Study of Ataluren (PTC124) in Cystic Fibrosis
- Registration Number
- NCT02107859
- Lead Sponsor
- PTC Therapeutics
- Brief Summary
The primary objective of this study is to determine the long-term safety and tolerability of ataluren in participants with nonsense mutation cystic fibrosis (nmCF) who completed participation in the double-blind study PTC124-GD-009-CF (NCT00803205), as assessed by adverse events and laboratory abnormalities. The secondary objective of this study includes the assessment of the efficacy of ataluren, as measured by forced expiratory volume in 1 second (FEV1) and pulmonary exacerbation rate, and other safety parameters (for example, 12-lead electrocardiogram \[ECG\] measurements, vital signs).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 61
- Ability to provide written informed consent (parental/guardian consent and participant assent if less than [<] 18 years of age).
- Evidence of completed participation in the double-blind study, PTC124-GD-009-CF (Study 009).
- Body weight greater than or equal to (≥) 16 kilograms (kg).
- Performance of a valid, reproducible spirometry test using the study-specific spirometer during the screening period.
- Confirmed laboratory values within the central laboratory ranges at screening.
- In male and female participants who are sexually active, willingness to abstain from sexual intercourse or employ a barrier or medical method of contraception during the study drug administration and 60-day follow-up period.
- Willingness and ability to comply with all study procedures and assessments, including scheduled visits, drug administration plan, laboratory tests, and study restrictions.
Key
- Chronic use of systemic tobramycin within 4 weeks prior to screening.
- Evidence of pulmonary exacerbation or acute upper or lower respiratory tract infection (including viral illnesses) within 3 weeks prior to screening or between screening and randomization.
- Any change (initiation, change in type of drug, dose modification, schedule modification, interruption, discontinuation, or re-initiation) in a chronic treatment/prophylaxis regimen for CF or for CF-related conditions within 4 weeks prior to screening and randomization.
- Known hypersensitivity to any of the ingredients or excipients of the study drug.
- Exposure to another investigational drug within 4 weeks prior to screening.
- Treatment with intravenous antibiotics within 3 weeks prior to screening.
- History of solid organ or hematological transplantation.
- Ongoing immunosuppressive therapy (other than corticosteroids).
- Positive hepatitis B surface antigen, hepatitis C antibody test or human immunodeficiency virus (HIV) test.
- Known portal hypertension.
- Pregnancy or breast-feeding.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Ataluren Ataluren Participants will receive ataluren suspension orally 3 times a day (TID), 10 milligrams/kilogram (mg/kg) at morning, 10 mg/kg at midday, and 20 mg/kg at evening (total daily dose 40 mg/kg) for 192 weeks.
- Primary Outcome Measures
Name Time Method Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Baseline (Day 1) up to end of study (Week 196) AE: any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Severity of an AE was classified as: mild (does not interfere with usual function), moderate (interferes to some extent with usual function), severe (interferes significantly with usual function), life threatening (results in potential threat to life), and fatal AEs. Drug-related AEs: AEs with a possible or probable relationship to study drug. Serious AEs: death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized participant and required medical intervention. TEAE: AE that occurred or worsened from first dose of study drug to 4 weeks after last dose of study drug. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Number of Participants With Clinically Significant Laboratory Abnormalities Baseline (Day 1) up to end of study (Week 196) Laboratory parameters tests included hematology, biochemistry assay (hepatic, renal, and serum electrolyte values), adrenal assays, and urinalysis. Clinical significance was defined as per investigator's judgement.
- Secondary Outcome Measures
Name Time Method Percentage of Participants With Pulmonary Exacerbation, As Assessed by Expanded Fuchs' Criteria Baseline up to Week 192 The expanded Fuchs' criteria defined exacerbation as the presence of at least 4 of the following 12 Fuchs' signs and symptoms requiring any form of antibiotic treatment (inhaled, oral, or intravenous): change in sputum; new or increased hemoptysis; increased cough; increased dyspnea; fatigue; temperature \>38°C; anorexia; sinus pain; change in sinus discharge; change in physical examination of the chest; decrease in pulmonary function by 10 percent or more from a previously recorded value; or radiographic changes indicative of pulmonary function.
Percentage of Participants With Pulmonary Exacerbation, As Assessed by Classic Fuchs' Criteria Baseline up to Week 192 The Classic Fuchs' criteria defined exacerbation as the presence of at least 4 of the following 12 Fuchs' signs and symptoms requiring treatment with parenteral antibiotics: change in sputum; new or increased hemoptysis; increased cough; increased dyspnea; fatigue; temperature \>38°C; anorexia; sinus pain; change in sinus discharge; change in physical examination of the chest; decrease in pulmonary function by 10 percent or more from a previously recorded value; or radiographic changes indicative of pulmonary function.
Percentage of Participants With Pulmonary Exacerbation, As Assessed by Modified Fuchs Criteria Baseline up to Week 192 The modified Fuchs' criteria defined exacerbation as the presence of at least 4 of the following 12 Fuchs' signs and symptoms without the requirement for treatment with antibiotics: change in sputum; new or increased hemoptysis; increased cough; increased dyspnea; fatigue; temperature greater than (\>) 38 degrees celsius (°C); anorexia; sinus pain; change in sinus discharge; change in physical examination of the chest; decrease in pulmonary function by 10 percent or more from a previously recorded value; or radiographic changes indicative of pulmonary function.
Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at the End of Treatment (Week 192), as Assessed by Spirometry Baseline, Week 192 FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Percent of predicted FEV1 = (observed value)/(predicted value) \* 100%. Change from baseline in percent predicted FEV1 at the end of treatment was reported.
Change From Baseline in 12-Lead Electrocardiogram (ECG) Parameters at Final Visit (Week 196) Baseline, Week 196 ECG parameters included RR duration, PR duration, QRS duration, QT duration, QTCB (Bazett's correction formula) duration, QTCF (Fridericia's correction formula) duration.
Change From Baseline in Heart Rate at Final Visit (Week 196), as Assessed by 12-Lead ECG Baseline, Week 196 Heart rate was measured using 12-lead ECG.
Change From Baseline in Vital Signs at Final Visit (Week 196) Baseline, Week 196 Vital Signs included systolic blood pressure (SBP) and diastolic blood pressure (DBP).
Trial Locations
- Locations (17)
University of Alabama-Birmingham
🇺🇸Birmingham, Alabama, United States
Miller Children's Hospital Long Beach
🇺🇸Long Beach, California, United States
Denver Children's Hospital
🇺🇸Aurora, Colorado, United States
Children's Hospital Chicago
🇺🇸Chicago, Illinois, United States
Beth Israel Medical Center
🇺🇸New York, New York, United States
Hôpital Universitaire des Enfants Reine Fabiola
🇧🇪Brussels, Belgium
Rainbow Babies & Children's Hospital
🇺🇸Cleveland, Ohio, United States
University Hospital Brussels
🇧🇪Brussels, Belgium
University Hospital Leuven
🇧🇪Leuven, Belgium
Hadassah University Hospital - Mount Scopus
🇮🇱Jerusalem, Israel
Hôpital des Enfants
🇫🇷Toulouse, France
Hôpital Necker - Enfants Malades
🇫🇷Paris, France
Università La Sapienza
🇮🇹Roma, Italy
Karolinska University Hospital, Huddinge
🇸🇪Stockholm, Sweden
Hospital Universitario La Paz
🇪🇸Madrid, Spain
Azienda Ospedaliera di Verona
🇮🇹Verona, Italy
Children's Hospital Boston
🇺🇸Boston, Massachusetts, United States