E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Nonsense Mutation Duchenne Muscular Dystrophy (nmDMD) |
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E.1.1.1 | Medical condition in easily understood language |
Nonsense Mutation Duchenne Muscular Dystrophy (nmDMD) |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess safety and tolerability of ataluren in male children with nmDMD aged ≥6 months to <2 years old. |
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E.2.2 | Secondary objectives of the trial |
To assess pharmacokinetics (PK) of ataluren in male children with nmDMD aged ≥6 months to <2 years old.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Males ≥6 months to <2 years of age • 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.
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E.4 | Principal 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: a. Systemic aminoglycoside therapy and/or intravenous (IV) vancomycin. b. Coumarin-based anticoagulants (for example, warfarin), phenytoin, tolbutamide, or paclitaxel. c. 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). |
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E.5 End points |
E.5.1 | Primary end point(s) |
Overall safety profile in terms of type, frequency, severity, seriousness, timing, and relationship to study therapy of any adverse event (AE) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Pharmacokinetic assessment including area under the concentration curve from time 0 to 24 hours (AUC0-24) and from time 0 to 6 hours (AUC0-6), time to maximal plasma concentration (Tmax), maximum concentration (Cmax), trough concentration (Ctrough) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
Will this trial be conducted at a single site globally?
| No |
E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | Yes |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 4 |
E.8.9.2 | In all countries concerned by the trial days | 21 |