A Study to Evaluate the Safety and Pharmacokinetics of Ataluren in Participants From ≥6 Months to <2 Years of Age With Nonsense Mutation Duchenne Muscular Dystrophy (nmDMD)

Study Overview
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Brief Summary
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This study is designed to evaluate safety, tolerability, and pharmacokinetics (PK) in male children with nmDMD aged ≥6 months to <2 years treated daily for 24 weeks with orally administered ataluren 10, 10, and 20 milligrams/kilogram (mg/kg) (morning, mid-day, and evening dose, respectively).

Detailed Description
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Participants who complete the 24-week treatment period in this study will be offered participation to a follow-up extension period for at least 52 weeks from the date of first administration of ataluren in this parent study.

Official Title
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An Open-Label Study Evaluating the Safety and Pharmacokinetics of Ataluren in Children From ≥6 Months to <2 Years of Age With Nonsense Mutation Duchenne Muscular Dystrophy

Conditions
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Nonsene Mutation Duchenne Muscular Dystrophy

Intervention / Treatment
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* Drug: Ataluren


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Body weight ≥7.5 kilograms (kg) Diagnosis of duchenne muscular dystrophy (DMD) based on an elevated serum creatine kinase and genotypic evidence of dystrophinopathy. Documentation of the presence of a nonsense mutation of the dystrophin gene as determined by gene sequencing prior to enrollment. Exclusion Criteria: Participation in any drug or device investigation or whose sibling is currently participating in a blinded portion of another ataluren study or received an investigational drug within three months prior to the Screening Visit or who anticipate participating in any other drug or device clinical investigation or receiving any other investigational drug within the duration of this study. Expectation of a major surgical procedure during the study period. Known hypersensitivity to any of the ingredients or excipients of the study drug (polydextrose, polyethylene glycol 3350, poloxamer 407, mannitol 25C, crospovidone XL10, hydroxyethyl cellulose, vanilla, colloidal silica, or magnesium stearate). Ongoing use of the following drugs: Systemic aminoglycoside therapy and/or intravenous (IV) vancomycin. Coumarin-based anticoagulants (for example, warfarin), phenytoin, tolbutamide, or paclitaxel. Inducers of UGT1A9 (for example, rifampicin), or substrates of OAT1 or OAT3 (for example, ciprofloxacin, adefovir, oseltamivir, aciclovir, captopril, furosemide, bumetanide, valsartan, pravastatin, rosuvastatin, atorvastatin, pitavastatin).

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 2 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ataluren<br>Participants will receive ataluren oral suspension 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening each day for 24 weeks. | Drug: Ataluren<br>* Ataluren will be administered as per the dose and schedule specified in the arm.<br>* Other names: PTC124;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment-Emergent Adverse Events |  | Baseline up to Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics: Area Under the Concentration Curve From Time 0 to 24 Hours (AUC0-24) of Ataluren |  | Predose, 1, 2, 3, and 4 hours post morning and mid-day doses; and pre-dose, 1, 2, 3, 4 and 12 (before the next day morning dose) hours post evening dose at Week 24 | 
| Pharmacokinetics: Area Under the Concentration Curve Between Dosing Interval (AUC0-τ) of Ataluren |  | Predose, 1, 2, 3, and 4 hours post morning and mid-day doses; and pre-dose, 1, 2, 3, 4 and 12 (before the next day morning dose) hours post evening dose at Week 24 | 
| Pharmacokinetics: Maximum Concentration (Cmax) of Ataluren |  | Predose, 1, 2, 3, and 4 hours post morning and mid-day doses; and pre-dose, 1, 2, 3, 4 and 12 (before the next day morning dose) hours post evening dose at Week 24 | 
| Pharmacokinetics: Time to Maximal Plasma Concentration (Tmax) of Ataluren |  | Predose, 1, 2, 3, and 4 hours post morning and mid-day doses; and pre-dose, 1, 2, 3, 4 and 12 (before the next day morning dose) hours post evening dose at Week 24 | 
| Pharmacokinetics: Trough Concentration (Ctrough) of Ataluren |  | Pre-morning dose at Week 24 |