Trial Outcomes & Findings for Study of the Effect of VX-770 on Hyperpolarized Helium-3 Magnetic Resonance Imaging in Subjects With Cystic Fibrosis and the G551D Mutation (NCT NCT01161537)

Last Updated: 2014-07-31

Results Overview

Subjects inhaled hyperpolarized helium-3 (3He) gas mixed with nitrogen to make a total volume of approximately one-third forced vital capacity (FVC) to a maximum of 1 liter and hold their breath for 20 seconds or less. Rapid magnetic resonance imaging (MRI) was performed during inhalation/exhalation and/or breath-hold. Areas of decreased ventilation were observed as ventilation defects that are visualized as decreased (and/or absent) 3He intensity in 3He-MRI. The total ventilation defect was defined as the ratio of total ventilation defect volume (L) to total lung volume (L), expressed as a percentage. Baseline was defined as the most recent non-missing measurement collected before initial administration of study drug in VX-770 treatment phase (Day 15 to 42).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

13 participants

Primary outcome timeframe

Part A: Baseline (pre-dose Day 15), Day 43

Results posted on

2014-07-31

Participant Flow

Study was initiated on October 10, 2010 after first eligible subject signed informed consent form and enrolled in study.

All results were planned to be reported separately for Part A and Part B of the study.

Participant milestones

Participant milestones
Measure	VX-770 Part A: Subjects received placebo tablets matched to VX-770 150 milligram (mg) orally twice daily from Day 1 to 14 (Placebo run-in period), followed by VX-770 150 mg tablets orally twice daily from Day 15 to 42 (VX-770 treatment period), and then placebo tablets matched to VX-770 150 mg orally twice daily from Day 43 to 57 (Placebo washout period) during Part A of the study. Part B: Subjects received VX-770 150 mg tablets orally twice daily for 48 weeks during Part B of the study. Part B included subjects from Part A and newly enrolled subjects.
Part A STARTED	8
Part A COMPLETED	8
Part A NOT COMPLETED	0
Part B STARTED	9
Part B COMPLETED	7
Part B NOT COMPLETED	2

Reasons for withdrawal

Reasons for withdrawal
Measure	VX-770 Part A: Subjects received placebo tablets matched to VX-770 150 milligram (mg) orally twice daily from Day 1 to 14 (Placebo run-in period), followed by VX-770 150 mg tablets orally twice daily from Day 15 to 42 (VX-770 treatment period), and then placebo tablets matched to VX-770 150 mg orally twice daily from Day 43 to 57 (Placebo washout period) during Part A of the study. Part B: Subjects received VX-770 150 mg tablets orally twice daily for 48 weeks during Part B of the study. Part B included subjects from Part A and newly enrolled subjects.
Part B Withdrawal by Subject	2

Baseline Characteristics

Study of the Effect of VX-770 on Hyperpolarized Helium-3 Magnetic Resonance Imaging in Subjects With Cystic Fibrosis and the G551D Mutation

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	VX-770 n=13 Participants Part A: Subjects received placebo tablets matched to VX-770 150 mg orally twice daily from Day 1 to 14 (Placebo run-in period), followed by VX-770 150 mg tablets orally twice daily from Day 15 to 42 (VX-770 treatment period), and then placebo tablets matched to VX-770 150 mg orally twice daily from Day 43 to 57 (Placebo washout period) during Part A of the study. Part B: Subjects received VX-770 150 mg tablets orally twice daily for 48 weeks during Part B of the study. Part B included subjects from Part A and newly enrolled subjects.
Age, Continuous Part A (n = 8)	18.9 years STANDARD_DEVIATION 4.64 • n=5 Participants
Age, Continuous Part B (n = 9)	24.4 years STANDARD_DEVIATION 10.3 • n=5 Participants
Sex/Gender, Customized Part A: Female (n = 8)	4 participants n=5 Participants
Sex/Gender, Customized Part A: Male (n = 8)	4 participants n=5 Participants
Sex/Gender, Customized Part B: Female (n = 9)	3 participants n=5 Participants
Sex/Gender, Customized Part B: Male (n = 9)	6 participants n=5 Participants
Race/Ethnicity, Customized Part A, Race: White (n = 8)	7 participants n=5 Participants
Race/Ethnicity, Customized Part A, Race: Black or African American (n = 8)	1 participants n=5 Participants
Race/Ethnicity, Customized Part A, Ethnicity: Not Hispanic or Latino (n = 8)	8 participants n=5 Participants
Race/Ethnicity, Customized Part B, Race: White (n = 9)	9 participants n=5 Participants
Race/Ethnicity, Customized Part B, Ethnicity: Not Hispanic or Latino (n = 9)	9 participants n=5 Participants
Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Part A: <70% (n = 8)	2 participants n=5 Participants
Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Part A: >=70%-<90% (n = 8)	1 participants n=5 Participants
Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Part A: >=90% (n = 8)	5 participants n=5 Participants
Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Part B: <70% (n = 9)	6 participants n=5 Participants
Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Part B: >=70%-<90% (n = 9)	1 participants n=5 Participants
Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Part B: >=90% (n = 9)	2 participants n=5 Participants
Body Weight Part A (n = 8)	66.31 kilogram (kg) STANDARD_DEVIATION 14.393 • n=5 Participants
Body Weight Part B (n = 9)	66.53 kilogram (kg) STANDARD_DEVIATION 13.693 • n=5 Participants
Height Part A (n = 8)	167.5 centimeter (cm) STANDARD_DEVIATION 9.66 • n=5 Participants
Height Part B (n = 9)	169.9 centimeter (cm) STANDARD_DEVIATION 11.82 • n=5 Participants
Body Mass Index (BMI) Part A (n = 8)	23.44 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 3.570 • n=5 Participants
Body Mass Index (BMI) Part B (n = 9)	22.96 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 4.066 • n=5 Participants

PRIMARY outcome

Timeframe: Part A: Baseline (pre-dose Day 15), Day 43

Population: FAS for Part A = all enrolled subjects who received at least 1 dose of study drug (VX-770 or placebo) in Part A.

Outcome measures

Outcome measures
Measure	VX-770 n=8 Participants Part A: Subjects received placebo tablets matched to VX-770 150 mg orally twice daily from Day 1 to 14 (Placebo run-in period), followed by VX-770 150 mg tablets orally twice daily from Day 15 to 42 (VX-770 treatment period), and then placebo tablets matched to VX-770 150 mg orally twice daily from Day 43 to 57 (Placebo washout period) during Part A of the study. Part B: Subjects received VX-770 150 mg tablets orally twice daily for 48 weeks during Part B of the study. Part B included subjects from Part A and newly enrolled subjects.	Part A VX-770 Treatment Subjects who received VX-770 150 mg tablets orally twice daily from Day 15 to 42 (VX-770 treatment period), during Part A of the study were assessed between Day 15 to 42 of Part A.
Part A: Change From Baseline in Total Ventilation Defect Defined by Hyperpolarized Helium 3 Magnetic Resonance Imaging (3He-MRI) at Day 43	-8.20 percentage of total lung volume Standard Deviation 9.013	—

PRIMARY outcome

Timeframe: Part B: Baseline (Day -1), Week 48

Population: FAS for Part B = all enrolled subjects who received at least 1 dose of study drug (VX-770) in Part B.

Subjects were asked to inhale hyperpolarized 3 He gas mixed with nitrogen to make a total volume of approximately one-third forced vital capacity (FVC) to a maximum of 1 liter and hold their breath for 20 seconds or less. Rapid MRI was performed during inhalation/exhalation and/or breath-hold. Areas of decreased ventilation were observed as ventilation defects that are visualized as decreased (and/or absent) 3He intensity in 3He MRI. The total ventilation defect was defined as the ratio of total ventilation defect volume (L) to total lung volume (L), expressed as a percentage. Baseline was defined as the most recent non-missing measurement collected before initial administration of study drug in Part B (48 weeks).

Outcome measures

Outcome measures
Measure	VX-770 n=9 Participants Part A: Subjects received placebo tablets matched to VX-770 150 mg orally twice daily from Day 1 to 14 (Placebo run-in period), followed by VX-770 150 mg tablets orally twice daily from Day 15 to 42 (VX-770 treatment period), and then placebo tablets matched to VX-770 150 mg orally twice daily from Day 43 to 57 (Placebo washout period) during Part A of the study. Part B: Subjects received VX-770 150 mg tablets orally twice daily for 48 weeks during Part B of the study. Part B included subjects from Part A and newly enrolled subjects.	Part A VX-770 Treatment Subjects who received VX-770 150 mg tablets orally twice daily from Day 15 to 42 (VX-770 treatment period), during Part A of the study were assessed between Day 15 to 42 of Part A.
Part B: Change From Baseline in Total Ventilation Defect Defined by Hyperpolarized Helium 3 Magnetic Resonance Imaging (3He-MRI) at Week 48	-6.33 percentage of total lung volume Standard Deviation 11.859	—

SECONDARY outcome

Timeframe: Part A: Day 1 up to Day 57

Population: Safety Set for Part A = all enrolled subjects who received at least 1 dose of study drug (VX-770 or placebo) in Part A. Data was reported as per the intervention received (Placebo \[Placebo Run in/Washout\] or VX-770 \[VX-770 Treatment\]).

AE: any adverse change from subject'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.

Outcome measures

Outcome measures
Measure	VX-770 n=8 Participants Part A: Subjects received placebo tablets matched to VX-770 150 mg orally twice daily from Day 1 to 14 (Placebo run-in period), followed by VX-770 150 mg tablets orally twice daily from Day 15 to 42 (VX-770 treatment period), and then placebo tablets matched to VX-770 150 mg orally twice daily from Day 43 to 57 (Placebo washout period) during Part A of the study. Part B: Subjects received VX-770 150 mg tablets orally twice daily for 48 weeks during Part B of the study. Part B included subjects from Part A and newly enrolled subjects.	Part A VX-770 Treatment n=8 Participants Subjects who received VX-770 150 mg tablets orally twice daily from Day 15 to 42 (VX-770 treatment period), during Part A of the study were assessed between Day 15 to 42 of Part A.
Part A: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Related AEs AEs	2 participants	3 participants
Part A: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Related AEs SAEs	0 participants	0 participants
Part A: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Related AEs Related AEs	0 participants	0 participants

SECONDARY outcome

Timeframe: Part A: Baseline (pre-dose Day 15), Day 43

Population: FAS for Part A = all enrolled subjects who received at least 1 dose of study drug (VX-770 or placebo) in Part A.

FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Predicted FEV1 (for age, gender, and height) was calculated using the Knudson method. Baseline was defined as the most recent non-missing measurement collected before initial administration of study drug in VX-770 treatment phase (Day 15 to 42).

Outcome measures

Outcome measures
Measure	VX-770 n=8 Participants Part A: Subjects received placebo tablets matched to VX-770 150 mg orally twice daily from Day 1 to 14 (Placebo run-in period), followed by VX-770 150 mg tablets orally twice daily from Day 15 to 42 (VX-770 treatment period), and then placebo tablets matched to VX-770 150 mg orally twice daily from Day 43 to 57 (Placebo washout period) during Part A of the study. Part B: Subjects received VX-770 150 mg tablets orally twice daily for 48 weeks during Part B of the study. Part B included subjects from Part A and newly enrolled subjects.	Part A VX-770 Treatment Subjects who received VX-770 150 mg tablets orally twice daily from Day 15 to 42 (VX-770 treatment period), during Part A of the study were assessed between Day 15 to 42 of Part A.
Part A: Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Day 43	12.78 percent predicted of FEV1 Standard Deviation 9.203	—

SECONDARY outcome

Timeframe: Part A: Baseline (pre-dose Day 15), Day 43

Population: FAS for Part A = all enrolled subjects who received at least 1 dose of study drug (VX-770 or placebo) in Part A.

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. Baseline was defined as the most recent non-missing measurement collected before initial administration of study drug in VX-770 treatment phase (Day 15 to 42).

Outcome measures

Outcome measures
Measure	VX-770 n=8 Participants Part A: Subjects received placebo tablets matched to VX-770 150 mg orally twice daily from Day 1 to 14 (Placebo run-in period), followed by VX-770 150 mg tablets orally twice daily from Day 15 to 42 (VX-770 treatment period), and then placebo tablets matched to VX-770 150 mg orally twice daily from Day 43 to 57 (Placebo washout period) during Part A of the study. Part B: Subjects received VX-770 150 mg tablets orally twice daily for 48 weeks during Part B of the study. Part B included subjects from Part A and newly enrolled subjects.	Part A VX-770 Treatment Subjects who received VX-770 150 mg tablets orally twice daily from Day 15 to 42 (VX-770 treatment period), during Part A of the study were assessed between Day 15 to 42 of Part A.
Part A: Absolute Change From Baseline in Sweat Chloride at Day 43	-42.31 millimole per liter (mmol/L) Standard Deviation 13.475	—

SECONDARY outcome

Timeframe: Baseline (pre-dose Day 15), Day 43

Population: FAS for Part A = all enrolled subjects who received at least 1 dose of study drug (VX-770 or placebo) in Part A.

The CFQ-R is a validated patient-reported outcome measuring health-related quality of life for subjects with cystic fibrosis. 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 non-missing measurement collected before initial administration of study drug in VX-770 treatment phase (Day 15 to 42).

Outcome measures

Outcome measures
Measure	VX-770 n=8 Participants Part A: Subjects received placebo tablets matched to VX-770 150 mg orally twice daily from Day 1 to 14 (Placebo run-in period), followed by VX-770 150 mg tablets orally twice daily from Day 15 to 42 (VX-770 treatment period), and then placebo tablets matched to VX-770 150 mg orally twice daily from Day 43 to 57 (Placebo washout period) during Part A of the study. Part B: Subjects received VX-770 150 mg tablets orally twice daily for 48 weeks during Part B of the study. Part B included subjects from Part A and newly enrolled subjects.	Part A VX-770 Treatment Subjects who received VX-770 150 mg tablets orally twice daily from Day 15 to 42 (VX-770 treatment period), during Part A of the study were assessed between Day 15 to 42 of Part A.
Part A: Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score At Day 43	-7.64 units on a scale Standard Deviation 27.529	—

SECONDARY outcome

Timeframe: Part B: Day 1 up to Week 48

Population: Safety Set for Part B = all enrolled subjects who received at least 1 dose of study drug (VX-770 or placebo) in Part B.

Outcome measures

Outcome measures
Measure	VX-770 n=9 Participants Part A: Subjects received placebo tablets matched to VX-770 150 mg orally twice daily from Day 1 to 14 (Placebo run-in period), followed by VX-770 150 mg tablets orally twice daily from Day 15 to 42 (VX-770 treatment period), and then placebo tablets matched to VX-770 150 mg orally twice daily from Day 43 to 57 (Placebo washout period) during Part A of the study. Part B: Subjects received VX-770 150 mg tablets orally twice daily for 48 weeks during Part B of the study. Part B included subjects from Part A and newly enrolled subjects.	Part A VX-770 Treatment Subjects who received VX-770 150 mg tablets orally twice daily from Day 15 to 42 (VX-770 treatment period), during Part A of the study were assessed between Day 15 to 42 of Part A.
Part B: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Related AEs AEs	6 participants	—
Part B: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Related AEs SAEs	1 participants	—
Part B: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Related AEs Related AEs	4 participants	—

SECONDARY outcome

Timeframe: Part B: Baseline (Day -1), Week 48

Population: FAS for Part B = all enrolled subjects who received at least 1 dose of study drug (VX-770) in Part B. Here, "Number of participants analyzed" signifies those subjects who were evaluable for this outcome measure.

Outcome measures

Outcome measures
Measure	VX-770 n=8 Participants Part A: Subjects received placebo tablets matched to VX-770 150 mg orally twice daily from Day 1 to 14 (Placebo run-in period), followed by VX-770 150 mg tablets orally twice daily from Day 15 to 42 (VX-770 treatment period), and then placebo tablets matched to VX-770 150 mg orally twice daily from Day 43 to 57 (Placebo washout period) during Part A of the study. Part B: Subjects received VX-770 150 mg tablets orally twice daily for 48 weeks during Part B of the study. Part B included subjects from Part A and newly enrolled subjects.	Part A VX-770 Treatment Subjects who received VX-770 150 mg tablets orally twice daily from Day 15 to 42 (VX-770 treatment period), during Part A of the study were assessed between Day 15 to 42 of Part A.
Part B: Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Week 48	5.17 percent predicted of FEV1 Standard Deviation 9.422	—

SECONDARY outcome

Timeframe: Part B: Baseline (Day -1), Week 48

Outcome measures

Outcome measures
Measure	VX-770 n=8 Participants Part A: Subjects received placebo tablets matched to VX-770 150 mg orally twice daily from Day 1 to 14 (Placebo run-in period), followed by VX-770 150 mg tablets orally twice daily from Day 15 to 42 (VX-770 treatment period), and then placebo tablets matched to VX-770 150 mg orally twice daily from Day 43 to 57 (Placebo washout period) during Part A of the study. Part B: Subjects received VX-770 150 mg tablets orally twice daily for 48 weeks during Part B of the study. Part B included subjects from Part A and newly enrolled subjects.	Part A VX-770 Treatment Subjects who received VX-770 150 mg tablets orally twice daily from Day 15 to 42 (VX-770 treatment period), during Part A of the study were assessed between Day 15 to 42 of Part A.
Part B: Absolute Change From Baseline in Sweat Chloride at Week 48	-48.88 mmol/L Standard Deviation 22.271	—

SECONDARY outcome

Timeframe: Part B: Baseline (Day -1), Week 48

Outcome measures

Outcome measures
Measure	VX-770 n=7 Participants Part A: Subjects received placebo tablets matched to VX-770 150 mg orally twice daily from Day 1 to 14 (Placebo run-in period), followed by VX-770 150 mg tablets orally twice daily from Day 15 to 42 (VX-770 treatment period), and then placebo tablets matched to VX-770 150 mg orally twice daily from Day 43 to 57 (Placebo washout period) during Part A of the study. Part B: Subjects received VX-770 150 mg tablets orally twice daily for 48 weeks during Part B of the study. Part B included subjects from Part A and newly enrolled subjects.	Part A VX-770 Treatment Subjects who received VX-770 150 mg tablets orally twice daily from Day 15 to 42 (VX-770 treatment period), during Part A of the study were assessed between Day 15 to 42 of Part A.
Part B: Absolute Change From Baseline in in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score At Week 48	15.08 units on a scale Standard Deviation 7.667	—

Adverse Events

Part A Placebo Run in/Washout

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Part A VX-770 Treatment

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Part B VX-770 Treatment

Serious events: 1 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Part A Placebo Run in/Washout n=8 participants at risk Subjects who received placebo tablets matched to VX-770 150 mg orally twice daily from Day 1 to 14 (Placebo run-in period) and from Day 43 to 57 (Placebo washout period) during Part A of the study were assessed between Day 1 to 14 and Day 43 to 57 of Part A.	Part A VX-770 Treatment n=8 participants at risk Subjects who received VX-770 150 mg tablets orally twice daily from Day 15 to 42 (VX-770 treatment period), during Part A of the study were assessed between Day 15 to 42 of Part A.	Part B VX-770 Treatment n=9 participants at risk Subjects who received VX-770 150 mg tablets orally twice daily for 48 weeks during Part B of the study were assessed between Day 1 to Week 48 of Part B. Part B included subjects from Part A and newly enrolled subjects.
Infections and infestations INFECTIVE PULMONARY EXACERBATION OF CYSTIC FIBROSIS	0.00% 0/8 • Part A: Day 1 through Day 57; Part B: Day 1 through Week 48 A Participant with multiple events within a system organ class or preferred term was counted only once within the system organ class or preferred term, respectively.	0.00% 0/8 • Part A: Day 1 through Day 57; Part B: Day 1 through Week 48 A Participant with multiple events within a system organ class or preferred term was counted only once within the system organ class or preferred term, respectively.	11.1% 1/9 • Part A: Day 1 through Day 57; Part B: Day 1 through Week 48 A Participant with multiple events within a system organ class or preferred term was counted only once within the system organ class or preferred term, respectively.

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	Part A Placebo Run in/Washout n=8 participants at risk Subjects who received placebo tablets matched to VX-770 150 mg orally twice daily from Day 1 to 14 (Placebo run-in period) and from Day 43 to 57 (Placebo washout period) during Part A of the study were assessed between Day 1 to 14 and Day 43 to 57 of Part A.	Part A VX-770 Treatment n=8 participants at risk Subjects who received VX-770 150 mg tablets orally twice daily from Day 15 to 42 (VX-770 treatment period), during Part A of the study were assessed between Day 15 to 42 of Part A.	Part B VX-770 Treatment n=9 participants at risk Subjects who received VX-770 150 mg tablets orally twice daily for 48 weeks during Part B of the study were assessed between Day 1 to Week 48 of Part B. Part B included subjects from Part A and newly enrolled subjects.
Congenital, familial and genetic disorders CYSTIC FIBROSIS LUNG	0.00% 0/8 • Part A: Day 1 through Day 57; Part B: Day 1 through Week 48 A Participant with multiple events within a system organ class or preferred term was counted only once within the system organ class or preferred term, respectively.	12.5% 1/8 • Part A: Day 1 through Day 57; Part B: Day 1 through Week 48 A Participant with multiple events within a system organ class or preferred term was counted only once within the system organ class or preferred term, respectively.	0.00% 0/9 • Part A: Day 1 through Day 57; Part B: Day 1 through Week 48 A Participant with multiple events within a system organ class or preferred term was counted only once within the system organ class or preferred term, respectively.
Gastrointestinal disorders ABDOMINAL DISTENSION	0.00% 0/8 • Part A: Day 1 through Day 57; Part B: Day 1 through Week 48 A Participant with multiple events within a system organ class or preferred term was counted only once within the system organ class or preferred term, respectively.	12.5% 1/8 • Part A: Day 1 through Day 57; Part B: Day 1 through Week 48 A Participant with multiple events within a system organ class or preferred term was counted only once within the system organ class or preferred term, respectively.	0.00% 0/9 • Part A: Day 1 through Day 57; Part B: Day 1 through Week 48 A Participant with multiple events within a system organ class or preferred term was counted only once within the system organ class or preferred term, respectively.
Gastrointestinal disorders ABDOMINAL PAIN	0.00% 0/8 • Part A: Day 1 through Day 57; Part B: Day 1 through Week 48 A Participant with multiple events within a system organ class or preferred term was counted only once within the system organ class or preferred term, respectively.	0.00% 0/8 • Part A: Day 1 through Day 57; Part B: Day 1 through Week 48 A Participant with multiple events within a system organ class or preferred term was counted only once within the system organ class or preferred term, respectively.	11.1% 1/9 • Part A: Day 1 through Day 57; Part B: Day 1 through Week 48 A Participant with multiple events within a system organ class or preferred term was counted only once within the system organ class or preferred term, respectively.
Gastrointestinal disorders NAUSEA	0.00% 0/8 • Part A: Day 1 through Day 57; Part B: Day 1 through Week 48 A Participant with multiple events within a system organ class or preferred term was counted only once within the system organ class or preferred term, respectively.	0.00% 0/8 • Part A: Day 1 through Day 57; Part B: Day 1 through Week 48 A Participant with multiple events within a system organ class or preferred term was counted only once within the system organ class or preferred term, respectively.	11.1% 1/9 • Part A: Day 1 through Day 57; Part B: Day 1 through Week 48 A Participant with multiple events within a system organ class or preferred term was counted only once within the system organ class or preferred term, respectively.
General disorders PAIN	12.5% 1/8 • Part A: Day 1 through Day 57; Part B: Day 1 through Week 48 A Participant with multiple events within a system organ class or preferred term was counted only once within the system organ class or preferred term, respectively.	0.00% 0/8 • Part A: Day 1 through Day 57; Part B: Day 1 through Week 48 A Participant with multiple events within a system organ class or preferred term was counted only once within the system organ class or preferred term, respectively.	11.1% 1/9 • Part A: Day 1 through Day 57; Part B: Day 1 through Week 48 A Participant with multiple events within a system organ class or preferred term was counted only once within the system organ class or preferred term, respectively.
General disorders PYREXIA	0.00% 0/8 • Part A: Day 1 through Day 57; Part B: Day 1 through Week 48 A Participant with multiple events within a system organ class or preferred term was counted only once within the system organ class or preferred term, respectively.	0.00% 0/8 • Part A: Day 1 through Day 57; Part B: Day 1 through Week 48 A Participant with multiple events within a system organ class or preferred term was counted only once within the system organ class or preferred term, respectively.	22.2% 2/9 • Part A: Day 1 through Day 57; Part B: Day 1 through Week 48 A Participant with multiple events within a system organ class or preferred term was counted only once within the system organ class or preferred term, respectively.
Nervous system disorders HEADACHE	0.00% 0/8 • Part A: Day 1 through Day 57; Part B: Day 1 through Week 48 A Participant with multiple events within a system organ class or preferred term was counted only once within the system organ class or preferred term, respectively.	12.5% 1/8 • Part A: Day 1 through Day 57; Part B: Day 1 through Week 48 A Participant with multiple events within a system organ class or preferred term was counted only once within the system organ class or preferred term, respectively.	11.1% 1/9 • Part A: Day 1 through Day 57; Part B: Day 1 through Week 48 A Participant with multiple events within a system organ class or preferred term was counted only once within the system organ class or preferred term, respectively.
Infections and infestations UPPER RESPIRATORY TRACT INFECTION	0.00% 0/8 • Part A: Day 1 through Day 57; Part B: Day 1 through Week 48 A Participant with multiple events within a system organ class or preferred term was counted only once within the system organ class or preferred term, respectively.	0.00% 0/8 • Part A: Day 1 through Day 57; Part B: Day 1 through Week 48 A Participant with multiple events within a system organ class or preferred term was counted only once within the system organ class or preferred term, respectively.	44.4% 4/9 • Part A: Day 1 through Day 57; Part B: Day 1 through Week 48 A Participant with multiple events within a system organ class or preferred term was counted only once within the system organ class or preferred term, respectively.
Infections and infestations INFECTIVE PULMONARY EXACERBATION OF CYSTIC FIBROSIS	0.00% 0/8 • Part A: Day 1 through Day 57; Part B: Day 1 through Week 48 A Participant with multiple events within a system organ class or preferred term was counted only once within the system organ class or preferred term, respectively.	0.00% 0/8 • Part A: Day 1 through Day 57; Part B: Day 1 through Week 48 A Participant with multiple events within a system organ class or preferred term was counted only once within the system organ class or preferred term, respectively.	22.2% 2/9 • Part A: Day 1 through Day 57; Part B: Day 1 through Week 48 A Participant with multiple events within a system organ class or preferred term was counted only once within the system organ class or preferred term, respectively.
Infections and infestations BRONCHITIS	0.00% 0/8 • Part A: Day 1 through Day 57; Part B: Day 1 through Week 48 A Participant with multiple events within a system organ class or preferred term was counted only once within the system organ class or preferred term, respectively.	0.00% 0/8 • Part A: Day 1 through Day 57; Part B: Day 1 through Week 48 A Participant with multiple events within a system organ class or preferred term was counted only once within the system organ class or preferred term, respectively.	11.1% 1/9 • Part A: Day 1 through Day 57; Part B: Day 1 through Week 48 A Participant with multiple events within a system organ class or preferred term was counted only once within the system organ class or preferred term, respectively.
Infections and infestations LABYRINTHITIS	0.00% 0/8 • Part A: Day 1 through Day 57; Part B: Day 1 through Week 48 A Participant with multiple events within a system organ class or preferred term was counted only once within the system organ class or preferred term, respectively.	0.00% 0/8 • Part A: Day 1 through Day 57; Part B: Day 1 through Week 48 A Participant with multiple events within a system organ class or preferred term was counted only once within the system organ class or preferred term, respectively.	11.1% 1/9 • Part A: Day 1 through Day 57; Part B: Day 1 through Week 48 A Participant with multiple events within a system organ class or preferred term was counted only once within the system organ class or preferred term, respectively.
Infections and infestations NASOPHARYNGITIS	0.00% 0/8 • Part A: Day 1 through Day 57; Part B: Day 1 through Week 48 A Participant with multiple events within a system organ class or preferred term was counted only once within the system organ class or preferred term, respectively.	0.00% 0/8 • Part A: Day 1 through Day 57; Part B: Day 1 through Week 48 A Participant with multiple events within a system organ class or preferred term was counted only once within the system organ class or preferred term, respectively.	11.1% 1/9 • Part A: Day 1 through Day 57; Part B: Day 1 through Week 48 A Participant with multiple events within a system organ class or preferred term was counted only once within the system organ class or preferred term, respectively.
Infections and infestations PHARYNGITIS STREPTOCOCCAL	0.00% 0/8 • Part A: Day 1 through Day 57; Part B: Day 1 through Week 48 A Participant with multiple events within a system organ class or preferred term was counted only once within the system organ class or preferred term, respectively.	0.00% 0/8 • Part A: Day 1 through Day 57; Part B: Day 1 through Week 48 A Participant with multiple events within a system organ class or preferred term was counted only once within the system organ class or preferred term, respectively.	11.1% 1/9 • Part A: Day 1 through Day 57; Part B: Day 1 through Week 48 A Participant with multiple events within a system organ class or preferred term was counted only once within the system organ class or preferred term, respectively.
Infections and infestations VULVOVAGINAL MYCOTIC INFECTION	0.00% 0/8 • Part A: Day 1 through Day 57; Part B: Day 1 through Week 48 A Participant with multiple events within a system organ class or preferred term was counted only once within the system organ class or preferred term, respectively.	0.00% 0/8 • Part A: Day 1 through Day 57; Part B: Day 1 through Week 48 A Participant with multiple events within a system organ class or preferred term was counted only once within the system organ class or preferred term, respectively.	11.1% 1/9 • Part A: Day 1 through Day 57; Part B: Day 1 through Week 48 A Participant with multiple events within a system organ class or preferred term was counted only once within the system organ class or preferred term, respectively.
Investigations BODY MASS INDEX INCREASED	0.00% 0/8 • Part A: Day 1 through Day 57; Part B: Day 1 through Week 48 A Participant with multiple events within a system organ class or preferred term was counted only once within the system organ class or preferred term, respectively.	0.00% 0/8 • Part A: Day 1 through Day 57; Part B: Day 1 through Week 48 A Participant with multiple events within a system organ class or preferred term was counted only once within the system organ class or preferred term, respectively.	22.2% 2/9 • Part A: Day 1 through Day 57; Part B: Day 1 through Week 48 A Participant with multiple events within a system organ class or preferred term was counted only once within the system organ class or preferred term, respectively.
Investigations SPIROMETRY ABNORMAL	0.00% 0/8 • Part A: Day 1 through Day 57; Part B: Day 1 through Week 48 A Participant with multiple events within a system organ class or preferred term was counted only once within the system organ class or preferred term, respectively.	0.00% 0/8 • Part A: Day 1 through Day 57; Part B: Day 1 through Week 48 A Participant with multiple events within a system organ class or preferred term was counted only once within the system organ class or preferred term, respectively.	22.2% 2/9 • Part A: Day 1 through Day 57; Part B: Day 1 through Week 48 A Participant with multiple events within a system organ class or preferred term was counted only once within the system organ class or preferred term, respectively.
Investigations BACTERIAL TEST POSITIVE	0.00% 0/8 • Part A: Day 1 through Day 57; Part B: Day 1 through Week 48 A Participant with multiple events within a system organ class or preferred term was counted only once within the system organ class or preferred term, respectively.	0.00% 0/8 • Part A: Day 1 through Day 57; Part B: Day 1 through Week 48 A Participant with multiple events within a system organ class or preferred term was counted only once within the system organ class or preferred term, respectively.	11.1% 1/9 • Part A: Day 1 through Day 57; Part B: Day 1 through Week 48 A Participant with multiple events within a system organ class or preferred term was counted only once within the system organ class or preferred term, respectively.
Ear and labyrinth disorders CERUMEN IMPACTION	0.00% 0/8 • Part A: Day 1 through Day 57; Part B: Day 1 through Week 48 A Participant with multiple events within a system organ class or preferred term was counted only once within the system organ class or preferred term, respectively.	0.00% 0/8 • Part A: Day 1 through Day 57; Part B: Day 1 through Week 48 A Participant with multiple events within a system organ class or preferred term was counted only once within the system organ class or preferred term, respectively.	11.1% 1/9 • Part A: Day 1 through Day 57; Part B: Day 1 through Week 48 A Participant with multiple events within a system organ class or preferred term was counted only once within the system organ class or preferred term, respectively.
Injury, poisoning and procedural complications STRESS FRACTURE	0.00% 0/8 • Part A: Day 1 through Day 57; Part B: Day 1 through Week 48 A Participant with multiple events within a system organ class or preferred term was counted only once within the system organ class or preferred term, respectively.	0.00% 0/8 • Part A: Day 1 through Day 57; Part B: Day 1 through Week 48 A Participant with multiple events within a system organ class or preferred term was counted only once within the system organ class or preferred term, respectively.	11.1% 1/9 • Part A: Day 1 through Day 57; Part B: Day 1 through Week 48 A Participant with multiple events within a system organ class or preferred term was counted only once within the system organ class or preferred term, respectively.
Musculoskeletal and connective tissue disorders TENDONITIS	0.00% 0/8 • Part A: Day 1 through Day 57; Part B: Day 1 through Week 48 A Participant with multiple events within a system organ class or preferred term was counted only once within the system organ class or preferred term, respectively.	0.00% 0/8 • Part A: Day 1 through Day 57; Part B: Day 1 through Week 48 A Participant with multiple events within a system organ class or preferred term was counted only once within the system organ class or preferred term, respectively.	11.1% 1/9 • Part A: Day 1 through Day 57; Part B: Day 1 through Week 48 A Participant with multiple events within a system organ class or preferred term was counted only once within the system organ class or preferred term, respectively.
Respiratory, thoracic and mediastinal disorders COUGH	0.00% 0/8 • Part A: Day 1 through Day 57; Part B: Day 1 through Week 48 A Participant with multiple events within a system organ class or preferred term was counted only once within the system organ class or preferred term, respectively.	0.00% 0/8 • Part A: Day 1 through Day 57; Part B: Day 1 through Week 48 A Participant with multiple events within a system organ class or preferred term was counted only once within the system organ class or preferred term, respectively.	11.1% 1/9 • Part A: Day 1 through Day 57; Part B: Day 1 through Week 48 A Participant with multiple events within a system organ class or preferred term was counted only once within the system organ class or preferred term, respectively.
Skin and subcutaneous tissue disorders RASH	0.00% 0/8 • Part A: Day 1 through Day 57; Part B: Day 1 through Week 48 A Participant with multiple events within a system organ class or preferred term was counted only once within the system organ class or preferred term, respectively.	0.00% 0/8 • Part A: Day 1 through Day 57; Part B: Day 1 through Week 48 A Participant with multiple events within a system organ class or preferred term was counted only once within the system organ class or preferred term, respectively.	11.1% 1/9 • Part A: Day 1 through Day 57; Part B: Day 1 through Week 48 A Participant with multiple events within a system organ class or preferred term was counted only once within the system organ class or preferred term, respectively.
Respiratory, thoracic and mediastinal disorders DRY THROAT	12.5% 1/8 • Part A: Day 1 through Day 57; Part B: Day 1 through Week 48 A Participant with multiple events within a system organ class or preferred term was counted only once within the system organ class or preferred term, respectively.	0.00% 0/8 • Part A: Day 1 through Day 57; Part B: Day 1 through Week 48 A Participant with multiple events within a system organ class or preferred term was counted only once within the system organ class or preferred term, respectively.	0.00% 0/9 • Part A: Day 1 through Day 57; Part B: Day 1 through Week 48 A Participant with multiple events within a system organ class or preferred term was counted only once within the system organ class or preferred term, respectively.
Respiratory, thoracic and mediastinal disorders OROPHARYNGEAL PAIN	12.5% 1/8 • Part A: Day 1 through Day 57; Part B: Day 1 through Week 48 A Participant with multiple events within a system organ class or preferred term was counted only once within the system organ class or preferred term, respectively.	0.00% 0/8 • Part A: Day 1 through Day 57; Part B: Day 1 through Week 48 A Participant with multiple events within a system organ class or preferred term was counted only once within the system organ class or preferred term, respectively.	0.00% 0/9 • Part A: Day 1 through Day 57; Part B: Day 1 through Week 48 A Participant with multiple events within a system organ class or preferred term was counted only once within the system organ class or preferred term, respectively.