DELPHI: Efficacy and Tolerability of Idebenone in Boys With Cardiac Dysfunction Associated With Duchenne Muscular Dystrophy

• Sponsor: Santhera Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00654784
• Collaborator: (none)
• Enrollment: 21
• Location: 1
• Arms: 2
• Duration (Months): 22
• Patients Per Site Per Month: 1

Study Details

Study Description

Brief Summary

Idebenone is a synthetic analogue of coenzyme Q10 and is a powerful antioxidant and essential constituent of the process of energy production on the cellular level. It can protect mitochondria from oxidative damage and boost their impaired function. It is thought that this mechanism will slow decline in heart function that is part of the disease process of Duchenne Muscular Dystrophy (DMD). It is possible that patients may benefit in terms of muscle strength and respiratory function. This pilot trial is designed to investigate this.

Condition or Disease	Intervention/Treatment	Phase
Duchenne Muscular Dystrophy (DMD)	Drug: idebenone; Drug: placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 21 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase IIa Double Blind, Randomised, Placebo Controlled, Single Centre Study at the University of Leuven to Assess the Efficacy and Tolerability of Idebenone in 8 - 16 Year Old Males With Cardiac Dysfunction Associated With Duchenne Muscular Dystrophy
• Study Start Date: Oct 1, 2005
• Actual Primary Completion Date: Aug 1, 2007
• Actual Study Completion Date: Aug 1, 2007

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1	Drug: idebenone; idebenone 450 mg/day (150 mg three times a day)
Placebo Comparator: 2	Drug: placebo

Outcome Measures

Primary Outcome Measures

1. The Relative Change in Peak Systolic Radial Strain of the Left Ventricle (LV) Inferolateral Wall From Baseline (at Screening) to Week 52, Assessed by Color Doppler Myocardial Imaging (CDMI). [baseline and Week 52]

   Assessing the peak systolic radial strain of the left ventricle inferolateral wall is used to characterize the cardiac involvement in the DMD patients. Color Doppler Myocardial Imaging technique is used to quantify regional myocardial function. The cardiac involvement in DMD is characterized by degeneration, atrophy and fibrosis of the myocardium, leading to dilated cardiomyopathy. The process begins in the posterolateral wall of the left ventricle, with septal involvement appearing at later stages.

Secondary Outcome Measures

1. Respiratory Function: Forced Vital Capacity (FVC), Forced Expiratory Volume in 1 Second (FEV1), Maximal Inspiratory Pressure (MIP) and Peak Flow (PF) [1 year]

2. Skeletal Muscle Strength (Upper Limb, Right and Left): Hand Grip, Elbow Flexors and Elbow Extensors (Upper Limb Score) Timed Walking Test (10 Metres) (Ambulant Patients Only) [1 year]

3. Safety and Tolerability, Assessed by Adverse Events, Blood and Urine Laboratory Measures, ECG. [1 year]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 8 Years to 16 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients 8 - 16 years of age at time of enrolment

• Male

• Presence of cardiac involvement/dysfunction, defined by abnormal peak systolic strain in left ventricle (LV) inferolateral wall

• Confirmed diagnosis of DMD (out of frame dystrophin gene deletion OR absent/<5% dystrophin protein on muscle biopsy; clinical picture consistent of typical DMD)

• If on chronic glucocorticosteroids treatment (deflazacort, prednisone) for DMD (or any other disease) (i.e. concomitant medication): dosage must be stable (unchanged) 6 months prior to inclusion

• If on chronic medication for DMD associated cardiomyopathy (β-blocker, diuretics): dosage must be stable (unchanged) 3 months prior to inclusion

• Ability to provide reproducible repeat quantitative muscle testing (QMT) upper limb score within 15% of first assessment score (at Visit1/Day 1 versus Screening Visit

Exclusion Criteria:

• Symptomatic cardiomyopathy or heart failure

• Asymptomatic but severe cardiac dysfunction on baseline (Screening) evaluation: Fractional shortening (FS) < 20% and/or Ejection fraction (EF) < 40%

• Use of ACE-inhibitors

• Previous history of ventricular arrhythmias (other than isolated ventricular extrasystole); ventricular arrhythmias presented at Screening

• Previous (6 months or less) participation in any other therapeutic trial for DMD

• Use of coenzymeQ10, idebenone, creatine, glutamine, oxatomide, or any herbal medicines within the last 6 months

• History of significant concomitant illness or significant impairment of renal or hepatic function

• Known individual hypersensitivity to idebenone

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children's Hospital, University Hospital	Leuven		Belgium

Sponsors and Collaborators

• Santhera Pharmaceuticals

Investigators

• Principal Investigator: Gunnar Buyse, MD PhD, Universitaire Ziekenhuizen Leuven

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00654784
• Other Study ID Numbers: SNT-II-001
• First Posted: Apr 9, 2008
• Last Update Posted: Aug 1, 2011
• Last Verified: Jul 1, 2011

• Keywords provided by , ,: Duchenne Muscular Dystrophy; DMD; Duchenne
• Additional relevant MeSH terms: Muscular Dystrophies; Muscular Dystrophy, Duchenne; Idebenone

Study Results

Participant Flow

Arm/Group Title	Idebenone 450 mg/ Day	Placebo
Arm/Group Description	idebenone 150 mg tablet: One tablet 3 times a day (Tid) with meals	Placebo tablet: One tablet 3 times a day (Tid) with meals
Period Title: Overall Study
STARTED	13	8
COMPLETED	13	8
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Idebenone 450 mg/ Day	Placebo	Total
Arm/Group Description	idebenone 150 mg tablet: One tablet 3 times a day (Tid) with meals	Placebo tablet: One tablet 3 times a day (Tid) with meals	Total of all reporting groups
Overall Participants	13	8	21
Age (Count of Participants)
<=18 years	13 100%	8 100%	21 100%
Between 18 and 65 years	0 0%	0 0%	0 0%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	13.4 (2.1)	10.8 (1.9)	12.4 (2.0)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	13 100%	8 100%	21 100%
Region of Enrollment (participants) [Number]
Belgium	13 100%	8 100%	21 100%

Outcome Measures

1. Primary Outcome

Title	The Relative Change in Peak Systolic Radial Strain of the Left Ventricle (LV) Inferolateral Wall From Baseline (at Screening) to Week 52, Assessed by Color Doppler Myocardial Imaging (CDMI).
Description	Assessing the peak systolic radial strain of the left ventricle inferolateral wall is used to characterize the cardiac involvement in the DMD patients. Color Doppler Myocardial Imaging technique is used to quantify regional myocardial function. The cardiac involvement in DMD is characterized by degeneration, atrophy and fibrosis of the myocardium, leading to dilated cardiomyopathy. The process begins in the posterolateral wall of the left ventricle, with septal involvement appearing at later stages.
Time Frame	baseline and Week 52

Outcome Measure Data

Analysis Population Description

At Week 52, data from only 18 patients were available for the primary endpoint analysis due to missing data from 2 patients and the inability to acquire data from a 3rd patient. The efficacy comparison for the primary endpoint was conducted using the LOCF method in the ITT population. In addition, the analysis was repeated using the OC dataset.

Arm/Group Title	Idebenone 450 mg/ Day	Placebo
Arm/Group Description	idebenone 150 mg tablet: One tablet 3 times a day (Tid) with meals	Placebo tablet: One tablet 3 times a day (Tid) with meals
Measure Participants	11	7
Mean (Standard Deviation) [% change in peak systolic]	104.4 (92.0)	28.9 (40.7)

2. Secondary Outcome

Title	Respiratory Function: Forced Vital Capacity (FVC), Forced Expiratory Volume in 1 Second (FEV1), Maximal Inspiratory Pressure (MIP) and Peak Flow (PF)
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

3. Secondary Outcome

Title	Skeletal Muscle Strength (Upper Limb, Right and Left): Hand Grip, Elbow Flexors and Elbow Extensors (Upper Limb Score) Timed Walking Test (10 Metres) (Ambulant Patients Only)
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Secondary Outcome

Title	Safety and Tolerability, Assessed by Adverse Events, Blood and Urine Laboratory Measures, ECG.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Arm/Group Title	Idebenone 450 mg/ Day		Placebo
Arm/Group Description	idebenone 150 mg tablet: One tablet 3 times a day (Tid) with meals		Placebo tablet: One tablet 3 times a day (Tid) with meals
All Cause Mortality
	Idebenone 450 mg/ Day		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Idebenone 450 mg/ Day		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/13 (7.7%)		1/8 (12.5%)
Injury, poisoning and procedural complications
Ankle fracture	1/13 (7.7%)	1	0/8 (0%)	0
Femur fracture	0/13 (0%)	0	1/8 (12.5%)	1
Other (Not Including Serious) Adverse Events
	Idebenone 450 mg/ Day		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/13 (92.3%)		8/8 (100%)
Gastrointestinal disorders
Gastrointestinal disorders	4/13 (30.8%)	5	5/8 (62.5%)	6
General disorders
General disorders	2/13 (15.4%)	4	1/8 (12.5%)	1
Infections and infestations
Infections	8/13 (61.5%)	19	5/8 (62.5%)	12

Limitations/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.