 2, had at least 1 baseline and 1 post baseline biopsy and no major protocol violations. 19 Subjects completed Part 2, 1 subject was excluded by this analysis due to biopsy not readable. Results data are reported only for the "overall" Givinostat population.

Arm/Group Title	Overall
Arm/Group Description:	Givinostat was administered as 2 oral doses daily while the child is in fed state. Givinostat, oral suspension 10 mg/mL or oral capsules 50 mg, was administered at the dose of 25 mg BID, 37.5 mg BID, and 50 mg BID during Part 1, and 25 mg BID and 37.5 mg BID during Part 2.
Overall Number of Participants Analyzed	18
Median (Full Range); Unit of Measure: percentage change
	12.76; (6.17 to 21.23)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Overall
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	The paired t-test or non-parametric signed rank test for 2 means (paired observations) (as is appropriate) was applied for testing the statistical significance of the Change From Baseline to End of Study. MFA% P < 0.05 was set as significant.
	Method	t-test, 2 sided
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	mean
	Estimated Value	13.906
	Confidence Interval	(2-Sided) 95%; 11.5657 to 16.2466
	Estimation Comments	[Not Specified]

2. Secondary Outcome

Title	Change From Baseline to End of Study in Cross Sectional Area (CSA)
Description	This histological parameter was evaluated on the brachial biceps biopsies taken prior to the first dose of study drug and after 12 months of treatment with givinostat.
Time Frame	At 12 months

Outcome Measure Data

Analysis Population Description

The ITT population included all children who were enrolled in the Part 1 or entered the Part 2 of the study. For histology parameters patients were analyzed "overall" for Givinostat population. 19 completed part 2 but only 18 subejcts had 2 biopsies readable

Arm/Group Title	Overall
Arm/Group Description:	Givinostat was administered as 2 oral doses daily while the child is in fed state. Givinostat, oral suspension 10 mg/mL or oral capsules 50 mg, was administered at the dose of 25 mg BID, 37.5 mg BID, and 50 mg BID during Part 1, and 25 mg BID and 37.5 mg BID during Part 2.
Overall Number of Participants Analyzed	18
Mean (Standard Deviation); Unit of Measure: μm2
	865.269 (555.3543)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Overall
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	< 0.0001
	Comments	[Not Specified]
	Method	t-test, 2 sided
	Comments	[Not Specified]

3. Secondary Outcome

Title	Change From Baseline to End of Study in Fibrosis, Necrosis, Fatty Replacement
Description	These histological parameters were evaluated on the brachial biceps biopsies taken prior to the first dose of study drug and after 12 months of treatment with givinostat.
Time Frame	After 12 months

Outcome Measure Data

Analysis Population Description

The ITT population included all children who were enrolled in the Part 1 or entered the Part 2 of the study. For histology parameters patients were analyzed "overall" for Givinostat population. 19 Subjects completed Part 2 but only 18 had 2 biopsies readable.

Arm/Group Title	Baseline
Arm/Group Description:	Givinostat was administered as 2 oral doses daily while the child is in fed state. Givinostat, oral suspension 10 mg/mL or oral capsules 50 mg, was administered at the dose of 25 mg BID, 37.5 mg BID, and 50 mg BID during Part 1, and 25 mg BID and 37.5 mg BID during Part 2.
Overall Number of Participants Analyzed	18
Mean (Standard Deviation); Unit of Measure: percentage of total area
Total fibrosis	-12.640 (4.6493)
Perimysial fibrosis	-7.585 (6.4779)
Endomysial fibrosis	-5.056 (6.2531)
Fatty replacement	-0.302 (0.2756)
Necrosis	-0.964 (0.6260)

4. Secondary Outcome

Title	Change From Baseline to End of Study in Number of Hypercontracted Fibers
Description	This histological parameter was evaluated on the brachial biceps biopsies taken prior to the first dose of study drug and after 12 months of treatment with givinostat. The number of fibers is calculated per microscopic field (20x).
Time Frame	At 12 months

Outcome Measure Data

Analysis Population Description

The ITT population included all children who were enrolled in the Part 1 or entered the Part 2 of the study. For histology parameters patients were analyzed "overall" for Givinostat population.19 Subjects completed Part 2 but only 18 had 2 biopsies readable.

Arm/Group Title	Overall
Arm/Group Description:	Givinostat was administered as 2 oral doses daily while the child is in fed state. Givinostat, oral suspension 10 mg/mL or oral capsules 50 mg, was administered at the dose of 25 mg BID, 37.5 mg BID, and 50 mg BID during Part 1, and 25 mg BID and 37.5 mg BID during Part 2.
Overall Number of Participants Analyzed	18
Mean (Standard Deviation); Unit of Measure: number of fibers
	-1.204 (0.6621)

5. Secondary Outcome

Title	Change From Baseline in Muscular Function After 12 Months of Treatment With Givinostat at the Selected Daily Dose Based on the 6-Minute Walk Test
Description	This test measures the distance that a patient can quickly walk on a flat, hard surface in a period of 6 minutes. The 6-Minute Walk Test is a useful measure of functional capacity targeted at people with at least moderately severe impairment. The longer the walked distance the better the outcome.
Time Frame	At 12 months

Outcome Measure Data

Analysis Population Description

The ITT population included all children who were enrolled in the Part 1 portion or entered the Part 2 portion of the study. Results data are reported only for the "overall" Givinostat population, due to a small sample. 19 subjects completed Part 2 of the study 19 but only 18 performed the 6-Minute Walk Test

Arm/Group Title	Overall
Arm/Group Description:	Givinostat was administered as 2 oral doses daily while the child is in fed state. Givinostat, oral suspension 10 mg/mL or oral capsules 50 mg, was administered at the dose of 25 mg BID, 37.5 mg BID, and 50 mg BID during Part 1, and 25 mg BID and 37.5 mg BID during Part 2.
Overall Number of Participants Analyzed	18
Mean (Standard Deviation); Unit of Measure: meters
	-24.6 (36.11)

6. Secondary Outcome

Title	Change From Baseline in Muscular Function After 12 Months of Treatment With Givinostat at the Selected Daily Dose Based on the North Star Ambulatory Assessment (NSAA)
Description	The NSAA, which is composed by 17 items, was graded, for each item, using the standard scorecard with each assessment rated as 0 - unable to achieve independently, 1 - modified method but achieves goal independent of physical assistance from another, or 2 - normal with no obvious modification of activity. The subscales scores are summed up to compute a total score, ranging from 0 to 34. The higher the total score, the better the outcome. The mean Change From Baseline to EoS in NSAA total score is reported hereunder.
Time Frame	At 12 months

Outcome Measure Data

Analysis Population Description

The ITT population included all children who were enrolled in the Part 1 portion or entered the Part 2 portion of the study. Patients were analyzed "overall" due to a small sample size. Although different Givinostat dose levels were administered, results data are reported only for the "overall" Givinostat population

Arm/Group Title	Overall
Arm/Group Description:	Givinostat was administered as 2 oral doses daily while the child is in fed state. Givinostat, oral suspension 10 mg/mL or oral capsules 50 mg, was administered at the dose of 25 mg BID, 37.5 mg BID, and 50 mg BID during Part 1, and 25 mg BID and 37.5 mg BID during Part 2.
Overall Number of Participants Analyzed	19
Mean (Standard Deviation); Unit of Measure: score on a scale
	-2.8 (3.15)

7. Secondary Outcome

Title	Change From Baseline in Muscular Function After 12 Months of Treatment With Givinostat at the Selected Daily Dose Based on the Performance of Upper Limb (PUL)
Description	The PUL (version 1.2) was used to assess the change in motor performance of the upper limb over time in patients with Becker and Duchenne muscular dystrophy, from when they are still ambulant, until they loose all arm function when non-ambulant. The revised version of the PUL included 22 items. These include one entry item to define the starting functional level, and 21 items subdivided into: shoulder level (Question B to E; minimum score 0 and maximum score 16); elbow level (Question F to N; minimum score 0 and maximum score 34); distal level dimension (Question O to V; minimum score 0 and maximum score 24) The total score is calculated by the sum of all the scores of the three subscales (total score range: 0-74) (scores from Question A "entry item" did not contribute). For all items, the higher the score, the better the outcome.
Time Frame	At 12 months

Outcome Measure Data

Analysis Population Description

The ITT population included all children who were enrolled in the Part 1 portion or entered the Part 2 portion of the study. Patients were analyzed overall, due to a small sample size. Although different Givinostat dose levels were administered, results data are reported only for the "overall" Givinostat population.

Arm/Group Title	Overall
Arm/Group Description:	Givinostat was administered as 2 oral doses daily while the child is in fed state. Givinostat, oral suspension 10 mg/mL or oral capsules 50 mg, was administered at the dose of 25 mg BID, 37.5 mg BID, and 50 mg BID during Part 1, and 25 mg BID and 37.5 mg BID during Part 2.
Overall Number of Participants Analyzed	19
Mean (Standard Deviation); Unit of Measure: score on a scale
	-0.2 (2.69)

8. Secondary Outcome

Title	Change From Baseline in Muscular Function After After 24 (Extension 1), 36 (Extension 2), and 52 Months (Extension 3) of Treatment With Givinostat at the Selected Daily Dose Based on the 6-Minute Walk Test
Description	This test measures the distance that a patient can quickly walk on a flat, hard surface in a period of 6 minutes. The 6-Minute Walk Test is a useful measure of functional capacity targeted at people with at least moderately severe impairment. The longer the walked distance the better the outcome.
Time Frame	At 24, 36, and 52 months

Outcome Measure Data

Analysis Population Description

The ITT population included all children who were enrolled in the Part 1 portion or entered the Part 2 portion of the study. Patients were analyzed overall, due to a small sample size. Although different Givinostat dose levels were administered, results data are reported only for the "overall" Givinostat population.

Arm/Group Title		Overall
Arm/Group Description:		Givinostat was administered as 2 oral doses daily while the child is in fed state. Givinostat, oral suspension 10 mg/mL or oral capsules 50 mg, was administered at the dose of 25 mg BID, 37.5 mg BID, and 50 mg BID during Part 1, and 25 mg BID and 37.5 mg BID during Part 2. Givinostat oral suspension 10 mg/mL was administered orally at the dose of 25 mg BID or 37.5 mg BID during Extension 1; the dose was modified as per patient's weight during Extensions 2 and 3.
Overall Number of Participants Analyzed		19
Mean (Standard Deviation); Unit of Measure: meters
Extension 1	Number Analyzed	19 participants
		-80.0 (110.69)
Extension 2	Number Analyzed	19 participants
		-127.0 (110.40)
Extension 3	Number Analyzed	18 participants
		-287.8 (159.47)

9. Secondary Outcome

Title	Change From Baseline in Muscular Function After 24 (Extension 1), 36 (Extension 2), and 52 Months (Extension 3) of Treatment With Givinostat at the Selected Daily Dose Based on the North Star Ambulatory Assessment (NSAA)
Description	The NSAA, which is composed by 17 items, was graded, for each item, using the standard scorecard with each assessment rated as 0 - unable to achieve independently, 1 - modified method but achieves goal independent of physical assistance from another, or 2 - normal with no obvious modification of activity. The subscales scores are summed up to compute a total score, ranging from 0 to 34. The higher the total score, the better the outcome. The mean Change From Baseline to EoS in NSAA total score is reported hereunder.
Time Frame	At 24, 36, and 52 months

Outcome Measure Data

Analysis Population Description

The ITT population included all children who were enrolled in the Part 1 portion or entered the Part 2 portion of the study. Patients were analyzed overall due to a small sample size. Although different Givinostat dose levels were administered, results data are reported only for the "overall" Givinostat population.

Arm/Group Title	Overall
Arm/Group Description:	Givinostat was administered as 2 oral doses daily while the child is in fed state. Givinostat, oral suspension 10 mg/mL or oral capsules 50 mg, was administered at the dose of 25 mg BID, 37.5 mg BID, and 50 mg BID during Part 1, and 25 mg BID and 37.5 mg BID during Part 2. Givinostat oral suspension 10 mg/mL was administered orally at the dose of 25 mg BID or 37.5 mg BID during Extension 1; the dose was modified as per patient's weight during Extensions 2 and 3.
Overall Number of Participants Analyzed	18
Mean (Standard Deviation); Unit of Measure: score on a scale
Extension 1	-5.2 (5.06)
Extension 2	-7.4 (5.90)
Extension 3	-15.2 (7.83)

10. Secondary Outcome

Title	Change From Baseline in Muscular Function After 24 (Extension 1), 36 (Extension 2), and 52 Months (Extension 3) of Treatment With Givinostat at the Selected Daily Dose Based on the Performance of Upper Limb (PUL)
Description	The PUL (version 1.2) was used to assess the change in motor performance of the upper limb over time in patients with Becker and Duchenne muscular dystrophy, from when they are still ambulant, until they loose all arm function when non-ambulant. The revised version of the PUL included 22 items taking. These include one entry item to define the starting functional level, and 21 items subdivided into: shoulder level (Question B to E; minimum score 0 and maximum score 16); elbow level (Question F to N; minimum score 0 and maximum score 34); distal level dimension (Question O to V; minimum score 0 and maximum score 24) The total score is calculated by the sum of all the scores of the three subscales (total score range: 0-74) (scores from Question A "entry item" did not contribute). For all items, the higher the score, the better the outcome.
Time Frame	At 24, 36, and 52 months

Outcome Measure Data

Analysis Population Description

The ITT population included all children who were enrolled in the Part 1 portion or entered the Part 2 portion of the study. Patients were analyzed overall due to a small sample size. Although different Givinostat dose levels were administered, results data are reported only for the "overall" Givinostat population.

Arm/Group Title		Overall
Arm/Group Description:		Givinostat was administered as 2 oral doses daily while the child is in fed state. Givinostat, oral suspension 10 mg/mL or oral capsules 50 mg, was administered at the dose of 25 mg BID, 37.5 mg BID, and 50 mg BID during Part 1, and 25 mg BID and 37.5 mg BID during Part 2. Givinostat oral suspension 10 mg/mL was administered orally at the dose of 25 mg BID or 37.5 mg BID during Extension 1; the dose was modified as per patient's weight during Extensions 2 and 3.
Overall Number of Participants Analyzed		19
Mean (Standard Deviation); Unit of Measure: score on a scale
Extension 1	Number Analyzed	18 participants
		-0.2 (2.71)
Extension 2	Number Analyzed	18 participants
		-0.2 (2.75)
Extension 3	Number Analyzed	18 participants
		-4.4 (6.09)

11. Secondary Outcome

Title	Number of Children Experiencing Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Type and Severity of TEAEs
Description	Summary of Treatment-emergent Adverse Events (TEAE) Reporting from Baseline to the End of Extension 3 (Month 52). In the analysis were included: Any TEAE, Any treatment-related TEAE, Any mild or moderate or severe TEAE, Any life-threatening or disabling TEAE, Any TEAE resulting in death, any serious adverse event, and Any TEAE resulting in study discontinuation.
Time Frame	Part 1, Part 2, and Extensions 1, 2, and 3

Outcome Measure Data

Analysis Population Description

The safety population included all children who received any investigational product. Although different Givinostat dose levels were administered, results data are reported only for the "overall" Givinostat population. During the extension period the dosage was adjusted by patient weight

Arm/Group Title	Overall
Arm/Group Description:	Givinostat was administered as 2 oral doses daily while the child is in fed state. Givinostat, oral suspension 10 mg/mL or oral capsules 50 mg, was administered at the dose of 25 mg BID, 37.5 mg BID, and 50 mg BID during Part 1, and 25 mg BID and 37.5 mg BID during Part 2. Givinostat oral suspension 10 mg/mL was administered orally at the dose of 25 mg BID or 37.5 mg BID during Extension 1; the dose was modified as per patient's weight during Extensions 2 and 3.
Overall Number of Participants Analyzed	20
Measure Type: Number; Unit of Measure: participants
TEAEs	20
Any treatment-related TEAE	20
Any mild TEAE	20
Any moderate TEAE	16
Any severe TEAE	9
Any life-threatening or disabling TEAE	1
Ant TEAE resulting in death	0
Any SAE	8
Any TEAE resulting in study discontinuation	1

Adverse Events

Time Frame	Adverse events (AE) were assessed throughout the study: in Part 1 (screen, weeks 0, 1, 2, 3, 4, 5); Part 2 (months 0, 1, 2, 3, 4.5, 6, 7.5, 9, 10.5,12); Extension 1 (months 14,16,18, 20, 22, 24, FU); Extension 2 (months 26,28, 30,32, 34, 36, FU); Extension 3 (months 40, 44, 48, 52, FU). Extensions 1, 2 and 3 together represent Part 3 of the study.
Adverse Event Reporting Description	TEAEs by Primary System Organ Class, Preferred Term, and Relationship to Study Drug are reported for each dose separately in Part 1 and Part 2 of the study (i.e. Part 1 25.0 mg, Part 1 37.5 mg, Part 1 50 mg; Part 2 25.0 mg, Part 2 37.5 mg) and are reported to represent all participants and all parts of this study including the extension period altogether (i.e. Part 1 + Part 2 + Extensions 1, 2, and 3). Adverse events were not assessed by dose nor separately for the extension period.
Arm/Group Title	Part 1 - 25 mg		Part 1 - 50 mg		Part 1 - 37.5 mg		Part 2 - 37.5 mg		Part 2 - 25 mg		Overall (Part 1 + Part 2 + Extensions 1, 2, 3 )
Arm/Group Description	The safety population included all children who received any investigational product. The dose level under which the patient was analyzed was the dose of investigational product that was actually received. 19 patients were included in the safety population of Part 1.		The safety population included all children who received any investigational product. The dose level under which the patient was analyzed was the dose of investigational product that was actually received. 19 patients were included in the safety population of Part 1.		The safety population included all children who received any investigational product. The dose level under which the patient was analyzed was the dose of investigational product that was actually received. 19 patients were included in the safety population of Part 1.		The safety population included all children who received any investigational product. The dose level under which the patient was analyzed was the dose of investigational product that was actually received. 19 patients were included in the safety population of Part 2.		The safety population included all children who received any investigational product. The dose level under which the patient was analyzed was the dose of investigational product that was actually received. 19 patients were included in the safety population of Part 2.		The safety population included all children who received any investigational product. The dose level under which the patient was analyzed was the dose of investigational product that was actually received. 19 patients were included in the safety population of Part 1 and 19 patients were included in the safety population of Part 2. In all Extensions, the Safety Analysis Population was set up to 20 patients (100%), including all patients who received any investigational product.
All-Cause Mortality
	Part 1 - 25 mg		Part 1 - 50 mg		Part 1 - 37.5 mg		Part 2 - 37.5 mg		Part 2 - 25 mg		Overall (Part 1 + Part 2 + Extensions 1, 2, 3 )
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	0/4 (0.00%)		0/12 (0.00%)		0/7 (0.00%)		0/19 (0.00%)		0/12 (0.00%)		0/20 (0.00%)
Serious Adverse Events
	Part 1 - 25 mg		Part 1 - 50 mg		Part 1 - 37.5 mg		Part 2 - 37.5 mg		Part 2 - 25 mg		Overall (Part 1 + Part 2 + Extensions 1, 2, 3 )
	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	0/4 (0.00%)		1/12 (8.33%)		0/7 (0.00%)		1/19 (5.26%)		1/12 (8.33%)		8/20 (40.00%)
Endocrine disorders
Cushing's syndrome † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	0/7 (0.00%)	0	0/19 (0.00%)	0	0/12 (0.00%)	0	1/20 (5.00%)	1
Eye disorders
Cataracts † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	0/7 (0.00%)	0	0/19 (0.00%)	0	0/12 (0.00%)	0	1/20 (5.00%)	2
General disorders
Chest pain † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	0/7 (0.00%)	0	0/19 (0.00%)	0	0/12 (0.00%)	0	1/20 (5.00%)	1
Lower limb fracture † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	0/7 (0.00%)	0	0/19 (0.00%)	0	1/12 (8.33%)	1	1/20 (5.00%)	1
Injury, poisoning and procedural complications
Femural fracture † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	0/7 (0.00%)	0	0/19 (0.00%)	0	0/12 (0.00%)	0	2/20 (10.00%)	2
Investigations
Platelet count decreased † 1	0/4 (0.00%)	0	1/12 (8.33%)	1	0/7 (0.00%)	0	0/19 (0.00%)	0	0/12 (0.00%)	0	2/20 (10.00%)	2
Musculoskeletal and connective tissue disorders
Rhabdomyolysis † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	0/7 (0.00%)	0	1/19 (5.26%)	1	0/12 (0.00%)	0	1/20 (5.00%)	1
Renal and urinary disorders
Haematuria † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	0/7 (0.00%)	0	0/19 (0.00%)	0	0/12 (0.00%)	0	1/20 (5.00%)	1
Vascular disorders
Hypertension † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	0/7 (0.00%)	0	0/19 (0.00%)	0	0/12 (0.00%)	0	1/20 (5.00%)	1
1 Term from vocabulary, MedDRA (17.0); † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Part 1 - 25 mg		Part 1 - 50 mg		Part 1 - 37.5 mg		Part 2 - 37.5 mg		Part 2 - 25 mg		Overall (Part 1 + Part 2 + Extensions 1, 2, 3 )
	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	3/4 (75.00%)		12/12 (100.00%)		6/7 (85.71%)		19/19 (100.00%)		12/12 (100.00%)		20/20 (100.00%)
Blood and lymphatic system disorders
Lymphadenopathy † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	0/7 (0.00%)	0	0/19 (0.00%)	0	0/12 (0.00%)	0	1/20 (5.00%)	1
Cardiac disorders
Cardiac discomfort † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	0/7 (0.00%)	0	0/19 (0.00%)	0	0/12 (0.00%)	0	1/20 (5.00%)	1
Extrasystoles † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	0/7 (0.00%)	0	1/19 (5.26%)	1	0/12 (0.00%)	0	1/20 (5.00%)	1
Left ventricular dilatation † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	0/7 (0.00%)	0	0/19 (0.00%)	0	0/12 (0.00%)	0	1/20 (5.00%)	1
Left ventricular disfunction † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	0/7 (0.00%)	0	0/19 (0.00%)	0	0/12 (0.00%)	0	2/20 (10.00%)	2
Palpitations † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	0/7 (0.00%)	0	1/19 (5.26%)	1	0/12 (0.00%)	0	1/20 (5.00%)	2
Sinus tachycardia † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	0/7 (0.00%)	0	0/19 (0.00%)	0	0/12 (0.00%)	0	1/20 (5.00%)	1
Tachycardia † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	0/7 (0.00%)	0	0/19 (0.00%)	0	0/12 (0.00%)	0	1/20 (5.00%)	1
Ventricular extrasystoles † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	0/7 (0.00%)	0	0/19 (0.00%)	0	0/12 (0.00%)	0	1/20 (5.00%)	1
Congenital, familial and genetic disorders
Gilbert's syndrome † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	0/7 (0.00%)	0	0/19 (0.00%)	0	0/12 (0.00%)	0	1/20 (5.00%)	1
Ear and labyrinth disorders
Ear pain † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	1/7 (14.29%)	1	1/19 (5.26%)	1	1/12 (8.33%)	1	2/20 (10.00%)	3
Endocrine disorders
Adrenal insufficiency † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	0/7 (0.00%)	0	0/19 (0.00%)	0	0/12 (0.00%)	0	1/20 (5.00%)	1
Autoimmune thyroiditis † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	0/7 (0.00%)	0	1/19 (5.26%)	1	0/12 (0.00%)	0	1/20 (5.00%)	1
Delayed puberty † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	0/7 (0.00%)	0	0/19 (0.00%)	0	0/12 (0.00%)	0	2/20 (10.00%)	2
Hypothyroidism † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	0/7 (0.00%)	0	1/19 (5.26%)	1	0/12 (0.00%)	0	3/20 (15.00%)	3
Secondary adrenocartical insufficiency † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	0/7 (0.00%)	0	1/19 (5.26%)	1	0/12 (0.00%)	0	1/20 (5.00%)	1
Eye disorders
Cataract † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	0/7 (0.00%)	0	0/19 (0.00%)	0	0/12 (0.00%)	0	2/20 (10.00%)	4
Lens discoloration † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	0/7 (0.00%)	0	0/19 (0.00%)	0	1/12 (8.33%)	1	1/20 (5.00%)	1
Lenticular opacity † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	0/7 (0.00%)	0	1/19 (5.26%)	1	0/12 (0.00%)	0	2/20 (10.00%)	2
Gastrointestinal disorders
Abdominal pain † 1	0/4 (0.00%)	0	1/12 (8.33%)	3	2/7 (28.57%)	3	5/19 (26.32%)	6	0/12 (0.00%)	0	11/20 (55.00%)	19
Colitis † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	0/7 (0.00%)	0	0/19 (0.00%)	0	1/12 (8.33%)	1	1/20 (5.00%)	1
Diarrhoea † 1	2/4 (50.00%)	2	5/12 (41.67%)	8	3/7 (42.86%)	4	9/19 (47.37%)	23	6/12 (50.00%)	14	15/20 (75.00%)	66
Faeces soft † 1	0/4 (0.00%)	0	1/12 (8.33%)	1	1/7 (14.29%)	1	0/19 (0.00%)	0	0/12 (0.00%)	0	2/20 (10.00%)	2
Frequent bowel movements † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	1/7 (14.29%)	1	1/19 (5.26%)	2	0/12 (0.00%)	0	2/20 (10.00%)	3
Haemorrhoids † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	0/7 (0.00%)	0	0/19 (0.00%)	0	0/12 (0.00%)	0	2/20 (10.00%)	2
Stomatitis † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	0/7 (0.00%)	0	0/19 (0.00%)	0	0/12 (0.00%)	0	1/20 (5.00%)	2
Vomiting † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	1/7 (14.29%)	1	2/19 (10.53%)	2	3/12 (25.00%)	3	8/20 (40.00%)	11
General disorders
Chest pain † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	0/7 (0.00%)	0	1/19 (5.26%)	1	0/12 (0.00%)	0	1/20 (5.00%)	1
Fatigue † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	0/7 (0.00%)	0	2/19 (10.53%)	2	0/12 (0.00%)	0	3/20 (15.00%)	3
Gait disturbance † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	0/7 (0.00%)	0	0/19 (0.00%)	0	1/12 (8.33%)	1	1/20 (5.00%)	1
Non cardiac chest pain † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	1/7 (14.29%)	1	1/19 (5.26%)	1	0/12 (0.00%)	0	1/20 (5.00%)	2
Peripheral swelling † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	0/7 (0.00%)	0	0/19 (0.00%)	0	0/12 (0.00%)	0	1/20 (5.00%)	1
Pyrexia † 1	0/4 (0.00%)	0	1/12 (8.33%)	1	1/7 (14.29%)	1	3/19 (15.79%)	3	3/12 (25.00%)	3	9/20 (45.00%)	20
Infections and infestations
Bronchitis † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	0/7 (0.00%)	0	0/19 (0.00%)	0	0/12 (0.00%)	0	1/20 (5.00%)	2
Ear infection † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	0/7 (0.00%)	0	1/19 (5.26%)	1	1/12 (8.33%)	1	3/20 (15.00%)	4
Gastroenteritis † 1	0/4 (0.00%)	0	1/12 (8.33%)	1	0/7 (0.00%)	0	0/19 (0.00%)	0	1/12 (8.33%)	1	5/20 (25.00%)	6
Gastrointestinal viral infection † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	0/7 (0.00%)	0	0/19 (0.00%)	0	0/12 (0.00%)	0	1/20 (5.00%)	1
Influenza † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	1/7 (14.29%)	1	2/19 (10.53%)	2	1/12 (8.33%)	1	9/20 (45.00%)	14
Molluscum contagiosum † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	0/7 (0.00%)	0	0/19 (0.00%)	0	1/12 (8.33%)	1	1/20 (5.00%)	1
Nasopharyngitis † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	0/7 (0.00%)	0	0/19 (0.00%)	0	1/12 (8.33%)	1	3/20 (15.00%)	3
Paronychia † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	0/7 (0.00%)	0	0/19 (0.00%)	0	0/12 (0.00%)	0	1/20 (5.00%)	1
Pharyngitis † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	0/7 (0.00%)	0	0/19 (0.00%)	0	0/12 (0.00%)	0	1/20 (5.00%)	1
Respiratory tract infection † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	0/7 (0.00%)	0	0/19 (0.00%)	0	2/12 (16.67%)	2	2/20 (10.00%)	2
Rhinitis † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	0/7 (0.00%)	0	1/19 (5.26%)	1	0/12 (0.00%)	0	2/20 (10.00%)	2
Tooth infection † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	0/7 (0.00%)	0	0/19 (0.00%)	0	0/12 (0.00%)	0	1/20 (5.00%)	1
Upper respiratory tract infection † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	1/7 (14.29%)	1	0/19 (0.00%)	0	0/12 (0.00%)	0	2/20 (10.00%)	3
Urinary tract infection † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	0/7 (0.00%)	0	1/19 (5.26%)	1	0/12 (0.00%)	0	2/20 (10.00%)	2
Varicella † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	0/7 (0.00%)	0	1/19 (5.26%)	1	0/12 (0.00%)	0	1/20 (5.00%)	1
Injury, poisoning and procedural complications
Contusion † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	0/7 (0.00%)	0	0/19 (0.00%)	0	0/12 (0.00%)	0	1/20 (5.00%)	1
Fall † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	1/7 (14.29%)	1	1/19 (5.26%)	1	2/12 (16.67%)	2	8/20 (40.00%)	9
Femur fracture † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	0/7 (0.00%)	0	0/19 (0.00%)	0	0/12 (0.00%)	0	2/20 (10.00%)	2
Foot fracture † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	0/7 (0.00%)	0	0/19 (0.00%)	0	0/12 (0.00%)	0	1/20 (5.00%)	1
Head injury † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	0/7 (0.00%)	0	0/19 (0.00%)	0	1/12 (8.33%)	1	1/20 (5.00%)	1
Joint injury † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	0/7 (0.00%)	0	1/19 (5.26%)	1	0/12 (0.00%)	0	2/20 (10.00%)	2
Laceration † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	1/7 (14.29%)	1	0/19 (0.00%)	0	0/12 (0.00%)	0	1/20 (5.00%)	1
Legament injury † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	0/7 (0.00%)	0	1/19 (5.26%)	1	0/12 (0.00%)	0	1/20 (5.00%)	1
Legament sprain † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	0/7 (0.00%)	0	1/19 (5.26%)	2	0/12 (0.00%)	0	5/20 (25.00%)	7
Limb injury † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	0/7 (0.00%)	0	0/19 (0.00%)	0	0/12 (0.00%)	0	3/20 (15.00%)	3
Lower limb fracture † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	0/7 (0.00%)	0	0/19 (0.00%)	0	1/12 (8.33%)	1	1/20 (5.00%)	1
Muscle strain † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	0/7 (0.00%)	0	0/19 (0.00%)	0	0/12 (0.00%)	0	1/20 (5.00%)	1
Spinal compression fracture † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	0/7 (0.00%)	0	0/19 (0.00%)	0	0/12 (0.00%)	0	1/20 (5.00%)	1
Spinal cord injury sacral † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	0/7 (0.00%)	0	0/19 (0.00%)	0	0/12 (0.00%)	0	1/20 (5.00%)	1
Tendon injury † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	0/7 (0.00%)	0	0/19 (0.00%)	0	0/12 (0.00%)	0	1/20 (5.00%)	1
Tibia fracture † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	0/7 (0.00%)	0	0/19 (0.00%)	0	0/12 (0.00%)	0	2/20 (10.00%)	2
Investigations
Blood bilirubin increased † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	0/7 (0.00%)	0	0/19 (0.00%)	0	0/12 (0.00%)	0	1/20 (5.00%)	1
Intraocular pressure increased † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	0/7 (0.00%)	0	0/19 (0.00%)	0	0/12 (0.00%)	0	1/20 (5.00%)	1
Neutrophil count decreased † 1	0/4 (0.00%)	0	1/12 (8.33%)	1	0/7 (0.00%)	0	2/19 (10.53%)	3	0/12 (0.00%)	0	3/20 (15.00%)	4
Platelet count decreased † 1	0/4 (0.00%)	0	1/12 (8.33%)	1	0/7 (0.00%)	0	13/19 (68.42%)	18	5/12 (41.67%)	7	13/20 (65.00%)	39
White blood cell count decreased † 1	0/4 (0.00%)	0	4/12 (33.33%)	6	0/7 (0.00%)	0	1/19 (5.26%)	1	0/12 (0.00%)	0	4/20 (20.00%)	7
Metabolism and nutrition disorders
Decreased appetite † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	1/7 (14.29%)	1	4/19 (21.05%)	5	2/12 (16.67%)	2	7/20 (35.00%)	8
Hypertryglyceridaemia † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	0/7 (0.00%)	0	0/19 (0.00%)	0	0/12 (0.00%)	0	1/20 (5.00%)	1
Musculoskeletal and connective tissue disorders
Arthralgia † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	0/7 (0.00%)	0	0/19 (0.00%)	0	1/12 (8.33%)	1	4/20 (20.00%)	4
Back pain † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	1/7 (14.29%)	1	0/19 (0.00%)	0	0/12 (0.00%)	0	3/20 (15.00%)	3
Fracture pain † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	0/7 (0.00%)	0	0/19 (0.00%)	0	0/12 (0.00%)	0	1/20 (5.00%)	1
Muscular weakness † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	0/7 (0.00%)	0	1/19 (5.26%)	1	0/12 (0.00%)	0	2/20 (10.00%)	2
Myalgia † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	1/7 (14.29%)	1	0/19 (0.00%)	0	0/12 (0.00%)	0	2/20 (10.00%)	2
Neck pain † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	0/7 (0.00%)	0	0/19 (0.00%)	0	1/12 (8.33%)	2	2/20 (10.00%)	5
Osteopenia † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	0/7 (0.00%)	0	0/19 (0.00%)	0	0/12 (0.00%)	0	1/20 (5.00%)	1
Pain in extremity † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	0/7 (0.00%)	0	0/19 (0.00%)	0	0/12 (0.00%)	0	3/20 (15.00%)	3
Tendinous contracture † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	0/7 (0.00%)	0	0/19 (0.00%)	0	2/12 (16.67%)	2	2/20 (10.00%)	3
Tendon pain † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	0/7 (0.00%)	0	0/19 (0.00%)	0	1/12 (8.33%)	1	1/20 (5.00%)	1
Tendonitis † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	0/7 (0.00%)	0	0/19 (0.00%)	0	0/12 (0.00%)	0	1/20 (5.00%)	1
Nervous system disorders
Dizziness † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	0/7 (0.00%)	0	0/19 (0.00%)	0	0/12 (0.00%)	0	1/20 (5.00%)	1
Headache † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	0/7 (0.00%)	0	1/19 (5.26%)	2	2/12 (16.67%)	2	4/20 (20.00%)	6
Renal and urinary disorders
Haematuria † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	0/7 (0.00%)	0	1/19 (5.26%)	1	0/12 (0.00%)	0	2/20 (10.00%)	2
Respiratory, thoracic and mediastinal disorders
Cough † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	0/7 (0.00%)	0	2/19 (10.53%)	2	0/12 (0.00%)	0	10/20 (50.00%)	12
Dyspnoea † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	0/7 (0.00%)	0	0/19 (0.00%)	0	0/12 (0.00%)	0	1/20 (5.00%)	1
Epistaxis † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	0/7 (0.00%)	0	0/19 (0.00%)	0	1/12 (8.33%)	1	1/20 (5.00%)	2
Laryngeal inflammation † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	0/7 (0.00%)	0	1/19 (5.26%)	1	0/12 (0.00%)	0	1/20 (5.00%)	1
Nasal congestion † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	0/7 (0.00%)	0	1/19 (5.26%)	1	0/12 (0.00%)	0	1/20 (5.00%)	1
Oropharyngeal pain † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	0/7 (0.00%)	0	1/19 (5.26%)	1	0/12 (0.00%)	0	1/20 (5.00%)	1
Pharyngeal erythema † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	0/7 (0.00%)	0	1/19 (5.26%)	1	0/12 (0.00%)	0	1/20 (5.00%)	1
Skin and subcutaneous tissue disorders
Dermatosis † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	0/7 (0.00%)	0	0/19 (0.00%)	0	0/12 (0.00%)	0	1/20 (5.00%)	1
Ecchymosis † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	0/7 (0.00%)	0	0/19 (0.00%)	0	1/12 (8.33%)	1	1/20 (5.00%)	1
Erythema † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	0/7 (0.00%)	0	0/19 (0.00%)	0	1/12 (8.33%)	1	1/20 (5.00%)	1
Erythema annulare † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	0/7 (0.00%)	0	0/19 (0.00%)	0	0/12 (0.00%)	0	1/20 (5.00%)	1
Intertrigo † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	0/7 (0.00%)	0	0/19 (0.00%)	0	0/12 (0.00%)	0	1/20 (5.00%)	1
Nail dystrophy † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	0/7 (0.00%)	0	0/19 (0.00%)	0	0/12 (0.00%)	0	1/20 (5.00%)	1
Rash † 1	1/4 (25.00%)	1	1/12 (8.33%)	1	0/7 (0.00%)	0	0/19 (0.00%)	0	0/12 (0.00%)	0	2/20 (10.00%)	2
Seborrhoeic dermatitis † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	0/7 (0.00%)	0	0/19 (0.00%)	0	0/12 (0.00%)	0	1/20 (5.00%)	1
Skin lesion † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	0/7 (0.00%)	0	0/19 (0.00%)	0	0/12 (0.00%)	0	1/20 (5.00%)	1
Solar dermatitis † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	0/7 (0.00%)	0	0/19 (0.00%)	0	1/12 (8.33%)	1	1/20 (5.00%)	1
Vascular disorders
Hypertension † 1	0/4 (0.00%)	0	0/12 (0.00%)	0	0/7 (0.00%)	0	0/19 (0.00%)	0	0/12 (0.00%)	0	3/20 (15.00%)	5
1 Term from vocabulary, MedDRA (17.0); † 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 NOT 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.

Results Point of Contact

• Name/Title: Paolo Bettica, MD
• Organization: Italfarmaco SpA
• Phone: +39 02 64431
• EMail: p.bettica@italfarmaco.com

Publications of Results:

Bettica P, Petrini S, D'Oria V, D'Amico A, Catteruccia M, Pane M, Sivo S, Magri F, Brajkovic S, Messina S, Vita GL, Gatti B, Moggio M, Puri PL, Rocchetti M, De Nicolao G, Vita G, Comi GP, Bertini E, Mercuri E. Histological effects of givinostat in boys with Duchenne muscular dystrophy. Neuromuscul Disord. 2016 Oct;26(10):643-649. doi: 10.1016/j.nmd.2016.07.002. Epub 2016 Jul 11.

• Responsible Party: Italfarmaco
• ClinicalTrials.gov Identifier: NCT01761292
• Other Study ID Numbers: DSC/11/2357/43; 2012-002566-12 ( EudraCT Number )
• First Submitted: December 20, 2012
• First Posted: January 4, 2013
• Results First Submitted: January 27, 2020
• Results First Posted: June 23, 2020
• Last Update Posted: November 7, 2023