Study of Ivacaftor in Cystic Fibrosis Subjects 2 Through 5 Years of Age With a CFTR Gating Mutation

• Sponsor: Vertex Pharmaceuticals Incorporated (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01705145
• Collaborator: Cystic Fibrosis Foundation (Other)
• Enrollment: 35
• Locations: 20
• Arm: 1
• Duration (Months): 13.9
• Patients Per Site: 1.8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the safety, pharmacokinetics (PK), and pharmacodynamics (PD), of ivacaftor in children with cystic fibrosis (CF) who are 2 through 5 years of age and have a CF Transmembrane Conductance Regulator (CFTR) gating mutation in at least 1 allele.

Part A is designed to evaluate the safety and PK of multiple-dose administration of ivacaftor in participants 2 through 5 years of age and to confirm the doses for Part B. Part B is designed to evaluate the safety, PK, PD, and efficacy of ivacaftor in participants 2 through 5 years of age.

Condition or Disease	Intervention/Treatment	Phase
Cystic Fibrosis	Drug: Ivacaftor	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 35 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 3, 2-Part, Open-Label Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of Ivacaftor in Subjects With Cystic Fibrosis Who Are 2 Through 5 Years of Age and Have a CFTR Gating Mutation
• Study Start Date: Jan 1, 2013
• Actual Primary Completion Date: Mar 1, 2014
• Actual Study Completion Date: Mar 1, 2014

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Ivacaftor Part A: Ivacaftor 50 milligram (mg) (for participants weighing less than [<] 14 kilograms [kg]) or 75 mg (for participants weighing greater than or equal to [>=] 14 kg) every 12 hours (q12h) from Day 1 through Day 3 and 1 morning dose on Day 4 during Part A of the study.. Part B: Ivacaftor 50 mg (for participants weighing <14 kg) or 75 mg (for participants weighing >=14 kg) q12h for 24 weeks during Part B of the study.

Drug: Ivacaftor; Other Names: Kalydeco VX-770

Outcome Measures

Primary Outcome Measures

1. Part A: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Related AEs [Part A: Up to 93 Days]

   AE: any adverse change from participant's baseline (pre-treatment) condition, including any adverse experience, abnormal recording/clinical laboratory assessment which occurs during course of study, whether it is considered related to study drug or not. SAE: medical event or condition, which falls into any of following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, in-patient hospitalization/prolonged hospitalization, persistent/significant disability/incapacity, congenital anomaly/birth defect, important medical event. Related AEs includes all AEs for which the causality was either related to study drug or possibly related to study drug. Data was reported as per the dose received and for overall participants.

2. Part B: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Related AEs [Part B: Up to 28 Weeks]

   AE: any adverse change from participant's baseline (pre-treatment) condition, including any adverse experience, abnormal recording/clinical laboratory assessment which occurs during course of study, whether it is considered related to study drug or not. AE includes both serious and non-serious AE. SAE: medical event or condition, which falls into any of following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, in-patient hospitalization/prolonged hospitalization, persistent/significant disability/incapacity, congenital anomaly/birth defect, important medical event. Related AEs includes all AEs for which the causality was either related to study drug or possibly related to study drug. Data was reported as per the dose received.

3. Part A: Plasma Concentration of Ivacaftor and Its Metabolites [Part A: up to 24 hours post-dose on Day 4]

   Plasma concentration was reported for ivacaftor and its metabolites (hydroxymethyl ivacaftor [M1] and ivacaftor carboxylate [M6]) up to 24 hours post-dose on Day 4 (Hour 0 [pre-dose] on Day 1 and Day 4; 2, 3, 6, 24 hours post-dose on Day 4). Data was planned to be reported for overall participants in the period.

Secondary Outcome Measures

1. Part B: Plasma Concentration of Ivacaftor and Its Metabolites [Part B: up to 24 hours post-dose on Day 168]

   Plasma concentration was reported for ivacaftor and its metabolites (M1 and M6) up to 24 hours post-dose on Day 168 (Hour 0 [predose] on Day 1, 14, 56, 112, and 168; 2, 3, 6 hours post-dose on Day 14; 1 hour post-dose on Day 56; 4, 6 hours post-dose on Day 112; 24 hours post-dose on Day 168). Data was planned to be reported for overall participants in the period.

2. Part B: Absolute Change From Baseline in Sweat Chloride at Week 24 [Part B: Baseline, Week 24]

   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 reported as per the dose received and for overall participants.

3. Part B: Absolute Change From Baseline in Weight at Week 24 [Part B: Baseline, Week 24]

   Data was reported as per the dose received and for overall participants.

4. Part B: Absolute Change From Baseline in Stature at Week 24 [Part B: Baseline, Week 24]

   Stature was measured as height if children could stand unassisted and follow directions; otherwise, stature was measured as length. Data was reported as per the dose received and for overall participants.

5. Part B: Absolute Change From Baseline in Body Mass Index (BMI) at Week 24 [Baseline, Week 24]

   BMI = (Weight [in kg]) divided by (Stature [in meters])^2. Data was reported as per the dose received and for overall participants.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 2 Years to 5 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male or female with confirmed diagnosis of CF

• Must have a CFTR gating mutation in at least 1 allele

• Aged 2 through 5 years at screening and Day 1

• Weight >= 8 kg at screening and Day 1

• Hematology, serum chemistry, coagulation, and vital signs results at screening with no clinically significant abnormalities that would interfere with the study assessments, as judged by the investigator

Exclusion Criteria:

• History of any illness or condition that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering study drug to the participant

• An acute upper or lower respiratory infection, or pulmonary exacerbation, or changes in therapy for pulmonary disease within 4 weeks before Day 1

• Abnormal liver function, at screening

• History of solid organ or hematological transplantation

• Use of any moderate or strong inducers or inhibitors of cytochrome P450 (CYP) 3A within 2 weeks before Day 1

• Participation in a clinical study involving administration of either an investigational or a marketed drug within 30 days or 5 terminal half-lives before screening

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Birmingham	Alabama	United States
2		Aurora	Colorado	United States
3		Atlanta	Georgia	United States
4		Indianapolis	Indiana	United States
5		Lexington	Kentucky	United States
6		Boston	Massachusetts	United States
7		Detroit	Michigan	United States
8		Grand Rapids	Michigan	United States
9		Minneapolis	Minnesota	United States
10		Kansas City	Missouri	United States
11		Omaha	Nebraska	United States
12		Pittsburgh	Pennsylvania	United States
13		Salt Lake City	Utah	United States
14		Charlottesville	Virginia	United States
15		Richmond	Virginia	United States
16		Seattle	Washington	United States
17		Vancouver		Canada
18		Edinburgh		United Kingdom
19		Liverpool		United Kingdom
20		London		United Kingdom

Sponsors and Collaborators

• Vertex Pharmaceuticals Incorporated
• Cystic Fibrosis Foundation

Investigators

• Principal Investigator: Margaret Rosenfeld, MD, Seattle Children's Hospital
• Principal Investigator: Jane Davies, MD, Imperial College London

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Vertex Pharmaceuticals Incorporated
• ClinicalTrials.gov Identifier: NCT01705145
• Other Study ID Numbers: VX11-770-108; KIWI
• First Posted: Oct 12, 2012
• Last Update Posted: Apr 5, 2016
• Last Verified: Mar 1, 2016

• Keywords provided by Vertex Pharmaceuticals Incorporated: Cystic Fibrosis
• Additional relevant MeSH terms: Cystic Fibrosis; Fibrosis; Ivacaftor

Study Results

Participant Flow

Arm/Group Title	Ivacaftor
Arm/Group Description	Part A: Ivacaftor 50 milligram (mg) (for participants weighing less than [<] 14 kilograms [kg]) or 75 mg (for participants weighing greater than or equal to [>=] 14 kg) every 12 hours (q12h) from Day 1 through Day 3 and 1 morning dose on Day 4 during Part A of the study. Part B: Ivacaftor 50 mg (for participants weighing <14 kg) or 75 mg (for participants weighing >=14 kg) q12h for 24 weeks during Part B of the study. Part B included participants from Part A and newly enrolled participants.
Period Title: Part A
STARTED	9
COMPLETED	9
NOT COMPLETED	0
Period Title: Part A
STARTED	34
COMPLETED	33
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Ivacaftor
Arm/Group Description	Part A: Ivacaftor 50 mg (for participants weighing <14 kg) or 75 mg (for participants weighing >=14 kg) q12h from Day 1 through Day 3 and 1 morning dose on Day 4 during Part A of the study. Part B: Ivacaftor 50 mg (for participants weighing <14 kg) or 75 mg (for participants weighing >=14 kg) q12h for 24 weeks during Part B of the study. Part B included participants from Part A and newly enrolled participants.
Overall Participants	35
Age (years) [Mean (Standard Deviation) ]
Part A (n = 9)	3.1 (1.17)
Part B (n = 34)	3.2 (0.96)
Sex/Gender, Customized (participants) [Number]
Part A (n = 9): Female	3 8.6%
Part A (n = 9): Male	6 17.1%
Part B (n = 34): Female	6 17.1%
Part B (n = 34): Male	28 80%

Outcome Measures

1. Primary Outcome

Title	Part A: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Related AEs
Description	AE: any adverse change from participant's baseline (pre-treatment) condition, including any adverse experience, abnormal recording/clinical laboratory assessment which occurs during course of study, whether it is considered related to study drug or not. SAE: medical event or condition, which falls into any of following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, in-patient hospitalization/prolonged hospitalization, persistent/significant disability/incapacity, congenital anomaly/birth defect, important medical event. Related AEs includes all AEs for which the causality was either related to study drug or possibly related to study drug. Data was reported as per the dose received and for overall participants.
Time Frame	Part A: Up to 93 Days

Outcome Measure Data

Analysis Population Description

Part A Safety set included all participants who received at least 1 dose of study drug in part A.

Arm/Group Title	Part A: Ivacaftor 50 mg	Part A: Ivacaftor 75 mg	Part A: Overall Ivacaftor
Arm/Group Description	Ivacaftor 50 mg (for participants weighing <14 kg) q12h from Day 1 through Day 3 and 1 morning dose on Day 4 during Part A of the study.	Ivacaftor 75 mg (for participants weighing >=14 kg) q12h from Day 1 through Day 3 and 1 morning dose on Day 4 during Part A of the study.	Ivacaftor 50 mg (for participants weighing <14 kg) or 75 mg (for participants weighing >=14 kg) q12h from Day 1 through Day 3 and 1 morning dose on Day 4 during Part A of the study.
Measure Participants	4	5	9
AEs	3 8.6%	5 NaN	8 NaN
SAEs	0 0%	0 NaN	0 NaN
Related AEs	1 2.9%	3 NaN	4 NaN

2. Primary Outcome

Title	Part B: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Related AEs
Description	AE: any adverse change from participant's baseline (pre-treatment) condition, including any adverse experience, abnormal recording/clinical laboratory assessment which occurs during course of study, whether it is considered related to study drug or not. AE includes both serious and non-serious AE. SAE: medical event or condition, which falls into any of following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, in-patient hospitalization/prolonged hospitalization, persistent/significant disability/incapacity, congenital anomaly/birth defect, important medical event. Related AEs includes all AEs for which the causality was either related to study drug or possibly related to study drug. Data was reported as per the dose received.
Time Frame	Part B: Up to 28 Weeks

Outcome Measure Data

Analysis Population Description

Part B Safety set included all participants who received at least 1 dose of study drug in part B.

Arm/Group Title	Part B: Ivacaftor 50 mg	Part B: Ivacaftor 75 mg	Part B: Overall Ivacaftor
Arm/Group Description	Ivacaftor 50 mg (for participants weighing <14 kg) q12h for 24 weeks during Part B of the study. Part B included participants from Part A and newly enrolled participants.	Ivacaftor 75 mg (for participants weighing >=14 kg) q12h for 24 weeks during Part B of the study. Part B included participants from Part A and newly enrolled participants.	Ivacaftor 50 mg (for participants weighing <14 kg) or 75 mg (for participants weighing >=14 kg) q12h for 24 weeks during Part B of the study. Part B included participants from Part A and newly enrolled participants.
Measure Participants	10	24	34
AEs	10 28.6%	23 NaN	33 NaN
SAEs	3 8.6%	3 NaN	6 NaN
Related AEs	3 8.6%	8 NaN	11 NaN

3. Secondary Outcome

Title	Part B: Plasma Concentration of Ivacaftor and Its Metabolites
Description	Plasma concentration was reported for ivacaftor and its metabolites (M1 and M6) up to 24 hours post-dose on Day 168 (Hour 0 [predose] on Day 1, 14, 56, 112, and 168; 2, 3, 6 hours post-dose on Day 14; 1 hour post-dose on Day 56; 4, 6 hours post-dose on Day 112; 24 hours post-dose on Day 168). Data was planned to be reported for overall participants in the period.
Time Frame	Part B: up to 24 hours post-dose on Day 168

Outcome Measure Data

Analysis Population Description

Part B Safety set included all participants who received at least 1 dose of study drug in part B.

Arm/Group Title	Part B: Overall Ivacaftor
Arm/Group Description	Ivacaftor 50 mg (for participants weighing <14 kg) or 75 mg (for participants weighing >=14 kg) q12h for 24 weeks during Part B of the study. Part B included participants from Part A and newly enrolled participants.
Measure Participants	34
Ivacaftor: Hour 0 on Day 1	0.00 (0.00)
Ivacaftor: Hour 0 on Day 14	614 (590)
Ivacaftor: 2 Hours Post-Dose on Day 14	932 (541)
Ivacaftor: 3 Hours Post-Dose on Day 14	1080 (587)
Ivacaftor: 6 Hours Post-Dose on Day 14	1140 (627)
Ivacaftor: Hour 0 on Day 56	448 (455)
Ivacaftor: 1 Hour Post-Dose on Day 56	514 (421)
Ivacaftor: Hour 0 on Day 112	596 (747)
Ivacaftor: 4 Hours Post-Dose on Day 112	1080 (835)
Ivacaftor: 6 Hours Post-Dose on Day 112	1010 (885)
Ivacaftor: Hour 0 on Day 168	500 (545)
Ivacaftor: 24 Hours Post-Dose on Day 168	207 (372)
M1: Hour 0 on Day 1	0.00 (0.00)
M1: Hour 0 on Day 14	1580 (1030)
M1: 2 Hours Post-Dose on Day 14	1870 (924)
M1: 3 Hours Post-Dose on Day 14	2280 (1140)
M1: 6 Hours Post-Dose on Day 14	2670 (1080)
M1: Hour 0 on Day 56	1340 (880)
M1: 1 Hour Post-Dose on Day 56	1170 (698)
M1: Hour 0 on Day 112	1680 (1360)
M1: 4 Hours Post-Dose on Day 112	2450 (1510)
M1: 6 Hours Post-Dose on Day 112	2500 (1520)
M1: Hour 0 on Day 168	1460 (1200)
M1: 24 Hours Post-Dose on Day 168	602 (647)
M6: Hour 0 on Day 1	0.00 (0.00)
M6: Hour 0 on Day 14	1520 (1130)
M6: 2 Hours Post-Dose on Day 14	1430 (989)
M6: 3 Hours Post-Dose on Day 14	1630 (1130)
M6: 6 Hours Post-Dose on Day 14	2090 (1350)
M6: Hour 0 on Day 56	1510 (1080)
M6: 1 Hour Post-Dose on Day 56	1310 (974)
M6: Hour 0 on Day 112	1660 (1130)
M6: 4 Hours Post-Dose on Day 112	1810 (1230)
M6: 6 Hours Post-Dose on Day 112	2130 (1380)
M6: Hour 0 on Day 168	1520 (1130)
M6: 24 Hours Post-Dose on Day 168	632 (465)

4. Secondary Outcome

Title	Part B: Absolute Change From Baseline in Sweat Chloride at Week 24
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 reported as per the dose received and for overall participants.
Time Frame	Part B: Baseline, Week 24

Outcome Measure Data

Analysis Population Description

Part B Safety set included all participants who received at least 1 dose of study drug in part B. Number of participants analyzed is for participants who were evaluable for this outcome measure.

Arm/Group Title	Part B: Ivacaftor 50 mg	Part B: Ivacaftor 75 mg	Part B: Overall Ivacaftor
Arm/Group Description	Ivacaftor 50 mg (for participants weighing <14 kg) q12h for 24 weeks during Part B of the study. Part B included participants from Part A and newly enrolled participants.	Ivacaftor 75 mg (for participants weighing >=14 kg) q12h for 24 weeks during Part B of the study. Part B included participants from Part A and newly enrolled participants.	Ivacaftor 50 mg (for participants weighing <14 kg) or 75 mg (for participants weighing >=14 kg) q12h for 24 weeks during Part B of the study. Part B included participants from Part A and newly enrolled participants.
Measure Participants	7	18	25
Mean (Standard Deviation) [millimole per liter (mmol/L)]	-47.07 (24.256)	-46.78 (27.584)	-46.86 (26.193)

5. Secondary Outcome

Title	Part B: Absolute Change From Baseline in Weight at Week 24
Description	Data was reported as per the dose received and for overall participants.
Time Frame	Part B: Baseline, Week 24

Outcome Measure Data

Analysis Population Description

Part B Safety set included all participants who received at least 1 dose of study drug in part B. Number of participants analyzed is for participants who were evaluable for this outcome measure.

Arm/Group Title	Part B: Ivacaftor 50 mg	Part B: Ivacaftor 75 mg	Part B: Overall Ivacaftor
Arm/Group Description	Ivacaftor 50 mg (for participants weighing <14 kg) q12h for 24 weeks during Part B of the study. Part B included participants from Part A and newly enrolled participants.	Ivacaftor 75 mg (for participants weighing >=14 kg) q12h for 24 weeks during Part B of the study. Part B included participants from Part A and newly enrolled participants.	Ivacaftor 50 mg (for participants weighing <14 kg) or 75 mg (for participants weighing >=14 kg) q12h for 24 weeks during Part B of the study. Part B included participants from Part A and newly enrolled participants.
Measure Participants	9	24	33
Mean (Standard Deviation) [kilograms (kg)]	1.00 (0.418)	1.50 (0.552)	1.36 (0.561)

6. Secondary Outcome

Title	Part B: Absolute Change From Baseline in Stature at Week 24
Description	Stature was measured as height if children could stand unassisted and follow directions; otherwise, stature was measured as length. Data was reported as per the dose received and for overall participants.
Time Frame	Part B: Baseline, Week 24

Outcome Measure Data

Analysis Population Description

Part B Safety set included all participants who received at least 1 dose of study drug in part B. Number of participants analyzed is for participants who were evaluable for this outcome measure.

Arm/Group Title	Part B: Ivacaftor 50 mg	Part B: Ivacaftor 75 mg	Part B: Overall Ivacaftor
Arm/Group Description	Ivacaftor 50 mg (for participants weighing <14 kg) q12h for 24 weeks during Part B of the study. Part B included participants from Part A and newly enrolled participants.	Ivacaftor 75 mg (for participants weighing >=14 kg) q12h for 24 weeks during Part B of the study. Part B included participants from Part A and newly enrolled participants.	Ivacaftor 50 mg (for participants weighing <14 kg) or 75 mg (for participants weighing >=14 kg) q12h for 24 weeks during Part B of the study. Part B included participants from Part A and newly enrolled participants.
Measure Participants	9	23	32
Mean (Standard Deviation) [centimeters (cm)]	2.5 (1.45)	3.5 (0.93)	3.3 (1.17)

7. Primary Outcome

Title	Part A: Plasma Concentration of Ivacaftor and Its Metabolites
Description	Plasma concentration was reported for ivacaftor and its metabolites (hydroxymethyl ivacaftor [M1] and ivacaftor carboxylate [M6]) up to 24 hours post-dose on Day 4 (Hour 0 [pre-dose] on Day 1 and Day 4; 2, 3, 6, 24 hours post-dose on Day 4). Data was planned to be reported for overall participants in the period.
Time Frame	Part A: up to 24 hours post-dose on Day 4

Outcome Measure Data

Analysis Population Description

Part A Safety set included all participants who received at least 1 dose of study drug in part A.

Arm/Group Title	Part A: Overall Ivacaftor
Arm/Group Description	Ivacaftor 50 mg (for participants weighing <14 kg) or 75 mg (for participants weighing >=14 kg) q12h from Day 1 through Day 3 and 1 morning dose on Day 4 during Part A of the study.
Measure Participants	9
Ivacaftor: Hour 0 on Day 1	0.00 (0.00)
Ivacaftor: Hour 0 on Day 4	396 (337)
Ivacaftor: 2 Hours Post-Dose on Day 4	726 (284)
Ivacaftor: 3 Hours Post-Dose on Day 4	957 (283)
Ivacaftor: 6 Hours Post-Dose on Day 4	542 (241)
Ivacaftor: 24 Hours Post-Dose on Day 4	124 (149)
M1: Hour 0 on Day 1	0.00 (0.00)
M1: Hour 0 on Day 4	1240 (723)
M1: 2 Hours Post-Dose on Day 4	1540 (578)
M1: 3 Hours Post-Dose on Day 4	2310 (820)
M1: 6 Hours Post-Dose on Day 4	1580 (622)
M1: 24 Hours Post-Dose on Day 4	389 (336)
M6: Hour 0 on Day 1	0.00 (0.00)
M6: Hour 0 on Day 4	1150 (709)
M6: 2 Hours Post-Dose on Day 4	1050 (606)
M6: 3 Hours Post-Dose on Day 4	1300 (614)
M6: 6 Hours Post-Dose on Day 4	1390 (532)
M6: 24 Hours Post-Dose on Day 4	439 (355)

8. Secondary Outcome

Title	Part B: Absolute Change From Baseline in Body Mass Index (BMI) at Week 24
Description	BMI = (Weight [in kg]) divided by (Stature [in meters])^2. Data was reported as per the dose received and for overall participants.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

Part B Safety set included all participants who received at least 1 dose of study drug in part B. Number of participants analyzed is for participants who were evaluable for this outcome measure.

Arm/Group Title	Part B: Ivacaftor 50 mg	Part B: Ivacaftor 75 mg	Part B: Overall Ivacaftor
Arm/Group Description	Ivacaftor 50 mg (for participants weighing <14 kg) q12h for 24 weeks during Part B of the study. Part B included participants from Part A and newly enrolled participants.	Ivacaftor 75 mg (for participants weighing >=14 kg) q12h for 24 weeks during Part B of the study. Part B included participants from Part A and newly enrolled participants.	Ivacaftor 50 mg (for participants weighing <14 kg) or 75 mg (for participants weighing >=14 kg) q12h for 24 weeks during Part B of the study. Part B included participants from Part A and newly enrolled participants.
Measure Participants	9	23	32
Mean (Standard Deviation) [kilogram per square meter (kg/m^2)]	0.332 (0.5393)	0.314 (0.5492)	0.319 (0.5378)

Adverse Events

Time Frame	Part A: up to 93 days; Part B: up to 28 weeks
Adverse Event Reporting Description	Adverse events were reported separately for each part and as per the dose received and for overall participants in each part.
Arm/Group Title	Part A: Ivacaftor 50 mg		Part A: Ivacaftor 75 mg		Part A: Overall Ivacaftor		Part B: Ivacaftor 50 mg		Part B: Ivacaftor 75 mg		Part B: Overall Ivacaftor
Arm/Group Description	Ivacaftor 50 mg (for participants weighing <14 kg) q12h from Day 1 through Day 3 and 1 morning dose on Day 4 during Part A of the study.		Ivacaftor 75 mg (for participants weighing >=14 kg) q12h from Day 1 through Day 3 and 1 morning dose on Day 4 during Part A of the study.		Ivacaftor 50 mg (for participants weighing <14 kg) or 75 mg (for participants weighing >=14 kg) q12h from Day 1 through Day 3 and 1 morning dose on Day 4 during Part A of the study.		Ivacaftor 50 mg (for participants weighing <14 kg) q12h for 24 weeks during Part B of the study. Part B included participants from Part A and newly enrolled participants.		Ivacaftor 75 mg (for participants weighing >=14 kg) q12h for 24 weeks during Part B of the study. Part B included participants from Part A and newly enrolled participants.		Ivacaftor 50 mg (for participants weighing <14 kg) or 75 mg (for participants weighing >=14 kg) q12h for 24 weeks during Part B of the study. Part B included participants from Part A and newly enrolled participants.
All Cause Mortality
	Part A: Ivacaftor 50 mg		Part A: Ivacaftor 75 mg		Part A: Overall Ivacaftor		Part B: Ivacaftor 50 mg		Part B: Ivacaftor 75 mg		Part B: Overall Ivacaftor
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Part A: Ivacaftor 50 mg		Part A: Ivacaftor 75 mg		Part A: Overall Ivacaftor		Part B: Ivacaftor 50 mg		Part B: Ivacaftor 75 mg		Part B: Overall Ivacaftor
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/4 (0%)		0/5 (0%)		0/9 (0%)		3/10 (30%)		3/24 (12.5%)		6/34 (17.6%)
Gastrointestinal disorders
Vomiting	0/4 (0%)		0/5 (0%)		0/9 (0%)		0/10 (0%)		1/24 (4.2%)		1/34 (2.9%)
Infections and infestations
Infective pulmonary exacerbation of cystic fibrosis	0/4 (0%)		0/5 (0%)		0/9 (0%)		1/10 (10%)		1/24 (4.2%)		2/34 (5.9%)
Device related sepsis	0/4 (0%)		0/5 (0%)		0/9 (0%)		1/10 (10%)		0/24 (0%)		1/34 (2.9%)
Investigations
Pseudomonas test positive	0/4 (0%)		0/5 (0%)		0/9 (0%)		1/10 (10%)		0/24 (0%)		1/34 (2.9%)
Transaminases increased	0/4 (0%)		0/5 (0%)		0/9 (0%)		1/10 (10%)		0/24 (0%)		1/34 (2.9%)
Nervous system disorders
Convulsion	0/4 (0%)		0/5 (0%)		0/9 (0%)		0/10 (0%)		1/24 (4.2%)		1/34 (2.9%)
Other (Not Including Serious) Adverse Events
	Part A: Ivacaftor 50 mg		Part A: Ivacaftor 75 mg		Part A: Overall Ivacaftor		Part B: Ivacaftor 50 mg		Part B: Ivacaftor 75 mg		Part B: Overall Ivacaftor
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/4 (75%)		5/5 (100%)		8/9 (88.9%)		9/10 (90%)		23/24 (95.8%)		32/34 (94.1%)
Blood and lymphatic system disorders
Lymphadenopathy	0/4 (0%)		0/5 (0%)		0/9 (0%)		0/10 (0%)		1/24 (4.2%)		1/34 (2.9%)
Eye disorders
Amblyopia	0/4 (0%)		0/5 (0%)		0/9 (0%)		0/10 (0%)		1/24 (4.2%)		1/34 (2.9%)
Anisometropia	0/4 (0%)		0/5 (0%)		0/9 (0%)		0/10 (0%)		1/24 (4.2%)		1/34 (2.9%)
Eye inflammation	0/4 (0%)		0/5 (0%)		0/9 (0%)		0/10 (0%)		1/24 (4.2%)		1/34 (2.9%)
Gastrointestinal disorders
Vomiting	0/4 (0%)		2/5 (40%)		2/9 (22.2%)		3/10 (30%)		6/24 (25%)		9/34 (26.5%)
Constipation	0/4 (0%)		1/5 (20%)		1/9 (11.1%)		0/10 (0%)		4/24 (16.7%)		4/34 (11.8%)
Abdominal distension	0/4 (0%)		1/5 (20%)		1/9 (11.1%)		1/10 (10%)		0/24 (0%)		1/34 (2.9%)
Abdominal pain	0/4 (0%)		1/5 (20%)		1/9 (11.1%)		0/10 (0%)		1/24 (4.2%)		1/34 (2.9%)
Eructation	0/4 (0%)		0/5 (0%)		0/9 (0%)		0/10 (0%)		1/24 (4.2%)		1/34 (2.9%)
Lip blister	0/4 (0%)		0/5 (0%)		0/9 (0%)		0/10 (0%)		1/24 (4.2%)		1/34 (2.9%)
Nausea	0/4 (0%)		0/5 (0%)		0/9 (0%)		0/10 (0%)		1/24 (4.2%)		1/34 (2.9%)
Oral mucosal erythema	0/4 (0%)		0/5 (0%)		0/9 (0%)		0/10 (0%)		1/24 (4.2%)		1/34 (2.9%)
Retching	0/4 (0%)		0/5 (0%)		0/9 (0%)		0/10 (0%)		1/24 (4.2%)		1/34 (2.9%)
Teething	0/4 (0%)		0/5 (0%)		0/9 (0%)		1/10 (10%)		0/24 (0%)		1/34 (2.9%)
Diarrhoea	0/4 (0%)		1/5 (20%)		1/9 (11.1%)		0/10 (0%)		0/24 (0%)		0/34 (0%)
General disorders
Pyrexia	2/4 (50%)		2/5 (40%)		4/9 (44.4%)		4/10 (40%)		2/24 (8.3%)		6/34 (17.6%)
Application site rash	0/4 (0%)		0/5 (0%)		0/9 (0%)		0/10 (0%)		1/24 (4.2%)		1/34 (2.9%)
Fatigue	0/4 (0%)		1/5 (20%)		1/9 (11.1%)		0/10 (0%)		1/24 (4.2%)		1/34 (2.9%)
Product taste abnormal	0/4 (0%)		1/5 (20%)		1/9 (11.1%)		0/10 (0%)		1/24 (4.2%)		1/34 (2.9%)
Infections and infestations
Upper respiratory tract infection	0/4 (0%)		0/5 (0%)		0/9 (0%)		1/10 (10%)		7/24 (29.2%)		8/34 (23.5%)
Croup infectious	0/4 (0%)		0/5 (0%)		0/9 (0%)		2/10 (20%)		1/24 (4.2%)		3/34 (8.8%)
Infective pulmonary exacerbation of cystic fibrosis	0/4 (0%)		0/5 (0%)		0/9 (0%)		0/10 (0%)		3/24 (12.5%)		3/34 (8.8%)
Otitis media	0/4 (0%)		0/5 (0%)		0/9 (0%)		2/10 (20%)		1/24 (4.2%)		3/34 (8.8%)
Sinusitis	0/4 (0%)		0/5 (0%)		0/9 (0%)		2/10 (20%)		1/24 (4.2%)		3/34 (8.8%)
Gastroentritis	0/4 (0%)		0/5 (0%)		0/9 (0%)		0/10 (0%)		2/24 (8.3%)		2/34 (5.9%)
Rhinitis	0/4 (0%)		0/5 (0%)		0/9 (0%)		0/10 (0%)		2/24 (8.3%)		2/34 (5.9%)
Bacterial disease carrier	0/4 (0%)		0/5 (0%)		0/9 (0%)		0/10 (0%)		1/24 (4.2%)		1/34 (2.9%)
Genital candidiasis	0/4 (0%)		0/5 (0%)		0/9 (0%)		1/10 (10%)		0/24 (0%)		1/34 (2.9%)
Hand-foot-and-mouth disease	0/4 (0%)		0/5 (0%)		0/9 (0%)		0/10 (0%)		1/24 (4.2%)		1/34 (2.9%)
Infectious mononucleosis	0/4 (0%)		0/5 (0%)		0/9 (0%)		1/10 (10%)		0/24 (0%)		1/34 (2.9%)
Lung infection	0/4 (0%)		0/5 (0%)		0/9 (0%)		0/10 (0%)		1/24 (4.2%)		1/34 (2.9%)
Nasopharyngitis	0/4 (0%)		0/5 (0%)		0/9 (0%)		0/10 (0%)		1/24 (4.2%)		1/34 (2.9%)
Pharyngitis	0/4 (0%)		0/5 (0%)		0/9 (0%)		0/10 (0%)		1/24 (4.2%)		1/34 (2.9%)
Pharyngitis streptococcal	0/4 (0%)		0/5 (0%)		0/9 (0%)		1/10 (10%)		0/24 (0%)		1/34 (2.9%)
Respiratory tract infection viral	0/4 (0%)		0/5 (0%)		0/9 (0%)		0/10 (0%)		1/24 (4.2%)		1/34 (2.9%)
Viral rash	0/4 (0%)		0/5 (0%)		0/9 (0%)		1/10 (10%)		0/24 (0%)		1/34 (2.9%)
Viral upper respiratory tract infection	0/4 (0%)		0/5 (0%)		0/9 (0%)		0/10 (0%)		1/24 (4.2%)		1/34 (2.9%)
Bronchitis viral	0/4 (0%)		1/5 (20%)		1/9 (11.1%)		0/10 (0%)		0/24 (0%)		0/34 (0%)
Injury, poisoning and procedural complications
Contusion	0/4 (0%)		0/5 (0%)		0/9 (0%)		0/10 (0%)		2/24 (8.3%)		2/34 (5.9%)
Face injury	0/4 (0%)		0/5 (0%)		0/9 (0%)		0/10 (0%)		1/24 (4.2%)		1/34 (2.9%)
Fall	0/4 (0%)		0/5 (0%)		0/9 (0%)		0/10 (0%)		1/24 (4.2%)		1/34 (2.9%)
Mouth injury	0/4 (0%)		0/5 (0%)		0/9 (0%)		0/10 (0%)		1/24 (4.2%)		1/34 (2.9%)
Open wound	0/4 (0%)		0/5 (0%)		0/9 (0%)		0/10 (0%)		1/24 (4.2%)		1/34 (2.9%)
Traumatic haemorrhage	0/4 (0%)		0/5 (0%)		0/9 (0%)		0/10 (0%)		1/24 (4.2%)		1/34 (2.9%)
Upper limb fracture	0/4 (0%)		0/5 (0%)		0/9 (0%)		0/10 (0%)		1/24 (4.2%)		1/34 (2.9%)
Investigations
Bacterial test positive	0/4 (0%)		0/5 (0%)		0/9 (0%)		0/10 (0%)		3/24 (12.5%)		3/34 (8.8%)
Haemophilus test positive	0/4 (0%)		0/5 (0%)		0/9 (0%)		0/10 (0%)		3/24 (12.5%)		3/34 (8.8%)
Hepatic enzyme increased	0/4 (0%)		0/5 (0%)		0/9 (0%)		2/10 (20%)		0/24 (0%)		2/34 (5.9%)
Activated partial thromboplastin time prolonged	0/4 (0%)		0/5 (0%)		0/9 (0%)		1/10 (10%)		0/24 (0%)		1/34 (2.9%)
Alanine aminotransferase increased	0/4 (0%)		1/5 (20%)		1/9 (11.1%)		0/10 (0%)		1/24 (4.2%)		1/34 (2.9%)
Antibiotic resistant Staphylococcus test positive	0/4 (0%)		0/5 (0%)		0/9 (0%)		1/10 (10%)		0/24 (0%)		1/34 (2.9%)
Aspartate aminotransferase increased	0/4 (0%)		1/5 (20%)		1/9 (11.1%)		0/10 (0%)		1/24 (4.2%)		1/34 (2.9%)
Blood creatine increased	0/4 (0%)		0/5 (0%)		0/9 (0%)		0/10 (0%)		1/24 (4.2%)		1/34 (2.9%)
Blood creatinine increased	0/4 (0%)		0/5 (0%)		0/9 (0%)		0/10 (0%)		1/24 (4.2%)		1/34 (2.9%)
Liver function test abnormal	0/4 (0%)		0/5 (0%)		0/9 (0%)		0/10 (0%)		1/24 (4.2%)		1/34 (2.9%)
Lymphocyte count increased	0/4 (0%)		0/5 (0%)		0/9 (0%)		0/10 (0%)		1/24 (4.2%)		1/34 (2.9%)
Respiratory rate increased	0/4 (0%)		0/5 (0%)		0/9 (0%)		1/10 (10%)		0/24 (0%)		1/34 (2.9%)
Pancreatic enzyme increased	0/4 (0%)		1/5 (20%)		1/9 (11.1%)		0/10 (0%)		0/24 (0%)		0/34 (0%)
Staphylococcus test positive	0/4 (0%)		0/5 (0%)		0/9 (0%)		0/10 (0%)		1/24 (4.2%)		1/34 (2.9%)
White blood cell count increased	0/4 (0%)		0/5 (0%)		0/9 (0%)		0/10 (0%)		1/24 (4.2%)		1/34 (2.9%)
Metabolism and nutrition disorders
Decreased appetite	0/4 (0%)		0/5 (0%)		0/9 (0%)		1/10 (10%)		1/24 (4.2%)		2/34 (5.9%)
Weight gain poor	0/4 (0%)		0/5 (0%)		0/9 (0%)		0/10 (0%)		1/24 (4.2%)		1/34 (2.9%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/4 (0%)		0/5 (0%)		0/9 (0%)		0/10 (0%)		1/24 (4.2%)		1/34 (2.9%)
Pain in extremity	0/4 (0%)		0/5 (0%)		0/9 (0%)		0/10 (0%)		1/24 (4.2%)		1/34 (2.9%)
Nervous system disorders
Headache	0/4 (0%)		1/5 (20%)		1/9 (11.1%)		0/10 (0%)		2/24 (8.3%)		2/34 (5.9%)
Drooling	0/4 (0%)		0/5 (0%)		0/9 (0%)		0/10 (0%)		1/24 (4.2%)		1/34 (2.9%)
Sinus headache	0/4 (0%)		0/5 (0%)		0/9 (0%)		0/10 (0%)		1/24 (4.2%)		1/34 (2.9%)
Renal and urinary disorders
Chromaturia	0/4 (0%)		0/5 (0%)		0/9 (0%)		1/10 (10%)		0/24 (0%)		1/34 (2.9%)
Pollakiuria	0/4 (0%)		0/5 (0%)		0/9 (0%)		0/10 (0%)		1/24 (4.2%)		1/34 (2.9%)
Respiratory, thoracic and mediastinal disorders
Cough	0/4 (0%)		1/5 (20%)		1/9 (11.1%)		4/10 (40%)		15/24 (62.5%)		19/34 (55.9%)
Nasal congestion	0/4 (0%)		0/5 (0%)		0/9 (0%)		4/10 (40%)		5/24 (20.8%)		9/34 (26.5%)
Rhinorrhoea	0/4 (0%)		2/5 (40%)		2/9 (22.2%)		2/10 (20%)		5/24 (20.8%)		7/34 (20.6%)
Productive cough	0/4 (0%)		0/5 (0%)		0/9 (0%)		0/10 (0%)		3/24 (12.5%)		3/34 (8.8%)
Dysponea exertional	0/4 (0%)		0/5 (0%)		0/9 (0%)		1/10 (10%)		0/24 (0%)		1/34 (2.9%)
Epistaxis	0/4 (0%)		0/5 (0%)		0/9 (0%)		0/10 (0%)		1/24 (4.2%)		1/34 (2.9%)
Nasal inflamation	0/4 (0%)		0/5 (0%)		0/9 (0%)		0/10 (0%)		1/24 (4.2%)		1/34 (2.9%)
Oropharyngeal pain	0/4 (0%)		0/5 (0%)		0/9 (0%)		0/10 (0%)		1/24 (4.2%)		1/34 (2.9%)
Snoring	0/4 (0%)		0/5 (0%)		0/9 (0%)		0/10 (0%)		1/24 (4.2%)		1/34 (2.9%)
Tonsillar hypertrophy	0/4 (0%)		0/5 (0%)		0/9 (0%)		1/10 (10%)		0/24 (0%)		1/34 (2.9%)
Upper respiratory track congestion	0/4 (0%)		1/5 (20%)		1/9 (11.1%)		0/10 (0%)		1/24 (4.2%)		1/34 (2.9%)
Skin and subcutaneous tissue disorders
Rash	0/4 (0%)		0/5 (0%)		0/9 (0%)		2/10 (20%)		2/24 (8.3%)		4/34 (11.8%)
Acne	0/4 (0%)		0/5 (0%)		0/9 (0%)		0/10 (0%)		1/24 (4.2%)		1/34 (2.9%)
Dermatitis contact	0/4 (0%)		0/5 (0%)		0/9 (0%)		1/10 (10%)		0/24 (0%)		1/34 (2.9%)
Petechiae	0/4 (0%)		0/5 (0%)		0/9 (0%)		0/10 (0%)		1/24 (4.2%)		1/34 (2.9%)
Skin irritation	0/4 (0%)		0/5 (0%)		0/9 (0%)		1/10 (10%)		0/24 (0%)		1/34 (2.9%)
Urticaria	0/4 (0%)		0/5 (0%)		0/9 (0%)		1/10 (10%)		0/24 (0%)		1/34 (2.9%)
Ecchymosis	0/4 (0%)		2/5 (40%)		2/9 (22.2%)		0/10 (0%)		0/24 (0%)		0/34 (0%)
Rash macular	1/4 (25%)		0/5 (0%)		1/9 (11.1%)		0/10 (0%)		0/24 (0%)		0/34 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.