Trial Outcomes & Findings for A Study to Evaluate the Safety and Efficacy of VX-371 in Subjects With Cystic Fibrosis Who Are Homozygous for the F508del-CFTR Mutation (NCT NCT02709109)

Last Updated: 2021-07-29

Results Overview

An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. AEs included abnormal clinically significant findings for spirometry, clinical laboratory parameters, standard 12-lead electrocardiograms (ECGs), vital signs and ophthalmologic examinations. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug and up to 112 days (up to 28 days after last dose) that were absent before treatment or that worsened relative to pretreatment state. TEAEs included both serious and non-serious TEAEs.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

147 participants

Primary outcome timeframe

Baseline (Day 1) up to 28 days post last administration of study drug (up to 112 days)

Results posted on

2021-07-29

Participant Flow

Total 147 participants entered in this study, 5 participants discontinued from the study before the randomization. Of which 142 participants were randomized to receive 1 of the 4 treatment sequences: 1) VX-371 + hypertonic saline (HS), Then HS; 2) HS, Then VX-371 + HS; 3) VX-371 + Placebo, Then Placebo; 4) Placebo, Then VX-371 + Placebo.

Participant milestones

Participant milestones
Measure	Sequence 1: VX-371 + HS, Then HS Participants received 85 microgram (mcg) VX-371 diluted in 3 milliliter (mL) 4.2 percent (%) HS through oral nebulized inhalation twice daily for 28 days (Day 1 to Day 28) in treatment period 1 followed by a 28 days washout period (Day 29 to Day 56) and then received 3 mL 4.2% HS through oral nebulized inhalation twice daily for 28 days (Day 57 to Day 84) in treatment period 2. Participants also received a stable dose of 2 tablets of Orkambi (lumacaftor 400 milligram (mg)/ivacaftor 250 mg) orally every 12 hours with fat-containing food throughout the study as part of their cystic fibrosis (CF) standard of care.	Sequence 2: HS, Then VX-371 + HS Participants received 3 mL 4.2% HS through oral nebulized inhalation twice daily for 28 days (Day 1 to Day 28) in treatment period 1 followed by a 28 days washout period (Day 29 to Day 56) and then received 85 mcg VX-371 diluted in 3 mL 4.2% HS through oral nebulized inhalation twice daily for 28 days (Day 57 to Day 84) in treatment period 2. Participants also received a stable dose of 2 tablets of Orkambi (lumacaftor 400 mg/ivacaftor 250 mg) orally every 12 hours with fat-containing food throughout the study as part of their CF standard of care.	Sequence 3: VX-371 + Placebo, Then Placebo Participants received 85 mcg VX-371 diluted in 3 mL 0.17% Saline (placebo) through oral nebulized inhalation twice daily for 28 days (Day 1 to Day 28) in treatment period 1 followed by a 28 days washout period (Day 29 to Day 56) and then received 3 mL 0.17% saline (placebo) through oral nebulized inhalation twice daily for 28 days (Day 57 to Day 84) in treatment period 2. Participants also received a stable dose of 2 tablets of Orkambi (lumacaftor 400 mg/ivacaftor 250 mg) orally every 12 hours with fat-containing food throughout the study as part of their CF standard of care.	Sequence 4: Placebo, Then VX-371 + Placebo Participants received 3 mL 0.17% saline (placebo) through oral nebulized inhalation twice daily for 28 days (Day 1 to Day 28) in treatment period 1 followed by a 28 days washout period (Day 29 to Day 56) and then received 85 mcg VX-371 diluted in 3 mL 0.17% saline (placebo) through oral nebulized inhalation twice daily for 28 days (Day 57 to Day 84) in treatment period 2. Participants also received a stable dose of 2 tablets of Orkambi (lumacaftor 400 mg/ivacaftor 250 mg) orally every 12 hours with fat-containing food throughout the study as part of their CF standard of care.
Treatment Period 1 (28 Days) STARTED	49	47	22	24
Treatment Period 1 (28 Days) COMPLETED	45	42	21	24
Treatment Period 1 (28 Days) NOT COMPLETED	4	5	1	0
Washout Period (28 Days) STARTED	45	42	21	24
Washout Period (28 Days) COMPLETED	43	40	18	24
Washout Period (28 Days) NOT COMPLETED	2	2	3	0
Treatment Period 2 (28 Days) STARTED	43	40	18	24
Treatment Period 2 (28 Days) COMPLETED	41	36	15	24
Treatment Period 2 (28 Days) NOT COMPLETED	2	4	3	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Sequence 1: VX-371 + HS, Then HS Participants received 85 microgram (mcg) VX-371 diluted in 3 milliliter (mL) 4.2 percent (%) HS through oral nebulized inhalation twice daily for 28 days (Day 1 to Day 28) in treatment period 1 followed by a 28 days washout period (Day 29 to Day 56) and then received 3 mL 4.2% HS through oral nebulized inhalation twice daily for 28 days (Day 57 to Day 84) in treatment period 2. Participants also received a stable dose of 2 tablets of Orkambi (lumacaftor 400 milligram (mg)/ivacaftor 250 mg) orally every 12 hours with fat-containing food throughout the study as part of their cystic fibrosis (CF) standard of care.	Sequence 2: HS, Then VX-371 + HS Participants received 3 mL 4.2% HS through oral nebulized inhalation twice daily for 28 days (Day 1 to Day 28) in treatment period 1 followed by a 28 days washout period (Day 29 to Day 56) and then received 85 mcg VX-371 diluted in 3 mL 4.2% HS through oral nebulized inhalation twice daily for 28 days (Day 57 to Day 84) in treatment period 2. Participants also received a stable dose of 2 tablets of Orkambi (lumacaftor 400 mg/ivacaftor 250 mg) orally every 12 hours with fat-containing food throughout the study as part of their CF standard of care.	Sequence 3: VX-371 + Placebo, Then Placebo Participants received 85 mcg VX-371 diluted in 3 mL 0.17% Saline (placebo) through oral nebulized inhalation twice daily for 28 days (Day 1 to Day 28) in treatment period 1 followed by a 28 days washout period (Day 29 to Day 56) and then received 3 mL 0.17% saline (placebo) through oral nebulized inhalation twice daily for 28 days (Day 57 to Day 84) in treatment period 2. Participants also received a stable dose of 2 tablets of Orkambi (lumacaftor 400 mg/ivacaftor 250 mg) orally every 12 hours with fat-containing food throughout the study as part of their CF standard of care.
Treatment Period 1 (28 Days) Adverse Event	3	3	1
Treatment Period 1 (28 Days) Participant refused further dosing	0	2	0
Treatment Period 1 (28 Days) Non-compliance with study drug	1	0	0
Washout Period (28 Days) Other	2	2	3
Treatment Period 2 (28 Days) Adverse Event	2	3	0
Treatment Period 2 (28 Days) Other non-compliance	0	1	1
Treatment Period 2 (28 Days) Requires prohibited medication	0	0	1
Treatment Period 2 (28 Days) Other	0	0	1

Baseline Characteristics

A Study to Evaluate the Safety and Efficacy of VX-371 in Subjects With Cystic Fibrosis Who Are Homozygous for the F508del-CFTR Mutation

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Sequence 1: VX-371 + HS, Then HS n=49 Participants Participants received 85 mcg VX-371 diluted in 3 milliliter (mL) 4.2% HS through oral nebulized inhalation twice daily for 28 days (Day 1 to Day 28) in treatment period 1 followed by a 28 days washout period (Day 29 to Day 56) and then received 3 mL 4.2% HS through oral nebulized inhalation twice daily for 28 days (Day 57 to Day 84) in treatment period 2. Participants also received a stable dose of 2 tablets of Orkambi (lumacaftor 400 mg/ivacaftor 250 mg) orally every 12 hours with fat-containing food throughout the study as part of their CF standard of care.	Sequence 2: HS, Then VX-371 + HS n=47 Participants Participants received 3 mL 4.2% HS through oral nebulized inhalation twice daily for 28 days (Day 1 to Day 28) in treatment period 1 followed by a 28 days washout period (Day 29 to Day 56) and then received 85 mcg VX-371 diluted in 3 mL 4.2% HS through oral nebulized inhalation twice daily for 28 days (Day 57 to Day 84) in treatment period 2. Participants also received a stable dose of 2 tablets of Orkambi (lumacaftor 400 mg/ivacaftor 250 mg) orally every 12 hours with fat-containing food throughout the study as part of their CF standard of care.	Sequence 3: VX-371 + Placebo, Then Placebo n=22 Participants Participants received 85 mcg VX-371 diluted in 3 mL 0.17% Saline (placebo) through oral nebulized inhalation twice daily for 28 days (Day 1 to Day 28) in treatment period 1 followed by a 28 days washout period (Day 29 to Day 56) and then received 3 mL 0.17% saline (placebo) through oral nebulized inhalation twice daily for 28 days (Day 57 to Day 84) in treatment period 2. Participants also received a stable dose of 2 tablets of Orkambi (lumacaftor 400 mg/ivacaftor 250 mg) orally every 12 hours with fat-containing food throughout the study as part of their CF standard of care.	Sequence 4: Placebo, Then VX-371 + Placebo n=24 Participants Participants received 3 mL 0.17% saline (placebo) through oral nebulized inhalation twice daily for 28 days (Day 1 to Day 28) in treatment period 1 followed by a 28 days washout period (Day 29 to Day 56) and then received 85 mcg VX-371 diluted in 3 mL 0.17% saline (placebo) through oral nebulized inhalation twice daily for 28 days (Day 57 to Day 84) in treatment period 2. Participants also received a stable dose of 2 tablets of Orkambi (lumacaftor 400 mg/ivacaftor 250 mg) orally every 12 hours with fat-containing food throughout the study as part of their CF standard of care.	Total n=142 Participants Total of all reporting groups
Age, Continuous	23.6 years STANDARD_DEVIATION 9.07 • n=5 Participants	22.3 years STANDARD_DEVIATION 8.75 • n=7 Participants	26.0 years STANDARD_DEVIATION 10.95 • n=5 Participants	22.1 years STANDARD_DEVIATION 7.80 • n=4 Participants	23.3 years STANDARD_DEVIATION 9.08 • n=21 Participants
Sex: Female, Male Female	21 Participants n=5 Participants	16 Participants n=7 Participants	7 Participants n=5 Participants	11 Participants n=4 Participants	55 Participants n=21 Participants
Sex: Female, Male Male	28 Participants n=5 Participants	31 Participants n=7 Participants	15 Participants n=5 Participants	13 Participants n=4 Participants	87 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	49 Participants n=5 Participants	45 Participants n=7 Participants	22 Participants n=5 Participants	23 Participants n=4 Participants	139 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	3 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) White	49 Participants n=5 Participants	45 Participants n=7 Participants	22 Participants n=5 Participants	23 Participants n=4 Participants	139 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	2 Participants n=21 Participants

PRIMARY outcome

Timeframe: Baseline (Day 1) up to 28 days post last administration of study drug (up to 112 days)

Population: Safety set included all participants who received at least 1 dose of inhaled study drug.

Outcome measures

Outcome measures
Measure	VX-371 + Hypertonic Saline n=89 Participants Participants received 85 mcg VX-371 diluted in 3 mL 4.2% HS through oral nebulized inhalation twice daily for 28 days in either treatment period 1 or 2.	Hypertonic Saline n=90 Participants Participants received 3 mL 4.2% HS through oral nebulized inhalation twice daily for 28 days in either treatment period 1 or 2.	VX-371 + Placebo n=46 Participants Participants received 85 mcg VX-371 diluted in 3 mL 0.17% saline (placebo) through oral nebulized inhalation twice daily for 28 days in either treatment period 1 or 2.	Placebo n=42 Participants Participants received 3 mL 0.17% saline (placebo) through oral nebulized inhalation twice daily for 28 days in either treatment period 1 or 2.
Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs Participants With TEAEs	65 Participants	66 Participants	32 Participants	28 Participants
Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs Participants With Serious TEAEs	8 Participants	4 Participants	6 Participants	3 Participants

PRIMARY outcome

Timeframe: Study baseline, Day 28

Population: The full analysis set (FAS) included all randomized participants who carried the intended homozygous F508del-cystic fibrosis transmembrane conductance regulator (CFTR) mutation and received at least 1 dose of inhaled study drug. Here, "overall number of participants analyzed" signifies participants evaluable for this outcome measure.

FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Study Baseline was defined as the most recent non-missing measurement before the first dose of inhaled study drug in the study. Day 28 measurements after treatment discontinuation from the treatment period in which discontinuation occurred were included in the analysis.

Outcome measures

Outcome measures
Measure	VX-371 + Hypertonic Saline n=79 Participants Participants received 85 mcg VX-371 diluted in 3 mL 4.2% HS through oral nebulized inhalation twice daily for 28 days in either treatment period 1 or 2.	Hypertonic Saline n=77 Participants Participants received 3 mL 4.2% HS through oral nebulized inhalation twice daily for 28 days in either treatment period 1 or 2.	VX-371 + Placebo n=43 Participants Participants received 85 mcg VX-371 diluted in 3 mL 0.17% saline (placebo) through oral nebulized inhalation twice daily for 28 days in either treatment period 1 or 2.	Placebo n=38 Participants Participants received 3 mL 0.17% saline (placebo) through oral nebulized inhalation twice daily for 28 days in either treatment period 1 or 2.
Absolute Change From Study Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Day 28	0.1 percentage points Standard Error 0.8	-0.1 percentage points Standard Error 0.8	-0.8 percentage points Standard Error 1.1	0.8 percentage points Standard Error 1.1

SECONDARY outcome

Timeframe: Pre-dose (90 minutes prior inhaled study drug administration) and 60 minutes post-dose on Days 1, 14 and 28 within treatment period 1 and 2

Population: The Pharmacokinetic (PK) analysis set included all participants who received at least 1 dose of VX-371. Here, "overall number of participants analyzed" signifies participants evaluable for this outcome measure and "number analyzed" signifies those participants who were evaluable at specified time points.

Outcome measures

Outcome measures
Measure	VX-371 + Hypertonic Saline n=89 Participants Participants received 85 mcg VX-371 diluted in 3 mL 4.2% HS through oral nebulized inhalation twice daily for 28 days in either treatment period 1 or 2.	Hypertonic Saline n=45 Participants Participants received 3 mL 4.2% HS through oral nebulized inhalation twice daily for 28 days in either treatment period 1 or 2.	VX-371 + Placebo Participants received 85 mcg VX-371 diluted in 3 mL 0.17% saline (placebo) through oral nebulized inhalation twice daily for 28 days in either treatment period 1 or 2.	Placebo Participants received 3 mL 0.17% saline (placebo) through oral nebulized inhalation twice daily for 28 days in either treatment period 1 or 2.
Plasma Concentrations of VX-371 Day 1: Pre-dose	0.00 Picograms per milliliter (pg/mL) Standard Deviation 0.00	0.18 Picograms per milliliter (pg/mL) Standard Deviation 1.17	—	—
Plasma Concentrations of VX-371 Day 1: Post-dose	2.57 Picograms per milliliter (pg/mL) Standard Deviation 2.35	5.64 Picograms per milliliter (pg/mL) Standard Deviation 4.27	—	—
Plasma Concentrations of VX-371 Day 14: Pre-dose	1.63 Picograms per milliliter (pg/mL) Standard Deviation 3.06	2.77 Picograms per milliliter (pg/mL) Standard Deviation 4.77	—	—
Plasma Concentrations of VX-371 Day 14: Post-dose	5.81 Picograms per milliliter (pg/mL) Standard Deviation 5.44	11.0 Picograms per milliliter (pg/mL) Standard Deviation 9.74	—	—
Plasma Concentrations of VX-371 Day 28: Pre-dose	2.68 Picograms per milliliter (pg/mL) Standard Deviation 4.75	3.67 Picograms per milliliter (pg/mL) Standard Deviation 5.59	—	—
Plasma Concentrations of VX-371 Day 28: Post-dose	6.41 Picograms per milliliter (pg/mL) Standard Deviation 6.92	10.9 Picograms per milliliter (pg/mL) Standard Deviation 9.48	—	—

SECONDARY outcome

Timeframe: Pre-dose (90 minutes prior inhaled study drug administration) and 60 minutes post-dose on Days 1, 14 and 28 within treatment period 1 and 2

Population: The PK analysis set included all participants who received at least 1 dose of VX-371. Here, "overall number of participants analyzed" signifies participants evaluable for this outcome measure and "number analyzed" signifies those participants who were evaluable at specified time points.

Outcome measures

Outcome measures
Measure	VX-371 + Hypertonic Saline n=88 Participants Participants received 85 mcg VX-371 diluted in 3 mL 4.2% HS through oral nebulized inhalation twice daily for 28 days in either treatment period 1 or 2.	Hypertonic Saline n=45 Participants Participants received 3 mL 4.2% HS through oral nebulized inhalation twice daily for 28 days in either treatment period 1 or 2.	VX-371 + Placebo Participants received 85 mcg VX-371 diluted in 3 mL 0.17% saline (placebo) through oral nebulized inhalation twice daily for 28 days in either treatment period 1 or 2.	Placebo Participants received 3 mL 0.17% saline (placebo) through oral nebulized inhalation twice daily for 28 days in either treatment period 1 or 2.
Urine Concentrations of VX-371 Day 1: Pre-dose	0.0745 pg/mL Standard Deviation 0.699	0.00 pg/mL Standard Deviation 0.00	—	—
Urine Concentrations of VX-371 Day 1: Post-dose	7.78 pg/mL Standard Deviation 11.8	22.1 pg/mL Standard Deviation 38.4	—	—
Urine Concentrations of VX-371 Day 14: Pre-dose	41.0 pg/mL Standard Deviation 97.2	69.6 pg/mL Standard Deviation 107	—	—
Urine Concentrations of VX-371 Day 14: Post-dose	38.9 pg/mL Standard Deviation 64.8	75.0 pg/mL Standard Deviation 98.7	—	—
Urine Concentrations of VX-371 Day 28: Pre-dose	65.3 pg/mL Standard Deviation 155	98.6 pg/mL Standard Deviation 175	—	—
Urine Concentrations of VX-371 Day 28: Post-dose	49.1 pg/mL Standard Deviation 120	75.1 pg/mL Standard Deviation 108	—	—

Adverse Events

VX-371 + Hypertonic Saline

Serious events: 8 serious events

Other events: 49 other events

Deaths: 0 deaths

Hypertonic Saline

Serious events: 4 serious events

Other events: 55 other events

Deaths: 0 deaths

VX-371 + Placebo

Serious events: 6 serious events

Other events: 26 other events

Deaths: 0 deaths

Placebo

Serious events: 3 serious events

Other events: 20 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	VX-371 + Hypertonic Saline n=89 participants at risk Participants received 85 mcg VX-371 diluted in 3 mL 4.2% HS through oral nebulized inhalation twice daily for 28 days in either treatment period 1 or 2.	Hypertonic Saline n=90 participants at risk Participants received 3 mL 4.2% HS through oral nebulized inhalation twice daily for 28 days in either treatment period 1 or 2.	VX-371 + Placebo n=46 participants at risk Participants received 85 mcg VX-371 diluted in 3 mL 0.17% saline (placebo) through oral nebulized inhalation twice daily for 28 days in either treatment period 1 or 2.	Placebo n=42 participants at risk Participants received 3 mL 0.17% saline (placebo) through oral nebulized inhalation twice daily for 28 days in either treatment period 1 or 2.
Infections and infestations Infective pulmonary exacerbation of cystic	3.4% 3/89 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.	3.3% 3/90 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.	10.9% 5/46 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.	7.1% 3/42 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.
Congenital, familial and genetic disorders Cystic fibrosis related diabetes	1.1% 1/89 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.	0.00% 0/90 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.	0.00% 0/46 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.	0.00% 0/42 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.
Investigations Alanine aminotransferase increased	1.1% 1/89 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.	0.00% 0/90 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.	0.00% 0/46 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.	0.00% 0/42 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.
Investigations Aspartate aminotransferase increased	1.1% 1/89 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.	0.00% 0/90 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.	0.00% 0/46 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.	0.00% 0/42 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.
Investigations Blood creatine phosphokinase increased	1.1% 1/89 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.	0.00% 0/90 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.	0.00% 0/46 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.	0.00% 0/42 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.
Reproductive system and breast disorders Testicular torsion	1.1% 1/89 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.	0.00% 0/90 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.	0.00% 0/46 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.	0.00% 0/42 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.
Respiratory, thoracic and mediastinal disorders Bronchospasm	1.1% 1/89 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.	0.00% 0/90 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.	0.00% 0/46 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.	0.00% 0/42 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.00% 0/89 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.	2.2% 2/90 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.	2.2% 1/46 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.	0.00% 0/42 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.
Surgical and medical procedures Cystic fibrosis respiratory infection	1.1% 1/89 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.	0.00% 0/90 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.	0.00% 0/46 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.	0.00% 0/42 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/89 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.	1.1% 1/90 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.	0.00% 0/46 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.	0.00% 0/42 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.

Other adverse events

Additional Information

Alison Church

Parion Sciences

Phone: 919-313-1183

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: OTHER

Measure	VX-371 + Hypertonic Saline n=89 participants at risk Participants received 85 mcg VX-371 diluted in 3 mL 4.2% HS through oral nebulized inhalation twice daily for 28 days in either treatment period 1 or 2.	Hypertonic Saline n=90 participants at risk Participants received 3 mL 4.2% HS through oral nebulized inhalation twice daily for 28 days in either treatment period 1 or 2.	VX-371 + Placebo n=46 participants at risk Participants received 85 mcg VX-371 diluted in 3 mL 0.17% saline (placebo) through oral nebulized inhalation twice daily for 28 days in either treatment period 1 or 2.	Placebo n=42 participants at risk Participants received 3 mL 0.17% saline (placebo) through oral nebulized inhalation twice daily for 28 days in either treatment period 1 or 2.
Respiratory, thoracic and mediastinal disorders Cough	22.5% 20/89 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.	14.4% 13/90 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.	28.3% 13/46 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.	11.9% 5/42 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	9.0% 8/89 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.	6.7% 6/90 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.	8.7% 4/46 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.	2.4% 1/42 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.
Respiratory, thoracic and mediastinal disorders Nasal congestion	7.9% 7/89 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.	5.6% 5/90 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.	4.3% 2/46 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.	2.4% 1/42 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.
Respiratory, thoracic and mediastinal disorders Respiration abnormal	7.9% 7/89 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.	6.7% 6/90 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.	6.5% 3/46 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.	4.8% 2/42 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.
Respiratory, thoracic and mediastinal disorders Wheezing	6.7% 6/89 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.	2.2% 2/90 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.	0.00% 0/46 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.	2.4% 1/42 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.
Respiratory, thoracic and mediastinal disorders Haemoptysis	5.6% 5/89 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.	6.7% 6/90 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.	10.9% 5/46 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.	11.9% 5/42 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.
Respiratory, thoracic and mediastinal disorders Sputum increased	5.6% 5/89 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.	2.2% 2/90 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.	10.9% 5/46 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.	4.8% 2/42 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.
Infections and infestations Infective pulmonary exacerbation of cystic fibrosis	9.0% 8/89 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.	13.3% 12/90 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.	13.0% 6/46 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.	7.1% 3/42 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.
Infections and infestations Nasopharyngitis	0.00% 0/89 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.	5.6% 5/90 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.	4.3% 2/46 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.	4.8% 2/42 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.
Investigations Alanine aminotransferase increased	3.4% 3/89 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.	5.6% 5/90 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.	0.00% 0/46 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.	9.5% 4/42 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.
Investigations Pulmonary function test decreased	0.00% 0/89 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.	0.00% 0/90 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.	6.5% 3/46 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.	0.00% 0/42 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.
Gastrointestinal disorders Diarrhoea	5.6% 5/89 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.	4.4% 4/90 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.	4.3% 2/46 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.	2.4% 1/42 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.
Gastrointestinal disorders Nausea	2.2% 2/89 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.	3.3% 3/90 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.	6.5% 3/46 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.	0.00% 0/42 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.
Gastrointestinal disorders Vomiting	1.1% 1/89 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.	6.7% 6/90 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.	2.2% 1/46 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.	0.00% 0/42 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.
Nervous system disorders Headache	6.7% 6/89 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.	8.9% 8/90 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.	4.3% 2/46 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.	2.4% 1/42 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.
General disorders Pyrexia	1.1% 1/89 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.	5.6% 5/90 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.	10.9% 5/46 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.	11.9% 5/42 • Baseline up to 28 days post last administration of study drug, up to 112 days Safety set included all participants who received at least 1 dose of inhaled study drug.