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
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 14
- 试验地点
- 6
- 主要终点
- Number of Participants With Treatment Emergent Adverse Events (TEAEs), TEAEs Leading to Discontinuation, and Serious Adverse Events (SAEs)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 2 Years 至 5 Years（Child）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Males ≥2 to <5 years of age
- •Body weight ≥12 kg
- •Diagnosis of DMD
- •Nonsense mutation in at least 1 allele of the dystrophin gene
排除标准
- •Participation in any other drug or device clinical investigation
- •Ongoing use of prohibited concomitant medications
研究组 & 干预措施
Ataluren
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.
干预措施: Ataluren (Drug)
结局指标
主要结局
Number of Participants With Treatment Emergent Adverse Events (TEAEs), TEAEs Leading to Discontinuation, and Serious Adverse Events (SAEs)
时间窗: Baseline up to Week 56
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.
Number of Participants With a Clinically Meaningful Abnormal Clinical Laboratory (Biochemistry, Hematology, and Urinalysis) Parameter
时间窗: Baseline up to Week 56
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.
Number of Participants With a Dose-Limiting Toxicity as Measured by Hepatic and Renal Toxicity
时间窗: Baseline up to Week 56
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.
Number of Participants With a Clinically Meaningful Abnormal Electrocardiogram (ECG) Test Results
时间窗: Baseline up to Week 56
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.
次要结局
- Pharmacokinetics: Maximum Observed Plasma Concentration From Time Zero up to 6 Hours After the Morning Dose (Cmax0-6hr)(0 (predose), 1, 2, 4, and 6 (postdose) hours on Days 1 and 28)
- Pharmacokinetics: Time to Reach Maximum Observed Plasma Concentration From Time Zero up to 6 Hours After the Morning Dose (Tmax0-6hr)(0 (predose), 1, 2, 4, and 6 (postdose) hours on Days 1 and 28)
- Area Under the Plasma Concentration Time Curve From Time Zero up to 10 Hours After the Morning Dose (AUC0-10hr)(0 (predose), 1, 2, 4, 6, 8, and 10 (postdose) hours on Days 1 and 28)
- Pharmacokinetics: Concentration at the End of the First (Morning) Dose Interval (Ctrough6hr)(0 (predose), 1, 2, 4, and 6 (postdose) hours on Days 1 and 28)
- Change From Baseline in Proximal Muscle Function as Assessed by Speed During TFTs(Baseline, Week 28 and Week 52)
- Change From Baseline in Physical Function as Measured by the NSAA(Baseline, Week 28 and Week 52)
- Change From Baseline in Height of Participants at Weeks 4, 16, 28, 40, 52, and 56(Baseline, Weeks 4, 16, 28, 40, 52, and 56)
- Change From Baseline in Weight of Participants at Weeks 4, 16, 28, 40, 52, and 56(Baseline, Weeks 4, 16, 28, 40, 52, and 56)
- Change From Baseline in Body Mass Index of Participants at Weeks 4, 16, 28, 40, 52, and 56(Baseline, Weeks 4, 16, 28, 40, 52, and 56)
- Ataluren Palatability Characteristics as Determined by a Parent/Caregiver Questionnaire(Baseline up to Week 28)