A Study to Evaluate Efficacy of Ivacaftor in Subjects With Cystic Fibrosis Who Have a 3849 + 10KB C→T or D1152H CFTR Mutation

Study Overview
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Brief Summary
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This study will evaluate the efficacy of ivacaftor treatment in subjects with CF 6 years of age and older who have a 3849 + 10KB C→T or D1152H CFTR mutation.

Official Title
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A Randomized, Double-blind, Placebo-controlled, Crossover Study to Evaluate the Efficacy of Ivacaftor in Subjects With Cystic Fibrosis Who Are 6 Years of Age and Older and Have Either a 3849 + 10KB C→T or D1152H-CFTR Mutation

Conditions
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Cystic Fibrosis

Intervention / Treatment
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* Drug: Ivacaftor
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed diagnosis of CF based on protocol-specified clinical features and at least one of the following: increased sweat chloride level, identification of 2 CF causing mutations, or demonstration of abnormal nasal epithelial ion transport. A 3849 + 10KB C→T or D1152H mutation on at least 1 CFTR allele. FEV1 ≥40% of predicted and ≤105% of predicted at screening. Exclusion Criteria: A G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N, S549R, or R117H mutation. History of any illness or any clinical condition that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering study drug to the subject. Ongoing or prior participation in an investigational drug study within 30 days before the Screening Visit. Protocol-specified abnormal laboratory values at the Screening Visit For subjects <18 years of age at the Screening Visit, evidence of cataract/lens opacity determined to be clinically significant by the ophthalmologist or optometrist during the ophthalmologic examination (OE) at the Screening Visit. Use of any moderate or strong inducers or inhibitors of cytochrome P450 (CYP) 3A, including consumption of certain herbal medications and certain fruit and fruit juices, within 14 days before Day 1. Pregnant, breastfeeding, or planning to become pregnant during the study. Sexually active subjects of reproductive potential must be willing to use appropriate contraception.

Ages Eligible for Study
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Minimum Age: 6 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
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sequence 1: First Ivacaftor (IVA) Then Placebo<br>Participants received IVA 150 milligram (mg) every 12 hours (q12h) for 8 weeks in treatment period 1 followed by placebo matched to IVA for 8 weeks in treatment period 2. A washout period of 8 weeks was maintained between the 2 treatment periods. | Drug: Ivacaftor<br>* IVA 150 mg tablet.<br>* Other names: IVA;Drug: Placebo<br>* Placebo matched to IVA tablet.<br>|
| Experimental: Sequence 2: First Placebo Then IVA<br>Participants received placebo matched to IVA for 8 weeks in treatment period 1 followed by IVA 150 mg q12h for 8 weeks in treatment period 2. A washout period of 8 weeks was maintained between the 2 treatment periods. | Drug: Ivacaftor<br>* IVA 150 mg tablet.<br>* Other names: IVA;Drug: Placebo<br>* Placebo matched to IVA tablet.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Lung Clearance Index 2.5 (LCI2.5) | LCI2.5 represents the number of lung turnovers required to reduce the end tidal inert gas concentration to 1/40th of its starting value. | From baseline through 8 weeks |