Principal Investigator: Russell Butterfield
Keywords: DMD , Duchenne muscular dystrophy , muscular dystophy Department: Pediatric Administration
IRB Number: 00088876 Co Investigator: Nicholas Johnson
Specialty: Neurology, Neurology
Sub Specialties: Movement Disorders, Muscular Dystrophy
Recruitment Status: Recruiting

Contact Information

Bryant Gordon

Brief Summary

3.1. Primary Objective
The primary objective of this study is to:
• Evaluate the safety of ataluren as measured by type, frequency, severity, timing, and
relationship to study drug of TEAEs, laboratory abnormalities and ECGs
3.2. Secondary Objectives
The secondary objectives of this study are to:
• Evaluate the plasma PK of ataluren in patients aged ≥2 to <5 years old with nmDMD
• Assess proximal muscle function using TFTs
• Assess change in physical function using the NSAA
• Determine the effect of ataluren on weight, height, and BMI
• Assess the palatability of ataluren 3.3. Primary Endpoint
The primary endpoints of this study are:
• Overall safety profile in terms of the type, frequency, severity, timing, and relationship to
study therapy of any adverse events (AEs) or abnormalities of physical findings, laboratory
tests, or ECGs
• Occurrence of any dose-limiting toxicities (DLTs)
• Drug discontinuations due to AEs
• Serious adverse events (SAEs)
3.4. Secondary Endpoints
The secondary endpoints are:
• Pharmacokinetic parameters (tmax, t1/2, Cmax, Ctrough@6h, AUC0-10), CL/F, and Vc/F based on
frequent blood sampling for PK on Days 1 and 28 of ataluren treatment. On each of these
days, blood samples for ataluren concentration assessments will be collected immediately
pre-dose and at specified time points following the morning, midday, and evening doses.
Ataluren concentrations in plasma will be analyzed using a validated HPLC-MS/MS method.
• TFTs (time to walk/run 10 meters, time to climb 4 stairs, time to descend 4 stairs, and time to
stand up from a supine position) • NSAA
• Changes in body weight, height, and BMI
• Ataluren palatability characteristics as determined by a parent/caregiver questionnaire

Inclusion Criteria

Inclusion Criteria Patients must meet all of the following conditions to be eligible for enrollment into the study:
General inclusion criteria
1. Evidence of signed and dated informed consent document(s) indicating that the study
candidate (and/or a parent/legal guardian) has been informed of all pertinent aspects of the
study. Note: As all study candidates are considered children under local regulation, at least
one parent or legal guardian must provide written consent prior to initiation of study-related
procedures, in accordance with local regulation, and the study candidate may be required to
provide written assent. The rules of the responsible institutional review board/independent
ethics committee (IRB/IEC) regarding whether one or both parents must provide consent and
the appropriate ages for obtaining consent and assent from the patient should be followed.
2. Males ≥2 to <5 years of age
3. Body weight ≥12 kg
4. Willingness and ability to comply with scheduled visits, drug administration plan, study
procedures, and study restrictions.
5. No clinically significant abnormality based upon laboratory assessments during the screening
period, in the opinion of the Investigator; good general health, as determined during the
screening period by medical history and physical examination (including vital sign
measurements). DMD inclusion criteria 6. Diagnosis of DMD based on an elevated serum CK and genotypic evidence of dystrinopathy.
Medical documentation of phenotypic evidence of dystrophinopathy needs to be provided
upon request by the PTC Therapeutics medical monitor.
7. Documentation of the presence of a nonsense mutation in at least 1 allele of the dystrophin
8. Verification that a blood sample has been drawn for sequencing of the dystrophin gene.
Note: A patient who has written documentation of a nonsense mutation as the cause of
dystrophinopathy need not wait for confirmatory results to start study drug.

Exclusion Criteria

Exclusion Criteria The presence of any of the following conditions will exclude a patient from study enrollment:
General exclusion criteria
1. Patients participating in any drug or device clinical investigation or having received an
investigational drug within 3 months prior to Visit 1 (Screening) or who anticipate
participating in any other drug or device clinical investigation or receiving any other
investigational drug within the duration of this study.
2. Expectation of a major surgical procedure during the study period.
3. Prior or ongoing medical condition, medical history, physical findings, or laboratory
abnormality that, in the Investigator’s opinion, could adversely affect the safety of the
patient, or makes it unlikely that the course of study drug administration or follow-up would
be completed, or could impair the assessment of study results.
4. 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).
Drug therapies
5. Ongoing use of the following drugs:
Drugs metabolized by CYP2C8 (eg, paclitaxel) or CYP2C9 (eg, coumarin anticoagulants
[warfarin], phenytoin, or tolbutamide)
Drugs that are inhibitors of breast cancer resistant protein (BCRP) (eg, cyclosporine,
eltrombopag, geftinib)
Drugs that are substrates of UGT1A9 (eg, propofol, mycophenolate mofetil), OAT1, OAT3,
or OATP1B3 (eg, oseltamivir, acyclovir, captopril, furosemide, bumetanide, valsartan,
pravastatin, rosuvastatin, atorvastatin, pitavastatin)
Drugs that are general inhibitors of UGT (eg, probenecid, valproic acid)
6. Treatment with systemic aminoglycoside antibiotics within 3 months prior to start of study
7. Prior therapy with ataluren