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Study of Ataluren (PTC124) in Cystic Fibrosis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02107859
Recruitment Status : Terminated (Based on the results of study PTC124-GD-021-CF (NCT02139306), clinical development of ataluren in cystic fibrosis was discontinued and this study was closed.)
First Posted : April 8, 2014
Results First Posted : March 25, 2020
Last Update Posted : March 25, 2020
Sponsor:
Information provided by (Responsible Party):
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).

Condition or disease Intervention/treatment Phase
Cystic Fibrosis Drug: Ataluren Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 61 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-Label Safety and Efficacy Study for Patients With Nonsense Mutation Cystic Fibrosis Previously Treated With Ataluren (PTC124)
Actual Study Start Date : May 23, 2014
Actual Primary Completion Date : June 5, 2017
Actual Study Completion Date : June 5, 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Cystic Fibrosis

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




Primary Outcome Measures :
  1. Number of Participants With Treatment-Emergent Adverse Events (TEAEs) [ Time Frame: 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.

  2. Number of Participants With Clinically Significant Laboratory Abnormalities [ Time Frame: 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 :
  1. Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at the End of Treatment (Week 192), as Assessed by Spirometry [ Time Frame: 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.

  2. Percentage of Participants With Pulmonary Exacerbation, As Assessed by Modified Fuchs Criteria [ Time Frame: 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.

  3. Percentage of Participants With Pulmonary Exacerbation, As Assessed by Expanded Fuchs' Criteria [ Time Frame: 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.

  4. Percentage of Participants With Pulmonary Exacerbation, As Assessed by Classic Fuchs' Criteria [ Time Frame: 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.

  5. Change From Baseline in 12-Lead Electrocardiogram (ECG) Parameters at Final Visit (Week 196) [ Time Frame: 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.

  6. Change From Baseline in Heart Rate at Final Visit (Week 196), as Assessed by 12-Lead ECG [ Time Frame: Baseline, Week 196 ]
    Heart rate was measured using 12-lead ECG.

  7. Change From Baseline in Vital Signs at Final Visit (Week 196) [ Time Frame: Baseline, Week 196 ]
    Vital Signs included systolic blood pressure (SBP) and diastolic blood pressure (DBP).


Other Outcome Measures:
  1. Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at the End of Treatment (Week 192), as Assessed by Spirometry [ Time Frame: Baseline, Week 192 ]
    FVC is the volume of air that can forcibly be blown out after full inspiration in the upright position. Percent of predicted FVC = (observed value)/(predicted value) * 100%. Change from baseline in percent predicted FVC at the end of treatment was reported.

  2. Change From Baseline in Percent Predicted Forced Expiratory Flow Between 25% and 75% of Expiration (FEF25-75) at the End of Treatment (Week 192), as Assessed by Spirometry [ Time Frame: Baseline, Week 192 ]
    FEF25-75 is the forced expiratory flow between 25 and 75% of vital capacity.



Information from the National Library of Medicine

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Ages Eligible for Study:   6 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • 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 Exclusion Criteria:

  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02107859


Locations
Show Show 17 study locations
Sponsors and Collaborators
PTC Therapeutics
Investigators
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Study Director: Joseph McIntosh, MD PTC Therapeutics, Inc.
  Study Documents (Full-Text)

Documents provided by PTC Therapeutics:
Statistical Analysis Plan  [PDF] July 14, 2017
Study Protocol  [PDF] February 8, 2016

Additional Information:
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Responsible Party: PTC Therapeutics
ClinicalTrials.gov Identifier: NCT02107859    
Other Study ID Numbers: PTC124-GD-023-CF
2013-005449-35 ( EudraCT Number )
First Posted: April 8, 2014    Key Record Dates
Results First Posted: March 25, 2020
Last Update Posted: March 25, 2020
Last Verified: March 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by PTC Therapeutics:
Cystic fibrosis
Nonsense mutation
Premature stop codon
PTC124
Ataluren
Additional relevant MeSH terms:
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Cystic Fibrosis
Fibrosis
Pathologic Processes
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases