Phase 2a Extension Study of Ataluren (PTC124) in Duchenne Muscular Dystrophy (DMD) - Full Text View

Sponsors and Collaborators:	PTC Therapeutics Genzyme
Information provided by:	PTC Therapeutics
ClinicalTrials.gov Identifier:	NCT00759876

Purpose

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	Intervention	Phase
Duchenne Muscular Dystrophy	Drug: Ataluren	Phase II

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Single Group Assignment, Safety Study
Official Title:	A Phase 2a Extension Study of PTC124 in Subjects With Nonsense-Mutation-Mediated Duchenne Muscular Dystrophy

Resource links provided by NLM:

Genetics Home Reference related topics: Duchenne and Becker muscular dystrophy L1 syndrome

MedlinePlus related topics: Muscular Dystrophy

U.S. FDA Resources

Further study details as provided by PTC Therapeutics:

Primary Outcome Measures:

Long-term safety [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Ambulation [ Time Frame: 2 years ] [ Designated as safety issue: No ]
Proximal muscle function [ Time Frame: 2 years ] [ Designated as safety issue: No ]
Heart rate [ Time Frame: 2 years ] [ Designated as safety issue: No ]
Cognitive ability [ Time Frame: 2 years ] [ Designated as safety issue: No ]
Quality of life [ Time Frame: 2 years ] [ Designated as safety issue: No ]
Activities of daily living [ Time Frame: 2 years ] [ Designated as safety issue: No ]
Muscle fragility [ Time Frame: 2 years ] [ Designated as safety issue: No ]
Biceps muscle dystrophin expression [ Time Frame: 2 years ] [ Designated as safety issue: No ]
Compliance with PTC124 treatment [ Time Frame: 2 years ] [ Designated as safety issue: No ]
PTC124 pharmacokinetics [ Time Frame: 2 years ] [ Designated as safety issue: No ]
PTC124 effect on corticosteroid pharmacokinetics [ Time Frame: 2 years ] [ Designated as safety issue: No ]
Muscle composition as assessed by magnetic resonance [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment:	38
Study Start Date:	July 2008
Estimated Study Completion Date:	June 2011
Estimated Primary Completion Date:	March 2011 (Final data collection date for primary outcome measure)

Intervention Details:

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.

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.

Eligibility

Genders Eligible for Study:	Male
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00759876

Locations

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

Investigators

Study Director:

Leone Atkinson

PTC Therapeutics, Inc.

More Information

Additional Information:

Related Info This link exits the ClinicalTrials.gov site

Publications:

Hirawat S, Welch EM, Elfring GL, Northcutt VJ, Paushkin S, Hwang S, Leonard EM, Almstead NG, Ju W, Peltz SW, Miller LL. Safety, tolerability, and pharmacokinetics of PTC124, a nonaminoglycoside nonsense mutation suppressor, following single- and multiple-dose administration to healthy male and female adult volunteers. J Clin Pharmacol. 2007 Apr;47(4):430-44.

Welch EM, Barton ER, Zhuo J, Tomizawa Y, Friesen WJ, Trifillis P, Paushkin S, Patel M, Trotta CR, Hwang S, Wilde RG, Karp G, Takasugi J, Chen G, Jones S, Ren H, Moon YC, Corson D, Turpoff AA, Campbell JA, Conn MM, Khan A, Almstead NG, Hedrick J, Mollin A, Risher N, Weetall M, Yeh S, Branstrom AA, Colacino JM, Babiak J, Ju WD, Hirawat S, Northcutt VJ, Miller LL, Spatrick P, He F, Kawana M, Feng H, Jacobson A, Peltz SW, Sweeney HL. PTC124 targets genetic disorders caused by nonsense mutations. Nature. 2007 May 3;447(7140):87-91. Epub 2007 Apr 22.

Responsible Party:	PTC Therapeutics, Inc. ( Leone Atkinson )
Study ID Numbers:	PTC124-GD-004e-DMD
Study First Received:	September 23, 2008
Last Updated:	March 19, 2009
ClinicalTrials.gov Identifier:	NCT00759876 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by PTC Therapeutics:

Duchenne muscular dystrophy
Nonsense mutation
Premature stop codon

DMD
PTC124
Ataluren

Study placed in the following topic categories:

Becker's Muscular Dystrophy
Muscular Dystrophy, Duchenne and Becker Type
Muscular Dystrophies
Muscular Diseases
Muscular Disorders, Atrophic
Musculoskeletal Diseases
Neuromuscular Diseases

Genetic Diseases, Inborn
Muscular Dystrophy, Duchenne
Duchenne Muscular Dystrophy
Genetic Diseases, X-Linked
Atrophy
Muscular Dystrophy

Additional relevant MeSH terms:

Muscular Dystrophies
Muscular Diseases
Genetic Diseases, Inborn
Neuromuscular Diseases
Musculoskeletal Diseases

Muscular Disorders, Atrophic
Muscular Dystrophy, Duchenne
Nervous System Diseases
Genetic Diseases, X-Linked

ClinicalTrials.gov processed this record on September 11, 2009