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

• ClinicalTrials.gov Identifier: NCT00654784
• Recruitment Status: Completed
• First Posted: April 9, 2008
• Results First Posted: July 29, 2011
• Last Update Posted: August 1, 2011
• Sponsor: Santhera Pharmaceuticals
• Information provided by: Santhera Pharmaceuticals

Tracking Information

• First Submitted Date: April 3, 2008
• First Posted Date: April 9, 2008
• Results First Submitted Date: June 7, 2011
• Results First Posted Date: July 29, 2011
• Last Update Posted Date: August 1, 2011
• Study Start Date: October 2005
• Actual Primary Completion Date: August 2007 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 29, 2011)

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). [ Time Frame: 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.

• Original Primary Outcome Measures (submitted: April 3, 2008): The relative change from Baseline (at Screening) to Week 52 in peak systolic radial strain of the LV inferolateral wall, assessed by Color Doppler Myocardial Imaging (CDMI). [ Time Frame: 1 year ]

Current Secondary Outcome Measures (submitted: April 3, 2008)

• 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 ]
• 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 ]
• Safety and Tolerability, Assessed by Adverse Events, Blood and Urine Laboratory Measures, ECG. [ Time Frame: 1 year ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Efficacy and Tolerability of Idebenone in Boys With Cardiac Dysfunction Associated With Duchenne Muscular Dystrophy
• 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Duchenne Muscular Dystrophy (DMD)

Intervention

• Drug: idebenone
  idebenone 450 mg/day (150 mg three times a day)
• Drug: placebo

Study Arms

• Experimental: 1
  Intervention: Drug: idebenone
• Placebo Comparator: 2
  Intervention: Drug: placebo

• Publications *: Buyse GM, Goemans N, van den Hauwe M, Thijs D, de Groot IJ, Schara U, Ceulemans B, Meier T, Mertens L. Idebenone as a novel, therapeutic approach for Duchenne muscular dystrophy: results from a 12 month, double-blind, randomized placebo-controlled trial. Neuromuscul Disord. 2011 Jun;21(6):396-405. doi: 10.1016/j.nmd.2011.02.016. Epub 2011 Mar 23.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 3, 2008): 21
• Original Actual Enrollment: Same as current
• Actual Study Completion Date: August 2007
• Actual Primary Completion Date: August 2007 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 8 Years to 16 Years (Child)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belgium

Administrative Information

• NCT Number: NCT00654784
• Other Study ID Numbers: SNT-II-001
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Not Provided
• Study Sponsor: Santhera Pharmaceuticals
• Collaborators: Not Provided

Investigators

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

• PRS Account: Santhera Pharmaceuticals
• Verification Date: July 2011