Trial Outcomes & Findings for Phase III Study of Idebenone in Duchenne Muscular Dystrophy (DMD) (NCT NCT01027884)
NCT ID: NCT01027884
Last Updated: 2015-10-19
Results Overview
Change from Baseline in Percent Predicted Peak Expiratory Flow (PEF) at Week 52
COMPLETED
PHASE3
65 participants
Baseline and Week 52
2015-10-19
Participant Flow
Recruiting centres were in Belgium, Germany, the Netherlands, Switzerland, France, Sweden, Austria, Italy, Spain, and the USA. Patients were enrolled between July 27, 2009 (study start date), and Dec 14, 2012; the study end date (last patient completed the study) was Jan 14, 2014.
65 patients were randomly assigned and two patients were allocated to the same treatment as their randomly assigned siblings. One patient never took study medication, resulting in 66 patients who were treated and included in the safety population (34 in the placebo group and 32 in the idebenone group).
Participant milestones
| Measure |
Placebo
Two matching placebo tablets were taken three times a day with meals
|
Idebenone
Two150 mg tablets were taken three times a day with meals (total dose 900 mg daily).
|
|---|---|---|
|
Overall Study
STARTED
|
34
|
32
|
|
Overall Study
COMPLETED
|
30
|
25
|
|
Overall Study
NOT COMPLETED
|
4
|
7
|
Reasons for withdrawal
| Measure |
Placebo
Two matching placebo tablets were taken three times a day with meals
|
Idebenone
Two150 mg tablets were taken three times a day with meals (total dose 900 mg daily).
|
|---|---|---|
|
Overall Study
Adverse Event
|
2
|
1
|
|
Overall Study
Protocol Violation
|
1
|
0
|
|
Overall Study
Non-compliance
|
1
|
1
|
|
Overall Study
Withdrawal by Subject
|
0
|
1
|
|
Overall Study
Lost to Follow-up
|
0
|
1
|
|
Overall Study
Spinal fixation surgery
|
0
|
3
|
Baseline Characteristics
Phase III Study of Idebenone in Duchenne Muscular Dystrophy (DMD)
Baseline characteristics by cohort
| Measure |
Placebo
n=34 Participants
Two matching placebo tablets were taken three times a day with meals
|
Idebenone
n=32 Participants
Two150 mg tablets were taken three times a day with meals (total dose 900 mg daily).
|
Total
n=66 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
15 years
STANDARD_DEVIATION 2.5 • n=5 Participants
|
13.5 years
STANDARD_DEVIATION 2.7 • n=7 Participants
|
14.3 years
STANDARD_DEVIATION 2.7 • n=5 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
34 Participants
n=5 Participants
|
32 Participants
n=7 Participants
|
66 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline and Week 52Population: This analysis was performed on the ITT population(n=64). This population included all randomized patients who received at least one dose of the study medication and provided at least one post-Baseline assessment. It excluded siblings who had been allocated to the same study treatment as a randomized sibling.
Change from Baseline in Percent Predicted Peak Expiratory Flow (PEF) at Week 52
Outcome measures
| Measure |
Placebo
n=33 Participants
Two matching placebo tablets were taken three times a day with meals
|
Idebenone
n=31 Participants
Two150 mg tablets were taken three times a day with meals (total dose 900 mg daily).
|
|---|---|---|
|
Change From Baseline in Percent Predicted Peak Expiratory Flow (PEF) at Week 52
|
-8.84 percentage
Interval -12.73 to -4.95
|
-2.57 percentage
Interval -6.68 to 1.54
|
SECONDARY outcome
Timeframe: Baseline and Week 52Population: This analysis was performed on the ITT population(n=64). This population included all randomized patients who received at least one dose of the study medication and provided at least one post-Baseline assessment. It excluded siblings who had been allocated to the same study treatment as a randomized sibling.
Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Week 52
Outcome measures
| Measure |
Placebo
n=33 Participants
Two matching placebo tablets were taken three times a day with meals
|
Idebenone
n=31 Participants
Two150 mg tablets were taken three times a day with meals (total dose 900 mg daily).
|
|---|---|---|
|
Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Week 52
|
-8.95 percentage of Predicted FVC
Interval -11.47 to -6.42
|
-5.67 percentage of Predicted FVC
Interval -8.36 to -2.99
|
SECONDARY outcome
Timeframe: Baseline and Week 52Population: The number of patients (N) in each treatment group is the number of patients with baseline assessments
The change from Baseline to Week 52 in muscle strength as measured by Hand-Held Myometry (HHM) was performed following standardized procedures. As almost all patients were non-ambulatory, only analyses of upper limb muscle strength were performed. Results for elbow flexors and for elbow extensors are reported below.The highest value of 3 consecutive measurements with an interval of at least 10 seconds were recorded. The HHM was measured using MicroFET2, a digital hand held muscle tester. The selected unit of measure was Newtons (N).
Outcome measures
| Measure |
Placebo
n=27 Participants
Two matching placebo tablets were taken three times a day with meals
|
Idebenone
n=25 Participants
Two150 mg tablets were taken three times a day with meals (total dose 900 mg daily).
|
|---|---|---|
|
Change From Baseline to Week 52 in Muscle Strength
Elbow Extensors
|
1.32 Newtons
Interval -2.53 to 5.18
|
0.26 Newtons
Interval -3.95 to 4.46
|
|
Change From Baseline to Week 52 in Muscle Strength
Elbow Flexors
|
0.13 Newtons
Interval -4.16 to 4.41
|
-2.32 Newtons
Interval -6.73 to 2.09
|
SECONDARY outcome
Timeframe: Baseline and Week 52Population: The number of patients (N) in each treatment group is the number of patients with Baseline assessments.
PedsQL Quality of Life Inventory contains paediatric HRQOL measurements: Physical, Emotional,Social and School Functioning. Item Scaling: 5-point Likert scale from 0 (Never) to 4 (Almost always). 3-point scale: 0 (Not at all), 2 (Sometimes) and 4 (A lot) for the Young Child (ages 5-7). Scores are transformed on a scale from 0 to 100 ( 0=100, 1=75, 2=50, 3=25, 4=0) Total Score: Sum of all the items over the number of items answered on all the Scales. The values reported below are overall scores on Paediatric Quality of Life Inventory in Child/Teen Report. These scores were obtained by averaging scores for all the described subscales. The overall scores range between 0-100 with 0 = worst outcome and 100= best outcome
Outcome measures
| Measure |
Placebo
n=33 Participants
Two matching placebo tablets were taken three times a day with meals
|
Idebenone
n=30 Participants
Two150 mg tablets were taken three times a day with meals (total dose 900 mg daily).
|
|---|---|---|
|
Change From Baseline to Week 52 in Quality of Life Assessed by PedsQL™ Paediatric Quality of Life Inventory
|
2.46 units on a scale
Interval -1.77 to 6.69
|
-1.34 units on a scale
Interval -5.99 to 3.31
|
SECONDARY outcome
Timeframe: 52 WeeksOutcome measures
| Measure |
Placebo
n=34 Participants
Two matching placebo tablets were taken three times a day with meals
|
Idebenone
n=32 Participants
Two150 mg tablets were taken three times a day with meals (total dose 900 mg daily).
|
|---|---|---|
|
Percentage of Patients Reporting Adverse Events
|
94.1 percentage of patients reporting AEs
|
93.8 percentage of patients reporting AEs
|
Adverse Events
Placebo
Idebenone
Serious adverse events
| Measure |
Placebo
n=34 participants at risk
Two matching placebo tablets were taken three times a day with meals
|
Idebenone
n=32 participants at risk
Two150 mg tablets were taken three times a day with meals (total dose 900 mg daily).
|
|---|---|---|
|
Injury, poisoning and procedural complications
Femur fracture
|
2.9%
1/34 • Number of events 1
|
0.00%
0/32
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
|
2.9%
1/34 • Number of events 1
|
0.00%
0/32
|
|
Respiratory, thoracic and mediastinal disorders
Pulmunary microemboli
|
2.9%
1/34 • Number of events 1
|
0.00%
0/32
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
0.00%
0/34
|
3.1%
1/32 • Number of events 1
|
|
General disorders
Pyrexia
|
2.9%
1/34 • Number of events 1
|
0.00%
0/32
|
|
Psychiatric disorders
Sleep apnoea syndrome
|
0.00%
0/34
|
3.1%
1/32
|
|
Gastrointestinal disorders
Vomitig
|
2.9%
1/34
|
0.00%
0/32
|
|
Skin and subcutaneous tissue disorders
Urticaria
|
0.00%
0/34
|
3.1%
1/32 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Tendinous contracture
|
2.9%
1/34 • Number of events 2
|
0.00%
0/32
|
|
Metabolism and nutrition disorders
Dehydration
|
2.9%
1/34 • Number of events 1
|
0.00%
0/32
|
|
Infections and infestations
Pneumonia
|
5.9%
2/34 • Number of events 3
|
0.00%
0/32
|
|
Infections and infestations
Nasopharyngitis
|
2.9%
1/34 • Number of events 1
|
0.00%
0/32
|
Other adverse events
| Measure |
Placebo
n=34 participants at risk
Two matching placebo tablets were taken three times a day with meals
|
Idebenone
n=32 participants at risk
Two150 mg tablets were taken three times a day with meals (total dose 900 mg daily).
|
|---|---|---|
|
Cardiac disorders
Left ventricular failure
|
2.9%
1/34 • Number of events 1
|
9.4%
3/32 • Number of events 3
|
|
Cardiac disorders
Electrocardiogram abnormal
|
2.9%
1/34 • Number of events 1
|
6.2%
2/32 • Number of events 3
|
|
Blood and lymphatic system disorders
Blood phosporus increased
|
8.8%
3/34 • Number of events 4
|
3.1%
1/32 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Bronchitis
|
17.6%
6/34 • Number of events 7
|
12.5%
4/32 • Number of events 5
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
5.9%
2/34 • Number of events 2
|
9.4%
3/32 • Number of events 3
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
2.9%
1/34 • Number of events 1
|
6.2%
2/32 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
2.9%
1/34 • Number of events 1
|
6.2%
2/32 • Number of events 2
|
|
Nervous system disorders
Headache
|
20.6%
7/34 • Number of events 15
|
18.8%
6/32 • Number of events 13
|
|
General disorders
Pyrexia
|
8.8%
3/34 • Number of events 4
|
15.6%
5/32 • Number of events 6
|
|
General disorders
Influenza like illness
|
2.9%
1/34 • Number of events 2
|
6.2%
2/32 • Number of events 2
|
|
Gastrointestinal disorders
Diarrhoea
|
11.8%
4/34 • Number of events 6
|
25.0%
8/32 • Number of events 10
|
|
Gastrointestinal disorders
Constipation
|
17.6%
6/34 • Number of events 6
|
9.4%
3/32 • Number of events 4
|
|
Gastrointestinal disorders
Abdominal pain
|
8.8%
3/34 • Number of events 5
|
9.4%
3/32 • Number of events 4
|
|
Gastrointestinal disorders
Nausea
|
5.9%
2/34 • Number of events 2
|
3.1%
1/32 • Number of events 2
|
|
Gastrointestinal disorders
Vomiting
|
5.9%
2/34 • Number of events 3
|
3.1%
1/32 • Number of events 1
|
|
Renal and urinary disorders
Chromaturia
|
0.00%
0/34
|
9.4%
3/32 • Number of events 3
|
|
Skin and subcutaneous tissue disorders
Seborrhoeic dermatitis
|
5.9%
2/34 • Number of events 2
|
3.1%
1/32 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
11.8%
4/34 • Number of events 6
|
6.2%
2/32 • Number of events 2
|
|
Musculoskeletal and connective tissue disorders
Scoliosis
|
2.9%
1/34 • Number of events 1
|
6.2%
2/32 • Number of events 2
|
|
Infections and infestations
Nasopharyngitis
|
26.5%
9/34 • Number of events 11
|
25.0%
8/32 • Number of events 12
|
|
Infections and infestations
Upper respiratory tract infection
|
17.6%
6/34 • Number of events 10
|
6.2%
2/32 • Number of events 2
|
|
Infections and infestations
Gastroenteritis
|
2.9%
1/34 • Number of events 1
|
18.8%
6/32 • Number of events 7
|
|
Infections and infestations
Rhinitis
|
17.6%
6/34 • Number of events 8
|
3.1%
1/32 • Number of events 1
|
|
Infections and infestations
Otitis media
|
0.00%
0/34
|
9.4%
3/32 • Number of events 3
|
Additional Information
Dr Gunnar Buyse
University Hospital Leuven-Children Hospital
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place