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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT02139306
Registration number
NCT02139306
Ethics application status
Date submitted
13/05/2014
Date registered
15/05/2014
Date last updated
14/05/2020
Titles & IDs
Public title
Study of Ataluren in Nonsense Mutation Cystic Fibrosis (ACT CF)
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Scientific title
A Phase 3 Efficacy and Safety Study of Ataluren (PTC124®) in Patients With Nonsense Mutation Cystic Fibrosis
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Secondary ID [1]
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2013-004581-34
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Secondary ID [2]
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PTC124-GD-021-CF
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Universal Trial Number (UTN)
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Trial acronym
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Cystic Fibrosis
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Condition category
Condition code
Human Genetics and Inherited Disorders
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Cystic fibrosis
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Respiratory
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0
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Other respiratory disorders / diseases
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Oral and Gastrointestinal
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0
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Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
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Inflammatory and Immune System
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0
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Connective tissue diseases
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Inflammatory and Immune System
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0
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Other inflammatory or immune system disorders
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - Ataluren (PTC124®)
Treatment: Drugs - Placebo
Experimental: Ataluren (PTC124®) - Participants received ataluren as oral powder for suspension at the dosages of 10, 10, and 20-mg/kg at morning, midday and evening, respectively for 48 weeks of treatment duration or until treatment discontinuation.
Placebo Comparator: Placebo - Participants received matching placebo orally at morning, midday and evening for 48 weeks of treatment duration or until treatment discontinuation.
Treatment: Drugs: Ataluren (PTC124®)
Oral Ataluren TID
Treatment: Drugs: Placebo
Oral Placebo TID
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Absolute Change From Baseline in Percent-predicted Forced Expiratory Volume in One Second (ppFEV1) at Week 48
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Assessment method [1]
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The FEV1 is the volume of air forcibly exhaled in one second and is measured using forced expiratory air spirometry. Change in ppFEV1 at Week 48 was defined as the average between the change from baseline at Week 40 and that at Week 48. Baseline for ppFEV1 was defined as an average of ppFEV1 at Screening (Weeks -4 to -1) and Baseline (Day 1) visits.
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Timepoint [1]
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From Baseline to Week 48
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Secondary outcome [1]
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48-week Rate of Pulmonary Exacerbations
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Assessment method [1]
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Pulmonary exacerbations were assessed using expanded Fuchs criteria. The expanded Fuchs exacerbation is defined as the presence of at least 4 of 12 Fuchs' signs and symptoms requiring treatment with any form of antibiotic treatment (inhaled, oral, or intravenous). Fuchs' signs and symptoms included increased cough; change in sputum volume, color, or consistency; new or increased hemoptysis; increased dyspnea during moderate or mild exertion, or at rest; sinus pain or tenderness; change in sinus discharge; malaise, fatigue, or lethargy; anorexia or weight loss; temperature above 38 degrees Celsius; change in findings on chest examination; relative 10% decrease in ppFEV1, and chest radiography results consistent with pulmonary infection. The 48-week rate was calculated as: 48-week rate = total number of events /treatment duration by week*48.
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Timepoint [1]
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Week 48
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Secondary outcome [2]
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Change From Baseline in the Cystic Fibrosis Questionnaire - Revised (CFQ-R) Respiratory Domain at Week 48
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Assessment method [2]
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The teen/adult CFQ-R was used for this study. It was developed specifically for participants with cystic fibrosis. It is a disease-specific instrument designed to measure impact on overall health, daily life, perceived well-being, and symptoms. The respiratory domain assessed respiratory symptoms like coughing, congestion, wheezing etc. Scaling of each item is done via 4-point Likert scales. Scores for each item are summed up to generate a domain score. Scores ranges from 0 to 100, with higher scores indicating better health and lower scores indicating worse health.
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Timepoint [2]
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Baseline (Day 1) and Week 48
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Secondary outcome [3]
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Change From Baseline in Body Mass Index (BMI) at Week 48
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Assessment method [3]
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Malnutrition is common in participants with cystic fibrosis. The BMI is an important clinical measure of nutritional status.
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Timepoint [3]
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Baseline (Day 1) and Week 48
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Secondary outcome [4]
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Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs)
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Assessment method [4]
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An adverse event (AE) is any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a study treatment, whether or not considered related to the study treatment. A TEAE is defined as an AE that occurs or worsens in the period extending from first dose of study drug to 4 weeks after last dose of study drug. An SAE is an untoward medical occurrence or effect associated with the use of a study drug at any dose, regardless of whether it is considered to be related to the study drug, which results in one of the following: death; inpatient hospitalization or prolongation of existing hospitalization; life threatening adverse event; persistent or significant disability or incapacity or substantial disruption of the ability to conduct normal life functions; any other medically important event; or a pregnancy resulting in spontaneous abortion, stillbirth, neonatal death, or congenital anomaly.
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Timepoint [4]
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From study drug administration to 4-week post treatment follow-up visit (approximately 52 weeks)
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Secondary outcome [5]
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Number of Participants With TEAEs by Severity and Relationship to Study Drugs
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Assessment method [5]
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The relationship of TEAEs to the study drugs were assessed as: probable related, possibly related, unlikely related, and unrelated. The severity of TEAEs were graded using the Common Terminology Criteria for Adverse Events, Version 3.0 as: Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), Grade 4 (life threatening), or Grade 5 (fatal).
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Timepoint [5]
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From study drug administration to 4-week post treatment follow-up visit (approximately 52 weeks)
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Secondary outcome [6]
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Number of Participants With SAEs by Severity and Relationship to Study Drugs
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Assessment method [6]
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The relationship of SAEs to the study drugs were assessed as: probable related, possibly related, unlikely related, and unrelated. The severity of SAEs were graded using the Common Terminology Criteria for Adverse Events, Version 3.0 as: Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), Grade 4 (life threatening), or Grade 5 (fatal).
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Timepoint [6]
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From study drug administration to 4-week post treatment follow-up visit (approximately 52 weeks)
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Secondary outcome [7]
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Number of Participants With Abnormal Vital Signs Reported as TEAEs
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Assessment method [7]
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Vital signs included systolic and diastolic blood pressure, pulse rate, pulse oximetry, and body temperature. Participants with abnormal vital signs who required clinical intervention or further investigation (beyond ordering a repeat [confirmatory] test) unless they are associated with an already reported clinical event are reported.
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Timepoint [7]
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From study drug administration to 4-week post treatment follow-up visit (approximately 52 weeks)
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Secondary outcome [8]
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Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs
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Assessment method [8]
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Clinical laboratory tests included haematology, biochemistry, and urinalysis. Participants with abnormal laboratory parameters who required clinical intervention or further investigation (beyond ordering a repeat [confirmatory] test) unless they are associated with an already reported clinical event are reported.
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Timepoint [8]
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From study drug administration to 4-week post treatment follow-up visit (approximately 52 weeks)
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Secondary outcome [9]
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Number of Participants With Abnormal Electrocardiogram Reported as TEAEs
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Assessment method [9]
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Participants with abnormal electrocardiogram who required clinical intervention or further investigation (beyond ordering a repeat [confirmatory] test) unless they are associated with an already reported clinical event are reported.
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Timepoint [9]
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From study drug administration to 4-week post treatment follow-up visit (approximately 52 weeks)
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Eligibility
Key inclusion criteria
- Evidence of signed and dated informed consent/assent document(s) indicating that the
subject (and/or his parent/legal guardian) has been informed of all pertinent aspects
of the trial
- Age >=6 years.
- Body weight >=16 kg.
- Sweat chloride >60 milliequivalent per liter (mEq/L)
- Documentation of the presence of a nonsense mutation in at least 1 allele of the
cystic fibrosis transmembrane conductance regulator (CFTR) gene, as determined by
genotyping performed at a laboratory certified by the College of American Pathologists
(CAP), or under the Clinical Laboratory Improvement Act/Amendment (CLIA), or by an
equivalent organization
- Verification that a blood sample has been drawn for sequencing of the CFTR gene
- Ability to perform a valid, reproducible spirometry test using the study-specific
spirometer with demonstration of an FEV1 >=40% and <=90% of predicted
- Demonstration at Visit 2 of a valid %-predicted FEV1 within 15% of the Screening %
predicted FEV1 value
- Resting oxygen saturation (as measured by pulse oximetry) >=92% on room air.
- Confirmed screening laboratory values within pre-specified ranges
- In subjects 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, study procedures, laboratory tests, and
study restrictions
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Minimum age
6
Years
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Maximum age
No limit
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key exclusion criteria
- Known hypersensitivity to any of the ingredients or excipients of the study drug
- Previous participation in the Phase 3 trial of ataluren (PTC124-GD-009-CF).
- Any change (initiation, change in type of drug, dose modification, schedule
modification, interruption, discontinuation, or re-initiation) in a chronic
treatment/prophylaxis regimen for Cystic Fibrosis (CF) or for CF-related conditions
within 4 weeks prior to screening
- Chronic use of inhaled aminoglycosides (eg, tobramycin) or use of inhaled
aminoglycosides within 4 weeks prior to screening.
- Exposure to another investigational drug within 4 weeks prior to screening
- Ongoing participation in any other therapeutic clinical trial
- Evidence of pulmonary exacerbation or acute upper or lower respiratory tract infection
(including viral illnesses) within 3 weeks prior to screening
- Treatment with intravenous antibiotics within 3 weeks prior to screening
- Ongoing immunosuppressive therapy (other than corticosteroids)
- Ongoing warfarin, phenytoin, or tolbutamide therapy
- History of solid organ or hematological transplantation
- Major complications of lung disease (including massive hemoptysis, pneumothorax, or
pleural effusion) within 8 weeks prior to screening
- Known portal hypertension
- Positive hepatitis B surface antigen, hepatitis C antibody test, or human
immunodeficiency virus (HIV) test
- Pregnancy or breast-feeding
- Current smoker or a smoking history of >=10 pack-years (number of cigarette packs/day
x number of years smoked).
- Prior or ongoing medical condition (eg, concomitant illness, alcoholism, drug abuse,
psychiatric condition), medical history, physical findings, electrocardiogram (ECG)
findings, or laboratory abnormality that, in the investigator's opinion, could
adversely affect the safety of the subject, makes it unlikely that the course of
treatment or follow-up would be completed, or could impair the assessment of study
results
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Blinded (masking used)
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Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
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Intervention assignment
Parallel
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Other design features
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Phase
Phase 3
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Completed
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
1/08/2014
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
1/11/2016
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Sample size
Target
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Accrual to date
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Final
279
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Recruitment in Australia
Recruitment state(s)
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Recruitment hospital [1]
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Royal Adelaide Hospital - Adelaide
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Recruitment hospital [2]
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Prince Charles Hospital - Chermside
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Recruitment hospital [3]
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Princess Margaret Hospital - Perth
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Recruitment postcode(s) [1]
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5000 - Adelaide
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Recruitment postcode(s) [2]
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4032 - Chermside
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Recruitment postcode(s) [3]
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6840 - Perth
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Recruitment outside Australia
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United States of America
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Alabama
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California
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Penarth
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Southampton
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Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
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Name
PTC Therapeutics
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Address
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Other collaborator category [1]
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Other
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Name [1]
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Cystic Fibrosis Foundation
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Other
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ECFS-Clinical Trial Network (ECFS-CTN)
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Ethics approval
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Summary
Brief summary
This is a Phase 3, international, multicenter, randomized, double-blind, placebo-controlled,
efficacy and safety study of ataluren in patients with nonsense mutation cystic fibrosis
(nmCF) not receiving chronic inhaled aminoglycosides.
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Trial website
https://clinicaltrials.gov/ct2/show/NCT02139306
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
Name
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Joseph McIntosh, MD
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Address
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PTC Therapeutics
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Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT02139306
Download to PDF