E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.1 |
E.1.2 | Level | SOC |
E.1.2 | Classification code | 10010331 |
E.1.2 | Term | Congenital, familial and genetic disorders |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the effect of ivacaftor on lung function in subjects aged 12 years and older with cystic fibrosis (CF) who have phenotypic or molecular evidence of residual CF transmembrane conductance regulator (CFTR) function. |
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E.2.2 | Secondary objectives of the trial |
- To evaluate the utility of home spirometry as a clinical endpoint - To evaluate the utility of a smart phone-based data collection |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•Male or female participants with confirmed diagnosis of CF •Clinical evidence of residual CFTR function based on any 1 of the following: 1) Clinically documented residual exocrine pancreatic function, 2) Sweat chloride value less than equal to (<=) 80 millimole per liter (mmol/L) at screening, or 3) Age of diagnosis greater than equal to (>=) 12 years and at least 1 copy of a CFTR mutation associated with residual CFTR function or defective mRNA splicing •FEV1 >= 40 percent (%) •12 years of age or older •Willing to agree to meet the contraception requirements •Able to swallow tablets
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E.4 | Principal exclusion criteria |
•A copy of any of the following CFTR mutations: G551D, G178R, S549N, S549R, G551S, G970R, G1244E, S1251N, S1255P, or G1349D •Unable to perform spirometry •An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy (including antibiotics) for pulmonary disease within 4 weeks before Day 1 •Ongoing participation in another therapeutic clinical study or prior participation in an investigational drug study within the 30 days prior to screening
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E.5 End points |
E.5.1 | Primary end point(s) |
- Cycle 1 and Cycle 2: Absolute Change From Baseline In Percent Predicted Forced Expiratory Volume In 1 Second (FEV1) After 2 Weeks of Treatment |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Cycle 1 (baseline, Day 15), Cycle 2 (baseline, Day 15) |
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E.5.2 | Secondary end point(s) |
- Cycle 1 and Cycle 2: Absolute Change In Lung Clearance Index (LCI) After 2 Weeks of Treatment - Open-label Period: Absolute Change From Baseline In Percent Predicted Forced Expiratory Volume In 1 Second (FEV1) after 8 weeks of treatment Efficacy after 8 weeks of treatment as determined by: - Absolute change from baseline in LCI - Absolute change from baseline in sweat chloride - Absolute change from baseline in weight - Correlation between absolute change from baseline in percent predicted FEV1 and LCI after 2 and 8 weeks of treatment - Absolute change from baseline in percent predicted FEV1 collected by home spirometry after 2 and 8 weeks of treatment - Safety, as determined by adverse events and vital signs |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Cycle 1 (baseline, Day 15), Cycle 2 (baseline, Day 15), Open-label Period: 8 weeks Correlation: evaluated at week 2 and week 8 Home spirometry: evaluated at week 2 and week 8 TEAEs - From first dose of study drug through completion of follow-up visit (up to 26 weeks)]
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 4 |
E.8.3 |
Will this trial be conducted at a single site globally?
| Yes |
E.8.4 | Will this trial be conducted at multiple sites globally? | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | Yes |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 23 |