Nonsense-Mutation-Mediated Duchenne/Becker Muscular Dystrophy MedDRA version: 12.0 Level: LLT Classification code 10013801 Term: Duchenne muscular dystrophy MedDRA version: 12.0 Level: LLT Classification code 10059117 Term: Becker's muscular dystrophy
Conditions
Interventions
Product Name: Ataluren 125 mg
Product Code: PTC124
Pharmaceutical Form: Powder for oral suspension
INN or Proposed INN: ATALUREN
CAS Number: 775304-57-9
Current Sponsor code: PTC124
Other descriptive
Sponsors
PTC Therapeutics Inc
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 1. Evidence of signed and dated informed consent/assent document(s) indicating that the subject (and/or his parent/legal guardian) has been informed of all pertinent aspects of the trial. Note: If the study candidate is considered a child under local regulation, a parent or legal guardian must provide written consent prior to initiation of study screening procedures and the study candidate may be required to provide written assent. The rules of the responsible Institutional Review Board/Independent Ethic Committee (IRB/IEC) regarding whether one or both parents must provide consent and the appropriate ages for obtaining consent and assent from the subject should be followed. 2. Male sex. 3. Age =7 years. 4. Phenotypic evidence of DMD/BMD based on the onset of characteristic clinical symptoms or signs and an elevated serum CK. Note: Electromyography or prior muscle biopsy are not required for entry into this study. Specifically distinguishing DMD from BMD is not required. 5. Documentation of the presence of a nonsense point mutation in the dystrophin gene as determined by gene sequencing from a laboratory certified by CAP, CLIA, or an equivalent organization. 6. Documentation that a blood sample has been drawn for confirmation of the presence of a nonsense mutation in the dystrophin gene. Note: A subject who has documentation of a nonsense mutation need not wait for confirmatory results to start study drug as long as the confirmatory genotyping blood sample has been drawn. 7. DMD/BMD-induced loss of ambulation for =1 year prior to start of study treatment resulting in inability to move independently for >10 meters without use of assistance (ie, long-leg braces, walker, wheel chair, or caregiver). 8. Presence of sufficient shoulder abduction and elbow flexion to perform study-related procedures (ie, Jebsen test and 9-hole peg test). 9. Ability to acquire evaluable pretreatment echocardiogram and spirometry assessments. 10. Confirmed screening laboratory values within the central laboratory ranges specified in the protocol. Note: Confirmation should be performed for out of range values to determine if the abnormality is real or artifactual. Values used to establish eligibility should be the last measurements obtained within the 6 week screening period. 11. 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. 12. Willingness and ability to comply with scheduled visits, drug administration plan, study procedures, laboratory tests, and study restrictions. Note: Psychological, social, familial, or geographical factors that might preclude adequate study participation should be considered. Are the trial subjects under 18? yes Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Treatment with systemic aminoglycoside antibiotics within 3 months prior to start of study treatment. 2. Initiation of systemic corticosteroid therapy within 6 months prior to start of study treatment. 3. Change in systemic corticosteroid therapy (eg, change in type of drug, dose modification not related to body weight change, schedule modification, interruption, discontinuation, or reinitiation) within 3 months prior to start of study treatment. Note: Increases in corticosteroid dose (increase of =5 mg of prednisone or =6 mg of deflazacort) to adjust for increases in body weight will not exclude a patient from participation. 4. Use of any intermittent systemic corticosteroid therapy regimen (eg, 10 days on followed by 10 days off, weekend dosing, every-other-day dosing). Note: Patients must either be receiving a daily dosing regimen of prednisone, prednisolone, or deflazacort at the time of enrollment into the study or must not be receiving any systemic corticosteroids. 5. Any change (initiation, change in type of drug, dose modification, schedule modification, interruption, discontinuation, or reinitiation) in prophylaxis/treatment for congestive heart failure (CHF) within 3 months prior to start of study treatment. 6. Ongoing warfarin or phenytoin therapy. 7. Prior therapy with ataluren. 8. Known hypersensitivity to any of the ingredients or excipients of ataluren (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). 9. Exposure to another investigational drug within 2 months prior to start of study treatment. 10. History of major surgical procedure within 1 month prior to start of study treatment. 11. Ongoing immunosuppressive therapy (other than corticosteroids). 12. Ongoing participation in any other clinical trial (except for substudies specifically approved by PTC Therapeutics). 13. Expectation of major surgical procedure (eg, scoliosis surgery) during the 12 month treatment period of the study. 14. Requirement for daytime ventilator assistance. Note: Evening ventilator assistance and use of bi-level positive airway pressure (Bi-PAP) therapy is allowed. 15. Uncontrolled clinical symptoms and signs of CHF (American College of Cardiology/American Heart Association Stage C or Stage D) [Hunt 2001]. 16. 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to assess the safety and tolerability of ataluren in nonambulatory subjects with nmDMD/BMD. ;Secondary Objective: The secondary objectives provide a comprehensive evaluation of the effects of ataluren on major clinical manifestations of nonambulatory patients with nmDMD/BMD and on the pathophysiology of the disease, and include the following: Physical Functioning • To determine the effect of ataluren on upper extremity function • To evaluate the effect of ataluren on upper extremity range of motion • To evaluate the effect of ataluren on upper extremity muscle strength in subjects who are able to perform myometry • To evaluate the effect of ataluren on hand fine motor coordination and dexterity Pulmonary Function • To evaluate the effect of ataluren on pulmonary function Cardiac Function • To evaluate the effect of ataluren on cardiac function Cognitive • To evaluate the effect of ataluren on cognitive ability Patient Reported Outcomes • To determine the effect of ataluren on HRQL • To assess the effect of ataluren on activities of daily living Pharmacodynamics • To ;Primary end point(s): The primary outcome measure for the study is the safety profile, which will be characterized by type, frequency, severity, timing, and relationship to ataluren of any adverse events or laboratory abnormalities. | — |
Countries
United Kingdom
Outcome results
None listed