CLEAN-PCD: Clearing Lungs With ENaC Inhibition in Primary Ciliary Dyskinesia

• Sponsor: Parion Sciences (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02871778
• Collaborator: Vertex Pharmaceuticals Incorporated (Industry)
• Enrollment: 123
• Locations: 34
• Arms: 8
• Actual Duration (Months): 27.6
• Patients Per Site: 3.6
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

To evaluate the safety and efficacy of treatment with VX-371 with and without ivacaftor, and the effect of VX-371 with and without ivacaftor on quality of life (QOL) in subjects with primary ciliary dyskinesia (PCD).

Condition or Disease	Intervention/Treatment	Phase
Primary Ciliary Dyskinesia	Drug: VX-371; Drug: Hypertonic Saline; Drug: Placebo (0.17% saline); Drug: VX-371 + HS; Drug: Ivacaftor	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 123 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 2a, 2-part,Randomized, Double-blind, Placebo-controlled, Incomplete Block Crossover Study to Evaluate the Safety and Efficacy of VX-371 Solution for Inhalation With and Without Oral Ivacaftor in Subjects With Primary Ciliary Dyskinesia
• Actual Study Start Date: Aug 1, 2016
• Actual Primary Completion Date: Nov 20, 2018
• Actual Study Completion Date: Nov 20, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part A: VX-371 in Hypertonic Saline (HS), Then HS Participants received 85 microgram (mcg) VX-371 diluted in 3 milliliter (mL) 4.2 percent (%) HS twice daily through oral nebulized inhalation from Day 1 through Day 29 in treatment period 1 followed by a 28 day washout period (from Day 29 through Day 56) and then received 3 mL 4.2% HS through oral nebulized inhalation twice daily for 28 days (from Day 57 through Day 85) in treatment period 2.	Drug: Hypertonic Saline; Drug: VX-371 + HS
Experimental: Part A: HS, Then VX-371 in HS Participants received 3 mL 4.2% HS through oral nebulized inhalation twice daily from Day 1 through Day 29 in treatment period 1 followed by a 28 day washout period (from Day 29 through Day 56) and then received 85 mcg VX-371 diluted in 3 mL 4.2% HS through oral nebulized inhalation twice daily for 28 days (from Day 57 through Day 85) in treatment period 2.	Drug: Hypertonic Saline; Drug: VX-371 + HS
Experimental: Part A: VX-371, Then Placebo Participants received 85 mcg VX-371 diluted in 3 mL 0.17% Saline (placebo) through oral nebulized inhalation twice daily from Day 1 through Day 29 in treatment period 1 followed by a 28 day washout period (from Day 29 through Day 56) and then received 3 mL 0.17% saline (placebo) through oral nebulized inhalation twice daily for 28 days (from Day 57 through Day 85) in treatment period 2.	Drug: VX-371; Drug: Placebo (0.17% saline)
Experimental: Part A: Placebo, Then VX-371 Participants received 3 mL 0.17% saline (placebo) through oral nebulized inhalation twice daily from Day 1 through Day 29 in treatment period 1 followed by a 28 day washout period (from Day 29 through Day 56) and then received 85 mcg VX-371 diluted in 3 mL 0.17% saline (placebo) through oral nebulized inhalation twice daily for 28 days (from Day 57 through Day 85) in treatment period 2.	Drug: VX-371; Drug: Placebo (0.17% saline)
Experimental: Part B: VX-371 in HS + Ivacaftor Participants who were on 85 mcg VX-371 diluted in 3 mL 4.2% HS through oral nebulized inhalation twice daily for 28 days (from Day 57 through Day 85) in treatment period 2 continued their inhaled study drug regimen from Treatment Period 2 and also received ivacaftor 150 mg tablet twice daily for 28 days (from Day 85 through Day 113) in treatment period 3.	Drug: VX-371 + HS; Drug: Ivacaftor
Experimental: Part B: HS + Ivacaftor Participants who were on 3 mL 4.2% HS through oral nebulized inhalation twice daily for 28 days (from Day 57 through Day 85) in treatment period 2 continued their inhaled study drug regimen from Treatment Period 2 and also received ivacaftor 150 mg tablet twice daily for 28 days (from Day 85 through Day 113) in treatment period 3.	Drug: Hypertonic Saline; Drug: Ivacaftor
Experimental: Part B: VX-371 + Ivacaftor Participants who were on 85 mcg VX-371 diluted in 3 mL 0.17% saline (placebo) through oral nebulized inhalation twice daily for 28 days (from Day 57 through Day 85) in treatment period 2 continued their inhaled study drug regimen from Treatment Period 2 and also received ivacaftor 150 mg tablet twice daily for 28 days (from Day 85 through Day 113) in treatment period 3.	Drug: VX-371; Drug: Ivacaftor
Placebo Comparator: Part B: Placebo + Ivacaftor Participants who were on 3 mL 0.17% saline (placebo) through oral nebulized inhalation twice daily for 28 days (from Day 57 through Day 85) in treatment period 2 continued their inhaled study drug regimen from Treatment Period 2 and also received ivacaftor 150 mg tablet twice daily for 28 days (from Day 85 through Day 113) in treatment period 3.	Drug: Placebo (0.17% saline); Drug: Ivacaftor

Outcome Measures

Primary Outcome Measures

1. Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs [Part A: From first dose of study drug up 84 days]

   An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. AEs included abnormal clinically significant findings for spirometry, clinical laboratory parameters, standard 12-lead electrocardiograms (ECGs), vital signs and pulse oximetry examinations. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug and up to 84 days that were absent before treatment or that worsened relative to pretreatment state. TEAEs included both serious and non-serious TEAEs.

2. Part B: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs [Part B: Day 85 up to 28 days after last dose of study drug (56 days)]

   An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. AEs included abnormal clinically significant findings for spirometry, clinical laboratory parameters, standard 12-lead electrocardiograms (ECGs), vital signs and pulse oximetry examinations. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug and up to up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. TEAEs included both serious and non-serious TEAEs.

3. Part A: Absolute Change From Study Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Day 29 [Part A: Study Baseline, Day 29 of each treatment period]

   FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. The study baseline is defined as the most recent non-missing measurement (scheduled or unscheduled) collected before the first dose of study drug in the study.

4. Part B: Absolute Change From Study Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Day 29 [Study Baseline, Day 29 of Part B]

   FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. The study baseline is defined as the most recent non-missing measurement (scheduled or unscheduled) collected before the first dose of study drug in the study.

5. Part B: Absolute Change From Part B Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Day 29 [Part B Baseline, Day 29 of Part B]

   FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Part B baseline was defined as the most recent non-missing measurement (scheduled or unscheduled) collected before the first dose of ivacaftor in Part B and after the last dose in Period 2.

Secondary Outcome Measures

1. Part A: Change From Study Baseline in Quality of Life-Primary Ciliary Dyskinesia (QOL-PCD) (Adult Version) Lower Respiratory Symptoms Domain Score at Day 29 [Study Baseline, Day 29 of Part A]

   QOL- PCD adult version has following 10 domains: lower respiratory symptoms, emotional functioning, treatment burden, role, social functioning, vitality, health perception, upper respiratory symptoms, physical functioning and hearing symptoms. The total numbers of items in the lower respiratory symptoms domain are 6 in the questionnaire for adults. All items are scored using a 4-point Likert scale. Scaled score calculated as: [Sum of scores - (n*1)] / [(n*4) - (n*1)]*100. Where 'n' is the number of questions in domain. The total score range is from 0-100, where higher score indicates greater improvement. Change from study baseline >0 indicated improvement. The study baseline is defined as the most recent non-missing measurement (scheduled or unscheduled) collected before the first dose of study drug in the study.

2. Part B: Change From Study Baseline in Quality of Life-Primary Ciliary Dyskinesia (QOL-PCD) (Adult Version) Lower Respiratory Symptoms Domain Score at Day 29 [Study Baseline, Day 29 of Part B]

   QOL- PCD adult version has following 10 domains: lower respiratory symptoms, emotional functioning, treatment burden, role, social functioning, vitality, health perception, upper respiratory symptoms, physical functioning and hearing symptoms. The total numbers of items in the lower respiratory symptoms domain are 6 in the questionnaire for adults. All items are scored using a 4-point Likert scale. Scaled score calculated as: [Sum of scores - (n*1)] / [(n*4) - (n*1)]*100. Where 'n' is the number of questions in domain. The total score range is from 0-100, where higher score indicates greater improvement. Change from study baseline >0 indicated improvement. The study baseline is defined as the most recent non-missing measurement (scheduled or unscheduled) collected before the first dose of study drug in the study.

3. Part B: Change From Part B Baseline in Quality of Life-Primary Ciliary Dyskinesia (QOL-PCD) (Adult Version) Lower Respiratory Symptoms Domain Score at Day 29 [Part B Baseline, Day 29 of Part B]

   QOL- PCD adult version has following 10 domains: lower respiratory symptoms, emotional functioning, treatment burden, role, social functioning, vitality, health perception, upper respiratory symptoms, physical functioning and hearing symptoms. The total numbers of items in the lower respiratory symptoms domain are 6 in the questionnaire for adults. All items are scored using a 4-point Likert scale. Scaled score calculated as: [Sum of scores - (n*1)] / [(n*4) - (n*1)]*100. Where 'n' is the number of questions in domain. The total score range is from 0-100, where higher score indicates greater improvement. Change from Part B baseline >0 indicated improvement. Part B baseline was defined as the most recent non-missing measurement (scheduled or unscheduled) collected before the first dose of ivacaftor in Part B and after the last dose in Period 2.

4. Part A: Change From Study Baseline in St. George's Respiratory Questionnaire (SGRQ) Total Score for Participants Aged Greater Than or Equals to (>=) 16 Years at Day 29 [Study Baseline, Day 29 of Part A]

   SGRQ measured health-related quality of life among participants with respiratory diseases. It is a 40 items questionnaire grouped into three domains (Symptoms, Activity, and Impacts). Total scores range from 0 to 100. Higher score reflected worse quality of life. The study baseline is defined as the most recent non-missing measurement (scheduled or unscheduled) collected before the first dose of study drug in the study.

5. Part B: Change From Study Baseline in St. George's Respiratory Questionnaire (SGRQ) Total Score for Participants Aged >=16 Years at Day 29 [Study Baseline, Day 29 of Part B]

   SGRQ measured health-related quality of life among participants with respiratory diseases. It is a 40 items questionnaire grouped into three domains (Symptoms, Activity, and Impacts). Total scores range from 0 to 100. Higher score reflected worse quality of life. The study baseline is defined as the most recent non-missing measurement (scheduled or unscheduled) collected before the first dose of study drug in the study.

6. Part B: Change From Part B Baseline in St. George's Respiratory Questionnaire (SGRQ) Total Score for Participants Aged >=16 Years at Day 29 [Part B Baseline, Day 29 of Part B]

   SGRQ measured health-related quality of life among participants with respiratory diseases. It is a 40 items questionnaire grouped into three domains (Symptoms, Activity, and Impacts). Total scores range from 0 to 100. Higher score reflected worse quality of life. Part B baseline was defined as the most recent non-missing measurement (scheduled or unscheduled) collected before the first dose of ivacaftor in Part B and after the last dose in Period 2.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• The subject must have evidence supportive of a PCD diagnosis.

• Subjects with percent predicted FEV1 of ≥40 to <90 percentage points

• Non-smoker for at least 90 days prior to the Screening Visit and less than a 5 pack-year lifetime history of smoking

• Stable regimen of medications and chest physiotherapy for the 28 days prior to Day 1

• If currently using daily inhaled HS, must be able to discontinue its use for the duration of the study.

• If taking daily chronic or chronic cycling antibiotics, has been on a consistent regimen for at least 4 months prior to the Screening Visit.

• Clinically stable (as deemed by the investigator) for at least 14 days prior to the Screening Visit

• Female subjects of childbearing potential must have a negative serum pregnancy test at the Screening Visit. Subjects of childbearing potential and who are sexually active must meet the contraception requirements.

Exclusion Criteria:

• Diagnosis of CF based on results of sweat chloride or nasal potential difference (NPD) tests or presence of 2 CF-causing mutations in CFTR gene.

• History of any organ transplantation or lung resection or chest wall surgery.

• Significant congenital heart defects, other than a laterality defect, at the discretion of the investigator

• Diagnosis of Cri du chat syndrome (chromosome 5p deletion syndrome).

• Inability to withhold short-acting bronchodilator use for 4 hours prior to clinic visit and long-acting bronchodilator use the night before the first and last clinic visit of each treatment period.

• Use of diuretics (including amiloride) or renin-angiotensin antihypertensive drugs

• Symptoms of acute upper or lower respiratory tract infection, acute pulmonary exacerbation, or treatment or was treated with systemic antibiotics for ear or sinus disease within 28 days before Day 1 (topical otic antibiotics allowed).

• History of significant intolerance to inhaled HS

• Pregnant and/or nursing females

• Any clinically significant laboratory abnormalities

• History of chronic B. cepacia complex or M. abscessus or M. avium

• Surgery that required general anesthesia and hospitalization within 3 months of Day 1

Additional Exclusion Criteria for Part B:

• In addition to the exclusion criteria above, subjects who participate in Part B and meet any of the following exclusion criteria will not be eligible to continue into Part B

• Unable to swallow tablets.

• Concomitant use of strong or moderate inhibitors or inducers of cytochrome P450 (CYP) 3A, including consumption of certain herbal medications (e.g., St. John's Wort), and grapefruit/grapefruit juice.

• Known hypersensitivity to ivacaftor.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Birmingham	Alabama	United States
2		Palo Alto	California	United States
3		Aurora	Colorado	United States
4		Washington	District of Columbia	United States
5		Miami	Florida	United States
6		Tampa	Florida	United States
7		Chicago	Illinois	United States
8		Indianapolis	Indiana	United States
9		Iowa City	Iowa	United States
10		Kansas City	Kansas	United States
11		Boston	Massachusetts	United States
12		Ann Arbor	Michigan	United States
13		Minneapolis	Minnesota	United States
14		Kansas City	Missouri	United States
15		Saint Louis	Missouri	United States
16		New York	New York	United States
17		Chapel Hill	North Carolina	United States
18		Cleveland	Ohio	United States
19		Philadelphia	Pennsylvania	United States
20		Columbia	South Carolina	United States
21		Seattle	Washington	United States
22		Toronto	Ontario	Canada
23		Montreal	Quebec	Canada
24		Copenhagen		Denmark
25		Munster	North Rhine-Westphalia	Germany
26		Hannover		Germany
27		Heidelberg		Germany
28		Pisa		Italy
29		Amsterdam		Netherlands
30		Rotterdam		Netherlands
31		Rabka-Zdroj		Poland
32		Cambridge		United Kingdom
33		London		United Kingdom
34		Southampton		United Kingdom

Sponsors and Collaborators

• Parion Sciences
• Vertex Pharmaceuticals Incorporated

Investigators

• Study Chair: Karl Donn, Parion Sciences

Study Documents (Full-Text)

• Study Protocol - Oct 31, 2016
• Statistical Analysis Plan - Jul 24, 2018

More Information

Publications

None provided.

• Responsible Party: Parion Sciences
• ClinicalTrials.gov Identifier: NCT02871778
• Other Study ID Numbers: PS-G202; 2015-004917-26
• First Posted: Aug 18, 2016
• Last Update Posted: Dec 16, 2021
• Last Verified: Nov 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Ciliary Motility Disorders; Dyskinesias; Ivacaftor

Study Results

Participant Flow

Pre-assignment Detail	This study consisted of Part A and Part B. Total of 123 participants were randomized to 1 of 4 sequences in Part A to receive study drug.

Arm/Group Title	Part A: VX-371 in Hypertonic Saline (HS), Then HS	Part A: HS, Then VX-371 in HS	Part A: VX-371, Then Placebo	Part A: Placebo, Then VX-371	Part B: VX-371 in HS + Ivacaftor	Part B: HS + Ivacaftor	Part B: VX-371 + Ivacaftor	Part B: Placebo + Ivacaftor
Arm/Group Description	Participants received 85 microgram (mcg) VX-371 diluted in 3 milliliter (mL) 4.2 percent (%) HS twice daily through oral nebulized inhalation from Day 1 through Day 29 in treatment period 1 followed by a 28 day washout period (from Day 29 through Day 56) and then received 3 mL 4.2% HS through oral nebulized inhalation twice daily for 28 days (from Day 57 through Day 85) in treatment period 2.	Participants received 3 mL 4.2% HS through oral nebulized inhalation twice daily from Day 1 through Day 29 in treatment period 1 followed by a 28 day washout period (from Day 29 through Day 56) and then received 85 mcg VX-371 diluted in 3 mL 4.2% HS through oral nebulized inhalation twice daily for 28 days (from Day 57 through Day 85) in treatment period 2.	Participants received 85 mcg VX-371 diluted in 3 mL 0.17% Saline (placebo) through oral nebulized inhalation twice daily from Day 1 through Day 29 in treatment period 1 followed by a 28 day washout period (from Day 29 through Day 56) and then received 3 mL 0.17% saline (placebo) through oral nebulized inhalation twice daily for 28 days (from Day 57 through Day 85) in treatment period 2.	Participants received 3 mL 0.17% saline (placebo) through oral nebulized inhalation twice daily from Day 1 through Day 29 in treatment period 1 followed by a 28 day washout period (from Day 29 through Day 56) and then received 85 mcg VX-371 diluted in 3 mL 0.17% saline (placebo) through oral nebulized inhalation twice daily for 28 days (from Day 57 through Day 85) in treatment period 2.	Participants who were on 85 mcg VX-371 diluted in 3 mL 4.2% HS through oral nebulized inhalation twice daily for 28 days (from Day 57 through Day 85) in treatment period 2 continued their inhaled study drug regimen from Treatment Period 2 and also received ivacaftor 150 mg tablet twice daily for 28 days (from Day 85 through Day 113) in treatment period 3.	Participants who were on 3 mL 4.2% HS through oral nebulized inhalation twice daily for 28 days (from Day 57 through Day 85) in treatment period 2 continued their inhaled study drug regimen from Treatment Period 2 and also received ivacaftor 150 mg tablet twice daily for 28 days (from Day 85 through Day 113) in treatment period 3.	Participants who were on 85 mcg VX-371 diluted in 3 mL 0.17% saline (placebo) through oral nebulized inhalation twice daily for 28 days (from Day 57 through Day 85) in treatment period 2 continued their inhaled study drug regimen from Treatment Period 2 and also received ivacaftor 150 mg tablet twice daily for 28 days (from Day 85 through Day 113) in treatment period 3.	Participants who were on 3 mL 0.17% saline (placebo) through oral nebulized inhalation twice daily for 28 days (from Day 57 through Day 85) in treatment period 2 continued their inhaled study drug regimen from Treatment Period 2 and also received ivacaftor 150 mg tablet twice daily for 28 days (from Day 85 through Day 113) in treatment period 3.
Period Title: Part A: Treatment Period 1
STARTED	43	41	21	18	0	0	0	0
Safety Analysis Set	44	40	21	18	0	0	0	0
COMPLETED	40	37	18	16	0	0	0	0
NOT COMPLETED	3	4	3	2	0	0	0	0
Period Title: Part A: Treatment Period 1
STARTED	40	37	18	16	0	0	0	0
Safety Analysis Set	40	37	18	16	0	0	0	0
COMPLETED	37	35	17	15	0	0	0	0
NOT COMPLETED	3	2	1	1	0	0	0	0
Period Title: Part A: Treatment Period 1
STARTED	0	0	0	0	11	27	7	12
Safety Analysis Set	0	0	0	0	11	27	7	12
COMPLETED	0	0	0	0	10	26	6	12
NOT COMPLETED	0	0	0	0	1	1	1	0

Baseline Characteristics

Arm/Group Title	Part A: VX-371 in HS, Then HS	Part A: HS, Then VX-371 in HS	Part A: VX-371, Then Placebo	Part A: Placebo, Then VX-371	Total
Arm/Group Description	Participants received 85 mcg VX-371 diluted in 3 mL 4.2% HS twice daily through oral nebulized inhalation from Day 1 through Day 29 in treatment period 1 followed by a 28 day washout period (from Day 29 through Day 56) and then received 3 mL 4.2% HS through oral nebulized inhalation twice daily for 28 days (from Day 57 through Day 85) in treatment period 2.	Participants received 3 mL 4.2% HS through oral nebulized inhalation twice daily from Day 1 through Day 29 in treatment period 1 followed by a 28 day washout period (from Day 29 through Day 56) and then received 85 mcg VX-371 diluted in 3 mL 4.2% HS through oral nebulized inhalation twice daily for 28 days (from Day 57 through Day 85) in treatment period 2.	Participants received 85 mcg VX-371 diluted in 3 mL 0.17% Saline (placebo) through oral nebulized inhalation twice daily from Day 1 through Day 29 in treatment period 1 followed by a 28 day washout period (from Day 29 through Day 56) and then received 3 mL 0.17% saline (placebo) through oral nebulized inhalation twice daily for 28 days (from Day 57 through Day 85) in treatment period 2.	Participants received 3 mL 0.17% saline (placebo) through oral nebulized inhalation twice daily from Day 1 through Day 29 in treatment period 1 followed by a 28 day washout period (from Day 29 through Day 56) and then received 85 mcg VX-371 diluted in 3 mL 0.17% saline (placebo) through oral nebulized inhalation twice daily for 28 days (from Day 57 through Day 85) in treatment period 2.	Total of all reporting groups
Overall Participants	43	41	21	18	123
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	29.19 (10.861)	27.98 (13.104)	27.62 (16.633)	24.33 (12.866)	27.80 (12.954)
Sex: Female, Male (Count of Participants)
Female	29 67.4%	24 58.5%	15 71.4%	10 55.6%	78 63.4%
Male	14 32.6%	17 41.5%	6 28.6%	8 44.4%	45 36.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 4.7%	3 7.3%	2 9.5%	0 0%	7 5.7%
Not Hispanic or Latino	41 95.3%	37 90.2%	18 85.7%	18 100%	114 92.7%
Unknown or Not Reported	0 0%	1 2.4%	1 4.8%	0 0%	2 1.6%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	1 2.3%	3 7.3%	1 4.8%	3 16.7%	8 6.5%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	2 4.7%	1 2.4%	1 4.8%	1 5.6%	5 4.1%
White	39 90.7%	36 87.8%	17 81%	14 77.8%	106 86.2%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	1 2.3%	1 2.4%	2 9.5%	0 0%	4 3.3%

Outcome Measures

1. Primary Outcome

Title	Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs
Description	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. AEs included abnormal clinically significant findings for spirometry, clinical laboratory parameters, standard 12-lead electrocardiograms (ECGs), vital signs and pulse oximetry examinations. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug and up to 84 days that were absent before treatment or that worsened relative to pretreatment state. TEAEs included both serious and non-serious TEAEs.
Time Frame	Part A: From first dose of study drug up 84 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: VX-371 in HS	Part A: HS	Part A: VX-371	Part A: Placebo
Arm/Group Description	Participants received 85 mcg VX-371 diluted in 3 mL 4.2% HS through oral nebulized inhalation twice daily for 28 days in either treatment period 1 or 2.	Participants received 3 mL 4.2% HS through oral nebulized inhalation twice daily for 28 days in either treatment period 1 or 2.	Participants received 85 mcg VX-371 diluted in 3 mL 0.17% Saline (placebo) through oral nebulized inhalation twice daily for 28 days in either treatment period 1 or 2.	Participants received 3 mL 0.17% saline (placebo) through oral nebulized inhalation twice daily for 28 days in either treatment period 1 or 2.
Measure Participants	81	80	37	36
Participants with TEAEs	52 120.9%	46 112.2%	22 104.8%	23 127.8%
Participants with Serious TEAEs	1 2.3%	1 2.4%	1 4.8%	1 5.6%

2. Primary Outcome

Title	Part B: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs
Description	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. AEs included abnormal clinically significant findings for spirometry, clinical laboratory parameters, standard 12-lead electrocardiograms (ECGs), vital signs and pulse oximetry examinations. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug and up to up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. TEAEs included both serious and non-serious TEAEs.
Time Frame	Part B: Day 85 up to 28 days after last dose of study drug (56 days)

Outcome Measure Data

Analysis Population Description

Part B safety set included all participants who received at least 1 dose of ivacaftor in Part B.

Arm/Group Title	Part B: VX-371 in HS + IVA	Part B: HS + IVA	Part B: VX-371 + IVA	Part B: Placebo + IVA
Arm/Group Description	Participants who received 85 mcg VX-371 diluted in 3 mL 4.2% HS through oral nebulized inhalation twice daily for 28 days (from Day 57 to Day 85) in treatment period 2, continued their inhaled study drug regimen from Treatment Period 2 and also received ivacaftor 150 mg tablet twice daily for 28 days (from Day 85 to Day 113) in treatment period 3 (Part B).	Participants who received 3 mL 4.2% HS through oral nebulized inhalation twice daily for 28 days (from Day 57 to Day 85) in treatment period 2 continued their inhaled study drug regimen from Treatment Period 2 and also received ivacaftor 150 mg tablet twice daily for 28 days (from Day 85 to Day 113) in treatment period 3 (Part B).	Participants who received 85 mcg VX-371 diluted in 3 mL 0.17% saline (placebo) through oral nebulized inhalation twice daily for 28 days (from Day 57 to Day 85) in treatment period 2, continued their inhaled study drug regimen from Treatment Period 2 and also received ivacaftor 150 mg tablet twice daily for 28 days (from Day 85 to Day 113) in treatment period 3 (Part B).	Participants who received 3 mL 0.17% saline (placebo) through oral nebulized inhalation twice daily for 28 days (from Day 57 to Day 85) in treatment period 2, continued their inhaled study drug regimen from Treatment Period 2 and also received ivacaftor 150 mg tablet twice daily for 28 days (from Day 85 to Day 113) in treatment period 3 (Part B).
Measure Participants	11	27	7	12
Participants with TEAEs	5 11.6%	17 41.5%	5 23.8%	9 50%
Participants with Serious TEAEs	0 0%	0 0%	1 4.8%	0 0%

3. Primary Outcome

Title	Part A: Absolute Change From Study Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Day 29
Description	FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. The study baseline is defined as the most recent non-missing measurement (scheduled or unscheduled) collected before the first dose of study drug in the study.
Time Frame	Part A: Study Baseline, Day 29 of each treatment period

Outcome Measure Data

Analysis Population Description

Part A FAS included all randomized participants who received at least 1 dose of study drug in Part A and had a confirmed diagnosis of PCD. Here, "overall number of participants analyzed" signifies participants evaluable for this outcome measure.

Arm/Group Title	Part A: VX-371 in HS	Part A: HS	Part A: VX-371	Part A: Placebo
Arm/Group Description	Participants received 85 mcg VX-371 diluted in 3 mL 4.2% HS through oral nebulized inhalation twice daily for 28 days in either treatment period 1 or 2.	Participants received 3 mL 4.2% HS through oral nebulized inhalation twice daily for 28 days in either treatment period 1 or 2.	Participants received 85 mcg VX-371 diluted in 3 mL 0.17% Saline (placebo) through oral nebulized inhalation twice daily for 28 days in either treatment period 1 or 2.	Participants received 3 mL 0.17% saline (placebo) through oral nebulized inhalation twice daily for 28 days in either treatment period 1 or 2.
Measure Participants	78	75	34	34
Least Squares Mean (Standard Error) [Percentage of predicted FEV1]	0.989 (0.7097)	-0.531 (0.7202)	-0.491 (1.0736)	-1.329 (1.0730)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part A: VX-371 in HS, Part A: HS
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0437
	Comments
	Method	Mixed-effects Model
	Comments
Method of Estimation	Estimation Parameter	Least Square (LS) Mean difference
	Estimated Value	1.519
	Confidence Interval	(2-Sided) 95%; 0.044 to 2.995
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Part A: HS, Part A: VX-371
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9755
	Comments
	Method	Mixed-effects Model
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference
	Estimated Value	0.040
	Confidence Interval	(2-Sided) 95%; -2.509 to 2.589
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Part A: VX-371 in HS, Part A: Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0731
	Comments
	Method	Mixed-effects Model
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference
	Estimated Value	2.318
	Confidence Interval	(2-Sided) 95%; -0.22 to 4.856
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Part A: HS, Part A: Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5373
	Comments
	Method	Mixed-effects Model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.799
	Confidence Interval	(2-Sided) 95%; -1.751 to 3.348
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Part A: VX-371, Part A: Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.453
	Comments
	Method	Mixed-effects Model
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference
	Estimated Value	0.838
	Confidence Interval	(2-Sided) 95%; -1.368 to 3.045
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Primary Outcome

Title	Part B: Absolute Change From Study Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Day 29
Description	FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. The study baseline is defined as the most recent non-missing measurement (scheduled or unscheduled) collected before the first dose of study drug in the study.
Time Frame	Study Baseline, Day 29 of Part B

Outcome Measure Data

Analysis Population Description

Part B FAS included all participants who had a confirmed diagnosis of PCD and received at least 1 dose of ivacaftor in Part B. Here, "overall number of participants analyzed" signifies participants evaluable for this outcome measure.

Arm/Group Title	Part B: VX-371 in HS + Ivacaftor	Part B: HS + Ivacaftor	Part B: VX-371 + Ivacaftor	Part B: Placebo + Ivacaftor
Arm/Group Description	Participants who received 85 mcg VX-371 diluted in 3 mL 4.2% HS through oral nebulized inhalation twice daily for 28 days (from Day 57 to Day 85) in treatment period 2, continued their inhaled study drug regimen from Treatment Period 2 and also received ivacaftor 150 mg tablet twice daily for 28 days (from Day 85 to Day 113) in treatment period 3 (Part B).	Participants who received 3 mL 4.2% HS through oral nebulized inhalation twice daily for 28 days (from Day 57 to Day 85) in treatment period 2 continued their inhaled study drug regimen from Treatment Period 2 and also received ivacaftor 150 mg tablet twice daily for 28 days (from Day 85 to Day 113) in treatment period 3 (Part B).	Participants who received 85 mcg VX-371 diluted in 3 mL 0.17% saline (placebo) through oral nebulized inhalation twice daily for 28 days (from Day 57 to Day 85) in treatment period 2, continued their inhaled study drug regimen from Treatment Period 2 and also received ivacaftor 150 mg tablet twice daily for 28 days (from Day 85 to Day 113) in treatment period 3 (Part B).	Participants who received 3 mL 0.17% saline (placebo) through oral nebulized inhalation twice daily for 28 days (from Day 57 to Day 85) in treatment period 2, continued their inhaled study drug regimen from Treatment Period 2 and also received ivacaftor 150 mg tablet twice daily for 28 days (from Day 85 to Day 113) in treatment period 3 (Part B).
Measure Participants	10	26	6	12
Least Squares Mean (Standard Error) [Percentage of predicted FEV1]	4.721 (1.9314)	1.722 (1.1976)	-0.592 (2.5011)	-0.965 (1.8388)

5. Primary Outcome

Title	Part B: Absolute Change From Part B Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Day 29
Description	FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Part B baseline was defined as the most recent non-missing measurement (scheduled or unscheduled) collected before the first dose of ivacaftor in Part B and after the last dose in Period 2.
Time Frame	Part B Baseline, Day 29 of Part B

Outcome Measure Data

Analysis Population Description

Part B FAS included all participants who had a confirmed diagnosis of PCD and received at least 1 dose of ivacaftor in Part B. Here, "overall number of participants analyzed" signifies participants evaluable for this outcome measure.

Arm/Group Title	Part B: VX-371 in HS + Ivacaftor	Part B: HS + Ivacaftor	Part B: VX-371 + Ivacaftor	Part B: Placebo + Ivacaftor
Arm/Group Description	Participants who received 85 mcg VX-371 diluted in 3 mL 4.2% HS through oral nebulized inhalation twice daily for 28 days (from Day 57 to Day 85) in treatment period 2, continued their inhaled study drug regimen from Treatment Period 2 and also received ivacaftor 150 mg tablet twice daily for 28 days (from Day 85 to Day 113) in treatment period 3 (Part B).	Participants who received 3 mL 4.2% HS through oral nebulized inhalation twice daily for 28 days (from Day 57 to Day 85) in treatment period 2 continued their inhaled study drug regimen from Treatment Period 2 and also received ivacaftor 150 mg tablet twice daily for 28 days (from Day 85 to Day 113) in treatment period 3 (Part B).	Participants who received 85 mcg VX-371 diluted in 3 mL 0.17% saline (placebo) through oral nebulized inhalation twice daily for 28 days (from Day 57 to Day 85) in treatment period 2, continued their inhaled study drug regimen from Treatment Period 2 and also received ivacaftor 150 mg tablet twice daily for 28 days (from Day 85 to Day 113) in treatment period 3 (Part B).	Participants who received 3 mL 0.17% saline (placebo) through oral nebulized inhalation twice daily for 28 days (from Day 57 to Day 85) in treatment period 2, continued their inhaled study drug regimen from Treatment Period 2 and also received ivacaftor 150 mg tablet twice daily for 28 days (from Day 85 to Day 113) in treatment period 3 (Part B).
Measure Participants	10	26	6	12
Least Squares Mean (Standard Error) [Percentage of predicted FEV1]	2.528 (1.8633)	1.678 (1.1414)	-1.018 (2.3797)	-2.040 (1.7427)

6. Secondary Outcome

Title	Part A: Change From Study Baseline in Quality of Life-Primary Ciliary Dyskinesia (QOL-PCD) (Adult Version) Lower Respiratory Symptoms Domain Score at Day 29
Description	QOL- PCD adult version has following 10 domains: lower respiratory symptoms, emotional functioning, treatment burden, role, social functioning, vitality, health perception, upper respiratory symptoms, physical functioning and hearing symptoms. The total numbers of items in the lower respiratory symptoms domain are 6 in the questionnaire for adults. All items are scored using a 4-point Likert scale. Scaled score calculated as: [Sum of scores - (n*1)] / [(n*4) - (n*1)]*100. Where 'n' is the number of questions in domain. The total score range is from 0-100, where higher score indicates greater improvement. Change from study baseline >0 indicated improvement. The study baseline is defined as the most recent non-missing measurement (scheduled or unscheduled) collected before the first dose of study drug in the study.
Time Frame	Study Baseline, Day 29 of Part A

Outcome Measure Data

Analysis Population Description

Part A FAS included all randomized participants who received at least 1 dose of study drug in Part A and had a confirmed diagnosis of PCD. Here, "overall number of participants analyzed" signifies adult participants evaluable for this outcome measure.

Arm/Group Title	Part A: VX-371 in HS	Part A: HS	Part A: VX-371	Part A: Placebo
Arm/Group Description	Participants received 85 mcg VX-371 diluted in 3 mL 4.2% HS through oral nebulized inhalation twice daily for 28 days in either treatment period 1 or 2.	Participants received 3 mL 4.2% HS through oral nebulized inhalation twice daily for 28 days in either treatment period 1 or 2.	Participants received 85 mcg VX-371 diluted in 3 mL 0.17% Saline (placebo) through oral nebulized inhalation twice daily for 28 days in either treatment period 1 or 2.	Participants received 3 mL 0.17% saline (placebo) through oral nebulized inhalation twice daily for 28 days in either treatment period 1 or 2.
Measure Participants	46	45	17	15
Mean (Standard Deviation) [score on a scale]	4.23 (18.076)	3.58 (16.715)	0.98 (12.915)	7.04 (16.728)

7. Secondary Outcome

Title	Part B: Change From Study Baseline in Quality of Life-Primary Ciliary Dyskinesia (QOL-PCD) (Adult Version) Lower Respiratory Symptoms Domain Score at Day 29
Description	QOL- PCD adult version has following 10 domains: lower respiratory symptoms, emotional functioning, treatment burden, role, social functioning, vitality, health perception, upper respiratory symptoms, physical functioning and hearing symptoms. The total numbers of items in the lower respiratory symptoms domain are 6 in the questionnaire for adults. All items are scored using a 4-point Likert scale. Scaled score calculated as: [Sum of scores - (n*1)] / [(n*4) - (n*1)]*100. Where 'n' is the number of questions in domain. The total score range is from 0-100, where higher score indicates greater improvement. Change from study baseline >0 indicated improvement. The study baseline is defined as the most recent non-missing measurement (scheduled or unscheduled) collected before the first dose of study drug in the study.
Time Frame	Study Baseline, Day 29 of Part B

Outcome Measure Data

Analysis Population Description

Part B FAS included all participants who had a confirmed diagnosis of PCD and received at least 1 dose of ivacaftor in Part B. Here, "overall number of participants analyzed" signifies adult participants evaluable for this outcome measure.

Arm/Group Title	Part B: VX-371 in HS + Ivacaftor	Part B: HS + Ivacaftor	Part B: VX-371 + Ivacaftor	Part B: Placebo + Ivacaftor
Arm/Group Description	Participants who received 85 mcg VX-371 diluted in 3 mL 4.2% HS through oral nebulized inhalation twice daily for 28 days (from Day 57 to Day 85) in treatment period 2, continued their inhaled study drug regimen from Treatment Period 2 and also received ivacaftor 150 mg tablet twice daily for 28 days (from Day 85 to Day 113) in treatment period 3 (Part B).	Participants who received 3 mL 4.2% HS through oral nebulized inhalation twice daily for 28 days (from Day 57 to Day 85) in treatment period 2 continued their inhaled study drug regimen from Treatment Period 2 and also received ivacaftor 150 mg tablet twice daily for 28 days (from Day 85 to Day 113) in treatment period 3 (Part B).	Participants who received 85 mcg VX-371 diluted in 3 mL 0.17% saline (placebo) through oral nebulized inhalation twice daily for 28 days (from Day 57 to Day 85) in treatment period 2, continued their inhaled study drug regimen from Treatment Period 2 and also received ivacaftor 150 mg tablet twice daily for 28 days (from Day 85 to Day 113) in treatment period 3 (Part B).	Participants who received 3 mL 0.17% saline (placebo) through oral nebulized inhalation twice daily for 28 days (from Day 57 to Day 85) in treatment period 2, continued their inhaled study drug regimen from Treatment Period 2 and also received ivacaftor 150 mg tablet twice daily for 28 days (from Day 85 to Day 113) in treatment period 3 (Part B).
Measure Participants	6	16	3	6
Mean (Standard Deviation) [score on a scale]	16.67 (14.487)	1.39 (17.153)	7.41 (3.208)	-5.56 (23.307)

8. Secondary Outcome

Title	Part B: Change From Part B Baseline in Quality of Life-Primary Ciliary Dyskinesia (QOL-PCD) (Adult Version) Lower Respiratory Symptoms Domain Score at Day 29
Description	QOL- PCD adult version has following 10 domains: lower respiratory symptoms, emotional functioning, treatment burden, role, social functioning, vitality, health perception, upper respiratory symptoms, physical functioning and hearing symptoms. The total numbers of items in the lower respiratory symptoms domain are 6 in the questionnaire for adults. All items are scored using a 4-point Likert scale. Scaled score calculated as: [Sum of scores - (n*1)] / [(n*4) - (n*1)]*100. Where 'n' is the number of questions in domain. The total score range is from 0-100, where higher score indicates greater improvement. Change from Part B baseline >0 indicated improvement. Part B baseline was defined as the most recent non-missing measurement (scheduled or unscheduled) collected before the first dose of ivacaftor in Part B and after the last dose in Period 2.
Time Frame	Part B Baseline, Day 29 of Part B

Outcome Measure Data

Analysis Population Description

Part B FAS included all participants who had a confirmed diagnosis of PCD and received at least 1 dose of ivacaftor in Part B. Here, "overall number of participants analyzed" signifies adult participants evaluable for this outcome measure.

Arm/Group Title	Part B: VX-371 in HS + Ivacaftor	Part B: HS + Ivacaftor	Part B: VX-371 + Ivacaftor	Part B: Placebo + Ivacaftor
Arm/Group Description	Participants who received 85 mcg VX-371 diluted in 3 mL 4.2% HS through oral nebulized inhalation twice daily for 28 days (from Day 57 to Day 85) in treatment period 2, continued their inhaled study drug regimen from Treatment Period 2 and also received ivacaftor 150 mg tablet twice daily for 28 days (from Day 85 to Day 113) in treatment period 3 (Part B).	Participants who received 3 mL 4.2% HS through oral nebulized inhalation twice daily for 28 days (from Day 57 to Day 85) in treatment period 2 continued their inhaled study drug regimen from Treatment Period 2 and also received ivacaftor 150 mg tablet twice daily for 28 days (from Day 85 to Day 113) in treatment period 3 (Part B).	Participants who received 85 mcg VX-371 diluted in 3 mL 0.17% saline (placebo) through oral nebulized inhalation twice daily for 28 days (from Day 57 to Day 85) in treatment period 2, continued their inhaled study drug regimen from Treatment Period 2 and also received ivacaftor 150 mg tablet twice daily for 28 days (from Day 85 to Day 113) in treatment period 3 (Part B).	Participants who received 3 mL 0.17% saline (placebo) through oral nebulized inhalation twice daily for 28 days (from Day 57 to Day 85) in treatment period 2, continued their inhaled study drug regimen from Treatment Period 2 and also received ivacaftor 150 mg tablet twice daily for 28 days (from Day 85 to Day 113) in treatment period 3 (Part B).
Measure Participants	6	16	3	6
Mean (Standard Deviation) [score on a scale]	11.11 (15.713)	1.39 (19.928)	5.56 (16.667)	-7.41 (10.344)

9. Secondary Outcome

Title	Part A: Change From Study Baseline in St. George's Respiratory Questionnaire (SGRQ) Total Score for Participants Aged Greater Than or Equals to (>=) 16 Years at Day 29
Description	SGRQ measured health-related quality of life among participants with respiratory diseases. It is a 40 items questionnaire grouped into three domains (Symptoms, Activity, and Impacts). Total scores range from 0 to 100. Higher score reflected worse quality of life. The study baseline is defined as the most recent non-missing measurement (scheduled or unscheduled) collected before the first dose of study drug in the study.
Time Frame	Study Baseline, Day 29 of Part A

Outcome Measure Data

Analysis Population Description

Part A FAS included all randomized participants who received at least 1 dose of study drug in Part A and had a confirmed diagnosis of PCD. Here, "overall number of participants analyzed" signifies participants >=16 years of age evaluable for this outcome measure.

Arm/Group Title	Part A: VX-371 in HS	Part A: HS	Part A: VX-371	Part A: Placebo
Arm/Group Description	Participants received 85 mcg VX-371 diluted in 3 mL 4.2% HS through oral nebulized inhalation twice daily for 28 days in either treatment period 1 or 2.	Participants received 3 mL 4.2% HS through oral nebulized inhalation twice daily for 28 days in either treatment period 1 or 2.	Participants received 85 mcg VX-371 diluted in 3 mL 0.17% Saline (placebo) through oral nebulized inhalation twice daily for 28 days in either treatment period 1 or 2.	Participants received 3 mL 0.17% saline (placebo) through oral nebulized inhalation twice daily for 28 days in either treatment period 1 or 2.
Measure Participants	63	62	28	25
Mean (Standard Deviation) [score on a scale]	-1.28 (8.452)	-2.17 (6.462)	1.54 (8.576)	-1.52 (9.082)

10. Secondary Outcome

Title	Part B: Change From Study Baseline in St. George's Respiratory Questionnaire (SGRQ) Total Score for Participants Aged >=16 Years at Day 29
Description	SGRQ measured health-related quality of life among participants with respiratory diseases. It is a 40 items questionnaire grouped into three domains (Symptoms, Activity, and Impacts). Total scores range from 0 to 100. Higher score reflected worse quality of life. The study baseline is defined as the most recent non-missing measurement (scheduled or unscheduled) collected before the first dose of study drug in the study.
Time Frame	Study Baseline, Day 29 of Part B

Outcome Measure Data

Analysis Population Description

Part B FAS included all participants who had a confirmed diagnosis of PCD and received at least 1 dose of ivacaftor in Part B. Here, "overall number of participants analyzed" signifies participants >=16 years of age evaluable for this outcome measure.

Arm/Group Title	Part B: VX-371 in HS + Ivacaftor	Part B: HS + Ivacaftor	Part B: VX-371 + Ivacaftor	Part B: Placebo + Ivacaftor
Arm/Group Description	Participants who received 85 mcg VX-371 diluted in 3 mL 4.2% HS through oral nebulized inhalation twice daily for 28 days (from Day 57 to Day 85) in treatment period 2, continued their inhaled study drug regimen from Treatment Period 2 and also received ivacaftor 150 mg tablet twice daily for 28 days (from Day 85 to Day 113) in treatment period 3 (Part B).	Participants who received 3 mL 4.2% HS through oral nebulized inhalation twice daily for 28 days (from Day 57 to Day 85) in treatment period 2 continued their inhaled study drug regimen from Treatment Period 2 and also received ivacaftor 150 mg tablet twice daily for 28 days (from Day 85 to Day 113) in treatment period 3 (Part B).	Participants who received 85 mcg VX-371 diluted in 3 mL 0.17% saline (placebo) through oral nebulized inhalation twice daily for 28 days (from Day 57 to Day 85) in treatment period 2, continued their inhaled study drug regimen from Treatment Period 2 and also received ivacaftor 150 mg tablet twice daily for 28 days (from Day 85 to Day 113) in treatment period 3 (Part B).	Participants who received 3 mL 0.17% saline (placebo) through oral nebulized inhalation twice daily for 28 days (from Day 57 to Day 85) in treatment period 2, continued their inhaled study drug regimen from Treatment Period 2 and also received ivacaftor 150 mg tablet twice daily for 28 days (from Day 85 to Day 113) in treatment period 3 (Part B).
Measure Participants	6	25	5	8
Mean (Standard Deviation) [score on a scale]	-1.69 (7.442)	-6.87 (6.571)	0.78 (5.879)	4.52 (16.995)

11. Secondary Outcome

Title	Part B: Change From Part B Baseline in St. George's Respiratory Questionnaire (SGRQ) Total Score for Participants Aged >=16 Years at Day 29
Description	SGRQ measured health-related quality of life among participants with respiratory diseases. It is a 40 items questionnaire grouped into three domains (Symptoms, Activity, and Impacts). Total scores range from 0 to 100. Higher score reflected worse quality of life. Part B baseline was defined as the most recent non-missing measurement (scheduled or unscheduled) collected before the first dose of ivacaftor in Part B and after the last dose in Period 2.
Time Frame	Part B Baseline, Day 29 of Part B

Outcome Measure Data

Analysis Population Description

Part B FAS included all participants who had a confirmed diagnosis of PCD and received at least 1 dose of ivacaftor in Part B. Here, "overall number of participants analyzed" signifies participants >=16 years of age evaluable for this outcome measure.

Arm/Group Title	Part B: VX-371 in HS + Ivacaftor	Part B: HS + Ivacaftor	Part B: VX-371 + Ivacaftor	Part B: Placebo + Ivacaftor
Arm/Group Description	Participants who received 85 mcg VX-371 diluted in 3 mL 4.2% HS through oral nebulized inhalation twice daily for 28 days (from Day 57 to Day 85) in treatment period 2, continued their inhaled study drug regimen from Treatment Period 2 and also received ivacaftor 150 mg tablet twice daily for 28 days (from Day 85 to Day 113) in treatment period 3 (Part B).	Participants who received 3 mL 4.2% HS through oral nebulized inhalation twice daily for 28 days (from Day 57 to Day 85) in treatment period 2 continued their inhaled study drug regimen from Treatment Period 2 and also received ivacaftor 150 mg tablet twice daily for 28 days (from Day 85 to Day 113) in treatment period 3 (Part B).	Participants who received 85 mcg VX-371 diluted in 3 mL 0.17% saline (placebo) through oral nebulized inhalation twice daily for 28 days (from Day 57 to Day 85) in treatment period 2, continued their inhaled study drug regimen from Treatment Period 2 and also received ivacaftor 150 mg tablet twice daily for 28 days (from Day 85 to Day 113) in treatment period 3 (Part B).	Participants who received 3 mL 0.17% saline (placebo) through oral nebulized inhalation twice daily for 28 days (from Day 57 to Day 85) in treatment period 2, continued their inhaled study drug regimen from Treatment Period 2 and also received ivacaftor 150 mg tablet twice daily for 28 days (from Day 85 to Day 113) in treatment period 3 (Part B).
Measure Participants	6	25	5	8
Mean (Standard Deviation) [score on a scale]	-3.90 (4.331)	-2.64 (6.575)	0.97 (7.561)	3.19 (11.649)

Adverse Events

Time Frame	Part A: From first dose of study drug up to 84 days; Part B: Day 85 up to 28 days after last dose of study drug (56 days)
Adverse Event Reporting Description	Part A safety set included all participants who received at least 1 dose of study drug in Part A. Part B safety set included all participants who received at least 1 dose of ivacaftor in Part B.
Arm/Group Title	Part A: VX-371 in HS		Part A: HS		Part A: VX-371		Part A: Placebo		Part B: VX-371 in HS + Ivacaftor		Part B: HS + Ivacaftor		Part B: VX-371 + Ivacaftor		Part B: Placebo + Ivacaftor
Arm/Group Description	Participants received 85 mcg VX-371 diluted in 3 mL 4.2% HS through oral nebulized inhalation twice daily for 28 days in either treatment period 1 or 2.		Participants received 3 mL 4.2% HS through oral nebulized inhalation twice daily for 28 days in either treatment period 1 or 2.		Participants received 85 mcg VX-371 diluted in 3 mL 0.17% Saline (placebo) through oral nebulized inhalation twice daily for 28 days in either treatment period 1 or 2.		Participants received 3 mL 0.17% saline (placebo) through oral nebulized inhalation twice daily for 28 days in either treatment period 1 or 2.		Participants who were on 85 mcg VX-371 diluted in 3 mL 4.2% HS through oral nebulized inhalation twice daily for 28 days (from Day 57 through Day 85) in treatment period 2 continued their inhaled study drug regimen from Treatment Period 2 and also received ivacaftor 150 mg tablet twice daily for 28 days (from Day 85 through Day 113) in treatment period 3.		Participants who were on 3 mL 4.2% HS through oral nebulized inhalation twice daily for 28 days (from Day 57 through Day 85) in treatment period 2 continued their inhaled study drug regimen from Treatment Period 2 and also received ivacaftor 150 mg tablet twice daily for 28 days (from Day 85 through Day 113) in treatment period 3.		Participants who were on 85 mcg VX-371 diluted in 3 mL 0.17% saline (placebo) through oral nebulized inhalation twice daily for 28 days (from Day 57 through Day 85) in treatment period 2 continued their inhaled study drug regimen from Treatment Period 2 and also received ivacaftor 150 mg tablet twice daily for 28 days (from Day 85 through Day 113) in treatment period 3.		Participants who were on 3 mL 0.17% saline (placebo) through oral nebulized inhalation twice daily for 28 days (from Day 57 through Day 85) in treatment period 2 continued their inhaled study drug regimen from Treatment Period 2 and also received ivacaftor 150 mg tablet twice daily for 28 days (from Day 85 through Day 113) in treatment period 3.
All Cause Mortality
	Part A: VX-371 in HS		Part A: HS		Part A: VX-371		Part A: Placebo		Part B: VX-371 in HS + Ivacaftor		Part B: HS + Ivacaftor		Part B: VX-371 + Ivacaftor		Part B: Placebo + 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	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/81 (0%)		0/80 (0%)		0/37 (0%)		0/36 (0%)		0/11 (0%)		0/27 (0%)		0/7 (0%)		0/12 (0%)
Serious Adverse Events
	Part A: VX-371 in HS		Part A: HS		Part A: VX-371		Part A: Placebo		Part B: VX-371 in HS + Ivacaftor		Part B: HS + Ivacaftor		Part B: VX-371 + Ivacaftor		Part B: Placebo + 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	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/81 (1.2%)		1/80 (1.3%)		1/37 (2.7%)		1/36 (2.8%)		0/11 (0%)		0/27 (0%)		1/7 (14.3%)		0/12 (0%)
Infections and infestations
Pneumonia	0/81 (0%)		0/80 (0%)		0/37 (0%)		0/36 (0%)		0/11 (0%)		0/27 (0%)		1/7 (14.3%)		0/12 (0%)
Respiratory, thoracic and mediastinal disorders
Bronchiectasis	1/81 (1.2%)		0/80 (0%)		0/37 (0%)		0/36 (0%)		0/11 (0%)		0/27 (0%)		0/7 (0%)		0/12 (0%)
Haemoptysis	0/81 (0%)		0/80 (0%)		0/37 (0%)		1/36 (2.8%)		0/11 (0%)		0/27 (0%)		0/7 (0%)		0/12 (0%)
Lung disorder	0/81 (0%)		1/80 (1.3%)		1/37 (2.7%)		0/36 (0%)		0/11 (0%)		0/27 (0%)		0/7 (0%)		0/12 (0%)
Other (Not Including Serious) Adverse Events
	Part A: VX-371 in HS		Part A: HS		Part A: VX-371		Part A: Placebo		Part B: VX-371 in HS + Ivacaftor		Part B: HS + Ivacaftor		Part B: VX-371 + Ivacaftor		Part B: Placebo + 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	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	40/81 (49.4%)		27/80 (33.8%)		12/37 (32.4%)		16/36 (44.4%)		5/11 (45.5%)		15/27 (55.6%)		4/7 (57.1%)		9/12 (75%)
Ear and labyrinth disorders
Ear pain	0/81 (0%)		0/80 (0%)		0/37 (0%)		0/36 (0%)		0/11 (0%)		0/27 (0%)		0/7 (0%)		1/12 (8.3%)
Eye disorders
Eye pruritus	0/81 (0%)		0/80 (0%)		0/37 (0%)		0/36 (0%)		0/11 (0%)		0/27 (0%)		1/7 (14.3%)		0/12 (0%)
Vision blurred	0/81 (0%)		0/80 (0%)		0/37 (0%)		0/36 (0%)		0/11 (0%)		0/27 (0%)		1/7 (14.3%)		0/12 (0%)
Gastrointestinal disorders
Abdominal pain upper	0/81 (0%)		0/80 (0%)		1/37 (2.7%)		2/36 (5.6%)		0/11 (0%)		1/27 (3.7%)		0/7 (0%)		0/12 (0%)
Diarrhoea	0/81 (0%)		0/80 (0%)		0/37 (0%)		0/36 (0%)		0/11 (0%)		5/27 (18.5%)		1/7 (14.3%)		0/12 (0%)
Abdominal pain	0/81 (0%)		0/80 (0%)		0/37 (0%)		0/36 (0%)		0/11 (0%)		2/27 (7.4%)		0/7 (0%)		1/12 (8.3%)
Constipation	0/81 (0%)		0/80 (0%)		0/37 (0%)		0/36 (0%)		0/11 (0%)		2/27 (7.4%)		1/7 (14.3%)		0/12 (0%)
Abdominal distension	0/81 (0%)		0/80 (0%)		0/37 (0%)		0/36 (0%)		0/11 (0%)		0/27 (0%)		1/7 (14.3%)		0/12 (0%)
Nausea	0/81 (0%)		0/80 (0%)		0/37 (0%)		0/36 (0%)		1/11 (9.1%)		0/27 (0%)		0/7 (0%)		0/12 (0%)
General disorders
Chest discomfort	5/81 (6.2%)		6/80 (7.5%)		0/37 (0%)		1/36 (2.8%)		0/11 (0%)		3/27 (11.1%)		0/7 (0%)		0/12 (0%)
Pyrexia	4/81 (4.9%)		1/80 (1.3%)		2/37 (5.4%)		2/36 (5.6%)		0/11 (0%)		3/27 (11.1%)		1/7 (14.3%)		0/12 (0%)
Fatigue	2/81 (2.5%)		4/80 (5%)		2/37 (5.4%)		2/36 (5.6%)		2/11 (18.2%)		1/27 (3.7%)		1/7 (14.3%)		0/12 (0%)
Infections and infestations
Nasopharyngitis	4/81 (4.9%)		1/80 (1.3%)		0/37 (0%)		3/36 (8.3%)		0/11 (0%)		3/27 (11.1%)		1/7 (14.3%)		1/12 (8.3%)
Pseudomonas infection	0/81 (0%)		0/80 (0%)		0/37 (0%)		0/36 (0%)		0/11 (0%)		0/27 (0%)		1/7 (14.3%)		0/12 (0%)
Respiratory tract infection	0/81 (0%)		0/80 (0%)		0/37 (0%)		0/36 (0%)		1/11 (9.1%)		0/27 (0%)		0/7 (0%)		0/12 (0%)
Sinusitis	0/81 (0%)		0/80 (0%)		0/37 (0%)		0/36 (0%)		1/11 (9.1%)		0/27 (0%)		0/7 (0%)		0/12 (0%)
Investigations
Haemophilus test positive	1/81 (1.2%)		1/80 (1.3%)		3/37 (8.1%)		1/36 (2.8%)		0/11 (0%)		0/27 (0%)		0/7 (0%)		0/12 (0%)
Moraxella test positive	0/81 (0%)		0/80 (0%)		3/37 (8.1%)		0/36 (0%)		0/11 (0%)		0/27 (0%)		0/7 (0%)		0/12 (0%)
Lipase increased	0/81 (0%)		0/80 (0%)		0/37 (0%)		0/36 (0%)		0/11 (0%)		0/27 (0%)		0/7 (0%)		2/12 (16.7%)
Amylase increased	0/81 (0%)		0/80 (0%)		0/37 (0%)		0/36 (0%)		0/11 (0%)		0/27 (0%)		0/7 (0%)		1/12 (8.3%)
Forced expiratory volume decreased	0/81 (0%)		0/80 (0%)		0/37 (0%)		0/36 (0%)		0/11 (0%)		0/27 (0%)		0/7 (0%)		1/12 (8.3%)
Hepatic enzyme increased	0/81 (0%)		0/80 (0%)		0/37 (0%)		0/36 (0%)		1/11 (9.1%)		0/27 (0%)		0/7 (0%)		0/12 (0%)
Streptococcus test positive	0/81 (0%)		0/80 (0%)		0/37 (0%)		0/36 (0%)		0/11 (0%)		0/27 (0%)		0/7 (0%)		1/12 (8.3%)
Weight decreased	0/81 (0%)		0/80 (0%)		0/37 (0%)		0/36 (0%)		0/11 (0%)		0/27 (0%)		1/7 (14.3%)		0/12 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/81 (0%)		1/80 (1.3%)		0/37 (0%)		2/36 (5.6%)		0/11 (0%)		0/27 (0%)		0/7 (0%)		0/12 (0%)
Nervous system disorders
Dysgeusia	8/81 (9.9%)		3/80 (3.8%)		3/37 (8.1%)		1/36 (2.8%)		0/11 (0%)		0/27 (0%)		0/7 (0%)		0/12 (0%)
Headache	8/81 (9.9%)		7/80 (8.8%)		2/37 (5.4%)		6/36 (16.7%)		3/11 (27.3%)		4/27 (14.8%)		0/7 (0%)		3/12 (25%)
Reproductive system and breast disorders
Dysmenorrhoea	0/81 (0%)		0/80 (0%)		0/37 (0%)		0/36 (0%)		0/11 (0%)		0/27 (0%)		0/7 (0%)		1/12 (8.3%)
Respiratory, thoracic and mediastinal disorders
Cough	11/81 (13.6%)		8/80 (10%)		4/37 (10.8%)		3/36 (8.3%)		3/11 (27.3%)		2/27 (7.4%)		0/7 (0%)		1/12 (8.3%)
Oropharyngeal pain	8/81 (9.9%)		3/80 (3.8%)		3/37 (8.1%)		0/36 (0%)		0/11 (0%)		2/27 (7.4%)		2/7 (28.6%)		1/12 (8.3%)
Nasal congestion	5/81 (6.2%)		3/80 (3.8%)		1/37 (2.7%)		1/36 (2.8%)		0/11 (0%)		0/27 (0%)		0/7 (0%)		0/12 (0%)
Sputum increased	5/81 (6.2%)		1/80 (1.3%)		0/37 (0%)		0/36 (0%)		1/11 (9.1%)		1/27 (3.7%)		0/7 (0%)		0/12 (0%)
Rhinorrhoea	0/81 (0%)		0/80 (0%)		0/37 (0%)		0/36 (0%)		0/11 (0%)		3/27 (11.1%)		0/7 (0%)		0/12 (0%)
Dyspnoea	0/81 (0%)		0/80 (0%)		0/37 (0%)		0/36 (0%)		0/11 (0%)		1/27 (3.7%)		0/7 (0%)		1/12 (8.3%)
Dysphonia	0/81 (0%)		0/80 (0%)		0/37 (0%)		0/36 (0%)		0/11 (0%)		0/27 (0%)		1/7 (14.3%)		0/12 (0%)
Paranasal sinus hypersecretion	0/81 (0%)		0/80 (0%)		0/37 (0%)		0/36 (0%)		0/11 (0%)		0/27 (0%)		0/7 (0%)		1/12 (8.3%)
Sinus congestion	0/81 (0%)		0/80 (0%)		0/37 (0%)		0/36 (0%)		0/11 (0%)		0/27 (0%)		0/7 (0%)		1/12 (8.3%)
Wheezing	0/81 (0%)		0/80 (0%)		0/37 (0%)		0/36 (0%)		0/11 (0%)		0/27 (0%)		0/7 (0%)		1/12 (8.3%)
Skin and subcutaneous tissue disorders
Pruritus	0/81 (0%)		0/80 (0%)		0/37 (0%)		0/36 (0%)		0/11 (0%)		0/27 (0%)		0/7 (0%)		1/12 (8.3%)
Rash	0/81 (0%)		0/80 (0%)		0/37 (0%)		0/36 (0%)		0/11 (0%)		0/27 (0%)		1/7 (14.3%)		0/12 (0%)
Skin disorder	0/81 (0%)		0/80 (0%)		0/37 (0%)		0/36 (0%)		0/11 (0%)		0/27 (0%)		1/7 (14.3%)		0/12 (0%)
Rash pruritic	0/81 (0%)		0/80 (0%)		0/37 (0%)		0/36 (0%)		1/11 (9.1%)		0/27 (0%)		0/7 (0%)		0/12 (0%)
Vascular disorders
Hot flush	0/81 (0%)		0/80 (0%)		0/37 (0%)		0/36 (0%)		0/11 (0%)		2/27 (7.4%)		0/7 (0%)		0/12 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.