Trial Outcomes & Findings for Rollover Study of Ivacaftor in Subjects With Cystic Fibrosis and a Non G551D CFTR Mutation (NCT NCT01707290)

Last Updated: 2017-05-12

Results Overview

AE: any untoward medical occurrence in a participants during the study; the event does not necessarily have a causal relationship with the treatment. This includes any newly occurring event or previous condition that has increased in severity or frequency after informed consent form is signed. AE includes serious as well as non-serious AEs. SAE (subset of AE): medical event or condition, which falls into any of the following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, In-patient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. TEAEs were defined as adverse events with start date or increased severity on and after the first dose of study drug through Week 108.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

125 participants

Primary outcome timeframe

Day 1 up to Week 108 (Study 112)

Results posted on

2017-05-12

Participant Flow

The study consisted of 2 arms: Ivacaftor arm and Observational arm. The Ivacaftor arm enrolled subjects from Study VX11-770-110 (NCT01614457), Study VX12-770-111 (NCT01614470) and Study VX12-770-113 (NCT01685801). The Observational arm enrolled subjects from Study VX11-770-110 (NCT01614457) and Study VX12-770-111 (NCT01614470).

Participant milestones

Participant milestones
Measure	Ivacaftor Arm Participants who received Ivacaftor 150 milligram (mg) tablet and/or Placebo matched to Ivacaftor tablet, every 12 hours (q12h) in the previous study VX11-770-110 (Study 110; NCT01614457), VX12-770-111 (Study 111; NCT01614470) or VX12-770-113 (Study 113; NCT01685801); received Ivacaftor 150 mg tablet orally q12h in this VX12-770-112 (Study 112; NCT01707290) up to 104 weeks.	Observational Arm Participants who received Ivacaftor 150 mg tablet and/or Placebo matched to Ivacaftor tablet q12h in the previous Study 110 (NCT01614457) or Study 111 (NCT01614470), were observed (did not receive study drug) in this Study 112 (NCT01707290) for up to 2 years.
Overall Study STARTED	121	4
Overall Study COMPLETED	35	3
Overall Study NOT COMPLETED	86	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Ivacaftor Arm Participants who received Ivacaftor 150 milligram (mg) tablet and/or Placebo matched to Ivacaftor tablet, every 12 hours (q12h) in the previous study VX11-770-110 (Study 110; NCT01614457), VX12-770-111 (Study 111; NCT01614470) or VX12-770-113 (Study 113; NCT01685801); received Ivacaftor 150 mg tablet orally q12h in this VX12-770-112 (Study 112; NCT01707290) up to 104 weeks.	Observational Arm Participants who received Ivacaftor 150 mg tablet and/or Placebo matched to Ivacaftor tablet q12h in the previous Study 110 (NCT01614457) or Study 111 (NCT01614470), were observed (did not receive study drug) in this Study 112 (NCT01707290) for up to 2 years.
Overall Study Adverse event (AE)	1	0
Overall Study Physician Decision	1	0
Overall Study Lost to Follow-up	3	0
Overall Study Withdrawal of Consent (Not Due to AE)	4	0
Overall Study Commercial drug available	60	1
Overall Study Other unspecified	17	0

Baseline Characteristics

Rollover Study of Ivacaftor in Subjects With Cystic Fibrosis and a Non G551D CFTR Mutation

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ivacaftor Arm n=121 Participants Participants who received Ivacaftor 150 mg tablet and/or Placebo matched to Ivacaftor tablet, q12h in the previous study VX11-770-110 (Study 110; NCT01614457), VX12-770-111 (Study 111; NCT01614470) or VX12-770-113 (Study 113; NCT01685801); received Ivacaftor 150 mg tablet orally q12h in this VX12-770-112 (Study 112; NCT01707290) up to 104 weeks.	Observational Arm n=4 Participants Participants who received Ivacaftor 150 mg tablet and/or Placebo matched to Ivacaftor tablet q12h in the previous Study 110 (NCT01614457) or Study 111 (NCT01614470), were observed (did not receive study drug) in this Study 112 (NCT01707290) for up to 2 years.	Total n=125 Participants Total of all reporting groups
Age, Customized 6 to 11 years	21 participants n=5 Participants	1 participants n=7 Participants	22 participants n=5 Participants
Age, Customized 12 to 17 years	11 participants n=5 Participants	1 participants n=7 Participants	12 participants n=5 Participants
Age, Customized 18 years and over	89 participants n=5 Participants	2 participants n=7 Participants	91 participants n=5 Participants
Sex: Female, Male Female	61 Participants n=5 Participants	3 Participants n=7 Participants	64 Participants n=5 Participants
Sex: Female, Male Male	60 Participants n=5 Participants	1 Participants n=7 Participants	61 Participants n=5 Participants

PRIMARY outcome

Timeframe: Day 1 up to Week 108 (Study 112)

Population: Safety Set included all participants who received at least 1 dose of study drug (Ivacaftor).

Outcome measures

Outcome measures
Measure	Ivacaftor Arm n=121 Participants Participants who received Ivacaftor 150 mg tablet and/or Placebo matched to Ivacaftor tablet q12h in the previous study VX11-770-110 (Study 110; NCT01614457), VX12-770-111 (Study 111; NCT01614470) or VX12-770-113 (Study 113; NCT01685801); received Ivacaftor 150 mg tablet orally q12h in this VX12-770-112 (Study 112; NCT01707290) up to 104 weeks.	Ivacaftor Arm: Study 111 Participants who received Ivacaftor 150 mg tablet and/or Placebo matched to Ivacaftor tablet orally, q12h in the previous Study 111; received Ivacaftor 150 mg tablet q12h in this Study 112 up to 104 weeks.	Ivacaftor Arm: Study 113 Participants who received Ivacaftor 150 mg tablet and/or Placebo matched to Ivacaftor tablet orally, q12h in the previous Study 113; received Ivacaftor 150 mg tablet q12h in this Study 112 up to 104 weeks.
Number of Participants With Treatment Emergent Adverse Events (TEAEs) or Serious Adverse Events (SAEs) in Ivacaftor Arm Participants with TEAEs	117 participants	—	—
Number of Participants With Treatment Emergent Adverse Events (TEAEs) or Serious Adverse Events (SAEs) in Ivacaftor Arm Participants with SAEs	27 participants	—	—

SECONDARY outcome

Timeframe: Baseline, Week 2, 12, 24, 36, 48, 60, 72, 84, 96 and 104 (Study 112)

Population: Full Analysis Set (FAS) included all participants who received at least 1 dose of study drug (Ivacaftor). Here, "Number Analyzed" signifies those participants who were evaluable for this measure at the specified time point for each arm, respectively.

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 participants 18 years and older and female participants 16 years and older. The Wang standard was used for male participants aged 6 to 17 years and for female participants aged 6 to 15 years. Baseline was defined as the most recent measurement before intake of the first dose of study drug (Ivacaftor) in Study 112. Results were planned to be reported for Ivacaftor arm and were stratified by parent study 110, 111 and 113.

Outcome measures

Outcome measures
Measure	Ivacaftor Arm n=65 Participants Participants who received Ivacaftor 150 mg tablet and/or Placebo matched to Ivacaftor tablet q12h in the previous study VX11-770-110 (Study 110; NCT01614457), VX12-770-111 (Study 111; NCT01614470) or VX12-770-113 (Study 113; NCT01685801); received Ivacaftor 150 mg tablet orally q12h in this VX12-770-112 (Study 112; NCT01707290) up to 104 weeks.	Ivacaftor Arm: Study 111 n=35 Participants Participants who received Ivacaftor 150 mg tablet and/or Placebo matched to Ivacaftor tablet orally, q12h in the previous Study 111; received Ivacaftor 150 mg tablet q12h in this Study 112 up to 104 weeks.	Ivacaftor Arm: Study 113 n=21 Participants Participants who received Ivacaftor 150 mg tablet and/or Placebo matched to Ivacaftor tablet orally, q12h in the previous Study 113; received Ivacaftor 150 mg tablet q12h in this Study 112 up to 104 weeks.
Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Week 2, 12, 24, 36, 48, 60, 72, 84, 96, and 104 Baseline	71.8 Percent predicted of FEV1 Standard Deviation 20.4	78.3 Percent predicted of FEV1 Standard Deviation 21.1	62.8 Percent predicted of FEV1 Standard Deviation 22.2
Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Week 2, 12, 24, 36, 48, 60, 72, 84, 96, and 104 Change at Week 2	3.8 Percent predicted of FEV1 Standard Deviation 8	4.4 Percent predicted of FEV1 Standard Deviation 7.7	4 Percent predicted of FEV1 Standard Deviation 7.2
Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Week 2, 12, 24, 36, 48, 60, 72, 84, 96, and 104 Change at Week 12	5.4 Percent predicted of FEV1 Standard Deviation 8.9	5.5 Percent predicted of FEV1 Standard Deviation 8.3	4.9 Percent predicted of FEV1 Standard Deviation 6.7
Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Week 2, 12, 24, 36, 48, 60, 72, 84, 96, and 104 Change at Week 24	4.5 Percent predicted of FEV1 Standard Deviation 8.4	7.1 Percent predicted of FEV1 Standard Deviation 8.3	4.6 Percent predicted of FEV1 Standard Deviation 8.5
Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Week 2, 12, 24, 36, 48, 60, 72, 84, 96, and 104 Change at Week 36	4.4 Percent predicted of FEV1 Standard Deviation 7.1	7.5 Percent predicted of FEV1 Standard Deviation 8.2	4.9 Percent predicted of FEV1 Standard Deviation 8.2
Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Week 2, 12, 24, 36, 48, 60, 72, 84, 96, and 104 Change at Week 48	4.4 Percent predicted of FEV1 Standard Deviation 7.5	6.4 Percent predicted of FEV1 Standard Deviation 10.7	4.9 Percent predicted of FEV1 Standard Deviation 9
Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Week 2, 12, 24, 36, 48, 60, 72, 84, 96, and 104 Change at Week 60	4.5 Percent predicted of FEV1 Standard Deviation 8.4	8.2 Percent predicted of FEV1 Standard Deviation 8.3	4.5 Percent predicted of FEV1 Standard Deviation 8.8
Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Week 2, 12, 24, 36, 48, 60, 72, 84, 96, and 104 Change at Week 72	3.6 Percent predicted of FEV1 Standard Deviation 8.9	7.8 Percent predicted of FEV1 Standard Deviation 9.2	5.9 Percent predicted of FEV1 Standard Deviation 9.2
Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Week 2, 12, 24, 36, 48, 60, 72, 84, 96, and 104 Change at Week 84	5.4 Percent predicted of FEV1 Standard Deviation 13.5	7.7 Percent predicted of FEV1 Standard Deviation 7.6	4.8 Percent predicted of FEV1 Standard Deviation 7.2
Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Week 2, 12, 24, 36, 48, 60, 72, 84, 96, and 104 Change at Week 96	4.1 Percent predicted of FEV1 Standard Deviation 14.6	9.9 Percent predicted of FEV1 Standard Deviation 6.4	5.9 Percent predicted of FEV1 Standard Deviation 8.1
Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Week 2, 12, 24, 36, 48, 60, 72, 84, 96, and 104 Change at Week 104	4.6 Percent predicted of FEV1 Standard Deviation 13.2	4.9 Percent predicted of FEV1 Standard Deviation 5.8	6.3 Percent predicted of FEV1 Standard Deviation 10

SECONDARY outcome

Timeframe: Baseline, Week 2, 12, 24, 36, 48, 60, 72, 84, 96 and 104 (Study 112)

Population: FAS included all participants who received at least 1 dose of study drug (Ivacaftor). Here, "Number analyzed" signifies those participants who were evaluable for this measure at the specified time point for each arm, respectively.

BMI was defined as weight in kg divided by height in m\^2. Baseline was defined as the most recent measurement before intake of the first dose of study drug (Ivacaftor) in Study 112. Results were planned to be reported for Ivacaftor arm and were stratified by parent study 110, 111 and 113.

Outcome measures

Outcome measures
Measure	Ivacaftor Arm n=65 Participants Participants who received Ivacaftor 150 mg tablet and/or Placebo matched to Ivacaftor tablet q12h in the previous study VX11-770-110 (Study 110; NCT01614457), VX12-770-111 (Study 111; NCT01614470) or VX12-770-113 (Study 113; NCT01685801); received Ivacaftor 150 mg tablet orally q12h in this VX12-770-112 (Study 112; NCT01707290) up to 104 weeks.	Ivacaftor Arm: Study 111 n=35 Participants Participants who received Ivacaftor 150 mg tablet and/or Placebo matched to Ivacaftor tablet orally, q12h in the previous Study 111; received Ivacaftor 150 mg tablet q12h in this Study 112 up to 104 weeks.	Ivacaftor Arm: Study 113 n=21 Participants Participants who received Ivacaftor 150 mg tablet and/or Placebo matched to Ivacaftor tablet orally, q12h in the previous Study 113; received Ivacaftor 150 mg tablet q12h in this Study 112 up to 104 weeks.
Absolute Change From Baseline in Body Mass Index (BMI) at Week 2,12, 24, 36, 48, 60, 72, 84, 96 and 104 Baseline	23.75 kilogram per square meter (kg/m^2) Standard Deviation 5.63	23.15 kilogram per square meter (kg/m^2) Standard Deviation 5.28	24.81 kilogram per square meter (kg/m^2) Standard Deviation 5.76
Absolute Change From Baseline in Body Mass Index (BMI) at Week 2,12, 24, 36, 48, 60, 72, 84, 96 and 104 Change at Week 2	0.06 kilogram per square meter (kg/m^2) Standard Deviation 0.43	0.16 kilogram per square meter (kg/m^2) Standard Deviation 0.47	0.07 kilogram per square meter (kg/m^2) Standard Deviation 0.43
Absolute Change From Baseline in Body Mass Index (BMI) at Week 2,12, 24, 36, 48, 60, 72, 84, 96 and 104 Change at Week 12	0.32 kilogram per square meter (kg/m^2) Standard Deviation 0.59	0.39 kilogram per square meter (kg/m^2) Standard Deviation 0.62	0.22 kilogram per square meter (kg/m^2) Standard Deviation 0.6
Absolute Change From Baseline in Body Mass Index (BMI) at Week 2,12, 24, 36, 48, 60, 72, 84, 96 and 104 Change at Week 24	0.43 kilogram per square meter (kg/m^2) Standard Deviation 0.92	0.65 kilogram per square meter (kg/m^2) Standard Deviation 0.96	0.17 kilogram per square meter (kg/m^2) Standard Deviation 0.91
Absolute Change From Baseline in Body Mass Index (BMI) at Week 2,12, 24, 36, 48, 60, 72, 84, 96 and 104 Change at Week 36	0.62 kilogram per square meter (kg/m^2) Standard Deviation 1.04	0.64 kilogram per square meter (kg/m^2) Standard Deviation 1.07	0.02 kilogram per square meter (kg/m^2) Standard Deviation 1.27
Absolute Change From Baseline in Body Mass Index (BMI) at Week 2,12, 24, 36, 48, 60, 72, 84, 96 and 104 Change at Week 48	0.54 kilogram per square meter (kg/m^2) Standard Deviation 1.39	0.58 kilogram per square meter (kg/m^2) Standard Deviation 1.22	0.28 kilogram per square meter (kg/m^2) Standard Deviation 1.26
Absolute Change From Baseline in Body Mass Index (BMI) at Week 2,12, 24, 36, 48, 60, 72, 84, 96 and 104 Change at Week 60	0.72 kilogram per square meter (kg/m^2) Standard Deviation 1.32	0.25 kilogram per square meter (kg/m^2) Standard Deviation 1.09	0.38 kilogram per square meter (kg/m^2) Standard Deviation 1.22
Absolute Change From Baseline in Body Mass Index (BMI) at Week 2,12, 24, 36, 48, 60, 72, 84, 96 and 104 Change at Week 72	1.05 kilogram per square meter (kg/m^2) Standard Deviation 1.73	0.45 kilogram per square meter (kg/m^2) Standard Deviation 1.34	0.22 kilogram per square meter (kg/m^2) Standard Deviation 1.22
Absolute Change From Baseline in Body Mass Index (BMI) at Week 2,12, 24, 36, 48, 60, 72, 84, 96 and 104 Change at Week 84	0.72 kilogram per square meter (kg/m^2) Standard Deviation 1.51	0.33 kilogram per square meter (kg/m^2) Standard Deviation 1.42	0.23 kilogram per square meter (kg/m^2) Standard Deviation 0.92
Absolute Change From Baseline in Body Mass Index (BMI) at Week 2,12, 24, 36, 48, 60, 72, 84, 96 and 104 Change at Week 96	0.49 kilogram per square meter (kg/m^2) Standard Deviation 1.44	0.1 kilogram per square meter (kg/m^2) Standard Deviation 1.49	0.52 kilogram per square meter (kg/m^2) Standard Deviation 1.28
Absolute Change From Baseline in Body Mass Index (BMI) at Week 2,12, 24, 36, 48, 60, 72, 84, 96 and 104 Change at Week 104	0.42 kilogram per square meter (kg/m^2) Standard Deviation 1.49	0.16 kilogram per square meter (kg/m^2) Standard Deviation 1.37	0.88 kilogram per square meter (kg/m^2) Standard Deviation 1.39

SECONDARY outcome

Timeframe: Baseline, Week 2, 24, 48 and 104 (Study 112)

Population: FAS included all participants who received at least 1 dose of study drug (Ivacaftor). Here, "Number of participants analyzed" signifies those participants who were evaluable for this outcome and "Number Analyzed" signifies those participants who were evaluable for this measure at the specified time point for each arm respectively.

Sweat samples were collected using an approved collection device. Baseline was defined as the most recent measurement before intake of the first dose of study drug (Ivacaftor) in Study 112. Results were planned to be reported for Ivacaftor arm and were stratified by parent study 110, 111 and 113.

Outcome measures

Outcome measures
Measure	Ivacaftor Arm n=59 Participants Participants who received Ivacaftor 150 mg tablet and/or Placebo matched to Ivacaftor tablet q12h in the previous study VX11-770-110 (Study 110; NCT01614457), VX12-770-111 (Study 111; NCT01614470) or VX12-770-113 (Study 113; NCT01685801); received Ivacaftor 150 mg tablet orally q12h in this VX12-770-112 (Study 112; NCT01707290) up to 104 weeks.	Ivacaftor Arm: Study 111 n=33 Participants Participants who received Ivacaftor 150 mg tablet and/or Placebo matched to Ivacaftor tablet orally, q12h in the previous Study 111; received Ivacaftor 150 mg tablet q12h in this Study 112 up to 104 weeks.	Ivacaftor Arm: Study 113 n=21 Participants Participants who received Ivacaftor 150 mg tablet and/or Placebo matched to Ivacaftor tablet orally, q12h in the previous Study 113; received Ivacaftor 150 mg tablet q12h in this Study 112 up to 104 weeks.
Absolute Change From Baseline in Sweat Chloride at Week 2, 24, 48 and 104 Baseline	60.9 millimole per liter (mmol/L) Standard Deviation 19.4	80.2 millimole per liter (mmol/L) Standard Deviation 22.8	55.7 millimole per liter (mmol/L) Standard Deviation 22.2
Absolute Change From Baseline in Sweat Chloride at Week 2, 24, 48 and 104 Change at Week 2	-19.3 millimole per liter (mmol/L) Standard Deviation 10.7	-38.4 millimole per liter (mmol/L) Standard Deviation 27.5	-4.5 millimole per liter (mmol/L) Standard Deviation 10.9
Absolute Change From Baseline in Sweat Chloride at Week 2, 24, 48 and 104 Change at Week 24	-13 millimole per liter (mmol/L) Standard Deviation 18.4	-39.2 millimole per liter (mmol/L) Standard Deviation 27	1.1 millimole per liter (mmol/L) Standard Deviation 15.8
Absolute Change From Baseline in Sweat Chloride at Week 2, 24, 48 and 104 Change at Week 48	-13.5 millimole per liter (mmol/L) Standard Deviation 16.2	-40.6 millimole per liter (mmol/L) Standard Deviation 26.1	-1.9 millimole per liter (mmol/L) Standard Deviation 17.8
Absolute Change From Baseline in Sweat Chloride at Week 2, 24, 48 and 104 Change at Week 104	-13.7 millimole per liter (mmol/L) Standard Deviation 22.9	-32.9 millimole per liter (mmol/L) Standard Deviation 26.8	5.4 millimole per liter (mmol/L) Standard Deviation 18.1

SECONDARY outcome

Timeframe: Baseline, Week 2, 12, 24, 36, 48, 60, 72, 84, 96 and 104 (Study 112)

Population: FAS included all participants who received at least 1 dose of study drug (ivacaftor). Here, "Number Analyzed" signifies those participants who were evaluable for this measure at the specified time point for each arm respectively.

The CFQ-R is a validated participant reported outcome measuring health related quality of life for participants with CF. Respiratory domain assessed respiratory symptoms (for example, coughing, congestion, wheezing), score range: 0-100; higher scores indicating fewer symptoms and better health related quality of life. Baseline was defined as the most recent measurement before intake of the first dose of study drug (ivacaftor) in Study 112. Results were planned to be reported for Ivacaftor arm and were stratified by parent study 110, 111 and 113.

Outcome measures

Outcome measures
Measure	Ivacaftor Arm n=65 Participants Participants who received Ivacaftor 150 mg tablet and/or Placebo matched to Ivacaftor tablet q12h in the previous study VX11-770-110 (Study 110; NCT01614457), VX12-770-111 (Study 111; NCT01614470) or VX12-770-113 (Study 113; NCT01685801); received Ivacaftor 150 mg tablet orally q12h in this VX12-770-112 (Study 112; NCT01707290) up to 104 weeks.	Ivacaftor Arm: Study 111 n=35 Participants Participants who received Ivacaftor 150 mg tablet and/or Placebo matched to Ivacaftor tablet orally, q12h in the previous Study 111; received Ivacaftor 150 mg tablet q12h in this Study 112 up to 104 weeks.	Ivacaftor Arm: Study 113 n=21 Participants Participants who received Ivacaftor 150 mg tablet and/or Placebo matched to Ivacaftor tablet orally, q12h in the previous Study 113; received Ivacaftor 150 mg tablet q12h in this Study 112 up to 104 weeks.
Absolute Change From Baseline in Respiratory Domain of the Cystic Fibrosis Questionnaire Revised (CFQ-R) at Week 2, 12, 24, 36, 48, 60, 72, 84, 96 and 104 Baseline	68.6 units on a scale Standard Deviation 21.6	72.4 units on a scale Standard Deviation 20.3	65.9 units on a scale Standard Deviation 18.8
Absolute Change From Baseline in Respiratory Domain of the Cystic Fibrosis Questionnaire Revised (CFQ-R) at Week 2, 12, 24, 36, 48, 60, 72, 84, 96 and 104 Change at Week 2	5.5 units on a scale Standard Deviation 17.9	4.5 units on a scale Standard Deviation 17.5	13.2 units on a scale Standard Deviation 16.2
Absolute Change From Baseline in Respiratory Domain of the Cystic Fibrosis Questionnaire Revised (CFQ-R) at Week 2, 12, 24, 36, 48, 60, 72, 84, 96 and 104 Change at Week 12	11.6 units on a scale Standard Deviation 18	5.7 units on a scale Standard Deviation 18.5	13.5 units on a scale Standard Deviation 20
Absolute Change From Baseline in Respiratory Domain of the Cystic Fibrosis Questionnaire Revised (CFQ-R) at Week 2, 12, 24, 36, 48, 60, 72, 84, 96 and 104 Change at Week 24	6.7 units on a scale Standard Deviation 19	3.4 units on a scale Standard Deviation 18.7	8.5 units on a scale Standard Deviation 14.9
Absolute Change From Baseline in Respiratory Domain of the Cystic Fibrosis Questionnaire Revised (CFQ-R) at Week 2, 12, 24, 36, 48, 60, 72, 84, 96 and 104 Change at Week 36	12.1 units on a scale Standard Deviation 19.3	5.7 units on a scale Standard Deviation 13.8	7.9 units on a scale Standard Deviation 20.5
Absolute Change From Baseline in Respiratory Domain of the Cystic Fibrosis Questionnaire Revised (CFQ-R) at Week 2, 12, 24, 36, 48, 60, 72, 84, 96 and 104 Change at Week 48	9.5 units on a scale Standard Deviation 17.6	4.4 units on a scale Standard Deviation 13.2	11.4 units on a scale Standard Deviation 15.7
Absolute Change From Baseline in Respiratory Domain of the Cystic Fibrosis Questionnaire Revised (CFQ-R) at Week 2, 12, 24, 36, 48, 60, 72, 84, 96 and 104 Change at Week 60	7.1 units on a scale Standard Deviation 18.6	4.4 units on a scale Standard Deviation 10.9	8.6 units on a scale Standard Deviation 19.3
Absolute Change From Baseline in Respiratory Domain of the Cystic Fibrosis Questionnaire Revised (CFQ-R) at Week 2, 12, 24, 36, 48, 60, 72, 84, 96 and 104 Change at Week 72	10.4 units on a scale Standard Deviation 22.2	5.6 units on a scale Standard Deviation 11.8	8.6 units on a scale Standard Deviation 19
Absolute Change From Baseline in Respiratory Domain of the Cystic Fibrosis Questionnaire Revised (CFQ-R) at Week 2, 12, 24, 36, 48, 60, 72, 84, 96 and 104 Change at Week 84	10.5 units on a scale Standard Deviation 19.5	8.8 units on a scale Standard Deviation 14.1	4.9 units on a scale Standard Deviation 14.6
Absolute Change From Baseline in Respiratory Domain of the Cystic Fibrosis Questionnaire Revised (CFQ-R) at Week 2, 12, 24, 36, 48, 60, 72, 84, 96 and 104 Change at Week 96	8.8 units on a scale Standard Deviation 21.1	0 units on a scale Standard Deviation 9.5	9.4 units on a scale Standard Deviation 14.7
Absolute Change From Baseline in Respiratory Domain of the Cystic Fibrosis Questionnaire Revised (CFQ-R) at Week 2, 12, 24, 36, 48, 60, 72, 84, 96 and 104 Change at Week 104	9.2 units on a scale Standard Deviation 14	1.9 units on a scale Standard Deviation 8.8	19.9 units on a scale Standard Deviation 16

SECONDARY outcome

Timeframe: Through Week 104 (Study 112)

Population: FAS included all participants who received at least 1 dose of study drug (Ivacaftor).

Pulmonary exacerbation events include those events which require treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for greater than or equal to 4 sinopulmonary signs/symptoms. The number of events were reported. Results were planned to be reported for Ivacaftor arm and were stratified by parent study 110, 111 and 113.

Outcome measures

Outcome measures
Measure	Ivacaftor Arm n=65 Participants Participants who received Ivacaftor 150 mg tablet and/or Placebo matched to Ivacaftor tablet q12h in the previous study VX11-770-110 (Study 110; NCT01614457), VX12-770-111 (Study 111; NCT01614470) or VX12-770-113 (Study 113; NCT01685801); received Ivacaftor 150 mg tablet orally q12h in this VX12-770-112 (Study 112; NCT01707290) up to 104 weeks.	Ivacaftor Arm: Study 111 n=35 Participants Participants who received Ivacaftor 150 mg tablet and/or Placebo matched to Ivacaftor tablet orally, q12h in the previous Study 111; received Ivacaftor 150 mg tablet q12h in this Study 112 up to 104 weeks.	Ivacaftor Arm: Study 113 n=21 Participants Participants who received Ivacaftor 150 mg tablet and/or Placebo matched to Ivacaftor tablet orally, q12h in the previous Study 113; received Ivacaftor 150 mg tablet q12h in this Study 112 up to 104 weeks.
Number of Pulmonary Exacerbations Events	47 pulmonary exacerbation events	30 pulmonary exacerbation events	6 pulmonary exacerbation events

SECONDARY outcome

Timeframe: up to 2 years (Study 112)

Population: Analysis population included all participants who were included in the observational arm.

SAE was defined as a medical event or condition, which falls into any of the following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, In-patient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event.

Outcome measures

Outcome measures
Measure	Ivacaftor Arm n=4 Participants Participants who received Ivacaftor 150 mg tablet and/or Placebo matched to Ivacaftor tablet q12h in the previous study VX11-770-110 (Study 110; NCT01614457), VX12-770-111 (Study 111; NCT01614470) or VX12-770-113 (Study 113; NCT01685801); received Ivacaftor 150 mg tablet orally q12h in this VX12-770-112 (Study 112; NCT01707290) up to 104 weeks.	Ivacaftor Arm: Study 111 Participants who received Ivacaftor 150 mg tablet and/or Placebo matched to Ivacaftor tablet orally, q12h in the previous Study 111; received Ivacaftor 150 mg tablet q12h in this Study 112 up to 104 weeks.	Ivacaftor Arm: Study 113 Participants who received Ivacaftor 150 mg tablet and/or Placebo matched to Ivacaftor tablet orally, q12h in the previous Study 113; received Ivacaftor 150 mg tablet q12h in this Study 112 up to 104 weeks.
Number of Participants With Serious Adverse Events (SAEs) in Observational Arm	1 participants	—	—

Adverse Events

Ivacaftor Arm

Serious events: 27 serious events

Other events: 117 other events

Deaths: 0 deaths

Observational Arm

Serious events: 1 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Monitor

Vertex Pharmaceuticals Incorporated

Phone: 617-341-6777

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee PI is free to publish results of the study after (1) the first multi-center publication, (2) if the sponsor elects not to publish the results, or (3) 18 months after close of the study, whichever occurs first. Proposed publications are to be submitted to the sponsor for review and comment for a period of at least 45 days (which may be extended under certain circumstances related to protection of intellectual property); the sponsor cannot require changes to the proposed publications.
Publication restrictions are in place

Restriction type: OTHER

Measure	Ivacaftor Arm n=121 participants at risk Participants who received Ivacaftor 150 mg tablet and/or Placebo matched to Ivacaftor tablet q12h in the previous study VX11-770-110 (Study 110; NCT01614457), VX12-770-111 (Study 111; NCT01614470) or VX12-770-113 (Study 113; NCT01685801); received Ivacaftor 150 mg tablet orally q12h in this VX12-770-112 (Study 112; NCT01707290) up to 104 weeks.	Observational Arm n=4 participants at risk Participants who received Ivacaftor 150 mg tablet and/or Placebo matched to Ivacaftor tablet q12h in the previous Study 110 (NCT01614457) or Study 111 (NCT01614470), were observed (did not receive study drug) in this Study 112 (NCT01707290) for up to 2 years.
Investigations Influenza A virus test positive	0.83% 1/121 • Day 1 up to Week 108 for Ivacaftor arm; up to 2 years for Observational arm (Study 112) Non-SAEs were not collected for Observational arm. Only SAEs were planned to be collected for the Observational arm.	0.00% 0/4 • Day 1 up to Week 108 for Ivacaftor arm; up to 2 years for Observational arm (Study 112) Non-SAEs were not collected for Observational arm. Only SAEs were planned to be collected for the Observational arm.
Cardiac disorders Cardiomyopathy acute	0.83% 1/121 • Day 1 up to Week 108 for Ivacaftor arm; up to 2 years for Observational arm (Study 112) Non-SAEs were not collected for Observational arm. Only SAEs were planned to be collected for the Observational arm.	0.00% 0/4 • Day 1 up to Week 108 for Ivacaftor arm; up to 2 years for Observational arm (Study 112) Non-SAEs were not collected for Observational arm. Only SAEs were planned to be collected for the Observational arm.
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.83% 1/121 • Day 1 up to Week 108 for Ivacaftor arm; up to 2 years for Observational arm (Study 112) Non-SAEs were not collected for Observational arm. Only SAEs were planned to be collected for the Observational arm.	0.00% 0/4 • Day 1 up to Week 108 for Ivacaftor arm; up to 2 years for Observational arm (Study 112) Non-SAEs were not collected for Observational arm. Only SAEs were planned to be collected for the Observational arm.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.83% 1/121 • Day 1 up to Week 108 for Ivacaftor arm; up to 2 years for Observational arm (Study 112) Non-SAEs were not collected for Observational arm. Only SAEs were planned to be collected for the Observational arm.	0.00% 0/4 • Day 1 up to Week 108 for Ivacaftor arm; up to 2 years for Observational arm (Study 112) Non-SAEs were not collected for Observational arm. Only SAEs were planned to be collected for the Observational arm.
Gastrointestinal disorders Crohn's disease	0.83% 1/121 • Day 1 up to Week 108 for Ivacaftor arm; up to 2 years for Observational arm (Study 112) Non-SAEs were not collected for Observational arm. Only SAEs were planned to be collected for the Observational arm.	0.00% 0/4 • Day 1 up to Week 108 for Ivacaftor arm; up to 2 years for Observational arm (Study 112) Non-SAEs were not collected for Observational arm. Only SAEs were planned to be collected for the Observational arm.
Gastrointestinal disorders Abdominal pain	0.83% 1/121 • Day 1 up to Week 108 for Ivacaftor arm; up to 2 years for Observational arm (Study 112) Non-SAEs were not collected for Observational arm. Only SAEs were planned to be collected for the Observational arm.	0.00% 0/4 • Day 1 up to Week 108 for Ivacaftor arm; up to 2 years for Observational arm (Study 112) Non-SAEs were not collected for Observational arm. Only SAEs were planned to be collected for the Observational arm.
Gastrointestinal disorders Flatulence	0.83% 1/121 • Day 1 up to Week 108 for Ivacaftor arm; up to 2 years for Observational arm (Study 112) Non-SAEs were not collected for Observational arm. Only SAEs were planned to be collected for the Observational arm.	0.00% 0/4 • Day 1 up to Week 108 for Ivacaftor arm; up to 2 years for Observational arm (Study 112) Non-SAEs were not collected for Observational arm. Only SAEs were planned to be collected for the Observational arm.
Gastrointestinal disorders Pancreatitis	0.83% 1/121 • Day 1 up to Week 108 for Ivacaftor arm; up to 2 years for Observational arm (Study 112) Non-SAEs were not collected for Observational arm. Only SAEs were planned to be collected for the Observational arm.	0.00% 0/4 • Day 1 up to Week 108 for Ivacaftor arm; up to 2 years for Observational arm (Study 112) Non-SAEs were not collected for Observational arm. Only SAEs were planned to be collected for the Observational arm.
Renal and urinary disorders Renal failure acute	0.83% 1/121 • Day 1 up to Week 108 for Ivacaftor arm; up to 2 years for Observational arm (Study 112) Non-SAEs were not collected for Observational arm. Only SAEs were planned to be collected for the Observational arm.	0.00% 0/4 • Day 1 up to Week 108 for Ivacaftor arm; up to 2 years for Observational arm (Study 112) Non-SAEs were not collected for Observational arm. Only SAEs were planned to be collected for the Observational arm.
Skin and subcutaneous tissue disorders Angioedema	0.83% 1/121 • Day 1 up to Week 108 for Ivacaftor arm; up to 2 years for Observational arm (Study 112) Non-SAEs were not collected for Observational arm. Only SAEs were planned to be collected for the Observational arm.	0.00% 0/4 • Day 1 up to Week 108 for Ivacaftor arm; up to 2 years for Observational arm (Study 112) Non-SAEs were not collected for Observational arm. Only SAEs were planned to be collected for the Observational arm.
Skin and subcutaneous tissue disorders Urticaria	0.83% 1/121 • Day 1 up to Week 108 for Ivacaftor arm; up to 2 years for Observational arm (Study 112) Non-SAEs were not collected for Observational arm. Only SAEs were planned to be collected for the Observational arm.	0.00% 0/4 • Day 1 up to Week 108 for Ivacaftor arm; up to 2 years for Observational arm (Study 112) Non-SAEs were not collected for Observational arm. Only SAEs were planned to be collected for the Observational arm.
Infections and infestations Infective pulmonary exacerbation of cystic fibrosis	17.4% 21/121 • Day 1 up to Week 108 for Ivacaftor arm; up to 2 years for Observational arm (Study 112) Non-SAEs were not collected for Observational arm. Only SAEs were planned to be collected for the Observational arm.	25.0% 1/4 • Day 1 up to Week 108 for Ivacaftor arm; up to 2 years for Observational arm (Study 112) Non-SAEs were not collected for Observational arm. Only SAEs were planned to be collected for the Observational arm.
Infections and infestations Gastroenteritis	1.7% 2/121 • Day 1 up to Week 108 for Ivacaftor arm; up to 2 years for Observational arm (Study 112) Non-SAEs were not collected for Observational arm. Only SAEs were planned to be collected for the Observational arm.	0.00% 0/4 • Day 1 up to Week 108 for Ivacaftor arm; up to 2 years for Observational arm (Study 112) Non-SAEs were not collected for Observational arm. Only SAEs were planned to be collected for the Observational arm.
Infections and infestations Pneumonia	1.7% 2/121 • Day 1 up to Week 108 for Ivacaftor arm; up to 2 years for Observational arm (Study 112) Non-SAEs were not collected for Observational arm. Only SAEs were planned to be collected for the Observational arm.	0.00% 0/4 • Day 1 up to Week 108 for Ivacaftor arm; up to 2 years for Observational arm (Study 112) Non-SAEs were not collected for Observational arm. Only SAEs were planned to be collected for the Observational arm.
Infections and infestations Pharyngitis bacterial	0.83% 1/121 • Day 1 up to Week 108 for Ivacaftor arm; up to 2 years for Observational arm (Study 112) Non-SAEs were not collected for Observational arm. Only SAEs were planned to be collected for the Observational arm.	0.00% 0/4 • Day 1 up to Week 108 for Ivacaftor arm; up to 2 years for Observational arm (Study 112) Non-SAEs were not collected for Observational arm. Only SAEs were planned to be collected for the Observational arm.
Infections and infestations Gastroenteritis viral	0.83% 1/121 • Day 1 up to Week 108 for Ivacaftor arm; up to 2 years for Observational arm (Study 112) Non-SAEs were not collected for Observational arm. Only SAEs were planned to be collected for the Observational arm.	0.00% 0/4 • Day 1 up to Week 108 for Ivacaftor arm; up to 2 years for Observational arm (Study 112) Non-SAEs were not collected for Observational arm. Only SAEs were planned to be collected for the Observational arm.
Infections and infestations Sinusitis	0.83% 1/121 • Day 1 up to Week 108 for Ivacaftor arm; up to 2 years for Observational arm (Study 112) Non-SAEs were not collected for Observational arm. Only SAEs were planned to be collected for the Observational arm.	0.00% 0/4 • Day 1 up to Week 108 for Ivacaftor arm; up to 2 years for Observational arm (Study 112) Non-SAEs were not collected for Observational arm. Only SAEs were planned to be collected for the Observational arm.