Clinical Trial Results:
A Pilot Study Testing the Effect of Ivacaftor on Lung Function in Subjects With Cystic Fibrosis, Residual CFTR Function, and FEV1 ≥40% Predicted
Summary
|
|
EudraCT number |
2017-000673-37 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
03 Apr 2014
|
Results information
|
|
Results version number |
v1(current) |
This version publication date |
08 Jun 2017
|
First version publication date |
08 Jun 2017
|
Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
Trial identification
|
|||
Sponsor protocol code |
VX12-770-113
|
||
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
NCT01685801 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
|
|||
Sponsor organisation name |
Vertex Pharmaceuticals Incorporated
|
||
Sponsor organisation address |
50 Northern Avenue, Boston, Massachusetts, United States, 022101862
|
||
Public contact |
Medical Monitor, Vertex Pharmaceuticals Incorporated, 1 617-341-6777, medicalinfo@vrtx.com
|
||
Scientific contact |
Medical Monitor, Vertex Pharmaceuticals Incorporated, 1 617-341-6777, medicalinfo@vrtx.com
|
||
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
No
|
||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
|
||
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
24 Apr 2014
|
||
Is this the analysis of the primary completion data? |
No
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
03 Apr 2014
|
||
Was the trial ended prematurely? |
No
|
||
General information about the trial
|
|||
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 cystic fibrosis transmembrane conductance regulator (CFTR) function.
|
||
Protection of trial subjects |
The study was conducted in accordance with the ethical principles stated in the Declaration of Helsinki and the International Council on Harmonization (ICH) Guideline for Good Clinical Practice (GCP).
|
||
Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
11 Sep 2012
|
||
Long term follow-up planned |
No
|
||
Independent data monitoring committee (IDMC) involvement? |
No
|
||
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
United States: 24
|
||
Worldwide total number of subjects |
24
|
||
EEA total number of subjects |
0
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
0
|
||
Children (2-11 years) |
0
|
||
Adolescents (12-17 years) |
1
|
||
Adults (18-64 years) |
23
|
||
From 65 to 84 years |
0
|
||
85 years and over |
0
|
|
||||||||||||||||||||||||||
Recruitment
|
||||||||||||||||||||||||||
Recruitment details |
- | |||||||||||||||||||||||||
Pre-assignment
|
||||||||||||||||||||||||||
Screening details |
A total of 24 subjects were enrolled at a single site in United States. | |||||||||||||||||||||||||
Period 1
|
||||||||||||||||||||||||||
Period 1 title |
Cycle 1 Period 1 (2 Weeks)
|
|||||||||||||||||||||||||
Is this the baseline period? |
Yes | |||||||||||||||||||||||||
Allocation method |
Randomised - controlled
|
|||||||||||||||||||||||||
Blinding used |
Double blind | |||||||||||||||||||||||||
Roles blinded |
Subject, Investigator, Monitor, Carer | |||||||||||||||||||||||||
Arms
|
||||||||||||||||||||||||||
Are arms mutually exclusive |
Yes
|
|||||||||||||||||||||||||
Arm title
|
Ivacaftor, Placebo, Ivacaftor, Placebo (IPIP) - Intervention 1 | |||||||||||||||||||||||||
Arm description |
During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor. Subjects received Ivacaftor during first intervention period. | |||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||
Investigational medicinal product name |
Ivacaftor
|
|||||||||||||||||||||||||
Investigational medicinal product code |
VX-770
|
|||||||||||||||||||||||||
Other name |
||||||||||||||||||||||||||
Pharmaceutical forms |
Tablet
|
|||||||||||||||||||||||||
Routes of administration |
Oral use
|
|||||||||||||||||||||||||
Dosage and administration details |
Ivacaftor 150 mg tablet orally every 12 hours for 2 weeks during Cycle 1 Period 1.
|
|||||||||||||||||||||||||
Arm title
|
Ivacaftor, Placebo, Placebo, Ivacaftor (IPPI) - Intervention 1 | |||||||||||||||||||||||||
Arm description |
During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor. Subjects received Ivacaftor during first intervention period. | |||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||
Investigational medicinal product name |
Ivacaftor
|
|||||||||||||||||||||||||
Investigational medicinal product code |
VX-770
|
|||||||||||||||||||||||||
Other name |
||||||||||||||||||||||||||
Pharmaceutical forms |
Tablet
|
|||||||||||||||||||||||||
Routes of administration |
Oral use
|
|||||||||||||||||||||||||
Dosage and administration details |
Ivacaftor 150 mg tablet orally every 12 hours for 2 weeks during Cycle 1 Period 1.
|
|||||||||||||||||||||||||
Arm title
|
Placebo, Ivacaftor, Ivacaftor, Placebo (PIIP) - Intervention 1 | |||||||||||||||||||||||||
Arm description |
During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor. Subjects received Placebo matched to Ivacaftor during first intervention period. | |||||||||||||||||||||||||
Arm type |
Placebo | |||||||||||||||||||||||||
Investigational medicinal product name |
Placebo-matched-to-ivacaftor
|
|||||||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||||||
Other name |
||||||||||||||||||||||||||
Pharmaceutical forms |
Tablet
|
|||||||||||||||||||||||||
Routes of administration |
Oral use
|
|||||||||||||||||||||||||
Dosage and administration details |
Placebo-matched-to-ivacaftor tablet orally every 12 hours for 2 weeks during Cycle 1 Period 1.
|
|||||||||||||||||||||||||
Arm title
|
Placebo, Ivacaftor, Placebo, Ivacaftor (PIPI) - Intervention 1 | |||||||||||||||||||||||||
Arm description |
During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor. Subjects received Placebo matched to Ivacaftor during first intervention period. | |||||||||||||||||||||||||
Arm type |
Placebo | |||||||||||||||||||||||||
Investigational medicinal product name |
Placebo-matched-to-ivacaftor
|
|||||||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||||||
Other name |
||||||||||||||||||||||||||
Pharmaceutical forms |
Tablet
|
|||||||||||||||||||||||||
Routes of administration |
Oral use
|
|||||||||||||||||||||||||
Dosage and administration details |
Placebo-matched-to-ivacaftor tablet orally every 12 hours for 2 weeks during Cycle 1 Period 1.
|
|||||||||||||||||||||||||
|
||||||||||||||||||||||||||
Period 2
|
||||||||||||||||||||||||||
Period 2 title |
Cycle 1 Period 2 (2 Weeks)
|
|||||||||||||||||||||||||
Is this the baseline period? |
No | |||||||||||||||||||||||||
Allocation method |
Randomised - controlled
|
|||||||||||||||||||||||||
Blinding used |
Double blind | |||||||||||||||||||||||||
Roles blinded |
Subject, Investigator, Monitor, Carer | |||||||||||||||||||||||||
Arms
|
||||||||||||||||||||||||||
Are arms mutually exclusive |
Yes
|
|||||||||||||||||||||||||
Arm title
|
Ivacaftor, Placebo, Ivacaftor, Placebo (IPIP) - Intervention 2 | |||||||||||||||||||||||||
Arm description |
During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor. Subjects received Placebo matched to Ivacaftor during second intervention period. | |||||||||||||||||||||||||
Arm type |
Placebo | |||||||||||||||||||||||||
Investigational medicinal product name |
Placebo-matched-to-ivacaftor
|
|||||||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||||||
Other name |
||||||||||||||||||||||||||
Pharmaceutical forms |
Tablet
|
|||||||||||||||||||||||||
Routes of administration |
Oral use
|
|||||||||||||||||||||||||
Dosage and administration details |
Placebo-matched-to-ivacaftor tablet orally every 12 hours for 2 weeks during Cycle 1 Period 2.
|
|||||||||||||||||||||||||
Arm title
|
Ivacaftor, Placebo, Placebo, Ivacaftor (IPPI) - Intervention 2 | |||||||||||||||||||||||||
Arm description |
During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor. Subjects received Placebo matched to Ivacaftor during second intervention period. | |||||||||||||||||||||||||
Arm type |
Placebo | |||||||||||||||||||||||||
Investigational medicinal product name |
Placebo-matched-to-ivacaftor
|
|||||||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||||||
Other name |
||||||||||||||||||||||||||
Pharmaceutical forms |
Tablet
|
|||||||||||||||||||||||||
Routes of administration |
Oral use
|
|||||||||||||||||||||||||
Dosage and administration details |
Placebo-matched-to-ivacaftor tablet orally every 12 hours for 2 weeks during Cycle 1 Period 2.
|
|||||||||||||||||||||||||
Arm title
|
Placebo, Ivacaftor, Ivacaftor, Placebo (PIIP) - Intervention 2 | |||||||||||||||||||||||||
Arm description |
During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor. Subjects received Ivacaftor during second intervention period. | |||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||
Investigational medicinal product name |
Ivacaftor
|
|||||||||||||||||||||||||
Investigational medicinal product code |
VX-770
|
|||||||||||||||||||||||||
Other name |
||||||||||||||||||||||||||
Pharmaceutical forms |
Tablet
|
|||||||||||||||||||||||||
Routes of administration |
Oral use
|
|||||||||||||||||||||||||
Dosage and administration details |
Ivacaftor 150 mg tablet orally every 12 hours for 2 weeks during Cycle 1 Period 2.
|
|||||||||||||||||||||||||
Arm title
|
Placebo, Ivacaftor, Placebo, Ivacaftor (PIPI) - Intervention 2 | |||||||||||||||||||||||||
Arm description |
During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor. Subjects received Ivacaftor during second intervention period. | |||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||
Investigational medicinal product name |
Ivacaftor
|
|||||||||||||||||||||||||
Investigational medicinal product code |
VX-770
|
|||||||||||||||||||||||||
Other name |
||||||||||||||||||||||||||
Pharmaceutical forms |
Tablet
|
|||||||||||||||||||||||||
Routes of administration |
Oral use
|
|||||||||||||||||||||||||
Dosage and administration details |
Ivacaftor 150 mg tablet orally every 12 hours for 2 weeks during Cycle 1 Period 2.
|
|||||||||||||||||||||||||
|
||||||||||||||||||||||||||
Period 3
|
||||||||||||||||||||||||||
Period 3 title |
Washout Period 1 (4 Weeks)
|
|||||||||||||||||||||||||
Is this the baseline period? |
No | |||||||||||||||||||||||||
Allocation method |
Not applicable
|
|||||||||||||||||||||||||
Blinding used |
Not blinded | |||||||||||||||||||||||||
Arms
|
||||||||||||||||||||||||||
Are arms mutually exclusive |
Yes
|
|||||||||||||||||||||||||
Arm title
|
Ivacaftor, Placebo, Ivacaftor, Placebo (IPIP) - Washout Period | |||||||||||||||||||||||||
Arm description |
During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor. | |||||||||||||||||||||||||
Arm type |
No intervention | |||||||||||||||||||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
|
|||||||||||||||||||||||||
Arm title
|
Ivacaftor, Placebo, Placebo, Ivacaftor (IPPI) - Washout Period | |||||||||||||||||||||||||
Arm description |
During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor. | |||||||||||||||||||||||||
Arm type |
No intervention | |||||||||||||||||||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
|
|||||||||||||||||||||||||
Arm title
|
Placebo, Ivacaftor, Ivacaftor, Placebo (PIIP) - Washout Period | |||||||||||||||||||||||||
Arm description |
During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor. | |||||||||||||||||||||||||
Arm type |
No intervention | |||||||||||||||||||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
|
|||||||||||||||||||||||||
Arm title
|
Placebo, Ivacaftor, Placebo, Ivacaftor (PIPI) - Washout Period | |||||||||||||||||||||||||
Arm description |
During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor. | |||||||||||||||||||||||||
Arm type |
No intervention | |||||||||||||||||||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
|
|||||||||||||||||||||||||
|
||||||||||||||||||||||||||
Period 4
|
||||||||||||||||||||||||||
Period 4 title |
Cycle 2 Period 1 (2 Weeks)
|
|||||||||||||||||||||||||
Is this the baseline period? |
No | |||||||||||||||||||||||||
Allocation method |
Randomised - controlled
|
|||||||||||||||||||||||||
Blinding used |
Double blind | |||||||||||||||||||||||||
Roles blinded |
Subject, Investigator, Monitor, Carer | |||||||||||||||||||||||||
Arms
|
||||||||||||||||||||||||||
Are arms mutually exclusive |
Yes
|
|||||||||||||||||||||||||
Arm title
|
Ivacaftor, Placebo, Ivacaftor, Placebo (IPIP) - Intervention 3 | |||||||||||||||||||||||||
Arm description |
During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor. Subjects received Ivacaftor during third intervention period. | |||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||
Investigational medicinal product name |
Ivacaftor
|
|||||||||||||||||||||||||
Investigational medicinal product code |
VX-770
|
|||||||||||||||||||||||||
Other name |
||||||||||||||||||||||||||
Pharmaceutical forms |
Tablet
|
|||||||||||||||||||||||||
Routes of administration |
Oral use
|
|||||||||||||||||||||||||
Dosage and administration details |
Ivacaftor 150 mg tablet orally every 12 hours for 2 weeks during Cycle 2 Period 1.
|
|||||||||||||||||||||||||
Arm title
|
Ivacaftor, Placebo, Placebo, Ivacaftor (IPPI) - Intervention 3 | |||||||||||||||||||||||||
Arm description |
During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor. Subjects received Placebo matched to Ivacaftor during third intervention period. | |||||||||||||||||||||||||
Arm type |
Placebo | |||||||||||||||||||||||||
Investigational medicinal product name |
Placebo-matched-to-ivacaftor
|
|||||||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||||||
Other name |
||||||||||||||||||||||||||
Pharmaceutical forms |
Tablet
|
|||||||||||||||||||||||||
Routes of administration |
Oral use
|
|||||||||||||||||||||||||
Dosage and administration details |
Placebo-matched-to-ivacaftor tablet orally every 12 hours for 2 weeks during Cycle 2 Period 1.
|
|||||||||||||||||||||||||
Arm title
|
Placebo, Ivacaftor, Ivacaftor, Placebo (PIIP) - Intervention 3 | |||||||||||||||||||||||||
Arm description |
During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received Ivacaftor. Subjects received Ivacaftor during third intervention period. | |||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||
Investigational medicinal product name |
Ivacaftor
|
|||||||||||||||||||||||||
Investigational medicinal product code |
VX-770
|
|||||||||||||||||||||||||
Other name |
||||||||||||||||||||||||||
Pharmaceutical forms |
Tablet
|
|||||||||||||||||||||||||
Routes of administration |
Oral use
|
|||||||||||||||||||||||||
Dosage and administration details |
Ivacaftor 150 mg tablet orally every 12 hours for 2 weeks during Cycle 2 Period 1.
|
|||||||||||||||||||||||||
Arm title
|
Placebo, Ivacaftor, Placebo, Ivacaftor (PIPI) - Intervention 3 | |||||||||||||||||||||||||
Arm description |
During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received Ivacaftor. Subjects received Placebo matched Ivacaftor during third intervention period. | |||||||||||||||||||||||||
Arm type |
Placebo | |||||||||||||||||||||||||
Investigational medicinal product name |
Placebo-matched-to-ivacaftor
|
|||||||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||||||
Other name |
||||||||||||||||||||||||||
Pharmaceutical forms |
Tablet
|
|||||||||||||||||||||||||
Routes of administration |
Oral use
|
|||||||||||||||||||||||||
Dosage and administration details |
Placebo-matched-to-ivacaftor tablet orally every 12 hours for 2 weeks during Cycle 2 Period 1.
|
|||||||||||||||||||||||||
|
||||||||||||||||||||||||||
Period 5
|
||||||||||||||||||||||||||
Period 5 title |
Cycle 2 Period 2 (2 Weeks)
|
|||||||||||||||||||||||||
Is this the baseline period? |
No | |||||||||||||||||||||||||
Allocation method |
Randomised - controlled
|
|||||||||||||||||||||||||
Blinding used |
Double blind | |||||||||||||||||||||||||
Roles blinded |
Subject, Investigator, Monitor, Carer | |||||||||||||||||||||||||
Arms
|
||||||||||||||||||||||||||
Are arms mutually exclusive |
Yes
|
|||||||||||||||||||||||||
Arm title
|
Ivacaftor, Placebo, Ivacaftor, Placebo (IPIP) - Intervention 4 | |||||||||||||||||||||||||
Arm description |
During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received Ivacaftor. Subjects received Placebo matched to Ivacaftor during fourth intervention period. | |||||||||||||||||||||||||
Arm type |
Placebo | |||||||||||||||||||||||||
Investigational medicinal product name |
Placebo-matched-to-ivacaftor
|
|||||||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||||||
Other name |
||||||||||||||||||||||||||
Pharmaceutical forms |
Tablet
|
|||||||||||||||||||||||||
Routes of administration |
Oral use
|
|||||||||||||||||||||||||
Dosage and administration details |
Placebo-matched-to-ivacaftor tablet orally every 12 hours for 2 weeks during Cycle 2 Period 2.
|
|||||||||||||||||||||||||
Arm title
|
Ivacaftor, Placebo, Placebo, Ivacaftor (IPPI) - Intervention 4 | |||||||||||||||||||||||||
Arm description |
During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor. Subjects received Ivacaftor during fourth intervention period. | |||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||
Investigational medicinal product name |
Ivacaftor
|
|||||||||||||||||||||||||
Investigational medicinal product code |
VX-770
|
|||||||||||||||||||||||||
Other name |
||||||||||||||||||||||||||
Pharmaceutical forms |
Tablet
|
|||||||||||||||||||||||||
Routes of administration |
Oral use
|
|||||||||||||||||||||||||
Dosage and administration details |
Ivacaftor 150 mg tablet orally every 12 hours for 2 weeks during Cycle 2 Period 2.
|
|||||||||||||||||||||||||
Arm title
|
Placebo, Ivacaftor, Ivacaftor, Placebo (PIIP) - Intervention 4 | |||||||||||||||||||||||||
Arm description |
During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received Ivacaftor. Subjects received Placebo matched to Ivacaftor during fourth intervention period. | |||||||||||||||||||||||||
Arm type |
Placebo | |||||||||||||||||||||||||
Investigational medicinal product name |
Placebo-matched-to-ivacaftor
|
|||||||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||||||
Other name |
||||||||||||||||||||||||||
Pharmaceutical forms |
Tablet
|
|||||||||||||||||||||||||
Routes of administration |
Oral use
|
|||||||||||||||||||||||||
Dosage and administration details |
Placebo-matched-to-ivacaftor tablet orally every 12 hours for 2 weeks during Cycle 2 Period 2.
|
|||||||||||||||||||||||||
Arm title
|
Placebo, Ivacaftor, Placebo, Ivacaftor (PIPI) - Intervention 4 | |||||||||||||||||||||||||
Arm description |
During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor. Subjects received Ivacaftor during fourth intervention period. | |||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||
Investigational medicinal product name |
Ivacaftor
|
|||||||||||||||||||||||||
Investigational medicinal product code |
VX-770
|
|||||||||||||||||||||||||
Other name |
||||||||||||||||||||||||||
Pharmaceutical forms |
Tablet
|
|||||||||||||||||||||||||
Routes of administration |
Oral use
|
|||||||||||||||||||||||||
Dosage and administration details |
Ivacaftor 150 mg tablet orally every 12 hours for 2 weeks during Cycle 2 Period 2.
|
|||||||||||||||||||||||||
|
||||||||||||||||||||||||||
Period 6
|
||||||||||||||||||||||||||
Period 6 title |
Washout Period 2 (4 Weeks)
|
|||||||||||||||||||||||||
Is this the baseline period? |
No | |||||||||||||||||||||||||
Allocation method |
Not applicable
|
|||||||||||||||||||||||||
Blinding used |
Not blinded | |||||||||||||||||||||||||
Arms
|
||||||||||||||||||||||||||
Are arms mutually exclusive |
Yes
|
|||||||||||||||||||||||||
Arm title
|
Ivacaftor, Placebo, Ivacaftor, Placebo (IPIP) - Washout Period | |||||||||||||||||||||||||
Arm description |
During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor. | |||||||||||||||||||||||||
Arm type |
No intervention | |||||||||||||||||||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
|
|||||||||||||||||||||||||
Arm title
|
Ivacaftor, Placebo, Placebo, Ivacaftor (IPPI) - Washout Period | |||||||||||||||||||||||||
Arm description |
During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor. | |||||||||||||||||||||||||
Arm type |
No intervention | |||||||||||||||||||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
|
|||||||||||||||||||||||||
Arm title
|
Placebo, Ivacaftor, Ivacaftor, Placebo (PIIP) - Washout Period | |||||||||||||||||||||||||
Arm description |
During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor. | |||||||||||||||||||||||||
Arm type |
No intervention | |||||||||||||||||||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
|
|||||||||||||||||||||||||
Arm title
|
Placebo, Ivacaftor, Placebo, Ivacaftor (PIPI) - Washout Period | |||||||||||||||||||||||||
Arm description |
During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor. | |||||||||||||||||||||||||
Arm type |
No intervention | |||||||||||||||||||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
|
|||||||||||||||||||||||||
|
||||||||||||||||||||||||||
Period 7
|
||||||||||||||||||||||||||
Period 7 title |
Open-label Period (8 Weeks)
|
|||||||||||||||||||||||||
Is this the baseline period? |
No | |||||||||||||||||||||||||
Allocation method |
Not applicable
|
|||||||||||||||||||||||||
Blinding used |
Not blinded | |||||||||||||||||||||||||
Arms
|
||||||||||||||||||||||||||
Are arms mutually exclusive |
Yes
|
|||||||||||||||||||||||||
Arm title
|
Ivacaftor, Placebo, Ivacaftor, Placebo (IPIP) | |||||||||||||||||||||||||
Arm description |
During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor. | |||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||
Investigational medicinal product name |
Ivacaftor
|
|||||||||||||||||||||||||
Investigational medicinal product code |
VX-770
|
|||||||||||||||||||||||||
Other name |
||||||||||||||||||||||||||
Pharmaceutical forms |
Tablet
|
|||||||||||||||||||||||||
Routes of administration |
Oral use
|
|||||||||||||||||||||||||
Dosage and administration details |
Ivacaftor 150 mg tablet orally every 12 hours for 8 weeks in open-label period.
|
|||||||||||||||||||||||||
Arm title
|
Ivacaftor, Placebo, Placebo, Ivacaftor (IPPI) | |||||||||||||||||||||||||
Arm description |
During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor. | |||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||
Investigational medicinal product name |
Ivacaftor
|
|||||||||||||||||||||||||
Investigational medicinal product code |
VX-770
|
|||||||||||||||||||||||||
Other name |
||||||||||||||||||||||||||
Pharmaceutical forms |
Tablet
|
|||||||||||||||||||||||||
Routes of administration |
Oral use
|
|||||||||||||||||||||||||
Dosage and administration details |
Ivacaftor 150 mg tablet orally every 12 hours for 8 weeks in open-label period.
|
|||||||||||||||||||||||||
Arm title
|
Placebo, Ivacaftor, Ivacaftor, Placebo (PIIP) | |||||||||||||||||||||||||
Arm description |
During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor. | |||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||
Investigational medicinal product name |
Ivacaftor
|
|||||||||||||||||||||||||
Investigational medicinal product code |
VX-770
|
|||||||||||||||||||||||||
Other name |
||||||||||||||||||||||||||
Pharmaceutical forms |
Tablet
|
|||||||||||||||||||||||||
Routes of administration |
Oral use
|
|||||||||||||||||||||||||
Dosage and administration details |
Ivacaftor 150 mg tablet orally every 12 hours for 8 weeks in open-label period.
|
|||||||||||||||||||||||||
Arm title
|
Placebo, Ivacaftor, Placebo, Ivacaftor (PIPI) | |||||||||||||||||||||||||
Arm description |
During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor. | |||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||
Investigational medicinal product name |
Ivacaftor
|
|||||||||||||||||||||||||
Investigational medicinal product code |
VX-770
|
|||||||||||||||||||||||||
Other name |
||||||||||||||||||||||||||
Pharmaceutical forms |
Tablet
|
|||||||||||||||||||||||||
Routes of administration |
Oral use
|
|||||||||||||||||||||||||
Dosage and administration details |
Ivacaftor 150 mg tablet orally every 12 hours for 8 weeks in open-label period.
|
|||||||||||||||||||||||||
|
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Baseline characteristics reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Ivacaftor, Placebo, Ivacaftor, Placebo (IPIP) - Intervention 1
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor. Subjects received Ivacaftor during first intervention period. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Ivacaftor, Placebo, Placebo, Ivacaftor (IPPI) - Intervention 1
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor. Subjects received Ivacaftor during first intervention period. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo, Ivacaftor, Ivacaftor, Placebo (PIIP) - Intervention 1
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor. Subjects received Placebo matched to Ivacaftor during first intervention period. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo, Ivacaftor, Placebo, Ivacaftor (PIPI) - Intervention 1
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor. Subjects received Placebo matched to Ivacaftor during first intervention period. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
End points reporting groups
|
|||
Reporting group title |
Ivacaftor, Placebo, Ivacaftor, Placebo (IPIP) - Intervention 1
|
||
Reporting group description |
During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor. Subjects received Ivacaftor during first intervention period. | ||
Reporting group title |
Ivacaftor, Placebo, Placebo, Ivacaftor (IPPI) - Intervention 1
|
||
Reporting group description |
During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor. Subjects received Ivacaftor during first intervention period. | ||
Reporting group title |
Placebo, Ivacaftor, Ivacaftor, Placebo (PIIP) - Intervention 1
|
||
Reporting group description |
During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor. Subjects received Placebo matched to Ivacaftor during first intervention period. | ||
Reporting group title |
Placebo, Ivacaftor, Placebo, Ivacaftor (PIPI) - Intervention 1
|
||
Reporting group description |
During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor. Subjects received Placebo matched to Ivacaftor during first intervention period. | ||
Reporting group title |
Ivacaftor, Placebo, Ivacaftor, Placebo (IPIP) - Intervention 2
|
||
Reporting group description |
During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor. Subjects received Placebo matched to Ivacaftor during second intervention period. | ||
Reporting group title |
Ivacaftor, Placebo, Placebo, Ivacaftor (IPPI) - Intervention 2
|
||
Reporting group description |
During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor. Subjects received Placebo matched to Ivacaftor during second intervention period. | ||
Reporting group title |
Placebo, Ivacaftor, Ivacaftor, Placebo (PIIP) - Intervention 2
|
||
Reporting group description |
During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor. Subjects received Ivacaftor during second intervention period. | ||
Reporting group title |
Placebo, Ivacaftor, Placebo, Ivacaftor (PIPI) - Intervention 2
|
||
Reporting group description |
During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor. Subjects received Ivacaftor during second intervention period. | ||
Reporting group title |
Ivacaftor, Placebo, Ivacaftor, Placebo (IPIP) - Washout Period
|
||
Reporting group description |
During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor. | ||
Reporting group title |
Ivacaftor, Placebo, Placebo, Ivacaftor (IPPI) - Washout Period
|
||
Reporting group description |
During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor. | ||
Reporting group title |
Placebo, Ivacaftor, Ivacaftor, Placebo (PIIP) - Washout Period
|
||
Reporting group description |
During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor. | ||
Reporting group title |
Placebo, Ivacaftor, Placebo, Ivacaftor (PIPI) - Washout Period
|
||
Reporting group description |
During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor. | ||
Reporting group title |
Ivacaftor, Placebo, Ivacaftor, Placebo (IPIP) - Intervention 3
|
||
Reporting group description |
During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor. Subjects received Ivacaftor during third intervention period. | ||
Reporting group title |
Ivacaftor, Placebo, Placebo, Ivacaftor (IPPI) - Intervention 3
|
||
Reporting group description |
During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor. Subjects received Placebo matched to Ivacaftor during third intervention period. | ||
Reporting group title |
Placebo, Ivacaftor, Ivacaftor, Placebo (PIIP) - Intervention 3
|
||
Reporting group description |
During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received Ivacaftor. Subjects received Ivacaftor during third intervention period. | ||
Reporting group title |
Placebo, Ivacaftor, Placebo, Ivacaftor (PIPI) - Intervention 3
|
||
Reporting group description |
During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received Ivacaftor. Subjects received Placebo matched Ivacaftor during third intervention period. | ||
Reporting group title |
Ivacaftor, Placebo, Ivacaftor, Placebo (IPIP) - Intervention 4
|
||
Reporting group description |
During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received Ivacaftor. Subjects received Placebo matched to Ivacaftor during fourth intervention period. | ||
Reporting group title |
Ivacaftor, Placebo, Placebo, Ivacaftor (IPPI) - Intervention 4
|
||
Reporting group description |
During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor. Subjects received Ivacaftor during fourth intervention period. | ||
Reporting group title |
Placebo, Ivacaftor, Ivacaftor, Placebo (PIIP) - Intervention 4
|
||
Reporting group description |
During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received Ivacaftor. Subjects received Placebo matched to Ivacaftor during fourth intervention period. | ||
Reporting group title |
Placebo, Ivacaftor, Placebo, Ivacaftor (PIPI) - Intervention 4
|
||
Reporting group description |
During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor. Subjects received Ivacaftor during fourth intervention period. | ||
Reporting group title |
Ivacaftor, Placebo, Ivacaftor, Placebo (IPIP) - Washout Period
|
||
Reporting group description |
During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor. | ||
Reporting group title |
Ivacaftor, Placebo, Placebo, Ivacaftor (IPPI) - Washout Period
|
||
Reporting group description |
During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor. | ||
Reporting group title |
Placebo, Ivacaftor, Ivacaftor, Placebo (PIIP) - Washout Period
|
||
Reporting group description |
During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor. | ||
Reporting group title |
Placebo, Ivacaftor, Placebo, Ivacaftor (PIPI) - Washout Period
|
||
Reporting group description |
During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor. | ||
Reporting group title |
Ivacaftor, Placebo, Ivacaftor, Placebo (IPIP)
|
||
Reporting group description |
During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor. | ||
Reporting group title |
Ivacaftor, Placebo, Placebo, Ivacaftor (IPPI)
|
||
Reporting group description |
During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor. | ||
Reporting group title |
Placebo, Ivacaftor, Ivacaftor, Placebo (PIIP)
|
||
Reporting group description |
During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor. | ||
Reporting group title |
Placebo, Ivacaftor, Placebo, Ivacaftor (PIPI)
|
||
Reporting group description |
During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all subjects received ivacaftor. | ||
Subject analysis set title |
Cycle 1: Placebo
|
||
Subject analysis set type |
Full analysis | ||
Subject analysis set description |
Placebo-matched-to-ivacaftor tablet orally every 12 hours for 2 weeks during either in period 1 or 2 of Cycle 1.
|
||
Subject analysis set title |
Cycle 1: Ivacaftor
|
||
Subject analysis set type |
Full analysis | ||
Subject analysis set description |
Ivacaftor 150 mg tablet orally every 12 hours for 2 weeks during either in period 1 or 2 of Cycle 1.
|
||
Subject analysis set title |
Cycle 2: Placebo
|
||
Subject analysis set type |
Full analysis | ||
Subject analysis set description |
Placebo-matched-to-ivacaftor tablet orally every 12 hours for 2 weeks during either in period 1 or 2 of Cycle 2.
|
||
Subject analysis set title |
Cycle 2: Ivacaftor
|
||
Subject analysis set type |
Full analysis | ||
Subject analysis set description |
Ivacaftor 150 mg tablet orally every 12 hours for 2 weeks during either in period 1 or 2 of Cycle 2.
|
||
Subject analysis set title |
Open-Label Period: Ivacaftor
|
||
Subject analysis set type |
Full analysis | ||
Subject analysis set description |
Ivacaftor 150 mg tablet orally every 12 hours for 8 weeks during the open-label period after washout period 2.
|
||
Subject analysis set title |
Crossover Double-blind Period: Placebo
|
||
Subject analysis set type |
Full analysis | ||
Subject analysis set description |
Placebo matched to ivacaftor tablet orally every 12 hours for 2 weeks either during the double blind period 1 or 2 of cycle 1 and cycle 2.
|
||
Subject analysis set title |
Crossover Double-blind Period: Ivacaftor
|
||
Subject analysis set type |
Full analysis | ||
Subject analysis set description |
Ivacaftor 150 mg tablet orally every 12 hours for 2 weeks either during the double blind period 1 or 2 of cycle 1 and cycle 2.
|
|
||||||||||||||||||||||||||||||||||||
End point title |
Cycle 1 and Cycle 2: Absolute Change From Cycle Baseline In Percent Predicted Forced Expiratory Volume In 1 Second (FEV1) After 2 Weeks of Treatment | |||||||||||||||||||||||||||||||||||
End point description |
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Hankinson and Wang standards were used to calculate percent predicted FEV1 (for age, gender, and height). The Hankinson standard was used for male subjects 18 years and older and female subjects 16 years and older. The Wang standard was used for male subjects aged 12 to 17 years and for female subjects aged 12 to 15 years. Data was to be reported for each cycle (Cycle 1 and Cycle 2) and as per drug treatment, for overall subjects and as per genotype (residual function mutation and mRNA splice site mutation). Full Analysis Set (FAS) included all randomized subjects who received at least 1 dose of study drug (ivacaftor or placebo). Here, number of subjects analyzed signifies subject evaluable for this endpoint and "n" signifies subject who were evaluable for the specified category in each arm, respectively.
|
|||||||||||||||||||||||||||||||||||
End point type |
Primary
|
|||||||||||||||||||||||||||||||||||
End point timeframe |
Cycle 1 baseline, Cycle 1 Day 15 (for Cycle 1 reporting arms); Cycle 2 baseline, Cycle 2 Day 15 (for Cycle 2 reporting arms)
|
|||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||
Statistical analysis title |
Statistical Analysis 1 | |||||||||||||||||||||||||||||||||||
Statistical analysis description |
This statistical analysis is for “Overall” category. The posterior distribution of overall treatment difference was obtained using the Bayesian hierarchical model and 95% credible interval of the treatment effect (posterior mean) was calculated.
|
|||||||||||||||||||||||||||||||||||
Comparison groups |
Cycle 1: Placebo v Cycle 1: Ivacaftor v Cycle 2: Placebo v Cycle 2: Ivacaftor
|
|||||||||||||||||||||||||||||||||||
Number of subjects included in analysis |
94
|
|||||||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||||||||||
Analysis type |
superiority | |||||||||||||||||||||||||||||||||||
Method |
||||||||||||||||||||||||||||||||||||
Parameter type |
Posterior Mean | |||||||||||||||||||||||||||||||||||
Point estimate |
2.251
|
|||||||||||||||||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||||||||||||||||
level |
95% | |||||||||||||||||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||||||||||||||||
lower limit |
0.383 | |||||||||||||||||||||||||||||||||||
upper limit |
4.144 | |||||||||||||||||||||||||||||||||||
Variability estimate |
Standard deviation
|
|||||||||||||||||||||||||||||||||||
Dispersion value |
0.961
|
|
||||||||||||||||||||||||||||||||||||
End point title |
Cycle 1 and Cycle 2: Absolute Change From Cycle Baseline In Lung Clearance Index (LCI) After 2 Weeks of Treatment | |||||||||||||||||||||||||||||||||||
End point description |
LCI is a measure of ventilation inhomogeneity that is derived from a multiple-breath washout test. The LCI was calculated as the number of lung volume turnovers (cumulative expired volume divided by the functional residual capacity [FRC]) required to reduce end-tidal concentration of an inert gas to 1/40th of the starting value. Data was to be reported for each cycle (Cycle 1 and Cycle 2) and as per drug treatment. Data was to be reported for each cycle (Cycle 1 and Cycle 2) and as per drug treatment, for overall subjects and as per genotype (residual function mutation and mRNA splice site mutation). FAS population. Here, ''number of subjects analyzed'' signifies subjects evaluable for this endpoint and "n" signifies subjects who were evaluable for the specified category in each arm, respectively.
|
|||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||||||||||
End point timeframe |
Cycle 1 baseline, Cycle 1 Day 15 (for Cycle 1 reporting arms); Cycle 2 baseline, Cycle 2 Day 15 (for Cycle 2 reporting arms)
|
|||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||
End point title |
Open-label Period: Absolute Change From Open-label Baseline In Percent Predicted Forced Expiratory Volume In 1 Second (FEV1) at Day 57 | ||||||||||||||
End point description |
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Hankinson and Wang standards were used to calculate percent predicted FEV1 (for age, gender, and height). The Hankinson standard was used for male subjects 18 years and older and female subjects 16 years and older. The Wang standard was used for male subjects aged 12 to 17 years and for female subjects aged 12 to 15 years. Data was to be reported for overall subjects and as per genotype (residual function mutation and mRNA splice site mutation). FAS population. Here, '''number of subjects analyzed'' signifies subjects evaluable for this endpoint and "n" signifies subjects who were evaluable for the specified category.
|
||||||||||||||
End point type |
Secondary
|
||||||||||||||
End point timeframe |
Open-label Baseline, Open-label Day 57
|
||||||||||||||
|
|||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||
End point title |
Open-label Period: Absolute Change From Open-label Baseline In Lung Clearance Index (LCI) at Day 57 | ||||||||||||||
End point description |
LCI is a measure of ventilation inhomogeneity that is derived from a multiple-breath washout test. The LCI was calculated as the number of lung volume turnovers (cumulative expired volume divided by the functional residual capacity [FRC]) required to reduce end-tidal concentration of an inert gas to 1/40th of the starting value. Data was to be reported for overall subjects and as per genotype (residual function mutation and mRNA splice site mutation). FAS population. Here, ''number of subjects analyzed'' signifies subjects evaluable for this endpoint and "n" signifies subjects who were evaluable for the specified category.
|
||||||||||||||
End point type |
Secondary
|
||||||||||||||
End point timeframe |
Open-label Baseline, Open-label Day 57
|
||||||||||||||
|
|||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||
End point title |
Open-label Period: Absolute Change From Study Baseline In Sweat Chloride at Day 57 | ||||||||||||||
End point description |
Sweat samples were collected using an approved Macroduct (Wescor, Logan, Utah) collection device. A volume of greater than or equal to (>=) 15 microliter was required for determination of sweat chloride. Data was to be reported for overall subjects and as per genotype (residual function mutation and mRNA splice site mutation). FAS population. Here, ''number of subjects analyzed'' signifies subjects evaluable for this endpoint and "n" signifies subjects who were evaluable for the specified category.
|
||||||||||||||
End point type |
Secondary
|
||||||||||||||
End point timeframe |
Study Baseline, Open-label Day 57
|
||||||||||||||
|
|||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||
End point title |
Open-label Period: Absolute Change From Open-label Baseline In Weight at Day 57 | ||||||||||||||
End point description |
Data was to be reported for overall subjects and as per genotype (residual function mutation and mRNA splice site mutation). FAS population. Here, ''number of subjects analyzed'' signifies subjects evaluable for this endpoint and "n" signifies subjects who were evaluable for the specified category.
|
||||||||||||||
End point type |
Secondary
|
||||||||||||||
End point timeframe |
Open-label Baseline, Open-label Day 57
|
||||||||||||||
|
|||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||
End point title |
Number of Subjects With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | ||||||||||||||||||||
End point description |
AEs that started(or increased severity)from first dose of study drug to completion of Follow-up were TEAEs, with exception that if AE started during Washout Period & beyond 14 days from last dose date of preceding cycle, AE was “Washout Period” AE & not TEAE. TEAE was attributed to treatment in which it started/ to treatment in second cycling period of previous Crossover Period if it started during Washout Period. SAE:medical event/condition, which falls into any of these categories, regardless of relationship to study drug: death, life threatening adverse experience, in-patient hospitalization/prolongation of hospitalization, persistent/significant disability/incapacity, congenital anomaly/birth defect, important medical event. Data was to be reported by drug treatment for double-blind crossover period(Cycle 1 up to Washout Period 2)& open-label period. Safety set:all subjects who received at least 1 dose of study drug. Number of subjects analyzed=subject evaluable for this endpoint.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
From first dose of study drug through completion of follow-up visit (up to 26 weeks)
|
||||||||||||||||||||
|
|||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
From first dose of study drug through completion of follow-up visit (up to 26 weeks)
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
15.0
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Crossover Double-blind Period: Placebo
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Placebo matched to ivacaftor tablet orally every 12 hours for 2 weeks either during the double blind period 1 or 2 of cycle 1 and cycle 2. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Crossover Double-blind Period: Ivacaftor
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Ivacaftor 150 mg tablet orally every 12 hours for 2 weeks either during the double blind period 1 or 2 of cycle 1 and cycle 2. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Open-label Period: Ivacaftor
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Ivacaftor 150 mg tablet orally every 12 hours for 8 weeks during the open-label period after washout period 2. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
Substantial protocol amendments (globally) |
|||
Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
16 Oct 2012 |
- Secondary efficacy endpoint Cystic Fibrosis Questionnaire Revised (CFQ-R) was removed; - Assessment for alanine aminotransferase and aspartate aminotransferase was added; - Pulse oximetry assessment changed to twice daily; - Prior ivacaftor use was added as an exclusion criterion; - The analysis of the primary variable was updated. |
||
02 Apr 2013 |
- Subjects who completed this study were offered to enroll in Study VX12-770-112 (2012-000389-39); The number of subjects to be enrolled was increased |
||
29 Jul 2013 |
- Responder criteria for participation in Study VX12-770-112 were incorporated and relative change in percent predicted FEV1 was amended to absolute change to facilitate comparison of data among ivacaftor clinical studies.
|
||
Interruptions (globally) |
|||
Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |