A Study of VX-445 in Healthy Subjects and Subjects With Cystic Fibrosis

• Sponsor: Vertex Pharmaceuticals Incorporated (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03227471
• Collaborator: (none)
• Enrollment: 225
• Locations: 38
• Arms: 15
• Actual Duration (Months): 14.1
• Patients Per Site: 5.9
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

This is a first-in-human and proof-of-concept study of VX-445. The study includes 6 parts. Parts A, B, and C were conducted in healthy subjects. Parts D, E, and F were conducted in subjects with Cystic Fibrosis (CF) who are homozygous for the F508del mutation of the CF transmembrane conductance regulator (CFTR) gene (F/F genotype), or who are heterozygous for the F508del mutation and a minimal function (MF) CFTR mutation not likely to respond to TEZ, IVA, or TEZ/IVA (F/MF genotypes).

Condition or Disease	Intervention/Treatment	Phase
Cystic Fibrosis	Drug: IVA; Drug: TEZ/IVA; Drug: VX-445; Drug: Matched Placebo; Drug: TEZ; Drug: VX-561; Drug: VX-445	Phase 1/Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 225 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 1/2 Study of VX-445 in Healthy Subjects and Subjects With Cystic Fibrosis
• Actual Study Start Date: Jan 23, 2017
• Actual Primary Completion Date: Mar 27, 2018
• Actual Study Completion Date: Mar 27, 2018

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Part A: Pooled Placebo (Except Cohort A7) Participants without CF who received single dose of placebo matched to VX-445 in Cohort A1 to A5.	Drug: Matched Placebo; Matched placebo.
Experimental: Part A: VX-445 (Except Cohort A7) Participants without CF who received single ascending dose of VX-445 tablet starting from 20 milligrams (mg) to 360 mg in Cohort A1 to A5.	Drug: VX-445; VX-445 tablet for oral administration.; Other Names: ELX elexacaftor
Experimental: Part A: VX-445 (Cohort A7) Participants without CF who received single dose of VX-445 100 mg tablet on Day 1 in fasted state and on Day 7 in fed state, followed by VX-445 20 mg intravenous (IV) injection on Day 13 in fed state in Cohort A7.	Drug: VX-445; VX-445 tablet for oral administration.; Other Names: ELX elexacaftor ; Drug: VX-445; VX-445 IV injection; Other Names: ELX elexacaftor
Placebo Comparator: Part B: Pooled Placebo (Cohort B1 to B4) Participants without CF who received multiple doses of placebo matched to VX-445 once daily (qd) for 10 days in Cohort B1 to B4.	Drug: Matched Placebo; Matched placebo.
Experimental: Part B: VX-445 (Cohort B1 to B4) Participants without CF who received VX-445 tablet qd for 10 days in Cohort B1 (60 mg), B2 (120 mg), B3 (240 mg) and B4 (340 mg).	Drug: VX-445; VX-445 tablet for oral administration.; Other Names: ELX elexacaftor
Placebo Comparator: Part C: Pooled Placebo (Cohort C1 to C3) Participants without CF who received placebo matched to VX-445/TEZ/IVA triple combination (TC) qd in the morning and placebo matched to IVA in the evening for 14 days.	Drug: Matched Placebo; Matched placebo.
Experimental: Part C: VX-445/TEZ/IVA TC (Cohort C1 to C3) Participants without CF who received VX-445 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in Cohort C1; VX-445 280 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in Cohort C2 and VX-445 100 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in Cohort C3 for 14 days.	Drug: IVA; IVA tablet for oral administration; Other Names: VX-770 ivacaftor ; Drug: TEZ/IVA; TEZ/IVA fixed-dose combination for oral administration.; Other Names: VX-661/VX-770 tezacaftor/ivacaftor ; Drug: VX-445; VX-445 tablet for oral administration.; Other Names: ELX elexacaftor
Placebo Comparator: Part D: Placebo Participants with CF, F/MF genotype who received placebo matched to VX-445/TEZ/IVA TC qd in the morning and placebo matched to IVA qd in the evening for 4 weeks in the TC treatment period.	Drug: Matched Placebo; Matched placebo.
Experimental: Part D: VX-445/TEZ/IVA TC - Low Dose Participants with CF, F/MF genotype who received VX-445 50 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the TC treatment period.	Drug: IVA; IVA tablet for oral administration; Other Names: VX-770 ivacaftor ; Drug: TEZ/IVA; TEZ/IVA fixed-dose combination for oral administration.; Other Names: VX-661/VX-770 tezacaftor/ivacaftor ; Drug: VX-445; VX-445 tablet for oral administration.; Other Names: ELX elexacaftor
Experimental: Part D: VX-445/TEZ/IVA TC - Medium Dose Participants with CF, F/MF genotype who received VX-445 100 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the TC treatment period.	Drug: IVA; IVA tablet for oral administration; Other Names: VX-770 ivacaftor ; Drug: TEZ/IVA; TEZ/IVA fixed-dose combination for oral administration.; Other Names: VX-661/VX-770 tezacaftor/ivacaftor ; Drug: VX-445; VX-445 tablet for oral administration.; Other Names: ELX elexacaftor
Experimental: Part D: VX-445/TEZ/IVA TC - High Dose Participants with CF, F/MF genotype who received VX-445 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the TC treatment period.	Drug: IVA; IVA tablet for oral administration; Other Names: VX-770 ivacaftor ; Drug: TEZ/IVA; TEZ/IVA fixed-dose combination for oral administration.; Other Names: VX-661/VX-770 tezacaftor/ivacaftor ; Drug: VX-445; VX-445 tablet for oral administration.; Other Names: ELX elexacaftor
Active Comparator: Part E: TEZ/IVA Following run-in period of 4 weeks with TEZ/IVA, participants with CF, F/F genotype who received TEZ 100 mg qd/IVA 150 mg q12h and placebo matched to VX-445 for 4 weeks in the TC treatment period.	Drug: TEZ/IVA; TEZ/IVA fixed-dose combination for oral administration.; Other Names: VX-661/VX-770 tezacaftor/ivacaftor
Experimental: Part E: VX-445/TEZ/IVA TC Following run-in period of 4 weeks with TEZ/IVA, participants with CF, F/F genotype who received VX-445 200 mg qd/TEZ 100 mg qd /IVA 150 mg q12h for 4 weeks in the TC treatment period.	Drug: IVA; IVA tablet for oral administration; Other Names: VX-770 ivacaftor ; Drug: TEZ/IVA; TEZ/IVA fixed-dose combination for oral administration.; Other Names: VX-661/VX-770 tezacaftor/ivacaftor ; Drug: VX-445; VX-445 tablet for oral administration.; Other Names: ELX elexacaftor
Placebo Comparator: Part F: Placebo Participants with CF, F/MF genotype who received placebo matched to VX-445/TEZ/VX-561 for 4 weeks in the TC treatment period.	Drug: Matched Placebo; Matched placebo.
Experimental: Part F: VX-445/TEZ/VX-561 TC Participants with CF, F/MF genotype who received VX-445 200 mg qd/TEZ 100 mg qd/VX-561 150 mg qd for 4 weeks in the TC treatment period.	Drug: VX-445; VX-445 tablet for oral administration.; Other Names: ELX elexacaftor ; Drug: TEZ; Tablet for oral administration.; Other Names: VX-661 tezacaftor ; Drug: VX-561; Tablet for oral administration.; Other Names: CTP-656

Outcome Measures

Primary Outcome Measures

1. Parts A, B and C: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [From first dose of study drug in treatment period up to safety follow-up (up to 28 days)]

2. Parts D, E and F: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [From first dose of study drug in TC treatment period up to 28 days after last dose of study drug (up to 5 weeks)]

3. Part D: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) [From Baseline through Day 29]

   FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.

4. Part E: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) [From Baseline through Day 29]

   FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.

5. Part F: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) [From Baseline through Day 29]

   FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.

Secondary Outcome Measures

1. Part A: Maximum Observed Concentration (Cmax) of VX-445 [Cohort A1-A5: Pre-dose to 96 hours post-dose; Cohort A7: Pre-dose to 120 hours post-dose]

2. Part A: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of VX-445 [Cohort A1-5: Pre-dose to 96 hours post-dose; Cohort A7: Pre-dose to 120 hours post-dose]

3. Part B: Maximum Observed Concentration (Cmax) of VX-445 [Pre-dose to 96 hours post-dose on Day 1 and Day 10]

4. Part B: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of VX-445 [Pre-dose to 96 hours post-dose on Day 1 and Day 10]

5. Part B: Observed Pre-dose Plasma Concentration (Ctrough) of VX-445 [Pre-dose on Day 10]

6. Part C: Maximum Observed Concentration (Cmax) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) [Pre-dose to 96 hours post-dose on Day 1, Day 7 and Day 14]

7. Part C: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) [Pre-dose to 96 hours post-dose on Day 1, Day 7 and Day 14]

8. Part C: Maximum Observed Concentration (Cmax) of IVA and Its Metabolites (M1-IVA and M6-IVA) [Pre-dose to 96 hours post-dose on Day 1, Day 7 and Day 14]

9. Part C: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of IVA and Its Metabolites (M1-IVA and M6-IVA) [Pre-dose to 96 hours post-dose on Day 1, Day 7 and Day 14]

10. Part C: Observed Pre-dose Concentration (Ctrough) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) [Pre-dose on Day 7 and Day 14]

11. Part C: Observed Pre-dose Concentration (Ctrough) of IVA and Its Metabolites (M1-IVA and M6-IVA) [Pre-dose on Day 7 and Day 14]

12. Part D: Observed Pre-dose Plasma Concentration (Ctrough) of VX-445, TEZ and Its Metabolite (M1-TEZ), IVA and Its Metabolite (M1-IVA) [Pre-dose on Day 15 and Day 29]

13. Part E: Observed Pre-dose Concentration (Ctrough) of VX-445, TEZ and Its Metabolite (M1-TEZ) and IVA and Its Metabolite (M1-IVA) [Pre-dose on Day 15 and Day 29]

14. Part F: Observed Pre-dose Concentration (Ctrough) of VX-445, TEZ and Its Metabolite (M1-TEZ) and VX-561 [Pre-dose on Day 15 and Day 29]

15. Part D: Absolute Change in Sweat Chloride Concentration [From Baseline through Day 29]

    Sweat samples were collected using an approved collection device.

16. Part E: Absolute Change in Sweat Chloride Concentration [From Baseline through Day 29]

    Sweat samples were collected using an approved collection device.

17. Part F: Absolute Change in Sweat Chloride Concentration [From Baseline through Day 29]

    Sweat samples were collected using an approved collection device.

18. Part D: Relative Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) [From Baseline through Day 29]

    FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.

19. Part E: Relative Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) [From Baseline through Day 29]

    FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.

20. Part F: Relative Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) [From Baseline through Day 29]

    FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.

21. Part D: Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score [From Baseline through Day 29]

    The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with cystic fibrosis. Respiratory domain assessed respiratory symptoms, score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life.

22. Part E: Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score [From Baseline through Day 29]

    The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with cystic fibrosis. Respiratory domain assessed respiratory symptoms, score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life.

23. Part F: Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score [From Baseline through Day 29]

    The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with cystic fibrosis. Respiratory domain assessed respiratory symptoms, score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Key Inclusion Criteria:

Parts A, B, and C:

• Female subjects must be of non-childbearing potential.

• Between the ages of 18 and 55 years, inclusive.

• Body mass index (BMI) of 18.0 to 32.0 kg/m2, inclusive, and a total body weight >50 kg

Parts D, E, and F:

• Body weight ≥35 kg.

• Subjects must have an eligible CFTR genotype:

• Parts D and F: Heterozygous for F508del and an MF mutation (F/MF)

• Part E: Homozygous for F508del (F/F)

• FEV1 value ≥40% and ≤90% of predicted mean for age, sex, and height.

Key Exclusion Criteria:

Parts A, B, and C:

• Any condition possibly affecting drug absorption.

• History of febrile illness within 14 days before the first study drug dose.

• Glucose-6-phosphate dehydrogenase (G6PD) deficiency.

Parts D, E, and F:

• History of clinically significant cirrhosis with or without portal hypertension.

• Glucose-6-phosphate dehydrogenase (G6PD) deficiency.

• Lung infection with organisms associated with a more rapid decline in pulmonary status.

• History of solid organ or hematological transplantation.

Other protocol defined Inclusion/Exclusion criteria may apply.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Banner University of Arizona Medical Center	Tucson	Arizona	United States	85724
2	University of Arkansas for Medical Sciences	Little Rock	Arkansas	United States	72205
3	Valley Children's Healthcare	Madera	California	United States	93636
4	(Kaiser Permanente) Oakland Medical Center	Oakland	California	United States	96411
5	National Jewish Health	Denver	Colorado	United States	80206
6	Central Florida Pulmonary Group	Orlando	Florida	United States	32803
7	Tampa General Hospital Cardiac and Lung Transplant Clinic	Tampa	Florida	United States	33606
8	Children's Specialty Services at North Druid Hills	Atlanta	Georgia	United States	30324
9	Northwestern Memorial Hospital	Chicago	Illinois	United States	60611
10	Covance Clinical Research Unit Inc., Evansville Clinic [Parts A, B, C only]	Evansville	Indiana	United States	47710
11	University of Kansas Medical Center	Kansas City	Kansas	United States	66160
12	Tulane Medical Center	New Orleans	Louisiana	United States	70112
13	Harper University Hospital	Detroit	Michigan	United States	48201
14	Children's Respiratory and Critical Care Specialists, P.A., Children's Hospitals and Clinics of Minn	Minneapolis	Minnesota	United States	55404
15	Morristown Medical Center	Morristown	New Jersey	United States	07960
16	University of New Mexico School of Medicine	Albuquerque	New Mexico	United States	87131
17	UC Health Office of Clinical Research	Cincinnati	Ohio	United States	45267
18	University Hospitals Cleveland Medical Center/Rainbow Babies and Children's Hospital	Cleveland	Ohio	United States	44106
19	Nationwide Children's Hospital	Columbus	Ohio	United States	43205
20	Austin Children's Chest Associates	Austin	Texas	United States	78723
21	The University of Vermont	Burlington	Vermont	United States	05401
22	University of Virginia Health System	Charlottesville	Virginia	United States	22908
23	West Virginia University Hospitals	Morgantown	Virginia	United States	26506
24	Children's Hospital of the King's Daughters	Norfolk	Virginia	United States	23507
25	Virginia Commonwealth University	Richmond	Virginia	United States	23298
26	Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226
27	Monash Medical Center	Clayton	Victoria	Australia
28	The Alfred Hospital	Melbourne	Victoria	Australia
29	The Royal Children's Hospital Melbourne	Parkville	Victoria	Australia
30	Mater Adult Hospital	Brisbane		Australia
31	Royal Prince Alfred Hospital	Sydney		Australia
32	Westmead Hospital	Sydney		Australia
33	Antwerp University Hospital	Edegem		Belgium
34	Universitair Ziekenhuis Gent	Gent		Belgium
35	Academic Medical Centre	Amsterdam		Netherlands
36	HagaZiekenhuis van den Haag	Den Haag		Netherlands
37	Radboud UMC	Nijmegen		Netherlands
38	Erasmus Medical Center	Rotterdam		Netherlands

Sponsors and Collaborators

• Vertex Pharmaceuticals Incorporated

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Aug 8, 2017
• Statistical Analysis Plan - Oct 6, 2017

More Information

Publications

None provided.

• Responsible Party: Vertex Pharmaceuticals Incorporated
• ClinicalTrials.gov Identifier: NCT03227471
• Other Study ID Numbers: VX16-445-001; 2017-000797-11
• First Posted: Jul 24, 2017
• Last Update Posted: Jan 18, 2022
• Last Verified: Dec 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Cystic Fibrosis; Fibrosis; Ivacaftor; Elexacaftor

Study Results

Participant Flow

Pre-assignment Detail	This study included 6 parts: Parts A, B, and C were conducted in healthy adult participants; Part D, E, and F were conducted in adult cystic fibrosis (CF) participants.

Arm/Group Title	Part A: Pooled Placebo (Except Cohort A7)	Part A: VX-445 (Except Cohort A7)	Part A: VX-445 (Cohort A7)	Part B: Pooled Placebo (Cohort B1 to B4)	Part B: VX-445 (Cohort B1 to B4)	Part C: Pooled Placebo (Cohort C1 to C3)	Part C: VX-445/TEZ/IVA TC (Cohort C1 to C3)	Part D: Placebo	Part D: VX-445/TEZ/IVA TC - Low Dose	Part D: VX-445/TEZ/IVA TC - Medium Dose	Part D: VX-445/TEZ/IVA TC - High Dose	Part E: TEZ/IVA	Part E: VX-445/TEZ/IVA TC	Part F: Placebo	Part F: VX-445/TEZ/VX-561 TC
Arm/Group Description	Participants without CF who received single dose of placebo matched to VX-445 in Cohort A1 to A5.	Participants without CF who received single ascending dose of VX-445 tablet starting from 20 milligrams (mg) to 360 mg in Cohort A1 to A5.	Participants without CF who received single dose of VX-445 100 mg tablet on Day 1 in fasted state and on Day 7 in fed state, followed by VX-445 20 mg intravenous (IV) injection on Day 13 in fed state in Cohort A7.	Participants without CF who received multiple doses of placebo matched to VX-445 once daily (qd) for 10 days in Cohort B1 to B4.	Participants without CF who received VX-445 tablet once daily for 10 days in Cohort B1 (60 mg), B2 (120 mg), B3 (240 mg) and B4 (340 mg).	Participants without CF who received placebo matched to VX-445/TEZ/IVA triple combination (TC) once daily in the morning and placebo matched to IVA in the evening for 14 days.	Participants without CF who received VX-445 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in cohort C1; VX-445 280 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in cohort C2 and VX-445 100 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in Cohort C3 for 14 days.	Participants with CF, F/MF genotype who received placebo matched to VX-445/TEZ/IVA TC once daily in the morning and placebo matched to IVA in the evening for 4 weeks in the TC treatment period.	Participants with CF, F/MF genotype who received VX-445 50 mg qd /TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the TC treatment period.	Participants with CF, F/MF genotype who received VX-445 100 mg qd /TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the TC treatment period.	Participants with CF, F/MF genotype who received VX-445 200 mg qd /TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the TC treatment period.	Following run-in period of 4 weeks with TEZ/IVA, participants with CF, F/F genotype who received TEZ 100 mg qd/IVA 150 mg q12h and placebo matched to VX-445 for 4 weeks in the TC treatment period.	Following run-in period of 4 weeks with TEZ/IVA, participants with CF, F/F genotype who received VX-445 200 mg qd/TEZ 100 mg qd /IVA 150 mg q12h for 4 weeks in the TC treatment period.	Participants with CF, F/MF genotype who received placebo matched to VX-445/TEZ/VX-561 for 4 weeks in the TC treatment period.	Participants with CF, F/MF genotype who received VX-445 200 mg qd/TEZ 100 mg qd/VX-561 150 mg qd for 4 weeks in the TC treatment period.
Period Title: Overall Study
STARTED	9	30	8	7	25	6	17	12	10	22	21	7	21	8	22
Safety Set	9	30	8	7	25	6	17	12	10	22	21	7	21	8	21
COMPLETED	9	30	8	7	24	6	17	12	10	22	21	7	20	8	21
NOT COMPLETED	0	0	0	0	1	0	0	0	0	0	0	0	1	0	1

Baseline Characteristics

Arm/Group Title	Part A: Pooled Placebo (Except Cohort A7)	Part A: VX-445 (Except Cohort A7)	Part A: VX-445 (Cohort A7)	Part B: Pooled Placebo (Cohort B1 to B4)	Part B: VX-445 (Cohort B1 to B4)	Part C: Pooled Placebo (Cohort C1 to C3)	Part C: VX-445/TEZ/IVA TC (Cohort C1 to C3)	Part D: Placebo	Part D: VX-445/TEZ/IVA TC - Low Dose	Part D: VX-445/TEZ/IVA TC - Medium Dose	Part D: VX-445/TEZ/IVA TC - High Dose	Part E: TEZ/IVA	Part E: VX-445/TEZ/IVA TC	Part F: Placebo	Part F: VX-445/TEZ/VX-561 TC	Total
Arm/Group Description	Participants without CF who received single dose of placebo matched to VX-445 in Cohort A1 to A5.	Participants without CF who received single ascending dose of VX-445 tablet starting from 20 mg to 360 mg in Cohort A1 to A5.	Participants without CF who received single dose of VX-445 100 mg tablet on Day 1 in fasted state and on Day 7 in fed state, followed by VX-445 20 mg IV injection on Day 13 in fed state in Cohort A7.	Participants without CF who received multiple doses of placebo matched to VX-445 qd for 10 days in Cohort B1 to B4.	Participants without CF who received VX-445 tablet once daily for 10 days in Cohort B1 (60 mg), B2 (120 mg), B3 (240 mg) and B4 (340 mg).	Participants without CF who received placebo matched to VX-445/TEZ/IVA TC qd in the morning and placebo matched to IVA in the evening for 14 days.	Participants without CF who received VX-445 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in Cohort C1; VX-445 280 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in Cohort C2 and VX-445 100 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in Cohort C3 for 14 days.	Participants with CF, F/MF genotype who received placebo matched to VX-445/TEZ/IVA TC qd in the morning and placebo matched to IVA in the evening for 4 weeks in the TC treatment period.	Participants with CF, F/MF genotype who received VX-445 50 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the TC treatment period.	Participants with CF, F/MF genotype who received VX-445 100 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the TC treatment period.	Participants with CF, F/MF genotype who received VX-445 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the TC treatment period.	Following run-in period of 4 weeks with TEZ/IVA, participants with CF, F/F genotype who received TEZ 100 mg qd/IVA 150 mg q12h and placebo matched to VX-445 for 4 weeks in the TC treatment period.	Following run-in period of 4 weeks with TEZ/IVA, participants with CF, F/F genotype who received VX-445 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the TC treatment period.	Participants with CF, F/MF genotype who received placebo matched to VX-445/TEZ/VX-561 for 4 weeks in the TC treatment period.	Participants with CF, F/MF genotype who received VX-445 200 mg qd/TEZ 100 mg qd/VX-561 150 mg qd for 4 weeks in the TC treatment period.	Total of all reporting groups
Overall Participants	9	30	8	7	25	6	17	12	10	22	21	7	21	8	21	224
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	9 100%	30 100%	8 100%	7 100%	25 100%	6 100%	17 100%	12 100%	10 100%	22 100%	21 100%	7 100%	21 100%	8 100%	21 100%	224 100%
>=65 years	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	2 22.2%	2 6.7%	0 0%	0 0%	3 12%	0 0%	0 0%	2 16.7%	6 60%	7 31.8%	11 52.4%	1 14.3%	9 42.9%	5 62.5%	10 47.6%	58 25.9%
Male	7 77.8%	28 93.3%	8 100%	7 100%	22 88%	6 100%	17 100%	10 83.3%	4 40%	15 68.2%	10 47.6%	6 85.7%	12 57.1%	3 37.5%	11 52.4%	166 74.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	2 6.7%	2 25%	0 0%	1 4%	1 16.7%	5 29.4%	0 0%	0 0%	0 0%	1 4.8%	0 0%	1 4.8%	0 0%	0 0%	13 5.8%
Not Hispanic or Latino	9 100%	28 93.3%	6 75%	7 100%	24 96%	5 83.3%	12 70.6%	12 100%	10 100%	22 100%	20 95.2%	7 100%	20 95.2%	8 100%	20 95.2%	210 93.8%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 4.8%	1 0.4%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	2 28.6%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	2 0.9%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	4 44.4%	16 53.3%	4 50%	3 42.9%	9 36%	4 66.7%	1 5.9%	0 0%	1 10%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	42 18.8%
White	5 55.6%	14 46.7%	4 50%	2 28.6%	16 64%	2 33.3%	16 94.1%	12 100%	8 80%	22 100%	21 100%	7 100%	21 100%	8 100%	20 95.2%	178 79.5%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 10%	0 0%	0 0%	0 0%	0 0%	0 0%	1 4.8%	2 0.9%

Outcome Measures

1. Primary Outcome

Title	Parts A, B and C: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame	From first dose of study drug in treatment period up to safety follow-up (up to 28 days)

Outcome Measure Data

Analysis Population Description

Safety Set included all participants who received at least 1 dose of study drug.

Arm/Group Title	Part A: Pooled Placebo (Except Cohort A7)	Part A: VX-445 (Except Cohort A7)	Part A: VX-445 (Cohort A7)	Part B: Pooled Placebo (Cohort B1 to B4)	Part B: VX-445 (Cohort B1 to B4)	Part C: Pooled Placebo (Cohort C1 to C3)	Part C: VX-445/TEZ/IVA TC (Cohort C1 to C3)
Arm/Group Description	Participants without CF who received single dose of placebo matched to VX-445 in Cohort A1 to A5.	Participants without CF who received single ascending dose of VX-445 tablet starting from 20 milligrams (mg) to 360 mg in Cohort A1 to A5.	Participants without CF who received single dose of VX-445 100 mg tablet on Day 1 in fasted state and on Day 7 in fed state, followed by VX-445 20 mg intravenous (IV) injection on Day 13 in fed state in Cohort A7.	Participants without CF who received multiple doses of placebo matched to VX-445 qd for 10 days in Cohort B1 to B4.	Participants without CF who received VX-445 tablet once daily for 10 days in Cohort B1 (60 mg), B2 (120 mg), B3 (240 mg) and B4 (340 mg).	Participants without CF who received placebo matched to VX-445/TEZ/IVA triple combination (TC) once daily in the morning and placebo matched to IVA in the evening for 14 days.	Participants without CF who received VX-445 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in Cohort C1; VX-445 280 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in Cohort C2 and VX-445 100 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in Cohort C3 for 14 days.
Measure Participants	9	30	8	7	25	6	17
Participants with AEs	0 0%	3 10%	1 12.5%	2 28.6%	2 8%	2 33.3%	5 29.4%
Participants with SAEs	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%

2. Primary Outcome

Title	Parts D, E and F: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame	From first dose of study drug in TC treatment period up to 28 days after last dose of study drug (up to 5 weeks)

Outcome Measure Data

Analysis Population Description

The Safety Set will include all participants who received at least 1 dose of study drug.

Arm/Group Title	Part D: Placebo	Part D: VX-445/TEZ/IVA TC	Part E: TEZ/IVA	Part E: VX-445/TEZ/IVA TC	Part F: Placebo	Part F: VX-445/TEZ/VX-561 TC
Arm/Group Description	Participants with CF, F/MF genotype who received placebo matched to VX-445/TEZ/IVA TC once daily in the morning and placebo matched to IVA in the evening for 4 weeks in the TC treatment period.	Participants with CF, F/MF genotype who received VX-445/TEZ/IVA TC for 4 weeks in the TC treatment period.	Following run-in period of 4 weeks with TEZ/IVA, participants with CF, F/F genotype who received TEZ 100 mg qd/IVA 150 mg q12h and placebo matched to VX-445 for 4 weeks in the TC treatment period.	Following run-in period of 4 weeks with TEZ/IVA, participants with CF, F/F genotype who received VX-445 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the TC treatment period.	Participants with CF, F/MF genotype who received placebo matched to VX-445/TEZ/VX-561 for 4 weeks in the TC treatment period.	Participants with CF, F/MF genotype who received VX-445 200 mg qd/TEZ 100 mg qd/VX-561 150 mg qd for 4 weeks in the TC treatment period.
Measure Participants	12	53	7	21	8	21
Participants with AEs	12 133.3%	49 163.3%	5 62.5%	19 271.4%	7 28%	19 316.7%
Participants with SAEs	2 22.2%	3 10%	1 12.5%	0 0%	1 4%	0 0%

3. Primary Outcome

Title	Part D: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
Description	FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Time Frame	From Baseline through Day 29

Outcome Measure Data

Analysis Population Description

The full analysis set (FAS) included all randomized participants who carry the intended CFTR allele mutation and have received at least 1 dose of study drug in the TC treatment period.

Arm/Group Title	Part D: Placebo	Part D: VX-445/TEZ/IVA TC - Low Dose	Part D: VX-445/TEZ/IVA TC - Medium Dose	Part D: VX-445/TEZ/IVA TC - High Dose
Arm/Group Description	Participants with CF, F/MF genotype who received placebo matched to VX-445/TEZ/IVA TC once daily in the morning and placebo matched to IVA in the evening for 4 weeks in the TC treatment period.	Participants with CF, F/MF genotype who received VX-445 50 mg qd /TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the TC treatment period.	Participants with CF, F/MF genotype who received VX-445 100 mg qd /TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the TC treatment period.	Participants with CF, F/MF genotype who received VX-445 200 mg qd /TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the TC treatment period.
Measure Participants	12	10	22	21
Least Squares Mean (Standard Error) [percentage points]	0.0 (2.0)	11.1 (2.1)	7.9 (1.4)	13.8 (1.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part A: Pooled Placebo (Except Cohort A7)
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9943
	Comments	P value within treatment
	Method	Mixed-effects model for repeated measure
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Part A: VX-445 (Except Cohort A7)
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P value within treatment
	Method	Mixed-effects model for repeated measure
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Part A: VX-445 (Cohort A7)
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	P value within treatment
	Method	Mixed-effects model for repeated measure
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Part B: Pooled Placebo (Cohort B1 to B4)
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P value within treatment
	Method	Mixed-effects model for repeated measure
	Comments

4. Primary Outcome

Title	Part E: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
Description	FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Time Frame	From Baseline through Day 29

Outcome Measure Data

Analysis Population Description

FAS.

Arm/Group Title	Part E: TEZ/IVA	Part E: VX-445/TEZ/IVA TC
Arm/Group Description	Following run-in period of 4 weeks with TEZ/IVA, participants with CF, F/F genotype who received TEZ 100 mg qd/IVA 150 mg q12h and placebo matched to VX-445 for 4 weeks in the TC treatment period.	Following run-in period of 4 weeks with TEZ/IVA, participants with CF, F/F genotype who received VX-445 200 mg qd/TEZ 100 mg qd /IVA 150 mg q12h for 4 weeks in the TC treatment period.
Measure Participants	7	21
Least Squares Mean (Standard Error) [percentage points]	0.4 (2.8)	11.0 (1.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part A: Pooled Placebo (Except Cohort A7)
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8869
	Comments	P value within treatment.
	Method	Mixed-effects model for repeated measure
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Part A: VX-445 (Except Cohort A7)
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P value within treatment
	Method	Mixed-effects model for repeated measure
	Comments

5. Primary Outcome

Title	Part F: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
Description	FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Time Frame	From Baseline through Day 29

Outcome Measure Data

Analysis Population Description

FAS.

Arm/Group Title	Part F: Placebo	Part F: VX-445/TEZ/VX-561 TC
Arm/Group Description	Participants with CF, F/MF genotype who received placebo matched to VX-445/TEZ/VX-561 for 4 weeks in the TC treatment period.	Participants with CF, F/MF genotype who received VX-445 200 mg/TEZ 100 mg/VX-561 150 mg qd for 4 weeks in the TC treatment period.
Measure Participants	8	21
Least Squares Mean (Standard Error) [percentage points]	1.2 (2.6)	11.7 (1.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part A: Pooled Placebo (Except Cohort A7)
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6407
	Comments	P value within treatment
	Method	Mixed-effects model for repeated measure
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Part A: VX-445 (Except Cohort A7)
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P value within treatment.
	Method	mixed-effects model for repeated measure
	Comments

6. Secondary Outcome

Title	Part A: Maximum Observed Concentration (Cmax) of VX-445
Time Frame	Cohort A1-A5: Pre-dose to 96 hours post-dose; Cohort A7: Pre-dose to 120 hours post-dose

Outcome Measure Data

Analysis Population Description

The Pharmacokinetic Set included all participants who received at least 1 dose of study drug and for whom the primary PK data are considered sufficient and interpretable.

Arm/Group Title	Part A: VX-445 (Cohort A1)	Part A: VX-445 (Cohort A2)	Part A: VX-445 (Cohort A3)	Part A: VX-445 (Cohort A4)	Part A: VX-445 (Cohort A5)	Part A: VX-445 (Cohort A7-Fasted)	Part A: VX-445 (Cohort A7-Fed)	Part A: VX-445 (Cohort A7-IV)
Arm/Group Description	Participants received single dose of VX-445 20 mg tablet in Cohort A1.	Participants received single dose of VX-445 60 mg tablet in Cohort A2.	Participants received single dose of VX-445 120 mg tablet in Cohort A3.	Participants received single dose of VX-445 240 mg tablet in Cohort A4.	Participants received single dose of VX-445 360 mg tablet in Cohort A5.	Participants received single dose of VX-445 100 mg tablet on Day 1 in fasted state in Cohort A7.	Participants received single dose of VX-445 100 mg tablet on Day 7 in fed state in Cohort A7.	Participants received single IV injection of VX-445 20 mg on Day 13 in fed state in Cohort A7.
Measure Participants	6	6	6	6	6	8	7	7
Geometric Mean (Geometric Coefficient of Variation) [microgram per milliliter]	0.398 (23.0)	0.989 (35.1)	2.52 (13.0)	4.56 (28.2)	7.07 (19.1)	0.486 (27.4)	1.76 (14.6)	0.740 (27.1)

7. Secondary Outcome

Title	Part A: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of VX-445
Time Frame	Cohort A1-5: Pre-dose to 96 hours post-dose; Cohort A7: Pre-dose to 120 hours post-dose

Outcome Measure Data

Analysis Population Description

The Pharmacokinetic Set.

Arm/Group Title	Part A: VX-445 (Cohort A1)	Part A: VX-445 (Cohort A2)	Part A: VX-445 (Cohort A3)	Part A: VX-445 (Cohort A4)	Part A: VX-445 (Cohort A5)	Part A: VX-445 (Cohort A7-Fasted)	Part A: VX-445 (Cohort A7-Fed)	Part A: VX-445 (Cohort A7-IV)
Arm/Group Description	Participants received single dose of VX-445 20 mg tablet in Cohort A1.	Participants received single dose of VX-445 60 mg tablet in Cohort A2.	Participants received single dose of VX-445 120 mg tablet in Cohort A3.	Participants received single dose of VX-445 240 mg tablet in Cohort A4.	Participants received single dose of VX-445 360 mg tablet in Cohort A5.	Participants received single dose of VX-445 100 mg tablet on Day 1 in fasted state in Cohort A7.	Participants received single dose of VX-445 100 mg tablet on Day 7 in fed state in Cohort A7.	Participants received single IV injection of VX-445 20 mg on Day 13 in fed state in Cohort A7.
Measure Participants	6	6	6	6	6	8	7	7
Geometric Mean (Geometric Coefficient of Variation) [microgram*hour per milliliter]	11.4 (34.2)	30.8 (21.2)	87.1 (39.9)	125 (34.2)	286 (9.30)	21.8 (31.5)	55.1 (14.9)	13.6 (19.7)

8. Secondary Outcome

Title	Part B: Maximum Observed Concentration (Cmax) of VX-445
Time Frame	Pre-dose to 96 hours post-dose on Day 1 and Day 10

Outcome Measure Data

Analysis Population Description

The Pharmacokinetic Set.

Arm/Group Title	Part B: VX-445 (Cohort B1)	Part B: VX-445 (Cohort B2)	Part B: VX-445 (Cohort B3)	Part B: VX-445 (Cohort B4)
Arm/Group Description	Participants received VX-445 60 mg tablet once daily for 10 days in Cohort B1.	Participants received VX-445 120 mg tablet once daily for 10 days in Cohort B2.	Participants received VX-445 240 mg tablet once daily for 10 days in Cohort B3.	Participants received VX-445 340 mg tablet once daily for 10 days in Cohort B4.
Measure Participants	6	6	6	6
Day 1	1.18 (19.9)	2.82 (25.5)	3.47 (52.9)	9.56 (65.6)
Day 10	2.13 (15)	5.83 (28.1)	11.4 (27.2)	18.2 (29.5)

9. Secondary Outcome

Title	Part B: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of VX-445
Time Frame	Pre-dose to 96 hours post-dose on Day 1 and Day 10

Outcome Measure Data

Analysis Population Description

The Pharmacokinetic Set. Here "Number analyzed" signifies those participants who were evaluated for this outcome measure at specified time points.

Arm/Group Title	Part B: VX-445 (Cohort B1)	Part B: VX-445 (Cohort B2)	Part B: VX-445 (Cohort B3)	Part B: VX-445 (Cohort B4)
Arm/Group Description	Participants received VX-445 60 mg tablet once daily for 10 days in Cohort B1.	Participants received VX-445 120 mg tablet once daily for 10 days in Cohort B2.	Participants received VX-445 240 mg tablet once daily for 10 days in Cohort B3.	Participants received VX-445 340 mg tablet once daily for 10 days in Cohort B4.
Measure Participants	6	6	6	6
Day 1	17.9 (20.0)	42.2 (19.5)	57.9 (42.8)	119 (27.5)
Day 10	61.4 (21.8)	183 (32.7)	452 (41.5)	692 (47.6)

10. Secondary Outcome

Title	Part B: Observed Pre-dose Plasma Concentration (Ctrough) of VX-445
Time Frame	Pre-dose on Day 10

Outcome Measure Data

Analysis Population Description

The Pharmacokinetic Set.

Arm/Group Title	Part B: VX-445 (Cohort B1)	Part B: VX-445 (Cohort B2)	Part B: VX-445 (Cohort B3)	Part B: VX-445 (Cohort B4)
Arm/Group Description	Participants received VX-445 60 mg tablet once daily for 10 days in Cohort B1.	Participants received VX-445 120 mg tablet once daily for 10 days in Cohort B2.	Participants received VX-445 240 mg tablet once daily for 10 days in Cohort B3.	Participants received VX-445 340 mg tablet once daily for 10 days in Cohort B4.
Measure Participants	6	6	6	6
Geometric Mean (Geometric Coefficient of Variation) [microgram per milliliter]	1.05 (24.5)	2.81 (33.2)	7.10 (30.1)	11.5 (32.0)

11. Secondary Outcome

Title	Part C: Maximum Observed Concentration (Cmax) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ)
Time Frame	Pre-dose to 96 hours post-dose on Day 1, Day 7 and Day 14

Outcome Measure Data

Analysis Population Description

The Pharmacokinetic Set. Here "Number analyzed" signified those subjects who were evaluated at specified time points.

Arm/Group Title	Part C: VX-445/TEZ/IVA TC (Cohort C1)	Part C: VX-445/TEZ/IVA TC (Cohort C2)	Part C: VX-445/TEZ/IVA TC (Cohort C3)
Arm/Group Description	Participants received VX-445 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in cohort C1 for 14 days.	Participants received VX-445 280 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in cohort C2 for 14 days.	Participants received VX-445 100 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in cohort C3 for 14 days.
Measure Participants	5	6	6
VX-445: Day 1	3.04 (23.2)	4.86 (25.4)	1.72 (16.5)
VX-445: Day 7	8.29 (31.9)	10.3 (18.4)	3.58 (14.8)
VX-445: Day 14	8.71 (9.65)	14.0 (19.2)	4.73 (15.9)
TEZ: Day 1	3.81 (16.4)	5.67 (17.2)	5.38 (19.2)
TEZ: Day 7	7.09 (19.4)	8.29 (13.6)	7.01 (14.7)
TEZ: Day 14	8.11 (21.2)	9.07 (7.60)	8.60 (12.8)
M1-TEZ: Day 1	0.929 (35)	0.988 (31.7)	1.30 (17.3)
M1-TEZ: Day 7	4.34 (28.7)	5.19 (16.8)	5.86 (11.3)
M1-TEZ: Day 14	5.77 (24.6)	6.79 (14.9)	7.54 (11.8)
M2-TEZ: Day 1	0.553 (47.0)	0.667 (39.6)	0.716 (17.0)
M2-TEZ: Day 7	4.72 (30.3)	6.41 (33.2)	5.46 (29.4)
M2-TEZ: Day 14	7.69 (23.7)	10.1 (24.2)	7.93 (28.3)

12. Secondary Outcome

Title	Part C: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ)
Time Frame	Pre-dose to 96 hours post-dose on Day 1, Day 7 and Day 14

Outcome Measure Data

Analysis Population Description

The Pharmacokinetic Set. Here "Number analyzed" signified those subjects who were evaluated at specified time points.

Arm/Group Title	Part C: VX-445/TEZ/IVA TC (Cohort C1)	Part C: VX-445/TEZ/IVA TC (Cohort C2)	Part C: VX-445/TEZ/IVA TC (Cohort C3)
Arm/Group Description	Participants received VX-445 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in cohort C1 for 14 days.	Participants received VX-445 280 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in cohort C2 for 14 days.	Participants received VX-445 100 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in cohort C3 for 14 days.
Measure Participants	5	6	6
VX-445: Day 1	48.6 (22.7)	72.5 (20.7)	26.4 (13.8)
VX-445: Day 7	156 (37.1)	177 (30.0)	65.4 (20.7)
VX-445: Day 14	345 (30.7)	506 (31.5)	183 (18.8)
TEZ: Day 1	41.4 (27.5)	43.8 (9.91)	42.7 (20.9)
TEZ: Day 7	103 (35.8)	105 (16.5)	96.9 (18.9)
TEZ: Day 14	252 (35.1)	288 (13.6)	275 (19.5)
M1-TEZ: Day 1	17.7 (37.2)	20.1 (35.2)	25.5 (19.1)
M1-TEZ: Day 7	90.9 (29.9)	110 (17.8)	125 (14.1)
M1-TEZ: Day 14	380 (22.1)	477 (16.0)	512 (17.9)
M2-TEZ: Day 1	6.65 (48.6)	8.19 (52.5)	9.00 (16.6)
M2-TEZ: Day 7	108 (31.2)	143 (34.1)	123 (28.7)
M2-TEZ: Day 14	617 (23.2)	831 (29.5)	652 (31.2)

13. Secondary Outcome

Title	Part C: Maximum Observed Concentration (Cmax) of IVA and Its Metabolites (M1-IVA and M6-IVA)
Time Frame	Pre-dose to 96 hours post-dose on Day 1, Day 7 and Day 14

Outcome Measure Data

Analysis Population Description

The Pharmacokinetic Set. Here "Number analyzed" signified those subjects who were evaluated at specified time points.

Arm/Group Title	Part C: VX-445/TEZ/IVA TC (Cohort C1)	Part C: VX-445/TEZ/IVA TC (Cohort C2)	Part C: VX-445/TEZ/IVA TC (Cohort C3)
Arm/Group Description	Participants received VX-445 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in cohort C1 for 14 days.	Participants received VX-445 280 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in cohort C2 for 14 days.	Participants received VX-445 100 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in cohort C3 for 14 days.
Measure Participants	5	6	6
IVA: Day 1	425 (29.8)	461 (49.3)	437 (9.63)
IVA: Day 7	1290 (41.1)	1190 (42.4)	1070 (20.0)
IVA: Day 14	1360 (21.9)	1920 (33.7)	1410 (25.5)
M1-IVA: Day 1	1250 (29.9)	1190 (28.1)	1070 (28.6)
M1-IVA: Day 7	2460 (26.8)	2590 (28.1)	2070 (23.1)
M1-IVA: Day 14	2680 (19.4)	3900 (21.4)	2990 (28.3)
M6-IVA: Day 1	901 (38.2)	1180 (16.6)	631 (31.1)
M6-IVA: Day 7	1960 (38.1)	2590 (7.3)	1400 (29.8)
M6-IVA: Day 14	2060 (30.1)	3350 (17.4)	1980 (34.7)

14. Secondary Outcome

Title	Part C: Area Under Plasma Concentration Time Curve From Time of Dosing to Last Measurable Concentration (AUC0-tlast) of IVA and Its Metabolites (M1-IVA and M6-IVA)
Time Frame	Pre-dose to 96 hours post-dose on Day 1, Day 7 and Day 14

Outcome Measure Data

Analysis Population Description

The Pharmacokinetic Set. Here "Number analyzed" signified those subjects who were evaluated at specified time points.

Arm/Group Title	Part C: VX-445/TEZ/IVA TC (Cohort C1)	Part C: VX-445/TEZ/IVA TC (Cohort C2)	Part C: VX-445/TEZ/IVA TC (Cohort C3)
Arm/Group Description	Participants received VX-445 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in cohort C1 for 14 days.	Participants received VX-445 280 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in cohort C2 for 14 days.	Participants received VX-445 100 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in cohort C3 for 14 days.
Measure Participants	5	6	6
IVA: Day 1	6350 (40.9)	6210 (45.5)	5480 (28.5)
IVA: Day 7	21600 (65.6)	18800 (50.7)	16900 (28.4)
IVA: Day 14	27900 (48.7)	35000 (44.8)	32600 (40.6)
M1-IVA: Day 1	16900 (38.9)	14800 (32.3)	13300 (21.1)
M1-IVA: Day 7	47500 (43.6)	46300 (30.6)	36400 (25.9)
M1-IVA: Day 14	75300 (42.7)	97000 (31.3)	86100 (30.2)
M6-IVA: Day 1	11100 (49.9)	14100 (20.3)	9050 (26.1)
M6-IVA: Day 7	39700 (38.8)	51400 (13.0)	29100 (36.0)
M6-IVA: Day 14	66300 (44.9)	123000 (23.1)	67100 (42.3)

15. Secondary Outcome

Title	Part C: Observed Pre-dose Concentration (Ctrough) of VX-445, TEZ and Its Metabolites (M1-TEZ and M2-TEZ)
Time Frame	Pre-dose on Day 7 and Day 14

Outcome Measure Data

Analysis Population Description

The Pharmacokinetic Set.

Arm/Group Title	Part C: VX-445/TEZ/IVA TC (Cohort C1)	Part C: VX-445/TEZ/IVA TC (Cohort C2)	Part C: VX-445/TEZ/IVA TC (Cohort C3)
Arm/Group Description	Participants received VX-445 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in cohort C1 for 14 days.	Participants received VX-445 280 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in cohort C2 for 14 days.	Participants received VX-445 100 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in cohort C3 for 14 days.
Measure Participants	5	6	6
VX-445: Day 7	4.63 (46.8)	5.91 (35.5)	2.09 (14.9)
VX-445: Day 14	4.45 (38.9)	7.60 (29.8)	2.92 (13.2)
TEZ: Day 7	2.73 (48.7)	2.77 (19.2)	2.52 (23.0)
TEZ: Day 14	3.10 (33.4)	3.70 (16.0)	3.62 (24.6)
M1-TEZ: Day 7	3.36 (27.1)	3.98 (16.8)	4.71 (14.0)
M1-TEZ: Day 14	4.38 (20.5)	5.42 (16.1)	5.52 (12.9)
M2-TEZ: Day 7	4.06 (32.8)	5.63 (37.5)	4.92 (27.7)
M2-TEZ: Day 14	6.46 (22.5)	8.85 (29.9)	7.38 (29.6)

16. Secondary Outcome

Title	Part C: Observed Pre-dose Concentration (Ctrough) of IVA and Its Metabolites (M1-IVA and M6-IVA)
Time Frame	Pre-dose on Day 7 and Day 14

Outcome Measure Data

Analysis Population Description

The Pharmacokinetic Set.

Arm/Group Title	Part C: VX-445/TEZ/IVA TC (Cohort C1)	Part C: VX-445/TEZ/IVA TC (Cohort C2)	Part C: VX-445/TEZ/IVA TC (Cohort C3)
Arm/Group Description	Participants received VX-445 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in cohort C1 for 14 days.	Participants received VX-445 280 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in cohort C2 for 14 days.	Participants received VX-445 100 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in cohort C3 for 14 days.
Measure Participants	5	6	6
IVA: Day 7	753 (75)	759 (45.7)	604 (32.8)
IVA: Day 14	610 (55.6)	990 (43.4)	881 (35.3)
M1-IVA: Day 7	1790 (43.7)	1960 (21.4)	1400 (21.3)
M1-IVA: Day 14	1600 (46.2)	2210 (19.8)	1930 (16.9)
M6-IVA: Day 7	1530 (31.5)	2260 (11.9)	1270 (32.1)
M6-IVA: Day 14	1360 (49.1)	2600 (18.0)	1640 (27.0)

17. Secondary Outcome

Title	Part D: Observed Pre-dose Plasma Concentration (Ctrough) of VX-445, TEZ and Its Metabolite (M1-TEZ), IVA and Its Metabolite (M1-IVA)
Time Frame	Pre-dose on Day 15 and Day 29

Outcome Measure Data

Analysis Population Description

FAS. Here "number analyzed" signifies those participants who were evaluated at specified time points for this outcome measure.

Arm/Group Title	Part D: VX-445/TEZ/IVA TC - Low Dose	Part D: VX-445/TEZ/IVA TC - Medium Dose	Part D: VX-445/TEZ/IVA TC - High Dose
Arm/Group Description	Participants with CF, F/MF genotype who received VX-445 50 mg qd /TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the TC treatment period.	Participants with CF, F/MF genotype who received VX-445 100 mg qd /TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the TC treatment period.	Participants with CF, F/MF genotype who received VX-445 200 mg qd /TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the TC treatment period.
Measure Participants	10	21	21
VX-445: Day 15	1.04 (0.612)	2.15 (0.977)	5.77 (4.14)
VX-445: Day 29	1.27 (0.530)	2.18 (1.26)	5.57 (2.80)
TEZ: Day 15	1.85 (1.26)	1.68 (0.700)	1.76 (0.960)
TEZ: Day 29	2.16 (1.27)	1.77 (0.833)	2.22 (1.62)
M1-TEZ: Day 15	4.46 (1.96)	4.11 (1.47)	4.43 (1.79)
M1-TEZ: Day 29	4.77 (2.04)	4.30 (1.55)	4.74 (1.89)
IVA: Day 15	0.720 (0.484)	0.665 (0.414)	0.701 (0.593)
IVA: Day 29	0.753 (0.424)	0.704 (0.414)	0.658 (0.386)
M1-IVA: Day 15	1.29 (0.748)	1.21 (0.666)	1.45 (1.22)
M1-IVA: Day 29	1.57 (0.830)	1.20 (0.717)	1.29 (0.797)

18. Secondary Outcome

Title	Part E: Observed Pre-dose Concentration (Ctrough) of VX-445, TEZ and Its Metabolite (M1-TEZ) and IVA and Its Metabolite (M1-IVA)
Time Frame	Pre-dose on Day 15 and Day 29

Outcome Measure Data

Analysis Population Description

FAS. Here "Number analyzed" signifies those participants who were evaluated at specified time points for this outcome measure.

Arm/Group Title	Part E: TEZ/IVA	Part E: VX-445/TEZ/IVA TC
Arm/Group Description	Following run-in period of 4 weeks with TEZ/IVA, participants with CF, F/F genotype who received TEZ 100 mg qd/IVA 150 mg q12h and placebo matched to VX-445 for 4 weeks in the TC treatment period.	Following run-in period of 4 weeks with TEZ/IVA, participants with CF, F/F genotype who received VX-445 200 mg qd/TEZ 100 mg qd /IVA 150 mg q12h for 4 weeks in the TC treatment period.
Measure Participants	7	21
VX-445: Day 15	5.07 (2.47)
VX-445: Day 29	5.35 (3.73)
TEZ: Day 15	1.85 (0.863)	1.86 (1.09)
TEZ: Day 29	1.84 (1.28)	1.99 (1.55)
M1-TEZ: Day 15	3.96 (1.76)	4.57 (1.73)
M1-TEZ: Day 29	3.73 (1.51)	4.71 (1.86)
IVA: Day 15	0.766 (0.366)	0.659 (0.529)
IVA: Day 29	0.595 (0.303)	0.798 (0.901)
M1-IVA: Day 15	1.22 (0.470)	1.09 (0.973)
M1-IVA: Day 29	0.943 (0.431)	1.43 (1.54)

19. Secondary Outcome

Title	Part F: Observed Pre-dose Concentration (Ctrough) of VX-445, TEZ and Its Metabolite (M1-TEZ) and VX-561
Time Frame	Pre-dose on Day 15 and Day 29

Outcome Measure Data

Analysis Population Description

FAS. Here, "Number analyzed" signifies those participants who were evaluated at specified time points for this outcome measure.

Arm/Group Title	Part F: VX-445/TEZ/VX-561 TC
Arm/Group Description	Participants with CF, F/MF genotype who received VX-445 200 mg qd/TEZ 100 mg qd/VX-561 150 mg qd for 4 weeks in the TC treatment period.
Measure Participants	20
VX-445: Day 15	4.40 (1.54)
VX-445: Day 29	5.25 (2.88)
TEZ: Day 15	1.80 (0.658)
TEZ: Day 29	2.22 (1.65)
M1-TEZ: Day 15	4.99 (1.71)
M1-TEZ: Day 29	5.09 (1.37)
VX-561: Day 15	0.441 (0.174)
VX-561: Day 29	0.597 (0.473)

20. Secondary Outcome

Title	Part D: Absolute Change in Sweat Chloride Concentration
Description	Sweat samples were collected using an approved collection device.
Time Frame	From Baseline through Day 29

Outcome Measure Data

Analysis Population Description

FAS.

Arm/Group Title	Part D: Placebo	Part D: VX-445/TEZ/IVA TC - Low Dose	Part D: VX-445/TEZ/IVA TC - Medium Dose	Part D: VX-445/TEZ/IVA TC - High Dose
Arm/Group Description	Participants with CF, F/MF genotype who received placebo matched to VX-445/TEZ/IVA TC once daily in the morning and placebo matched to IVA in the evening for 4 weeks in the TC treatment period.	Participants with CF, F/MF genotype who received VX-445 50 mg qd /TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the TC treatment period.	Participants with CF, F/MF genotype who received VX-445 100 mg qd /TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the TC treatment period.	Participants with CF, F/MF genotype who received VX-445 200 mg qd /TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the TC treatment period.
Measure Participants	12	10	22	21
Least Squares Mean (Standard Error) [millimole per liter (mmol/L)]	-2.2 (3.9)	-38.2 (4.2)	-33.2 (2.8)	-39.1 (2.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part A: Pooled Placebo (Except Cohort A7)
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5802
	Comments	P value within treatment. These are nominal p-values without multiplicity control.
	Method	Mixed-effects model for repeated measure
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Part A: VX-445 (Except Cohort A7)
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P value within treatment. These are nominal p-values without multiplicity control.
	Method	Mixed-effects model for repeated measure
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Part A: VX-445 (Cohort A7)
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P value within treatment. These are nominal p-values without multiplicity control.
	Method	Mixed-effects model for repeated measure
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Part B: Pooled Placebo (Cohort B1 to B4)
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P value within treatment. These are nominal p-values without multiplicity control.
	Method	Mixed-effects model for repeated measure
	Comments

21. Secondary Outcome

Title	Part E: Absolute Change in Sweat Chloride Concentration
Description	Sweat samples were collected using an approved collection device.
Time Frame	From Baseline through Day 29

Outcome Measure Data

Analysis Population Description

FAS.

Arm/Group Title	Part E: TEZ/IVA	Part E: VX-445/TEZ/IVA TC
Arm/Group Description	Following run-in period of 4 weeks with TEZ/IVA, participants with CF, F/F genotype who received TEZ 100 mg qd/IVA 150 mg q12h and placebo matched to VX-445 for 4 weeks in the TC treatment period.	Following run-in period of 4 weeks with TEZ/IVA, participants with CF, F/F genotype who received VX-445 200 mg qd/TEZ 100 mg qd /IVA 150 mg q12h for 4 weeks in the TC treatment period.
Measure Participants	7	21
Least Squares Mean (Standard Error) [mmol/L]	0.8 (4.9)	-39.6 (2.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part A: Pooled Placebo (Except Cohort A7)
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8712
	Comments	P value within treatment. These are nominal p-values without multiplicity control.
	Method	mixed-effects model for repeated measure
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Part A: VX-445 (Except Cohort A7)
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P value within treatment. These are nominal p-values without multiplicity control.
	Method	mixed-effects model for repeated measure
	Comments

22. Secondary Outcome

Title	Part F: Absolute Change in Sweat Chloride Concentration
Description	Sweat samples were collected using an approved collection device.
Time Frame	From Baseline through Day 29

Outcome Measure Data

Analysis Population Description

FAS.

Arm/Group Title	Part F: Placebo	Part F: VX-445/TEZ/VX-561 TC
Arm/Group Description	Participants with CF, F/MF genotype who received placebo matched to VX-445/TEZ/VX-561 for 4 weeks in the TC treatment period.	Participants with CF, F/MF genotype who received VX-445 200 mg qd/TEZ 100 mg qd/VX-561 150 mg qd for 4 weeks in the TC treatment period.
Measure Participants	8	21
Least Squares Mean (Standard Error) [mmol/L]	1.0 (4.6)	-33.6 (2.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part A: Pooled Placebo (Except Cohort A7)
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8359
	Comments	P value within treatment. These are nominal p-values without multiplicity control.
	Method	mixed-effects model for repeated measure
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Part A: VX-445 (Except Cohort A7)
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P value within treatment. These are nominal p-values without multiplicity control.
	Method	mixed-effects model for repeated measure
	Comments

23. Secondary Outcome

Title	Part D: Relative Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
Description	FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Time Frame	From Baseline through Day 29

Outcome Measure Data

Analysis Population Description

FAS.

Arm/Group Title	Part D: Placebo	Part D: VX-445/TEZ/IVA TC - Low Dose	Part D: VX-445/TEZ/IVA TC - Medium Dose	Part D: VX-445/TEZ/IVA TC - High Dose
Arm/Group Description	Participants with CF, F/MF genotype who received placebo matched to VX-445/TEZ/IVA TC once daily in the morning and placebo matched to IVA in the evening for 4 weeks in the TC treatment period.	Participants with CF, F/MF genotype who received VX-445 50 mg qd /TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the TC treatment period.	Participants with CF, F/MF genotype who received VX-445 100 mg qd /TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the TC treatment period.	Participants with CF, F/MF genotype who received VX-445 200 mg qd /TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the TC treatment period.
Measure Participants	12	10	22	21
Least Squares Mean (Standard Error) [percent change]	0.3 (4.0)	19.3 (4.2)	13.8 (2.8)	26.2 (2.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part A: Pooled Placebo (Except Cohort A7)
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9453
	Comments	P value within treatment. These are nominal p-values without multiplicity control.
	Method	Mixed-effects model for repeated measure
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Part A: VX-445 (Except Cohort A7)
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P value within treatment. These are nominal p-values without multiplicity control.
	Method	Mixed-effects model for repeated measure
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Part A: VX-445 (Cohort A7)
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P value within treatment. These are nominal p-values without multiplicity control.
	Method	Mixed-effects model for repeated measure
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Part B: Pooled Placebo (Cohort B1 to B4)
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P value within treatment. These are nominal p-values without multiplicity control.
	Method	Mixed-effects model for repeated measure
	Comments

24. Secondary Outcome

Title	Part E: Relative Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
Description	FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Time Frame	From Baseline through Day 29

Outcome Measure Data

Analysis Population Description

FAS.

Arm/Group Title	Part E: TEZ/IVA	Part E: VX-445/TEZ/IVA TC
Arm/Group Description	Following run-in period of 4 weeks with TEZ/IVA, participants with CF, F/F genotype who received TEZ 100 mg qd/IVA 150 mg q12h and placebo matched to VX-445 for 4 weeks in the TC treatment period.	Following run-in period of 4 weeks with TEZ/IVA, participants with CF, F/F genotype who received VX-445 200 mg qd/TEZ 100 mg qd /IVA 150 mg q12h for 4 weeks in the TC treatment period.
Measure Participants	7	21
Least Squares Mean (Standard Error) [percent change]	1.4 (5.0)	19.2 (2.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part A: Pooled Placebo (Except Cohort A7)
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7849
	Comments	P value within treatment. These are nominal p-values without multiplicity control.
	Method	mixed-effects model for repeated measure
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Part A: VX-445 (Except Cohort A7)
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P value within treatment. These are nominal p-values without multiplicity control.
	Method	mixed-effects model for repeated measure
	Comments

25. Secondary Outcome

Title	Part F: Relative Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
Description	FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Time Frame	From Baseline through Day 29

Outcome Measure Data

Analysis Population Description

FAS.

Arm/Group Title	Part F: Placebo	Part F: VX-445/TEZ/VX-561 TC
Arm/Group Description	Participants with CF, F/MF genotype who received placebo matched to VX-445/TEZ/VX-561 for 4 weeks in the TC treatment period.	Participants with CF, F/MF genotype who received VX-445 200 mg qd/TEZ 100 mg qd/VX-561 150 mg qd for 4 weeks in the TC treatment period.
Measure Participants	8	21
Least Squares Mean (Standard Error) [percent change]	1.6 (4.6)	19.9 (2.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part A: Pooled Placebo (Except Cohort A7)
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7356
	Comments	P value within treatment. These are nominal p-values without multiplicity control.
	Method	mixed-effects model for repeated measure
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Part A: VX-445 (Except Cohort A7)
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P value within treatment. These are nominal p-values without multiplicity control.
	Method	mixed-effects model for repeated measure
	Comments

26. Secondary Outcome

Title	Part D: Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score
Description	The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with cystic fibrosis. Respiratory domain assessed respiratory symptoms, score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life.
Time Frame	From Baseline through Day 29

Outcome Measure Data

Analysis Population Description

FAS.

Arm/Group Title	Part D: Placebo	Part D: VX-445/TEZ/IVA TC - Low Dose	Part D: VX-445/TEZ/IVA TC - Medium Dose	Part D: VX-445/TEZ/IVA TC - High Dose
Arm/Group Description	Participants with CF, F/MF genotype who received placebo matched to VX-445/TEZ/IVA TC once daily in the morning and placebo matched to IVA in the evening for 4 weeks in the TC treatment period.	Participants with CF, F/MF genotype who received VX-445 50 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the TC treatment period.	Participants with CF, F/MF genotype who received VX-445 100 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the TC treatment period.	Participants with CF, F/MF genotype who received VX-445 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the TC treatment period.
Measure Participants	12	10	22	21
Least Squares Mean (Standard Error) [units on a scale]	4.2 (4.9)	20.8 (5.4)	15.4 (3.7)	25.7 (3.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part A: Pooled Placebo (Except Cohort A7)
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3940
	Comments	P value within treatment. These are nominal p-values without multiplicity control.
	Method	Mixed-effects model for repeated measure
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Part A: VX-445 (Except Cohort A7)
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0003
	Comments	P value within treatment. These are nominal p-values without multiplicity control.
	Method	Mixed-effects model for repeated measure
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Part A: VX-445 (Cohort A7)
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P value within treatment. These are nominal p-values without multiplicity control.
	Method	Mixed-effects model for repeated measure
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Part B: Pooled Placebo (Cohort B1 to B4)
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P value within treatment. These are nominal p-values without multiplicity control.
	Method	Mixed-effects model for repeated measure
	Comments

27. Secondary Outcome

Title	Part E: Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score
Description	The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with cystic fibrosis. Respiratory domain assessed respiratory symptoms, score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life.
Time Frame	From Baseline through Day 29

Outcome Measure Data

Analysis Population Description

FAS.

Arm/Group Title	Part E: TEZ/IVA	Part E: VX-445/TEZ/IVA TC
Arm/Group Description	Following run-in period of 4 weeks with TEZ/IVA, participants with CF, F/F genotype who received TEZ 100 mg qd/IVA 150 mg q12h and placebo matched to VX-445 for 4 weeks in the TC treatment period.	Following run-in period of 4 weeks with TEZ/IVA, participants with CF, F/F genotype who received VX-445 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the TC treatment period.
Measure Participants	7	21
Least Squares Mean (Standard Error) [units on a scale]	5.2 (7.1)	20.7 (4.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part A: Pooled Placebo (Except Cohort A7)
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4757
	Comments	P value within treatment. These are nominal p-values without multiplicity control.
	Method	mixed-effects model for repeated measure
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Part A: VX-445 (Except Cohort A7)
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P value within treatment. These are nominal p-values without multiplicity control.
	Method	mixed-effects model for repeated measure
	Comments

28. Secondary Outcome

Title	Part F: Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score
Description	The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with cystic fibrosis. Respiratory domain assessed respiratory symptoms, score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life.
Time Frame	From Baseline through Day 29

Outcome Measure Data

Analysis Population Description

FAS.

Arm/Group Title	Part F: Placebo	Part F: VX-445/TEZ/VX-561 TC
Arm/Group Description	Participants with CF, F/MF genotype who received placebo matched to VX-445/TEZ/VX-561 for 4 weeks in the TC treatment period.	Participants with CF, F/MF genotype who received VX-445 200 mg qd/TEZ 100 mg qd/VX-561 150 mg qd for 4 weeks in the TC treatment period.
Measure Participants	8	21
Least Squares Mean (Standard Error) [units on a scale]	20.2 (6.9)	20.2 (4.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part A: Pooled Placebo (Except Cohort A7)
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0070
	Comments	P value within treatment. These are nominal p-values without multiplicity control.
	Method	mixed-effects model for repeated measure
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Part A: VX-445 (Except Cohort A7)
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P value within treatment. These are nominal p-values without multiplicity control.
	Method	mixed-effects model for repeated measure
	Comments

Adverse Events

Time Frame	Parts A, B and C: From first dose of study drug in treatment period up to safety follow-up (up to 28 days); Parts D, E and F: From first dose of study drug in TC treatment period up to 28 days after last dose of study drug (up to 5 weeks)
Adverse Event Reporting Description	MedDRA version 19.1 for Parts A, B and C and MedDRA version 20.1 for Parts D, E and F.
Arm/Group Title	Part A: Pooled Placebo (Except Cohort A7)		Part A: VX-445 (Except Cohort A7)		Part A: VX-445 (Cohort A7)		Part B: Pooled Placebo (Cohort B1 to B4)		Part B: VX-445 (Cohort B1 to B4)		Part C: Pooled Placebo (Cohort C1 to C3)		Part C: VX-445/TEZ/IVA TC (Cohort C1 to C3)		Part D: Placebo		Part D: VX-445/TEZ/IVA TC - Low Dose		Part D: VX-445/TEZ/IVA TC - Medium Dose		Part D: VX-445/TEZ/IVA TC - High Dose		Part E: TEZ/IVA		Part E: VX-445/TEZ/IVA TC		Part F: Placebo		Part F: VX-445/TEZ/VX-561 TC
Arm/Group Description	Participants without CF who received single dose of placebo matched to VX-445 in Cohort A1 to A5.		Participants without CF who received single ascending dose of VX-445 tablet starting from 20 mg to 360 mg in Cohort A1 to A5.		Participants without CF who received single dose of VX-445 100 mg tablet on Day 1 in fasted state and on Day 7 in fed state, followed by VX-445 20 mg IV injection on Day 13 in fed state in Cohort A7.		Participants without CF who received multiple doses of placebo matched to VX-445 qd for 10 days in Cohort B1 to B4.		Participants without CF who received VX-445 tablet once daily for 10 days in Cohort B1 (60 mg), B2 (120 mg), B3 (240 mg) and B4 (340 mg).		Participants without CF who received placebo matched to VX-445/TEZ/IVA TC once daily in the morning and placebo matched to IVA in the evening for 14 days.		Participants without CF who received VX-445 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in Cohort C1; VX-445 280 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in Cohort C2 and VX-445 100 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in Cohort C3 for 14 days.		Participants with CF, F/MF genotype who received placebo matched to VX-445/TEZ/IVA TC once daily in the morning and placebo matched to IVA in the evening for 4 weeks in the TC treatment period.		Participants with CF, F/MF genotype who received VX-445 50 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the TC treatment period.		Participants with CF, F/MF genotype who received VX-445 100 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the TC treatment period.		Participants with CF, F/MF genotype who received VX-445 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the TC treatment period.		Following run-in period of 4 weeks with TEZ/IVA, participants with CF, F/F genotype who received TEZ 100 mg qd/IVA 150 mg q12h and placebo matched to VX-445 for 4 weeks in the TC treatment period.		Following run-in period of 4 weeks with TEZ/IVA, participants with CF, F/F genotype who received VX-445 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the TC treatment period.		Participants with CF, F/MF genotype who received placebo matched to VX-445/TEZ/VX-561 for 4 weeks in the TC treatment period.		Participants with CF, F/MF genotype who received VX-445 200 mg qd/TEZ 100 mg qd/VX-561 150 mg qd for 4 weeks in the TC treatment period.
All Cause Mortality
	Part A: Pooled Placebo (Except Cohort A7)		Part A: VX-445 (Except Cohort A7)		Part A: VX-445 (Cohort A7)		Part B: Pooled Placebo (Cohort B1 to B4)		Part B: VX-445 (Cohort B1 to B4)		Part C: Pooled Placebo (Cohort C1 to C3)		Part C: VX-445/TEZ/IVA TC (Cohort C1 to C3)		Part D: Placebo		Part D: VX-445/TEZ/IVA TC - Low Dose		Part D: VX-445/TEZ/IVA TC - Medium Dose		Part D: VX-445/TEZ/IVA TC - High Dose		Part E: TEZ/IVA		Part E: VX-445/TEZ/IVA TC		Part F: Placebo		Part F: VX-445/TEZ/VX-561 TC
	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	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	0/9 (0%)		0/30 (0%)		0/8 (0%)		0/7 (0%)		0/25 (0%)		0/6 (0%)		0/17 (0%)		0/12 (0%)		0/10 (0%)		0/22 (0%)		0/21 (0%)		0/7 (0%)		0/21 (0%)		0/8 (0%)		0/21 (0%)
Serious Adverse Events
	Part A: Pooled Placebo (Except Cohort A7)		Part A: VX-445 (Except Cohort A7)		Part A: VX-445 (Cohort A7)		Part B: Pooled Placebo (Cohort B1 to B4)		Part B: VX-445 (Cohort B1 to B4)		Part C: Pooled Placebo (Cohort C1 to C3)		Part C: VX-445/TEZ/IVA TC (Cohort C1 to C3)		Part D: Placebo		Part D: VX-445/TEZ/IVA TC - Low Dose		Part D: VX-445/TEZ/IVA TC - Medium Dose		Part D: VX-445/TEZ/IVA TC - High Dose		Part E: TEZ/IVA		Part E: VX-445/TEZ/IVA TC		Part F: Placebo		Part F: VX-445/TEZ/VX-561 TC
	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	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	0/9 (0%)		0/30 (0%)		0/8 (0%)		0/7 (0%)		0/25 (0%)		0/6 (0%)		0/17 (0%)		2/12 (16.7%)		1/10 (10%)		2/22 (9.1%)		0/21 (0%)		1/7 (14.3%)		0/21 (0%)		1/8 (12.5%)		0/21 (0%)
Gastrointestinal disorders
Distal intestinal obstruction syndrome	0/9 (0%)		0/30 (0%)		0/8 (0%)		0/7 (0%)		0/25 (0%)		0/6 (0%)		0/17 (0%)		0/12 (0%)		1/10 (10%)		0/22 (0%)		0/21 (0%)		0/7 (0%)		0/21 (0%)		0/8 (0%)		0/21 (0%)
Infections and infestations
Infective pulmonary exacerbation of cystic fibrosis	0/9 (0%)		0/30 (0%)		0/8 (0%)		0/7 (0%)		0/25 (0%)		0/6 (0%)		0/17 (0%)		1/12 (8.3%)		1/10 (10%)		2/22 (9.1%)		0/21 (0%)		1/7 (14.3%)		0/21 (0%)		1/8 (12.5%)		0/21 (0%)
Investigations
Influenza A virus test positive	0/9 (0%)		0/30 (0%)		0/8 (0%)		0/7 (0%)		0/25 (0%)		0/6 (0%)		0/17 (0%)		0/12 (0%)		0/10 (0%)		1/22 (4.5%)		0/21 (0%)		0/7 (0%)		0/21 (0%)		0/8 (0%)		0/21 (0%)
Respiratory, thoracic and mediastinal disorders
Haemoptysis	0/9 (0%)		0/30 (0%)		0/8 (0%)		0/7 (0%)		0/25 (0%)		0/6 (0%)		0/17 (0%)		1/12 (8.3%)		0/10 (0%)		0/22 (0%)		0/21 (0%)		0/7 (0%)		0/21 (0%)		0/8 (0%)		0/21 (0%)
Jugular vein thrombosis	0/9 (0%)		0/30 (0%)		0/8 (0%)		0/7 (0%)		0/25 (0%)		0/6 (0%)		0/17 (0%)		0/12 (0%)		1/10 (10%)		0/22 (0%)		0/21 (0%)		0/7 (0%)		0/21 (0%)		0/8 (0%)		0/21 (0%)
Other (Not Including Serious) Adverse Events
	Part A: Pooled Placebo (Except Cohort A7)		Part A: VX-445 (Except Cohort A7)		Part A: VX-445 (Cohort A7)		Part B: Pooled Placebo (Cohort B1 to B4)		Part B: VX-445 (Cohort B1 to B4)		Part C: Pooled Placebo (Cohort C1 to C3)		Part C: VX-445/TEZ/IVA TC (Cohort C1 to C3)		Part D: Placebo		Part D: VX-445/TEZ/IVA TC - Low Dose		Part D: VX-445/TEZ/IVA TC - Medium Dose		Part D: VX-445/TEZ/IVA TC - High Dose		Part E: TEZ/IVA		Part E: VX-445/TEZ/IVA TC		Part F: Placebo		Part F: VX-445/TEZ/VX-561 TC
	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	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	0/9 (0%)		3/30 (10%)		1/8 (12.5%)		2/7 (28.6%)		2/25 (8%)		2/6 (33.3%)		5/17 (29.4%)		12/12 (100%)		10/10 (100%)		19/22 (86.4%)		17/21 (81%)		5/7 (71.4%)		18/21 (85.7%)		7/8 (87.5%)		17/21 (81%)
Ear and labyrinth disorders
Tinnitus	0/9 (0%)		0/30 (0%)		0/8 (0%)		0/7 (0%)		0/25 (0%)		0/6 (0%)		0/17 (0%)		1/12 (8.3%)		0/10 (0%)		0/22 (0%)		0/21 (0%)		0/7 (0%)		0/21 (0%)		0/8 (0%)		0/21 (0%)
Eye disorders
Visual impairment	0/9 (0%)		0/30 (0%)		0/8 (0%)		0/7 (0%)		0/25 (0%)		0/6 (0%)		0/17 (0%)		1/12 (8.3%)		0/10 (0%)		0/22 (0%)		0/21 (0%)		0/7 (0%)		0/21 (0%)		0/8 (0%)		0/21 (0%)
Gastrointestinal disorders
Diarrhoea	0/9 (0%)		1/30 (3.3%)		0/8 (0%)		0/7 (0%)		0/25 (0%)		1/6 (16.7%)		1/17 (5.9%)		1/12 (8.3%)		1/10 (10%)		3/22 (13.6%)		0/21 (0%)		0/7 (0%)		0/21 (0%)		1/8 (12.5%)		1/21 (4.8%)
Nausea	0/9 (0%)		1/30 (3.3%)		0/8 (0%)		0/7 (0%)		0/25 (0%)		1/6 (16.7%)		0/17 (0%)		2/12 (16.7%)		2/10 (20%)		3/22 (13.6%)		1/21 (4.8%)		1/7 (14.3%)		1/21 (4.8%)		3/8 (37.5%)		2/21 (9.5%)
Constipation	0/9 (0%)		0/30 (0%)		0/8 (0%)		1/7 (14.3%)		1/25 (4%)		0/6 (0%)		0/17 (0%)		0/12 (0%)		0/10 (0%)		0/22 (0%)		0/21 (0%)		0/7 (0%)		0/21 (0%)		0/8 (0%)		0/21 (0%)
Abdominal pain	0/9 (0%)		0/30 (0%)		0/8 (0%)		0/7 (0%)		1/25 (4%)		0/6 (0%)		0/17 (0%)		1/12 (8.3%)		0/10 (0%)		1/22 (4.5%)		0/21 (0%)		0/7 (0%)		2/21 (9.5%)		1/8 (12.5%)		0/21 (0%)
Dysphagia	0/9 (0%)		0/30 (0%)		0/8 (0%)		0/7 (0%)		0/25 (0%)		0/6 (0%)		1/17 (5.9%)		0/12 (0%)		0/10 (0%)		0/22 (0%)		0/21 (0%)		0/7 (0%)		0/21 (0%)		0/8 (0%)		0/21 (0%)
Salivary hypersecretion	0/9 (0%)		0/30 (0%)		0/8 (0%)		0/7 (0%)		0/25 (0%)		0/6 (0%)		1/17 (5.9%)		0/12 (0%)		0/10 (0%)		0/22 (0%)		0/21 (0%)		0/7 (0%)		0/21 (0%)		0/8 (0%)		0/21 (0%)
Vomiting	0/9 (0%)		0/30 (0%)		0/8 (0%)		0/7 (0%)		0/25 (0%)		0/6 (0%)		1/17 (5.9%)		0/12 (0%)		0/10 (0%)		1/22 (4.5%)		1/21 (4.8%)		1/7 (14.3%)		0/21 (0%)		2/8 (25%)		0/21 (0%)
Abdominal pain upper	0/9 (0%)		0/30 (0%)		0/8 (0%)		0/7 (0%)		0/25 (0%)		0/6 (0%)		0/17 (0%)		0/12 (0%)		1/10 (10%)		1/22 (4.5%)		1/21 (4.8%)		1/7 (14.3%)		0/21 (0%)		0/8 (0%)		1/21 (4.8%)
Abdominal discomfort	0/9 (0%)		0/30 (0%)		0/8 (0%)		0/7 (0%)		0/25 (0%)		0/6 (0%)		0/17 (0%)		1/12 (8.3%)		0/10 (0%)		0/22 (0%)		0/21 (0%)		0/7 (0%)		0/21 (0%)		0/8 (0%)		0/21 (0%)
Gastrooesophageal reflux disease	0/9 (0%)		0/30 (0%)		0/8 (0%)		0/7 (0%)		0/25 (0%)		0/6 (0%)		0/17 (0%)		1/12 (8.3%)		0/10 (0%)		0/22 (0%)		0/21 (0%)		0/7 (0%)		0/21 (0%)		0/8 (0%)		0/21 (0%)
Dyspepsia	0/9 (0%)		0/30 (0%)		0/8 (0%)		0/7 (0%)		0/25 (0%)		0/6 (0%)		0/17 (0%)		0/12 (0%)		1/10 (10%)		0/22 (0%)		0/21 (0%)		0/7 (0%)		1/21 (4.8%)		0/8 (0%)		0/21 (0%)
General disorders
Catheter site pain	0/9 (0%)		0/30 (0%)		1/8 (12.5%)		0/7 (0%)		0/25 (0%)		0/6 (0%)		0/17 (0%)		0/12 (0%)		0/10 (0%)		0/22 (0%)		0/21 (0%)		0/7 (0%)		0/21 (0%)		0/8 (0%)		0/21 (0%)
Infusion site pain	0/9 (0%)		0/30 (0%)		0/8 (0%)		0/7 (0%)		0/25 (0%)		0/6 (0%)		1/17 (5.9%)		0/12 (0%)		0/10 (0%)		0/22 (0%)		0/21 (0%)		0/7 (0%)		0/21 (0%)		0/8 (0%)		0/21 (0%)
Fatigue	0/9 (0%)		0/30 (0%)		0/8 (0%)		0/7 (0%)		0/25 (0%)		0/6 (0%)		1/17 (5.9%)		4/12 (33.3%)		1/10 (10%)		0/22 (0%)		0/21 (0%)		0/7 (0%)		4/21 (19%)		0/8 (0%)		0/21 (0%)
Pyrexia	0/9 (0%)		0/30 (0%)		0/8 (0%)		0/7 (0%)		0/25 (0%)		0/6 (0%)		0/17 (0%)		1/12 (8.3%)		0/10 (0%)		5/22 (22.7%)		1/21 (4.8%)		1/7 (14.3%)		3/21 (14.3%)		0/8 (0%)		0/21 (0%)
Malaise	0/9 (0%)		0/30 (0%)		0/8 (0%)		0/7 (0%)		0/25 (0%)		0/6 (0%)		0/17 (0%)		1/12 (8.3%)		0/10 (0%)		1/22 (4.5%)		0/21 (0%)		0/7 (0%)		1/21 (4.8%)		0/8 (0%)		1/21 (4.8%)
Pain	0/9 (0%)		0/30 (0%)		0/8 (0%)		0/7 (0%)		0/25 (0%)		0/6 (0%)		0/17 (0%)		1/12 (8.3%)		0/10 (0%)		0/22 (0%)		1/21 (4.8%)		1/7 (14.3%)		1/21 (4.8%)		0/8 (0%)		0/21 (0%)
Chest pain	0/9 (0%)		0/30 (0%)		0/8 (0%)		0/7 (0%)		0/25 (0%)		0/6 (0%)		0/17 (0%)		0/12 (0%)		0/10 (0%)		0/22 (0%)		0/21 (0%)		0/7 (0%)		1/21 (4.8%)		0/8 (0%)		2/21 (9.5%)
Chills	0/9 (0%)		0/30 (0%)		0/8 (0%)		0/7 (0%)		0/25 (0%)		0/6 (0%)		0/17 (0%)		0/12 (0%)		0/10 (0%)		0/22 (0%)		0/21 (0%)		0/7 (0%)		3/21 (14.3%)		0/8 (0%)		0/21 (0%)
Chest discomfort	0/9 (0%)		0/30 (0%)		0/8 (0%)		0/7 (0%)		0/25 (0%)		0/6 (0%)		0/17 (0%)		0/12 (0%)		0/10 (0%)		0/22 (0%)		0/21 (0%)		0/7 (0%)		0/21 (0%)		1/8 (12.5%)		0/21 (0%)
Infections and infestations
Conjunctivitis	0/9 (0%)		0/30 (0%)		0/8 (0%)		0/7 (0%)		0/25 (0%)		0/6 (0%)		1/17 (5.9%)		0/12 (0%)		0/10 (0%)		0/22 (0%)		0/21 (0%)		0/7 (0%)		0/21 (0%)		0/8 (0%)		0/21 (0%)
Nasopharyngitis	0/9 (0%)		0/30 (0%)		0/8 (0%)		0/7 (0%)		0/25 (0%)		0/6 (0%)		0/17 (0%)		0/12 (0%)		1/10 (10%)		0/22 (0%)		4/21 (19%)		1/7 (14.3%)		1/21 (4.8%)		1/8 (12.5%)		0/21 (0%)
Sinusitis	0/9 (0%)		0/30 (0%)		0/8 (0%)		0/7 (0%)		0/25 (0%)		0/6 (0%)		0/17 (0%)		0/12 (0%)		0/10 (0%)		1/22 (4.5%)		0/21 (0%)		0/7 (0%)		0/21 (0%)		1/8 (12.5%)		1/21 (4.8%)
Upper respiratory tract infection	0/9 (0%)		0/30 (0%)		0/8 (0%)		0/7 (0%)		0/25 (0%)		0/6 (0%)		0/17 (0%)		0/12 (0%)		0/10 (0%)		0/22 (0%)		1/21 (4.8%)		0/7 (0%)		0/21 (0%)		0/8 (0%)		2/21 (9.5%)
Oral candidiasis	0/9 (0%)		0/30 (0%)		0/8 (0%)		0/7 (0%)		0/25 (0%)		0/6 (0%)		0/17 (0%)		0/12 (0%)		0/10 (0%)		0/22 (0%)		0/21 (0%)		0/7 (0%)		1/21 (4.8%)		1/8 (12.5%)		0/21 (0%)
Viral upper respiratory tract infection	0/9 (0%)		0/30 (0%)		0/8 (0%)		0/7 (0%)		0/25 (0%)		0/6 (0%)		0/17 (0%)		0/12 (0%)		1/10 (10%)		0/22 (0%)		0/21 (0%)		0/7 (0%)		1/21 (4.8%)		0/8 (0%)		0/21 (0%)
Gastroenteritis viral	0/9 (0%)		0/30 (0%)		0/8 (0%)		0/7 (0%)		0/25 (0%)		0/6 (0%)		0/17 (0%)		0/12 (0%)		0/10 (0%)		0/22 (0%)		0/21 (0%)		1/7 (14.3%)		0/21 (0%)		0/8 (0%)		0/21 (0%)
Otitis media	0/9 (0%)		0/30 (0%)		0/8 (0%)		0/7 (0%)		0/25 (0%)		0/6 (0%)		0/17 (0%)		1/12 (8.3%)		0/10 (0%)		0/22 (0%)		0/21 (0%)		0/7 (0%)		0/21 (0%)		0/8 (0%)		0/21 (0%)
Tonsillitis	0/9 (0%)		0/30 (0%)		0/8 (0%)		0/7 (0%)		0/25 (0%)		0/6 (0%)		0/17 (0%)		0/12 (0%)		0/10 (0%)		0/22 (0%)		0/21 (0%)		1/7 (14.3%)		0/21 (0%)		0/8 (0%)		0/21 (0%)
Viral infection	0/9 (0%)		0/30 (0%)		0/8 (0%)		0/7 (0%)		0/25 (0%)		0/6 (0%)		0/17 (0%)		0/12 (0%)		0/10 (0%)		0/22 (0%)		0/21 (0%)		1/7 (14.3%)		0/21 (0%)		0/8 (0%)		0/21 (0%)
Infective pulmonary exacerbation of cystic fibrosis	0/9 (0%)		0/30 (0%)		0/8 (0%)		0/7 (0%)		0/25 (0%)		0/6 (0%)		0/17 (0%)		4/12 (33.3%)		2/10 (20%)		4/22 (18.2%)		2/21 (9.5%)		0/7 (0%)		5/21 (23.8%)		3/8 (37.5%)		3/21 (14.3%)
Catheter site infection	0/9 (0%)		0/30 (0%)		0/8 (0%)		0/7 (0%)		0/25 (0%)		0/6 (0%)		0/17 (0%)		0/12 (0%)		1/10 (10%)		0/22 (0%)		0/21 (0%)		0/7 (0%)		0/21 (0%)		0/8 (0%)		0/21 (0%)
Injury, poisoning and procedural complications
Radiation injury	0/9 (0%)		0/30 (0%)		0/8 (0%)		0/7 (0%)		0/25 (0%)		0/6 (0%)		0/17 (0%)		1/12 (8.3%)		0/10 (0%)		0/22 (0%)		0/21 (0%)		0/7 (0%)		0/21 (0%)		0/8 (0%)		0/21 (0%)
Investigations
Blood bilirubin increased	0/9 (0%)		0/30 (0%)		0/8 (0%)		0/7 (0%)		0/25 (0%)		0/6 (0%)		0/17 (0%)		0/12 (0%)		0/10 (0%)		1/22 (4.5%)		2/21 (9.5%)		1/7 (14.3%)		0/21 (0%)		0/8 (0%)		1/21 (4.8%)
Blood creatine phosphokinase increased	0/9 (0%)		0/30 (0%)		0/8 (0%)		0/7 (0%)		0/25 (0%)		0/6 (0%)		0/17 (0%)		0/12 (0%)		0/10 (0%)		0/22 (0%)		1/21 (4.8%)		0/7 (0%)		4/21 (19%)		0/8 (0%)		1/21 (4.8%)
Aspartate aminotransferase increased	0/9 (0%)		0/30 (0%)		0/8 (0%)		0/7 (0%)		0/25 (0%)		0/6 (0%)		0/17 (0%)		0/12 (0%)		0/10 (0%)		0/22 (0%)		1/21 (4.8%)		0/7 (0%)		3/21 (14.3%)		0/8 (0%)		1/21 (4.8%)
Forced expiratory volume decreased	0/9 (0%)		0/30 (0%)		0/8 (0%)		0/7 (0%)		0/25 (0%)		0/6 (0%)		0/17 (0%)		1/12 (8.3%)		0/10 (0%)		0/22 (0%)		1/21 (4.8%)		0/7 (0%)		0/21 (0%)		0/8 (0%)		1/21 (4.8%)
Alanine aminotransferase increased	0/9 (0%)		0/30 (0%)		0/8 (0%)		0/7 (0%)		0/25 (0%)		0/6 (0%)		0/17 (0%)		0/12 (0%)		0/10 (0%)		0/22 (0%)		0/21 (0%)		0/7 (0%)		2/21 (9.5%)		0/8 (0%)		0/21 (0%)
Blood triglycerides increased	0/9 (0%)		0/30 (0%)		0/8 (0%)		0/7 (0%)		0/25 (0%)		0/6 (0%)		0/17 (0%)		1/12 (8.3%)		0/10 (0%)		0/22 (0%)		0/21 (0%)		0/7 (0%)		0/21 (0%)		0/8 (0%)		0/21 (0%)
Pulmonary function test decreased	0/9 (0%)		0/30 (0%)		0/8 (0%)		0/7 (0%)		0/25 (0%)		0/6 (0%)		0/17 (0%)		0/12 (0%)		0/10 (0%)		0/22 (0%)		0/21 (0%)		1/7 (14.3%)		0/21 (0%)		0/8 (0%)		0/21 (0%)
Metabolism and nutrition disorders
Decreased appetite	0/9 (0%)		0/30 (0%)		0/8 (0%)		0/7 (0%)		0/25 (0%)		0/6 (0%)		0/17 (0%)		0/12 (0%)		1/10 (10%)		0/22 (0%)		1/21 (4.8%)		0/7 (0%)		1/21 (4.8%)		0/8 (0%)		0/21 (0%)
Hypoglycaemia	0/9 (0%)		0/30 (0%)		0/8 (0%)		0/7 (0%)		0/25 (0%)		0/6 (0%)		0/17 (0%)		0/12 (0%)		1/10 (10%)		0/22 (0%)		1/21 (4.8%)		0/7 (0%)		0/21 (0%)		0/8 (0%)		0/21 (0%)
Musculoskeletal and connective tissue disorders
Myalgia	0/9 (0%)		1/30 (3.3%)		0/8 (0%)		0/7 (0%)		0/25 (0%)		0/6 (0%)		0/17 (0%)		1/12 (8.3%)		0/10 (0%)		0/22 (0%)		0/21 (0%)		0/7 (0%)		0/21 (0%)		0/8 (0%)		0/21 (0%)
Musculoskeletal pain	0/9 (0%)		0/30 (0%)		0/8 (0%)		0/7 (0%)		0/25 (0%)		0/6 (0%)		0/17 (0%)		0/12 (0%)		0/10 (0%)		1/22 (4.5%)		0/21 (0%)		1/7 (14.3%)		0/21 (0%)		0/8 (0%)		0/21 (0%)
Neck pain	0/9 (0%)		0/30 (0%)		0/8 (0%)		0/7 (0%)		0/25 (0%)		0/6 (0%)		0/17 (0%)		0/12 (0%)		0/10 (0%)		0/22 (0%)		1/21 (4.8%)		1/7 (14.3%)		1/21 (4.8%)		0/8 (0%)		0/21 (0%)
Musculoskeletal chest pain	0/9 (0%)		0/30 (0%)		0/8 (0%)		0/7 (0%)		0/25 (0%)		0/6 (0%)		0/17 (0%)		0/12 (0%)		1/10 (10%)		0/22 (0%)		0/21 (0%)		0/7 (0%)		0/21 (0%)		1/8 (12.5%)		0/21 (0%)
Arthralgia	0/9 (0%)		0/30 (0%)		0/8 (0%)		1/7 (14.3%)		0/25 (0%)		0/6 (0%)		0/17 (0%)		0/12 (0%)		0/10 (0%)		0/22 (0%)		0/21 (0%)		0/7 (0%)		0/21 (0%)		0/8 (0%)		0/21 (0%)
Nervous system disorders
Headache	0/9 (0%)		0/30 (0%)		0/8 (0%)		0/7 (0%)		1/25 (4%)		0/6 (0%)		2/17 (11.8%)		2/12 (16.7%)		2/10 (20%)		2/22 (9.1%)		2/21 (9.5%)		1/7 (14.3%)		0/21 (0%)		1/8 (12.5%)		1/21 (4.8%)
Dizziness	0/9 (0%)		0/30 (0%)		0/8 (0%)		0/7 (0%)		0/25 (0%)		0/6 (0%)		0/17 (0%)		0/12 (0%)		0/10 (0%)		1/22 (4.5%)		1/21 (4.8%)		0/7 (0%)		0/21 (0%)		1/8 (12.5%)		0/21 (0%)
Dysgeusia	0/9 (0%)		0/30 (0%)		0/8 (0%)		0/7 (0%)		0/25 (0%)		0/6 (0%)		0/17 (0%)		1/12 (8.3%)		0/10 (0%)		0/22 (0%)		0/21 (0%)		0/7 (0%)		0/21 (0%)		0/8 (0%)		0/21 (0%)
Psychiatric disorders
Abnormal dreams	0/9 (0%)		0/30 (0%)		0/8 (0%)		0/7 (0%)		0/25 (0%)		0/6 (0%)		1/17 (5.9%)		0/12 (0%)		0/10 (0%)		0/22 (0%)		0/21 (0%)		0/7 (0%)		0/21 (0%)		0/8 (0%)		0/21 (0%)
Anxiety	0/9 (0%)		0/30 (0%)		0/8 (0%)		0/7 (0%)		0/25 (0%)		0/6 (0%)		0/17 (0%)		0/12 (0%)		0/10 (0%)		0/22 (0%)		0/21 (0%)		1/7 (14.3%)		0/21 (0%)		0/8 (0%)		0/21 (0%)
Renal and urinary disorders
Pollakiuria	0/9 (0%)		0/30 (0%)		0/8 (0%)		0/7 (0%)		0/25 (0%)		0/6 (0%)		0/17 (0%)		0/12 (0%)		0/10 (0%)		0/22 (0%)		0/21 (0%)		0/7 (0%)		0/21 (0%)		1/8 (12.5%)		0/21 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	0/9 (0%)		0/30 (0%)		0/8 (0%)		0/7 (0%)		0/25 (0%)		0/6 (0%)		1/17 (5.9%)		1/12 (8.3%)		4/10 (40%)		5/22 (22.7%)		7/21 (33.3%)		1/7 (14.3%)		7/21 (33.3%)		2/8 (25%)		5/21 (23.8%)
Sputum increased	0/9 (0%)		0/30 (0%)		0/8 (0%)		0/7 (0%)		0/25 (0%)		0/6 (0%)		0/17 (0%)		3/12 (25%)		3/10 (30%)		4/22 (18.2%)		5/21 (23.8%)		0/7 (0%)		8/21 (38.1%)		1/8 (12.5%)		3/21 (14.3%)
Haemoptysis	0/9 (0%)		0/30 (0%)		0/8 (0%)		0/7 (0%)		0/25 (0%)		0/6 (0%)		0/17 (0%)		2/12 (16.7%)		0/10 (0%)		5/22 (22.7%)		2/21 (9.5%)		0/7 (0%)		3/21 (14.3%)		1/8 (12.5%)		1/21 (4.8%)
Oropharyngeal pain	0/9 (0%)		0/30 (0%)		0/8 (0%)		0/7 (0%)		0/25 (0%)		0/6 (0%)		0/17 (0%)		2/12 (16.7%)		2/10 (20%)		2/22 (9.1%)		2/21 (9.5%)		1/7 (14.3%)		1/21 (4.8%)		2/8 (25%)		5/21 (23.8%)
Nasal congestion	0/9 (0%)		0/30 (0%)		0/8 (0%)		0/7 (0%)		0/25 (0%)		0/6 (0%)		0/17 (0%)		2/12 (16.7%)		2/10 (20%)		2/22 (9.1%)		2/21 (9.5%)		0/7 (0%)		0/21 (0%)		1/8 (12.5%)		3/21 (14.3%)
Dyspnoea	0/9 (0%)		0/30 (0%)		0/8 (0%)		0/7 (0%)		0/25 (0%)		0/6 (0%)		0/17 (0%)		1/12 (8.3%)		0/10 (0%)		1/22 (4.5%)		0/21 (0%)		0/7 (0%)		1/21 (4.8%)		1/8 (12.5%)		0/21 (0%)
Sinus congestion	0/9 (0%)		0/30 (0%)		0/8 (0%)		0/7 (0%)		0/25 (0%)		0/6 (0%)		0/17 (0%)		0/12 (0%)		0/10 (0%)		1/22 (4.5%)		1/21 (4.8%)		1/7 (14.3%)		1/21 (4.8%)		0/8 (0%)		2/21 (9.5%)
Paranasal sinus hypersecretion	0/9 (0%)		0/30 (0%)		0/8 (0%)		0/7 (0%)		0/25 (0%)		0/6 (0%)		0/17 (0%)		0/12 (0%)		1/10 (10%)		1/22 (4.5%)		0/21 (0%)		0/7 (0%)		1/21 (4.8%)		0/8 (0%)		1/21 (4.8%)
Productive cough	0/9 (0%)		0/30 (0%)		0/8 (0%)		0/7 (0%)		0/25 (0%)		0/6 (0%)		0/17 (0%)		0/12 (0%)		0/10 (0%)		0/22 (0%)		0/21 (0%)		0/7 (0%)		0/21 (0%)		1/8 (12.5%)		2/21 (9.5%)
Respiration abnormal	0/9 (0%)		0/30 (0%)		0/8 (0%)		0/7 (0%)		0/25 (0%)		0/6 (0%)		0/17 (0%)		0/12 (0%)		0/10 (0%)		1/22 (4.5%)		1/21 (4.8%)		0/7 (0%)		2/21 (9.5%)		1/8 (12.5%)		0/21 (0%)
Sputum discoloured	0/9 (0%)		0/30 (0%)		0/8 (0%)		0/7 (0%)		0/25 (0%)		0/6 (0%)		0/17 (0%)		0/12 (0%)		0/10 (0%)		1/22 (4.5%)		0/21 (0%)		0/7 (0%)		2/21 (9.5%)		1/8 (12.5%)		1/21 (4.8%)
Rhinorrhoea	0/9 (0%)		0/30 (0%)		0/8 (0%)		0/7 (0%)		0/25 (0%)		0/6 (0%)		0/17 (0%)		0/12 (0%)		0/10 (0%)		3/22 (13.6%)		0/21 (0%)		0/7 (0%)		1/21 (4.8%)		0/8 (0%)		0/21 (0%)
Epistaxis	0/9 (0%)		0/30 (0%)		0/8 (0%)		0/7 (0%)		0/25 (0%)		0/6 (0%)		0/17 (0%)		0/12 (0%)		0/10 (0%)		1/22 (4.5%)		0/21 (0%)		0/7 (0%)		1/21 (4.8%)		1/8 (12.5%)		0/21 (0%)
Wheezing	0/9 (0%)		0/30 (0%)		0/8 (0%)		0/7 (0%)		0/25 (0%)		0/6 (0%)		0/17 (0%)		1/12 (8.3%)		0/10 (0%)		0/22 (0%)		1/21 (4.8%)		0/7 (0%)		1/21 (4.8%)		0/8 (0%)		0/21 (0%)
Lower respiratory tract congestion	0/9 (0%)		0/30 (0%)		0/8 (0%)		0/7 (0%)		0/25 (0%)		0/6 (0%)		0/17 (0%)		1/12 (8.3%)		0/10 (0%)		0/22 (0%)		0/21 (0%)		1/7 (14.3%)		0/21 (0%)		0/8 (0%)		0/21 (0%)
Pleuritic pain	0/9 (0%)		0/30 (0%)		0/8 (0%)		0/7 (0%)		0/25 (0%)		0/6 (0%)		0/17 (0%)		1/12 (8.3%)		0/10 (0%)		0/22 (0%)		1/21 (4.8%)		0/7 (0%)		0/21 (0%)		0/8 (0%)		0/21 (0%)
Bronchiectasis	0/9 (0%)		0/30 (0%)		0/8 (0%)		0/7 (0%)		0/25 (0%)		0/6 (0%)		0/17 (0%)		0/12 (0%)		0/10 (0%)		0/22 (0%)		0/21 (0%)		0/7 (0%)		0/21 (0%)		1/8 (12.5%)		0/21 (0%)
Pulmonary mass	0/9 (0%)		0/30 (0%)		0/8 (0%)		0/7 (0%)		0/25 (0%)		0/6 (0%)		0/17 (0%)		1/12 (8.3%)		0/10 (0%)		0/22 (0%)		0/21 (0%)		0/7 (0%)		0/21 (0%)		0/8 (0%)		0/21 (0%)
Paranasal sinus discomfort	0/9 (0%)		0/30 (0%)		0/8 (0%)		0/7 (0%)		0/25 (0%)		0/6 (0%)		0/17 (0%)		0/12 (0%)		1/10 (10%)		0/22 (0%)		0/21 (0%)		0/7 (0%)		1/21 (4.8%)		0/8 (0%)		2/21 (9.5%)
Upper-airway cough syndrome	0/9 (0%)		0/30 (0%)		0/8 (0%)		0/7 (0%)		0/25 (0%)		0/6 (0%)		0/17 (0%)		0/12 (0%)		0/10 (0%)		2/22 (9.1%)		0/21 (0%)		0/7 (0%)		0/21 (0%)		0/8 (0%)		0/21 (0%)
Skin and subcutaneous tissue disorders
Dermatitis	0/9 (0%)		0/30 (0%)		0/8 (0%)		0/7 (0%)		0/25 (0%)		1/6 (16.7%)		2/17 (11.8%)		0/12 (0%)		0/10 (0%)		0/22 (0%)		0/21 (0%)		0/7 (0%)		0/21 (0%)		0/8 (0%)		0/21 (0%)
Pruritus	0/9 (0%)		0/30 (0%)		0/8 (0%)		0/7 (0%)		0/25 (0%)		1/6 (16.7%)		1/17 (5.9%)		0/12 (0%)		0/10 (0%)		0/22 (0%)		0/21 (0%)		0/7 (0%)		0/21 (0%)		1/8 (12.5%)		0/21 (0%)
Acne	0/9 (0%)		0/30 (0%)		0/8 (0%)		0/7 (0%)		0/25 (0%)		0/6 (0%)		0/17 (0%)		0/12 (0%)		2/10 (20%)		0/22 (0%)		1/21 (4.8%)		0/7 (0%)		0/21 (0%)		0/8 (0%)		1/21 (4.8%)
Pruritus generalised	0/9 (0%)		0/30 (0%)		0/8 (0%)		0/7 (0%)		0/25 (0%)		0/6 (0%)		0/17 (0%)		1/12 (8.3%)		0/10 (0%)		0/22 (0%)		0/21 (0%)		0/7 (0%)		0/21 (0%)		0/8 (0%)		0/21 (0%)
Eczema	0/9 (0%)		0/30 (0%)		0/8 (0%)		0/7 (0%)		0/25 (0%)		0/6 (0%)		0/17 (0%)		0/12 (0%)		0/10 (0%)		0/22 (0%)		0/21 (0%)		0/7 (0%)		0/21 (0%)		1/8 (12.5%)		0/21 (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.