This is a Phase 2, multiple-dose, open-label study evaluating the safety, pharmacokinetics
      (PK), and pharmacodynamics (PD) of ataluren in participants aged ≥2 to <5 years old with
      Duchenne muscular dystrophy (DMD) caused by a nonsense mutation in the dystrophin gene.

Study of Ataluren in ≥2 to <5 Year-Old Male Participants With Duchenne Muscular Dystrophy

Duchenne Muscular Dystrophy

In nonsense mutation DMD (nmDMD), early start of treatment is important and necessary and,
      therefore, it is relevant to understand the correct and tolerable dose in this age group,
      particularly since ataluren is dosed by weight. This study included a 4-week screening
      period, a 52-week treatment period (the first 4 weeks of which included PK parameters), and a
      4-week follow-up period for participants who completed the treatment period (60 weeks total
      duration). The objective of the extension period (treatment period after PK parameters have
      been completed) was to assess the long-term safety of chronic administration of ataluren in
      this participant population.

Ataluren

A Phase 2 Study of the Safety, Pharmacokinetics, and Pharmacodynamics of Ataluren (PTC124®) in Patients Aged ≥2 to <5 Years Old With Nonsense Mutation Dystrophinopathy

A TEAE was any untoward medical occurrence or undesirable event that begins or worsens following administration of study drug, whether or not considered related to study drug by Investigator. An SAE was an adverse event (AE) resulting in any of the following outcomes or deemed significant for any other reason, death, initial or prolonged inpatient hospitalization, life-threatening experience (immediate risk of dying) or persistent or significant disability/incapacity not related to dystrophinopathy. An event was not reported as an SAE, if event was exclusively a relapse or expected change or progression of baseline dystrophinopathy. AEs included both SAEs and nonserious AEs. AEs classified according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 and coded using Medical Dictionary for Regulatory Activities. A summary of SAEs and all non-serious AEs, regardless of causality, is located in the Reported Adverse Events section.

Clinical laboratory results that were considered clinically meaningful were to be determined by the Investigator and Sponsor. Biochemistry parameters included sodium, potassium, chloride, bicarbonate, blood urea nitrogen, creatinine, magnesium, calcium, phosphorus, uric acid, glucose, total protein, albumin, bilirubin (total, direct, and indirect), aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transferase, creatine kinase, lactate dehydrogenase, alkaline phosphatase, total cholesterol, high-density lipoprotein, low-density lipoprotein, triglycerides, and cystatin C. Hematology parameters included white blood cell count with differential, hemoglobin, hematocrit, other red cell parameters, and platelet count. Urinalysis parameters included pH, specific gravity, glucose, ketones, blood, protein, urobilinogen, bilirubin, nitrite, and leukocyte esterase. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.

ECG results that were considered clinically meaningful were to be determined by the Investigator. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.

Dose-limiting toxicity was measured through clinical evaluations for potential hepatic and renal toxicities. The clinical evaluations included the following:
Hepatic: The participant's medical history, hepatitis screening results, all clinical blood values (particularly serum bilirubin, gamma-glutamyl transferase [GGT], aspartate aminotransferase [AST], and alanine aminotransferase [ALT] values), and all concomitant medications were reviewed.
Renal: The participant's medical history, all clinical blood and urine renal values, serum electrolytes, medications, and potential pre- or post-renal conditions were reviewed.

Ataluren concentrations in plasma were analyzed using a validated high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method.

Ataluren concentrations in plasma were analyzed using a validated HPLC-MS/MS method.

Ataluren concentrations in plasma were analyzed using a validated HPLC-MS/MS method. AUC0-10hr was measured using the linear trapezoidal rule during the ascending portion of the curve and the log-trapezoidal rule during the descending portion of the curve.

TFTs included time to stand from supine position (rise to standing), time to run/walk 10 meters (m), and time to ascend/descend 4 stairs. A decrease from baseline reflects faster completion of the functional task and, thus, better muscle function. If the time taken to perform a test exceeded 30 seconds or if a participant could not perform the test due to disease progression (PD), a value of 30 seconds was used.

NSAA consists of 17 activities, including items assessing abilities necessary to remain functionally ambulant (that is, ability to rise from floor, to get from lying to sitting/sitting to standing, and that are known to progressively deteriorate); items that can be partly present in DMD early stages (that is, assessing head raise and standing on heels); and a number of activities such as hopping, jumping, and running. Since the boys were <5 years old, revised 16 point, 8-point, and 3-point scales were used over the 17 point scale. Scores for evaluations=0 (Unable to achieve independently), 1 (Modified method but achieved goal independent of physical assistance), or 2 (Normal, no obvious modification of activity). Maximum total score for the 16-point scale=32, 8-point scale=16, and 3-point scale=6. If an activity couldn't be performed due to PD/loss of ambulation, a score of 0 was assigned. Change from Baseline calculated by subtracting Baseline value from value at Week 28 and Week 52.

Body mass index is an estimate of body fat based on body weight divided by height squared.

To assess palatability characteristics, participants/parents or guardians were asked to provide a response of "Strongly disagree", "Disagree", "Neither agree or disagree", "Agree", or "Strongly Agree" to the following 3 questions:
Question 1. "Is the medicine palatable?"
Question 2. "On the basis of reaction / facial expression of your child, do you think that the medication is pleasant?"
Question 3."You sometimes have problems in giving the medication to your child because he/she refuses to take it or throws it up?"

Participants will be administered ataluren orally at a dose of 10 milligrams/kilograms (mg/kg) in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening (for a total of 40 mg/kg/day) for up to 52 weeks. Dose will be provided based upon the weight of each participant, which will be assessed every 12 weeks.

Study of Ataluren in ≥2 to <5 Year-Old Male Participants With Duchenne Muscular Dystrophy

About this trial

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Phase

Placebo

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