Phase 2b Extension Study of Ataluren (PTC124) in Duchenne/Becker Muscular Dystrophy (DMD/BMD) - Full Text View

Sponsors and Collaborators:	PTC Therapeutics Genzyme
Information provided by:	PTC Therapeutics
ClinicalTrials.gov Identifier:	NCT00847379

Purpose

Duchenne/Becker muscular dystrophy (DMD/BMD) 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/BMD in approximately 10-15% of boys with the disease. Ataluren (PTC124) is an orally delivered, investigational drug that has the potential to overcome the effects of the nonsense mutation. This study is a Phase 2b extension trial that will evaluate the long-term safety of ataluren (PTC124) in boys with nonsense mutation DMD/BMD, as determined by adverse events and laboratory abnormalities. The study will also assess changes in walking, muscle function, and other important clinical and laboratory measures.

Condition	Intervention	Phase
Duchenne Muscular Dystrophy Becker Muscular Dystrophy	Drug: Ataluren (PTC124)	Phase II Phase III

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

MedlinePlus related topics: Muscular Dystrophy

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label, Single Group Assignment, Safety/Efficacy Study
Official Title:	A Phase 2b Extension Study of Ataluren (PTC124) in Subjects With Nonsense-Mutation Mediated Duchenne and Becker Muscular Dystrophy

Further study details as provided by PTC Therapeutics:

Primary Outcome Measures:

Long-term safety of PTC124 in boys with nonsense-mutation mediated DMD/BMD, as determined by adverse events and laboratory abnormalities [ 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 ]
Compliance with ataluren (PTC124) treatment [ Time Frame: 2 years ] [ Designated as safety issue: No ]
Ataluren (PTC124) pharmacokinetics [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment:	174
Study Start Date:	January 2009
Estimated Study Completion Date:	December 2011
Estimated Primary Completion Date:	December 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Ataluren (PTC124): Experimental Ataluren (PTC124)	Drug: Ataluren (PTC124) Oral powder for suspension taken 3 times per day (20 mg/kg with breakfast, 20 mg/kg with lunch, and 40 mg/kg with dinner) for up to 96 weeks.

Detailed Description:

This Phase 2b, open-label, safety and efficacy study is anticipated to be performed at 37 sites in 11 countries. The study will enroll up to 174 boys with nonsense mutation DMD/BMD who participated in a previous Phase 2b study of ataluren (PTC124) (PTC124-GD-007-DMD, NCT00592553). 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 2 visits 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 3 times during the course of the study.

Eligibility

Genders Eligible for Study:	Male
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Completion of blinded study drug treatment in the previous Phase 2b study (PTC124-GD-007-DMD).
Ability to provide written informed consent (parental/guardian consent if applicable)/assent (if <18 years of age).
In subjects who are sexually active, willingness to abstain from sexual intercourse or employ a barrier or medical method of contraception during PTC124 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:

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).
Ongoing participation in any other therapeutic clinical trial.
Prior or ongoing medical condition (eg, concomitant illness, psychiatric condition, behavioral disorder, alcoholism, drug abuse), medical history, physical findings, ECG 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: NCT00847379

Contacts

Contact: Diane Goetz

908 912 9256

dgoetz@ptcbio.com

Locations

United States, Ohio
Cincinnati Children's Hospital Medical Center	Recruiting
Cincinnati, Ohio, United States, 45229

Sponsors and Collaborators

PTC Therapeutics

Genzyme

Investigators

Study Director:

Leone Atkinson, M.D., Ph.D.

PTC Therapeutics

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 ( Leone Atkinson, M.D., Ph.D. )
Study ID Numbers:	PTC124-GD-007e-DMD
Study First Received:	February 16, 2009
Last Updated:	February 18, 2009
ClinicalTrials.gov Identifier:	NCT00847379 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by PTC Therapeutics:

Duchenne muscular dystrophy
Becker muscular dystrophy
Nonsense mutation
Premature stop codon

DMD
BMD
Ataluren
PTC124

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 May 07, 2009