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)

• ClinicalTrials.gov Identifier: NCT04336826
• Recruitment Status: Not yet recruiting
• First Posted: April 7, 2020
• Last Update Posted: June 22, 2021
• Sponsor: PTC Therapeutics
• Information provided by (Responsible Party): PTC Therapeutics

Study Description

Brief Summary:

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).

Condition or disease	Intervention/treatment	Phase
Nonsene Mutation Duchenne Muscular Dystrophy	Drug: Ataluren	Phase 2

Detailed Description:

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 10 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Estimated Study Start Date: July 31, 2021
• Estimated Primary Completion Date: December 20, 2022
• Estimated Study Completion Date: December 20, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: Ataluren; 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; Ataluren will be administered as per the dose and schedule specified in the arm.; Other Name: PTC124

Outcome Measures

Primary Outcome Measures :

1. Number of Participants With Treatment-Emergent Adverse Events [ Time Frame: Baseline up to Week 24 ]

Secondary Outcome Measures :

1. Pharmacokinetics: Area Under the Concentration Curve From Time 0 to 24 Hours (AUC0-24) of Ataluren [ Time Frame: 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 ]
2. Pharmacokinetics: Area Under the Concentration Curve From Time 0 to 6 Hours (AUC0-6) of Ataluren [ Time Frame: 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 ]
3. Pharmacokinetics: Maximum Concentration (Cmax) of Ataluren [ Time Frame: 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 ]
4. Pharmacokinetics: Time to Maximal Plasma Concentration (Tmax) of Ataluren [ Time Frame: 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 ]
5. Pharmacokinetics: Trough Concentration (Ctrough) of Ataluren [ Time Frame: Pre-morning dose at Week 24 ]

Eligibility Criteria

• Ages Eligible for Study: 6 Months to 2 Years (Child)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Criteria

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:

  1. Systemic aminoglycoside therapy and/or intravenous (IV) vancomycin.
  2. Coumarin-based anticoagulants (for example, warfarin), phenytoin, tolbutamide, or paclitaxel.
  3. 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).

Contacts and Locations

Contacts

Contact: Patient Advocacy Corporate Relations; 1-866-562-4620; medinfo@ptcbio.com

Sponsors and Collaborators

PTC Therapeutics

Investigators

• Study Director: Vinay Penematsa; PTC Therapeutics, Inc.

More Information

• Responsible Party: PTC Therapeutics
• ClinicalTrials.gov Identifier: NCT04336826
• Other Study ID Numbers: PTC124-GD-048-DMD; 2020-000980-21 ( EudraCT Number )
• First Posted: April 7, 2020
• Last Update Posted: June 22, 2021
• Last Verified: June 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Muscular Dystrophies; Muscular Dystrophy, Duchenne; Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked