Evaluation of Ivacaftor in Patients Using Ataluren for Nonsense Mutations

Study Overview
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Brief Summary
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The purpose of this study is to explore the combination of Ataluren and ivacaftor as a treatment for patients with a specific cystic fibrosis mutation

Detailed Description
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In about 10% of patients with CF, the defect in the gene is known as a stop mutation. This mutation truncates the cystic fibrosis transductive regulator (CFTR) protein production by introducing a premature stop in the messenger RNA (mRNA), this type of mutation is known as a stop mutation. Ataluren is a novel, oral drug that promotes this gene to work effectively and readthrough that premature stop sign. It is hypothesized that ivacaftor may increase the efficacy of Ataluren by activating a specific protein that may not be functioning properly.

Official Title
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An Open Label Study to Investigate the Role of Ivacaftor for the Treatment of Cystic Fibrosis in Combination With Ataluren (PTC124) in Cystic Fibrosis Patients Using Ataluren for Nonsense Mutations

Conditions
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Cystic Fibrosis

Intervention / Treatment
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* Drug: Ivacaftor/Ataluren


Participation Criteria
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Eligibility Criteria
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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 ≥19 years Body weight ≥16 kg Diagnosis of cystic fibrosis and documentation of the presence of a nonsense mutations of the CFTR gene, as determined by historical genotyping Ability to perform a valid, reproducible spirometry with demonstration of a forced expiratory volume in 1second (FEV1) ≥30% of predicted for age, gender, and height. If the subject is sexually active, willingness to abstain from sexual intercourse or employ a barrier or medical method of contraception during the study drug administration Willingness and ability to comply with all study procedures and assessments. Currently receiving Ataluren for nonsense mutations through other clinical trial access. Exclusion Criteria: 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 2 weeks prior to screening. Evidence of pulmonary exacerbation or acute upper or lower respiratory tract infection (including viral illnesses) within 2 weeks prior to screening. Ongoing immunosuppressive therapy (other than corticosteroids up to 10mg/d equivalent of prednisone) Ongoing warfarin, phenytoin, or tolbutamide therapy. History of solid organ or hematological transplantation. A history of positive hepatitis B surface antigen test, hepatitis C antibody test, or human immunodeficiency Major complications of lung disease (including massive hemoptysis, pneumothorax, or pleural effusion) within 4 weeks prior to screening. Pregnancy or breast-feeding. Current smoker or a smoking history of ≥10 pack-years (number of cigarette packs/day × number of years smoked). Prior or ongoing medical condition (eg, renal failure, alcoholism, drug abuse, psychiatric condition), medical history, physical findings, 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. -

Ages Eligible for Study
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Minimum Age: 19 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ivacaftor/Ataluren<br> | Drug: Ivacaftor/Ataluren<br>* Both drugs were given in combination for 48 week study period<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lung Function | change in lung function as measured by spirometry | Baseline through 48 weeks |