Help guide our efforts to modernize
Send us your comments by March 14, 2020. Menu

Phase 2a Extension Study of Ataluren (PTC124) in Duchenne Muscular Dystrophy (DMD)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00759876
Recruitment Status : Terminated
First Posted : September 25, 2008
Last Update Posted : April 8, 2019
Genzyme, a Sanofi Company
Information provided by (Responsible Party):
PTC Therapeutics

Brief Summary:
Duchenne muscular dystrophy (DMD) is a genetic disorder that develops in boys. It is caused by a mutation in the gene for dystrophin, a protein that is important for maintaining normal muscle structure and function. Loss of dystrophin causes muscle fragility that leads to weakness and loss of walking ability during childhood and teenage years. A specific type of mutation, called a nonsense (premature stop codon) mutation, is the cause of DMD in approximately 10-15% of boys with the disease. Ataluren is an orally delivered, investigational drug that has the potential to overcome the effects of the nonsense mutation. This study is a Phase 2a extension trial that will evaluate the long-term safety of ataluren in boys with nonsense mutation DMD, as determined by adverse events and laboratory abnormalities. The study will also assess changes in walking, muscle function, strength, and other important clinical and laboratory measures.

Condition or disease Intervention/treatment Phase
Duchenne Muscular Dystrophy Drug: Ataluren Phase 2

Detailed Description:
This Phase 2a, multicenter, open-label safety and efficacy study will be performed at 3 sites in the United States. The study will enroll up to 38 subjects with nonsense mutation Duchenne muscular dystrophy who participated in a previous Phase 2a study of ataluren (Protocol Number PTC124-GD-004-DMD). Subjects will receive study drug 3 times per day (at breakfast, lunch, and dinner) for approximately 96 weeks (approximately 2 years). Study assessments will be performed at clinic visits during screening, every 6 weeks for the first 24 weeks, and then every 12 weeks until the end of the study. Additional safety laboratory testing, which may be performed at the investigational site or at an accredited local laboratory or clinic, is required every 3 weeks for the first 24 weeks and then every 6 weeks from Week 24 to Week 48. Subjects will have a biceps muscle biopsy before ataluren treatment and again after 24 weeks of ataluren treatment to evaluate changes in muscle dystrophin expression. An evaluation of the effects of ataluren on corticosteroid pharmacokinetics will be performed. Associated with this ataluren clinical trial is a substudy that will use magnetic resonance evaluations to assess changes in the composition of muscles of the legs.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 36 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2a Extension Study of PTC124 in Subjects With Nonsense-Mutation-Mediated Duchenne Muscular Dystrophy
Actual Study Start Date : July 31, 2008
Actual Primary Completion Date : May 31, 2010
Actual Study Completion Date : May 31, 2010

Arm Intervention/treatment
Experimental: ataluren (ptc124)
Atalaluren (PTC124) 20-,20-,and 40-mg/kg TID PO for 96 weeks.
Drug: Ataluren
Oral powder in a sachet taken 3 times per day with dosing based on subject body weight. Doses are 20 mg/kg with breakfast, 20 mg/kg with lunch, and 40 mg/kg with dinner.
Other Name: PTC124

Primary Outcome Measures :
  1. Long-term safety [ Time Frame: 2 years ]

Secondary Outcome Measures :
  1. Ambulation [ Time Frame: 2 years ]
  2. Proximal muscle function [ Time Frame: 2 years ]
  3. Heart rate [ Time Frame: 2 years ]
  4. Cognitive ability [ Time Frame: 2 years ]
  5. Quality of life [ Time Frame: 2 years ]
  6. Activities of daily living [ Time Frame: 2 years ]
  7. Muscle fragility [ Time Frame: 2 years ]
  8. Biceps muscle dystrophin expression [ Time Frame: 2 years ]
  9. Compliance with PTC124 treatment [ Time Frame: 2 years ]
  10. PTC124 pharmacokinetics [ Time Frame: 2 years ]
  11. PTC124 effect on corticosteroid pharmacokinetics [ Time Frame: 2 years ]
  12. Muscle composition as assessed by magnetic resonance [ Time Frame: 2 years ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Completion of ataluren treatment in the previous Phase 2a study protocol (Protocol PTC124-GD-004-DMD).
  • Ability to provide written informed consent (parental/guardian consent if applicable)/assent (if <18 years of age).
  • Confirmed screening laboratory values within the central laboratory ranges.
  • In subjects who are sexually active, willingness to abstain from sexual intercourse or employ a barrier or medical method of contraception during ataluren administration and the 6-week follow up period.
  • Willingness and ability to comply with scheduled visits, drug administration plan, study procedures, laboratory tests, and study restrictions.

Exclusion Criteria:

  • Treatment with systemic aminoglycoside antibiotics within 3 months prior to start of study treatment.
  • Treatment with warfarin within 1 month prior to start of study treatment.
  • Known hypersensitivity to any of the ingredients or excipients of the study drug (Litesse® UltraTM [refined polydextrose], polyethylene glycol 3350, Lutrol® micro F127 [poloxamer 407], mannitol 25C, crospovidone XL10, hydroxyethyl cellulose, vanilla, Cab-O-Sil® M5P [colloidal silica], magnesium stearate).
  • Exposure to another investigational drug within 2 months prior to start of study treatment.
  • History of major surgical procedure within 1 month prior to start of study treatment.
  • Ongoing immunosuppressive therapy (other than corticosteroids).
  • Ongoing participation in any other clinical trial (except for substudies specifically approved by PTC Therapeutics).
  • Clinically significant symptoms and signs of congestive heart failure (CHF) (American College of Cardiology/American Heart Association Stage C or Stage D).
  • Prior or ongoing medical condition (eg, concomitant illness, psychiatric condition, behavioral disorder, alcoholism, drug abuse), medical history, physical findings, electrocardiogram findings, or laboratory abnormality that, in the investigator's opinion, could adversely affect the safety of the subject, makes it unlikely that the course of treatment or follow-up would be completed, or could impair the assessment of study results.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00759876

Layout table for location information
United States, Ohio
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229-3039
United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
United States, Utah
University of Utah
Salt Lake City, Utah, United States, 84112
Sponsors and Collaborators
PTC Therapeutics
Genzyme, a Sanofi Company
Layout table for investigator information
Study Director: Leone Atkinson PTC Therapeutics, Inc.

Additional Information:
Layout table for additonal information
Responsible Party: PTC Therapeutics Identifier: NCT00759876    
Other Study ID Numbers: PTC124-GD-004e-DMD
First Posted: September 25, 2008    Key Record Dates
Last Update Posted: April 8, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by PTC Therapeutics:
Duchenne muscular dystrophy
Nonsense mutation
Premature stop codon
Additional relevant MeSH terms:
Layout table for MeSH terms
Muscular Dystrophies
Muscular Dystrophy, Duchenne
Muscular Disorders, Atrophic
Muscular Diseases
Musculoskeletal Diseases
Neuromuscular Diseases
Nervous System Diseases
Genetic Diseases, Inborn
Genetic Diseases, X-Linked