Clearing Lungs With ENaC Inhibition in Primary Ciliary Dy... | NCT02871778 | Trialant
NCT02871778
Sponsor
Parion Sciences
Status
Completed
Last Update Posted
Dec 16, 2021Actual
Enrollment
123Actual
Phase
Phase 2
Conditions
Primary Ciliary Dyskinesia
Interventions
VX-371
Hypertonic Saline
Placebo (0.17% saline)
VX-371 + HS
Ivacaftor
Countries
United States
Canada
Denmark
Germany
Italy
Netherlands
Poland
United Kingdom
Protocol Section
Identification Module
NCT ID
NCT02871778
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
PS-G202
Secondary IDs
ID
Type
Description
Link
2015-004917-26
EudraCT Number
Brief Title
Clearing Lungs With ENaC Inhibition in Primary Ciliary Dyskinesia
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
Acronym
CLEAN-PCD
Organization
Parion SciencesINDUSTRY
Status Module
Record Verification Date
Nov 2021
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Aug 2016Actual
Primary Completion Date
Nov 20, 2018Actual
Completion Date
Nov 20, 2018Actual
First Submitted Date
Aug 12, 2016
First Submission Date that Met QC Criteria
Aug 12, 2016
First Posted Date
Aug 18, 2016Estimated
Results Waived
Not provided
Results First Submitted Date
Oct 5, 2021
Results First Submitted that Met QC Criteria
Nov 18, 2021
Results First Posted Date
Dec 16, 2021Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Nov 20, 2019
Certification/Extension First Submitted that Passed QC Review
Nov 20, 2019
Certification/Extension First Posted Date
Nov 25, 2019Actual
Last Update Submitted Date
Nov 18, 2021
Last Update Posted Date
Dec 16, 2021Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
Parion SciencesINDUSTRY
Collaborators
Name
Class
Vertex Pharmaceuticals Incorporated
INDUSTRY
Oversight Module
Has Data Monitoring Committee (DMC)
Yes
Is FDA Regulated Drug
Yes
Is FDA Regulated Device
No
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
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).
Detailed Description
Not provided
Conditions Module
Conditions
Primary Ciliary Dyskinesia
Keywords
Not provided
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 2
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
123Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
Part A: VX-371 in Hypertonic Saline (HS), Then HS
Experimental
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
Part A: HS, Then VX-371 in HS
Experimental
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
Part A: VX-371, Then Placebo
Experimental
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)
Part A: Placebo, Then VX-371
Experimental
Interventions
Name
Type
Description
Arm Group Labels
Other Names
VX-371
Drug
Part A: Placebo, Then VX-371
Part A: VX-371, Then Placebo
Part B: VX-371 + Ivacaftor
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs
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.
Part A: From first dose of study drug up 84 days
Part B: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs
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.
Part B: Day 85 up to 28 days after last dose of study drug (56 days)
Part A: Absolute Change From Study Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Day 29
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.
Secondary Outcomes
Measure
Description
Time Frame
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
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.
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
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.
Ringshausen FC, Shapiro AJ, Nielsen KG, Mazurek H, Pifferi M, Donn KH, van der Eerden MM, Loebinger MR, Zariwala MA, Leigh MW, Knowles MR, Ferkol TW; CLEAN-PCD investigators and study team. Safety and efficacy of the epithelial sodium channel blocker idrevloride in people with primary ciliary dyskinesia (CLEAN-PCD): a multinational, phase 2, randomised, double-blind, placebo-controlled crossover trial. Lancet Respir Med. 2024 Jan;12(1):21-33. doi: 10.1016/S2213-2600(23)00226-6. Epub 2023 Aug 31.
See Also Links
Not provided
Available IPD Information
Not provided
IPD Sharing Statement Module
No data available
No data is available for this block.
Results Section
Participant Flow Module
Pre-assignment Details
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.
Recruitment Details
Not provided
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
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.
Periods
Title
Milestones
Reasons Not Completed
Part A: Treatment Period 1
Type
Comment
Milestone Data
STARTED
Baseline Characteristics Module
Baseline Analysis Population Description
Outcome Measures Module
Outcome Measures
Adverse Events Module
Frequency Threshold
5
More Info Module
Limitations and Caveats
Not provided
Annotation Section
No data available
No data is available for this block.
Document Section
Large Document Module
Document Has No Statistical Analysis Plan (SAP)
Not provided
Uploaded Document Information
Type
Includes Protocol
Includes SAP
Includes ICF
Document Label
Document Date
Document Uploaded Date
Document File Name
Prot
Yes
No
No
Study Protocol
Oct 31, 2016
Oct 5, 2021
Derived Section
Miscellaneous Info Module
Version Holder
Jul 10, 2026
Removed Countries
Not provided
Submission Tracking
No data available
No data is available for this block.
Condition Browse Module
MeSH Terms
Intervention Browse Module
MeSH Terms
Randomized
Intervention Model
Crossover Assignment
Intervention Model Description
Not provided
Primary Purpose
Treatment
Observational Model
Not provided
Time Perspective
Not provided
Masking Info
Masking
Triple
Masking Description
Not provided
Who Masked
ParticipantInvestigatorOutcomes Assessor
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)
Part B: VX-371 in HS + Ivacaftor
Experimental
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
Part B: HS + Ivacaftor
Experimental
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
Part B: VX-371 + Ivacaftor
Experimental
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
Part B: Placebo + Ivacaftor
Placebo Comparator
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
Hypertonic Saline
Drug
Part A: HS, Then VX-371 in HS
Part A: VX-371 in Hypertonic Saline (HS), Then HS
Part B: HS + Ivacaftor
Placebo (0.17% saline)
Drug
Part A: Placebo, Then VX-371
Part A: VX-371, Then Placebo
Part B: Placebo + Ivacaftor
VX-371 + HS
Drug
Part A: HS, Then VX-371 in HS
Part A: VX-371 in Hypertonic Saline (HS), Then HS
Part B: VX-371 in HS + Ivacaftor
Ivacaftor
Drug
Part B: HS + Ivacaftor
Part B: Placebo + Ivacaftor
Part B: VX-371 + Ivacaftor
Part B: VX-371 in HS + Ivacaftor
Part A: Study Baseline, Day 29 of each treatment period
Part B: Absolute Change From Study Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Day 29
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.
Study Baseline, Day 29 of Part B
Part B: Absolute Change From Part B Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Day 29
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.
Part B Baseline, Day 29 of Part B
Study Baseline, Day 29 of Part A
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
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.
Study Baseline, Day 29 of Part B
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
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.
Part B Baseline, Day 29 of Part B
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
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.
Study Baseline, Day 29 of Part A
Part B: Change From Study Baseline in St. George's Respiratory Questionnaire (SGRQ) Total Score for Participants Aged >=16 Years at Day 29
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.
Study Baseline, Day 29 of Part B
Part B: Change From Part B Baseline in St. George's Respiratory Questionnaire (SGRQ) Total Score for Participants Aged >=16 Years at Day 29
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.
Part B Baseline, Day 29 of Part B
Palo Alto
California
United States
Aurora
Colorado
United States
Washington D.C.
District of Columbia
United States
Miami
Florida
United States
Tampa
Florida
United States
Chicago
Illinois
United States
Indianapolis
Indiana
United States
Iowa City
Iowa
United States
Kansas City
Kansas
United States
Boston
Massachusetts
United States
Ann Arbor
Michigan
United States
Minneapolis
Minnesota
United States
Kansas City
Missouri
United States
St Louis
Missouri
United States
New York
New York
United States
Chapel Hill
North Carolina
United States
Cleveland
Ohio
United States
Philadelphia
Pennsylvania
United States
Columbia
South Carolina
United States
Seattle
Washington
United States
Toronto
Ontario
Canada
Montreal
Quebec
Canada
Copenhagen
Denmark
Münster
North Rhine-Westphalia
Germany
Hanover
Germany
Heidelberg
Germany
Pisa
Italy
Amsterdam
Netherlands
Rotterdam
Netherlands
Rabka-Zdrój
Poland
Cambridge
United Kingdom
London
United Kingdom
Southampton
United Kingdom
FG001
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.
FG002
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.
FG003
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.
FG004
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.
FG005
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.
FG006
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.
FG007
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.
FG00043 subjects
FG00141 subjects
FG00221 subjects
FG00318 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
Safety Analysis Set
FG00044 subjects1 participant was randomized to receive HS in Period 1, but instead received VX-371 in HS in Period 1.
FG00140 subjects
FG00221 subjects
FG00318 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
COMPLETED
FG00040 subjects
FG00137 subjects
FG00218 subjects
FG00316 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
NOT COMPLETED
FG0003 subjects
FG0014 subjects
FG0023 subjects
FG0032 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
Type
Comment
Reasons
Adverse Event
FG0001 subjects
FG0011 subjects
FG0021 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
Withdrawal of consent (not due to adverse event)
FG0002 subjects
FG0012 subjects
FG0020 subjects
FG0032 subjects
Noncompliant with study drug
FG0000 subjects
FG0010 subjects
FG0021 subjects
FG0030 subjects
FG004
Other withdrawal criteria met
FG0000 subjects
FG0010 subjects
FG0021 subjects
FG0030 subjects
FG004
Wrong drug shipment
FG0000 subjects
FG0011 subjects
FG0020 subjects
FG0030 subjects
FG004
Part A: Treatment Period 2
Type
Comment
Milestone Data
STARTED
FG00040 subjects
FG00137 subjects
FG00218 subjects
FG00316 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
Safety Analysis Set
FG00040 subjects
FG00137 subjects
FG00218 subjects
FG00316 subjects
FG004
COMPLETED
FG00037 subjects
FG00135 subjects
FG00217 subjects
FG00315 subjects
FG004
NOT COMPLETED
FG0003 subjects
FG0012 subjects
FG0021 subjects
FG0031 subjects
FG004
Type
Comment
Reasons
Adverse Event
FG0002 subjects
FG0012 subjects
FG0020 subjects
FG003
Part B: Treatment Period 3
Type
Comment
Milestone Data
STARTED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG00411 subjectsOut of 35 participants who were on VX-371 in HS in Treatment period 2 and completed Part A, 11 participants rolled-over to Part B.
FG00527 subjectsOut of 37 participants who were on HS in Treatment period 2 and completed Part A, 27 participants rolled-over to Part B.
FG0067 subjectsOut of 15 participants who were on VX-371 in Treatment period 2 and completed Part A, 7 participants rolled-over to Part B.
FG00712 subjectsOut of 17 participants who were on Placebo in Treatment period 2 and completed Part A, 12 participants rolled-over to Part B.
Safety Analysis Set
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Type
Comment
Reasons
Adverse Event
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG003
Part A Full analysis set (FAS) included all randomized participants who received at least 1 dose of study drug in Part A and had a confirmed diagnosis of primary ciliary dyskinesia (PCD).
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Part A: VX-371 in HS, Then HS
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.
BG001
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.
BG002
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.
BG003
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.
BG004
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG00043
BG00141
BG00221
BG00318
BG004123
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Continuous
Mean
Standard Deviation
years
Title
Denominators
Categories
Title
Measurements
BG00029.19± 10.861
BG00127.98± 13.104
BG00227.62± 16.633
BG003
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG00029
BG00124
BG002
Ethnicity (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Hispanic or Latino
BG0002
BG0013
BG002
Race (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
American Indian or Alaska Native
BG0000
BG0010
BG002
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
Primary
Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs
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.
Part A safety set included all participants who received at least 1 dose of study drug in Part A.
Posted
Count of Participants
Participants
Part A: From first dose of study drug up 84 days
ID
Title
Description
OG000
Part A: VX-371 in HS
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.
OG001
Part A: HS
Participants received 3 mL 4.2% HS through oral nebulized inhalation twice daily for 28 days in either treatment period 1 or 2.
OG002
Part A: VX-371
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.
OG003
Part A: Placebo
Participants received 3 mL 0.17% saline (placebo) through oral nebulized inhalation twice daily for 28 days in either treatment period 1 or 2.
Units
Counts
Participants
OG00081
OG00180
OG00237
OG003
Title
Denominators
Categories
Participants with TEAEs
Title
Measurements
OG00052
OG00146
OG00222
OG003
Primary
Part B: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs
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.
Part B safety set included all participants who received at least 1 dose of ivacaftor in Part B.
Posted
Count of Participants
Participants
Part B: Day 85 up to 28 days after last dose of study drug (56 days)
ID
Title
Description
OG000
Part B: VX-371 in HS + IVA
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).
OG001
Primary
Part A: Absolute Change From Study Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Day 29
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.
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.
Posted
Least Squares Mean
Standard Error
Percentage of predicted FEV1
Part A: Study Baseline, Day 29 of each treatment period
ID
Title
Description
OG000
Part A: VX-371 in HS
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.
OG001
Part A: HS
Participants received 3 mL 4.2% HS through oral nebulized inhalation twice daily for 28 days in either treatment period 1 or 2.
OG002
Part A: VX-371
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.
Primary
Part B: Absolute Change From Study Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Day 29
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.
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.
Posted
Least Squares Mean
Standard Error
Percentage of predicted FEV1
Study Baseline, Day 29 of Part B
ID
Title
Description
OG000
Part B: VX-371 in HS + Ivacaftor
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).
OG001
Part B: HS + Ivacaftor
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).
Primary
Part B: Absolute Change From Part B Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Day 29
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.
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.
Posted
Least Squares Mean
Standard Error
Percentage of predicted FEV1
Part B Baseline, Day 29 of Part B
ID
Title
Description
OG000
Part B: VX-371 in HS + Ivacaftor
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).
OG001
Part B: HS + Ivacaftor
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).
Secondary
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
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.
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.
Posted
Mean
Standard Deviation
score on a scale
Study Baseline, Day 29 of Part A
ID
Title
Description
OG000
Part A: VX-371 in HS
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.
OG001
Part A: HS
Secondary
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
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.
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.
Posted
Mean
Standard Deviation
score on a scale
Study Baseline, Day 29 of Part B
ID
Title
Description
OG000
Part B: VX-371 in HS + Ivacaftor
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).
Secondary
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
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.
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.
Posted
Mean
Standard Deviation
score on a scale
Part B Baseline, Day 29 of Part B
ID
Title
Description
OG000
Part B: VX-371 in HS + Ivacaftor
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).
Secondary
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
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.
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.
Posted
Mean
Standard Deviation
score on a scale
Study Baseline, Day 29 of Part A
ID
Title
Description
OG000
Part A: VX-371 in HS
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.
OG001
Part A: HS
Participants received 3 mL 4.2% HS through oral nebulized inhalation twice daily for 28 days in either treatment period 1 or 2.
OG002
Part A: VX-371
Secondary
Part B: Change From Study Baseline in St. George's Respiratory Questionnaire (SGRQ) Total Score for Participants Aged >=16 Years at Day 29
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.
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.
Posted
Mean
Standard Deviation
score on a scale
Study Baseline, Day 29 of Part B
ID
Title
Description
OG000
Part B: VX-371 in HS + Ivacaftor
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).
OG001
Part B: HS + Ivacaftor
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).
Secondary
Part B: Change From Part B Baseline in St. George's Respiratory Questionnaire (SGRQ) Total Score for Participants Aged >=16 Years at Day 29
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.
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.
Posted
Mean
Standard Deviation
score on a scale
Part B Baseline, Day 29 of Part B
ID
Title
Description
OG000
Part B: VX-371 in HS + Ivacaftor
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).
OG001
Part B: HS + Ivacaftor
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).
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)
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.
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
Part A: VX-371 in HS
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.
0
81
1
81
40
81
EG001
Part A: HS
Participants received 3 mL 4.2% HS through oral nebulized inhalation twice daily for 28 days in either treatment period 1 or 2.
0
80
1
80
27
80
EG002
Part A: VX-371
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.
0
37
1
37
12
37
EG003
Part A: Placebo
Participants received 3 mL 0.17% saline (placebo) through oral nebulized inhalation twice daily for 28 days in either treatment period 1 or 2.
0
36
1
36
16
36
EG004
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.
0
11
0
11
5
11
EG005
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.
0
27
0
27
15
27
EG006
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.
0
7
1
7
4
7
EG007
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.
Congenital, Hereditary, and Neonatal Diseases and Abnormalities
D030342
Genetic Diseases, Inborn
Browse Leaves
Not provided
Browse Branches
Not provided
ID
Term
D012462
Saline Solution, Hypertonic
D012965
Sodium Chloride
C545203
ivacaftor
Ancestor Terms
ID
Term
D006982
Hypertonic Solutions
D012996
Solutions
D004364
Pharmaceutical Preparations
D002712
Chlorides
D006851
Hydrochloric Acid
D017606
Chlorine Compounds
D007287
Inorganic Chemicals
D017670
Sodium Compounds
Browse Leaves
Not provided
Browse Branches
Not provided
FG004
0 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
0 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
0 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
0 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
0 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
0 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
0 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
0 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
Lost to Follow-up
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0031 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
Non-Compliant with Study Drug
FG0001 subjects
FG0010 subjects
FG0021 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
11 subjects
FG00527 subjects
FG0067 subjects
FG00712 subjects
10 subjects
FG00526 subjects
FG0066 subjects
FG00712 subjects
1 subjects
FG0051 subjects
FG0061 subjects
FG0070 subjects
0 subjects
FG0041 subjects
FG0051 subjects
FG0061 subjects
FG0070 subjects
24.33
± 12.866
BG00427.80± 12.954
15
BG00310
BG00478
Male
BG00014
BG00117
BG0026
BG0038
BG00445
2
BG0030
BG0047
Not Hispanic or Latino
BG00041
BG00137
BG00218
BG00318
BG004114
Unknown or Not Reported
BG0000
BG0011
BG0021
BG0030
BG0042
0
BG0030
BG0040
Asian
BG0001
BG0013
BG0021
BG0033
BG0048
Native Hawaiian or Other Pacific Islander
BG0000
BG0010
BG0020
BG0030
BG0040
Black or African American
BG0002
BG0011
BG0021
BG0031
BG0045
White
BG00039
BG00136
BG00217
BG00314
BG004106
More than one race
BG0000
BG0010
BG0020
BG0030
BG0040
Unknown or Not Reported
BG0001
BG0011
BG0022
BG0030
BG0044
36
23
Participants with Serious TEAEs
Title
Measurements
OG0001
OG0011
OG0021
OG0031
Part B: HS + IVA
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).
OG002
Part B: VX-371 + IVA
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).
OG003
Part B: Placebo + IVA
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).
Units
Counts
Participants
OG00011
OG00127
OG0027
OG00312
Title
Denominators
Categories
Participants with TEAEs
Title
Measurements
OG0005
OG00117
OG0025
OG0039
Participants with Serious TEAEs
Title
Measurements
OG0000
OG0010
OG0021
OG003
OG003
Part A: Placebo
Participants received 3 mL 0.17% saline (placebo) through oral nebulized inhalation twice daily for 28 days in either treatment period 1 or 2.
Units
Counts
Participants
OG00078
OG00175
OG00234
OG00334
Title
Denominators
Categories
Title
Measurements
OG0000.989± 0.7097
OG001-0.531± 0.7202
OG002-0.491± 1.0736
OG003-1.329± 1.0730
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Mixed-effects Model
0.0437
Least Square (LS) Mean difference
1.519
2-Sided
95
0.044
2.995
Superiority
OG001
OG002
Mixed-effects Model
0.9755
LS Mean difference
0.040
2-Sided
95
-2.509
2.589
Superiority
OG000
OG003
Mixed-effects Model
0.0731
LS Mean difference
2.318
2-Sided
95
-0.22
4.856
Superiority
OG001
OG003
Mixed-effects Model
0.5373
LS Mean Difference
0.799
2-Sided
95
-1.751
3.348
Superiority
OG002
OG003
Mixed-effects Model
0.453
LS Mean difference
0.838
2-Sided
95
-1.368
3.045
Superiority
OG002
Part B: VX-371 + Ivacaftor
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).
OG003
Part B: Placebo + Ivacaftor
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).
Units
Counts
Participants
OG00010
OG00126
OG0026
OG00312
Title
Denominators
Categories
Title
Measurements
OG0004.721± 1.9314
OG0011.722± 1.1976
OG002-0.592± 2.5011
OG003-0.965± 1.8388
OG002
Part B: VX-371 + Ivacaftor
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).
OG003
Part B: Placebo + Ivacaftor
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).
Units
Counts
Participants
OG00010
OG00126
OG0026
OG00312
Title
Denominators
Categories
Title
Measurements
OG0002.528± 1.8633
OG0011.678± 1.1414
OG002-1.018± 2.3797
OG003-2.040± 1.7427
Participants received 3 mL 4.2% HS through oral nebulized inhalation twice daily for 28 days in either treatment period 1 or 2.
OG002
Part A: VX-371
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.
OG003
Part A: Placebo
Participants received 3 mL 0.17% saline (placebo) through oral nebulized inhalation twice daily for 28 days in either treatment period 1 or 2.
Units
Counts
Participants
OG00046
OG00145
OG00217
OG00315
Title
Denominators
Categories
Title
Measurements
OG0004.23± 18.076
OG0013.58± 16.715
OG0020.98± 12.915
OG0037.04± 16.728
OG001
Part B: HS + Ivacaftor
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).
OG002
Part B: VX-371 + Ivacaftor
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).
OG003
Part B: Placebo + Ivacaftor
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).
Units
Counts
Participants
OG0006
OG00116
OG0023
OG0036
Title
Denominators
Categories
Title
Measurements
OG00016.67± 14.487
OG0011.39± 17.153
OG0027.41± 3.208
OG003-5.56± 23.307
OG001
Part B: HS + Ivacaftor
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).
OG002
Part B: VX-371 + Ivacaftor
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).
OG003
Part B: Placebo + Ivacaftor
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).
Units
Counts
Participants
OG0006
OG00116
OG0023
OG0036
Title
Denominators
Categories
Title
Measurements
OG00011.11± 15.713
OG0011.39± 19.928
OG0025.56± 16.667
OG003-7.41± 10.344
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.
OG003
Part A: Placebo
Participants received 3 mL 0.17% saline (placebo) through oral nebulized inhalation twice daily for 28 days in either treatment period 1 or 2.
Units
Counts
Participants
OG00063
OG00162
OG00228
OG00325
Title
Denominators
Categories
Title
Measurements
OG000-1.28± 8.452
OG001-2.17± 6.462
OG0021.54± 8.576
OG003-1.52± 9.082
OG002
Part B: VX-371 + Ivacaftor
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).
OG003
Part B: Placebo + Ivacaftor
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).
Units
Counts
Participants
OG0006
OG00125
OG0025
OG0038
Title
Denominators
Categories
Title
Measurements
OG000-1.69± 7.442
OG001-6.87± 6.571
OG0020.78± 5.879
OG0034.52± 16.995
OG002
Part B: VX-371 + Ivacaftor
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).
OG003
Part B: Placebo + Ivacaftor
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).