A Study to Evaluate the Safety and Efficacy of Long-term Treatment With TEZ/IVA in CF Subjects With an F508del CFTR Mutation

• Sponsor: Vertex Pharmaceuticals Incorporated (Industry)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT03537651
• Collaborator: (none)
• Enrollment: 130
• Locations: 55
• Arm: 1
• Anticipated Duration (Months): 52.2
• Patients Per Site: 2.4
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This study will evaluate the long-term safety and tolerability of tezacaftor in combination with ivacaftor (TEZ/IVA) in subjects with cystic fibrosis (CF) aged 6 years and older, homozygous or heterozygous for the F508del mutation.

Condition or Disease	Intervention/Treatment	Phase
Cystic Fibrosis	Drug: TEZ/IVA; Drug: IVA	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 130 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 3, Open-label, Rollover Study to Evaluate the Safety and Efficacy of Long-term Treatment With Tezacaftor in Combination With Ivacaftor in Subjects With Cystic Fibrosis Aged 6 Years and Older, Homozygous or Heterozygous for the F508del-CFTR Mutation
• Actual Study Start Date: Apr 25, 2018
• Actual Primary Completion Date: Oct 28, 2020
• Anticipated Study Completion Date: Sep 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: TEZ/IVA TEZ 50 mg once daily (qd)/IVA 75 mg every 12 hours (q12h) or TEZ 100 mg qd/IVA 150 mg q12h based on body weight for participants aged 6 through 11 years at enrollment and TEZ 100 mg qd/IVA 150 mg q12h for participants aged >=12 years at enrollment. Doses were adjusted upward for changes in body weight and/or age.	Drug: TEZ/IVA; Fixed-dose combination tablet for oral administration.; Other Names: VX-661/VX-770 tezacaftor/ivacaftor ; Drug: IVA; Tablet for oral administration.; Other Names: VX-770 ivacaftor

Outcome Measures

Primary Outcome Measures

1. Part A: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [Part A: Day 1 up to Week 100]

Secondary Outcome Measures

1. Part A: Absolute Change in Lung Clearance Index2.5 (LCI2.5) for 115/116 FAS (TEZ/IVA Group) [From Parent Study 115 Baseline at Week 96 (Study 116)]

   LCI2.5 represents the number of lung turnovers required to reduce the end tidal inert gas concentration to 1/40th of its starting value.

2. Part A: Absolute Change in LCI2.5 for 113B/116 LCI FAS [From Parent Study 113B Baseline at Week 96 (Study 116)]

   LCI2.5 represents the number of lung turnovers required to reduce the end tidal inert gas concentration to 1/40th of its starting value.

3. Part A: Absolute Change in Sweat Chloride for 115/116 FAS (TEZ/IVA Group) [From Parent Study 115 Baseline at Week 96 (Study 116)]

   Sweat samples were collected using an approved collection device.

4. Part A: Absolute Change in SwCl for 113B/116 FAS [From Parent Study 113B Baseline at Week 96 (Study 116)]

   Sweat samples were collected using an approved collection device.

5. Part A: Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score for 115/116 FAS (TEZ/IVA Group) [From Parent Study 115 Baseline at Week 96 (Study 116)]

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

6. Part A: Absolute Change in CFQ-R Respiratory Domain Score for 113B/116 FAS [From Parent Study 113B Baseline at Week 96 (Study 116)]

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

7. Part A: Absolute Change in Body Mass Index (BMI) for 115/116 FAS (TEZ/IVA Group) [From Parent Study 115 Baseline at Week 96 (Study 116)]

   BMI was defined as weight in kilograms (kg) divided by squared height in meters (m^2).

8. Part A: Absolute Change in BMI for 113B/116 FAS [From Parent Study 113B Baseline at Week 96 (Study 116)]

   BMI was defined as weight in kg divided by m^2.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 6 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Completed the Week 24 Visit in Study 113 Part B or the Week 8 Visit in Study 115.

• Eligible CFTR Mutation.

Exclusion Criteria:

• Pregnant and nursing females.

• History of poor compliance with study drug and/or procedures in a previous study as deemed by the investigator.

• Ongoing participation in another study with investigational drug.

Other protocol defined Inclusion/Exclusion criteria may apply.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35233
2	Providence Alaska Medical Center	Anchorage	Alaska	United States	99508
3	Arkansas Children's Hospital	Little Rock	Arkansas	United States	72202
4	Children's Hospital Los Angeles	Los Angeles	California	United States	90027
5	Children's Hospital Colorado	Aurora	Colorado	United States	80045
6	Nemours/ Alfred I. duPont Hospital for Children	Wilmington	Delaware	United States	19803
7	Johns Hopkins All Children's Hospital Outpatient Care Center	Saint Petersburg	Florida	United States	33701
8	Center for Advanced Pediatrics	Atlanta	Georgia	United States	30329
9	St. Luke's CF Center of Idaho	Boise	Idaho	United States	83702
10	Riley Hospital for Children Indiana University Health	Indianapolis	Indiana	United States	46202
11	Boston Children's Hospital	Boston	Massachusetts	United States	02115
12	Children's Hospital & Clinics of Minnesota	Minneapolis	Minnesota	United States	55404
13	The Children's Mercy Hospital	Kansas City	Missouri	United States	64108
14	Dartmouth Hitchcock Medical Center	Manchester	New Hampshire	United States	03756
15	UBMD Pediatrics/ CF Center of Western New York	Buffalo	New York	United States	14203
16	Columbia University Medical Center	New York	New York	United States	10032
17	SUNY Upstate Medical University	Syracuse	New York	United States	13202
18	Wake Forest Baptist Health	Winston-Salem	North Carolina	United States	27157
19	Rainbow Babies and Children's Hospital/University Hospitals Cleveland Medical Center	Cleveland	Ohio	United States	44106
20	Children's Hospital of Pittsburgh of UPMC	Pittsburgh	Pennsylvania	United States	15224
21	Medical University of South Carolina (MUSC)	Charleston	South Carolina	United States	29425
22	Sanford Children's Speciality Clinic	Sioux Falls	South Dakota	United States	57105
23	Austin Children's Chest Associates	Austin	Texas	United States	78723
24	Cook Children's Medical Center	Fort Worth	Texas	United States	76104
25	Baylor College of Medicine	Houston	Texas	United States	77030
26	Children's Hospital of The King's Daughters	Norfolk	Virginia	United States	23507
27	Seattle Children's Hospital	Seattle	Washington	United States	98105
28	Children's Hospital of Wisconsin	Milwaukee	Wisconsin	United States	53226
29	Perth Children's Hospital	Nedlands		Australia
30	John Hunter Hospital & Hunter Medical Research Institute and John Hunter Children's Hospital	New Lambton		Australia
31	Lady Cilento Children's Hospital	South Brisbane		Australia
32	The Children's Hospital at Westmead	Westmead		Australia
33	Universitair Ziekenhuis Brussel - Campus Jette	Brussels		Belgium
34	Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg	Leuven		Belgium
35	British Columbia's Children's Hospital	Vancouver	British Columbia	Canada
36	The Hospital for Sick Children	Toronto	Ontario	Canada
37	McGill University Health Centre, Glen Site, Montreal Children's Hospital	Montreal	Quebec	Canada
38	Juliane Marie Center, Rigshopitalet	Copenhagen		Denmark
39	Groupe Hospitaler Pellegrin, CHU De Bordeaux	Bordeaux cedex		France
40	Hopital Necker, Enfants Malades	Paris Cedex 15		France
41	Universitätsklinikum Essen	Essen		Germany
42	Clinic of J.W. Goethe University	Frankfurt		Germany
43	Justus-Leibig-Universitat Zentrum fur Kinderheilkunde und Jugendmedizin	Giessen		Germany
44	Medizinische Hochschule Hannover	Hannover		Germany
45	Universitaetsklinikum Jena, Mukoviszidose-Zentrum	Jena		Germany
46	Universitaetsklinkum Koeln, CF-Studienzentrum	Koeln		Germany
47	Universitaetsklinikum Tuebingen Klinik fuer Kinder- und Jugendmedizin	Tuebingen		Germany
48	Our Lady's Children's Hospital	Dublin		Ireland
49	University Hospital Limerick	Limerick		Ireland
50	Klinika Mukowiscydozy IMD Oddozial Chorob Pluc Szpzoz IM. Dzieci WarszaWY	Lomianki		Poland
51	Inselspital - Universitaetsspital Bern	Bern		Switzerland
52	Kinderspital Zuerich	Zürich		Switzerland
53	Leeds General Infirmary	Leeds		United Kingdom
54	Royal Brompton & Harefield NHS Foundation Trust, Royal Brompton Hospital	London		United Kingdom
55	Southampton General Hospital	Southampton		United Kingdom

Sponsors and Collaborators

• Vertex Pharmaceuticals Incorporated

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Nov 8, 2019
• Statistical Analysis Plan - Aug 19, 2020

More Information

Publications

None provided.

• Responsible Party: Vertex Pharmaceuticals Incorporated
• ClinicalTrials.gov Identifier: NCT03537651
• Other Study ID Numbers: VX17-661-116; 2017-002968-40
• First Posted: May 25, 2018
• Last Update Posted: Nov 26, 2021
• Last Verified: Oct 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

Study Results

Participant Flow

Recruitment Details	This study consists of 2 parts: Parts A and B. Part A has been completed while Part B is still ongoing. Primary completion was achieved based on Part A in October 2020. Therefore, only Part A results are reported. Complete results will be posted within 1 year of study completion date.
Pre-assignment Detail	This study was conducted in cystic fibrosis (CF) participants aged 6 years or older who participated in parent Studies VX15-661-113 Part B (Study 113B; NCT02953314) or VX16-661-115 (Study 115; NCT03559062). Eligible participants from parent studies were enrolled in Study 116.

Arm/Group Title	TEZ/IVA
Arm/Group Description	Participants from parent Studies 113B and 115 received tezacaftor (TEZ)/ivacaftor (IVA) (either TEZ 50 milligrams [mg] once daily [qd]/IVA 75 mg every 12 hours [q12h] or TEZ 100 mg qd/IVA 150 mg q12h based on body weight for participants aged 6 through 11 years at enrollment and TEZ 100 mg qd/IVA 150 mg q12h for participants aged >=12 years at enrollment) for 96 weeks in Part A of Study 116. Doses were adjusted upward for changes in body weight and/or age.
Period Title: Overall Study
STARTED	130
113B/116 FAS	64
113B/116 LCI FAS	30
115/116 FAS	66
115/116 FAS (TEZ/IVA Group)	53
COMPLETED	69
NOT COMPLETED	61

Baseline Characteristics

Arm/Group Title	TEZ/IVA
Arm/Group Description	Participants from parent Studies 113B and 115 received TEZ/IVA (either TEZ 50 mg qd/IVA 75 mg q12h or TEZ 100 mg qd/IVA 150 mg q12h based on body weight for participants aged 6 through 11 years at enrollment and TEZ 100 mg qd/IVA 150 mg q12h for participants aged >=12 years at enrollment) for 96 weeks in Part A of Study 116. Doses were adjusted upward for changes in body weight and/or age.
Overall Participants	130
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	8.3 (1.7)
Sex: Female, Male (Count of Participants)
Female	67 51.5%
Male	63 48.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	4 3.1%
Not Hispanic or Latino	119 91.5%
Unknown or Not Reported	7 5.4%
Race/Ethnicity, Customized (Count of Participants)
White	125 96.2%
Black or African American	1 0.8%
Asian	1 0.8%
Other	1 0.8%
Not Collected per Local Regulations	2 1.5%

Outcome Measures

1. Primary Outcome

Title	Part A: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame	Part A: Day 1 up to Week 100

Outcome Measure Data

Analysis Population Description

Safety Set included all participants who were enrolled and received at least 1 dose of TEZ/IVA in Part A of Study 116.

Arm/Group Title	TEZ/IVA
Arm/Group Description	Participants from parent Studies 113B and 115 received TEZ/IVA (either TEZ 50 mg qd/IVA 75 mg q12h or TEZ 100 mg qd/IVA 150 mg q12h based on body weight for participants aged 6 through 11 years at enrollment and TEZ 100 mg qd/IVA 150 mg q12h for participants aged >=12 years at enrollment) for 96 weeks in Part A of Study 116. Doses were adjusted upward for changes in body weight and/or age.
Measure Participants	130
Participants With AEs	129 99.2%
Participants With SAEs	31 23.8%

2. Secondary Outcome

Title	Part A: Absolute Change in Lung Clearance Index2.5 (LCI2.5) for 115/116 FAS (TEZ/IVA Group)
Description	LCI2.5 represents the number of lung turnovers required to reduce the end tidal inert gas concentration to 1/40th of its starting value.
Time Frame	From Parent Study 115 Baseline at Week 96 (Study 116)

Outcome Measure Data

Analysis Population Description

115/116 Full analysis set (FAS) (TEZ/IVA group) included all enrolled participants who were randomized to the TEZ/IVA treatment group in parent Study 115 and received at least 1 dose of TEZ/IVA in Study 116 and had an eligible genotype. As pre-specified in the SAP, model-based efficacy analysis for participants from parent Study 115 was planned only for the TEZ/IVA treatment group.

Arm/Group Title	TEZ/IVA
Arm/Group Description	Participants who were administered TEZ/IVA in parent Study 115 received TEZ/IVA (either TEZ 50 mg qd/IVA 75 mg q12h or TEZ 100 mg qd/IVA 150 mg q12h based on body weight for participants aged 6 through 11 years at enrollment and TEZ 100 mg qd/IVA 150 mg q12h for participants aged >=12 years at enrollment) for 96 weeks in Part A of Study 116. Doses were adjusted upward for changes in body weight and/or age.
Measure Participants	53
Least Squares Mean (95% Confidence Interval) [lung clearance index]	-0.95

3. Secondary Outcome

Title	Part A: Absolute Change in LCI2.5 for 113B/116 LCI FAS
Description	LCI2.5 represents the number of lung turnovers required to reduce the end tidal inert gas concentration to 1/40th of its starting value.
Time Frame	From Parent Study 113B Baseline at Week 96 (Study 116)

Outcome Measure Data

Analysis Population Description

113B/116 LCI FAS included all enrolled participants who participated in the LCI sub study in parent Study 113B and received at least 1 dose of TEZ/IVA in Study 116 and had an eligible genotype. As pre-specified in the SAP, only descriptive summary statistics were planned to be reported for the 113B/116 LCI FAS.

Arm/Group Title	TEZ/IVA
Arm/Group Description	Participants from parent Study 113B received TEZ/IVA (either TEZ 50 mg qd/IVA 75 mg q12h or TEZ 100 mg qd/IVA 150 mg q12h based on body weight for participants aged 6 through 11 years at enrollment and TEZ 100 mg qd/IVA 150 mg q12h for participants aged >=12 years at enrollment) for 96 weeks in Part A of Study 116. Doses were adjusted upward for changes in body weight and/or age.
Measure Participants	30
Mean (Standard Deviation) [lung clearance index]	-2.04 (1.73)

4. Secondary Outcome

Title	Part A: Absolute Change in Sweat Chloride for 115/116 FAS (TEZ/IVA Group)
Description	Sweat samples were collected using an approved collection device.
Time Frame	From Parent Study 115 Baseline at Week 96 (Study 116)

Outcome Measure Data

Analysis Population Description

115/116 FAS (TEZ/IVA group). As pre-specified in the SAP, model-based efficacy analysis for participants from parent Study 115 was planned only for the TEZ/IVA treatment group.

Arm/Group Title	TEZ/IVA
Arm/Group Description	Participants who were administered TEZ/IVA in parent Study 115 received TEZ/IVA (either TEZ 50 mg qd/IVA 75 mg q12h or TEZ 100 mg qd/IVA 150 mg q12h based on body weight for participants aged 6 through 11 years at enrollment and TEZ 100 mg qd/IVA 150 mg q12h for participants aged >=12 years at enrollment) for 96 weeks in Part A of Study 116. Doses were adjusted upward for changes in body weight and/or age.
Measure Participants	53
Least Squares Mean (95% Confidence Interval) [millimole per liter (mmol/L)]	-13.8

5. Secondary Outcome

Title	Part A: Absolute Change in SwCl for 113B/116 FAS
Description	Sweat samples were collected using an approved collection device.
Time Frame	From Parent Study 113B Baseline at Week 96 (Study 116)

Outcome Measure Data

Analysis Population Description

113B/116 FAS included all enrolled participants from parent Study 113B who received at least 1 dose of TEZ/IVA in Study 116 and had an eligible genotype.

Arm/Group Title	TEZ/IVA
Arm/Group Description	Participants from parent Study 113B received TEZ/IVA (either TEZ 50 mg qd/IVA 75 mg q12h or TEZ 100 mg qd/IVA 150 mg q12h based on body weight for participants aged 6 through 11 years at enrollment and TEZ 100 mg qd/IVA 150 mg q12h for participants aged >=12 years at enrollment) for 96 weeks in Part A of Study 116. Doses were adjusted upward for changes in body weight and/or age.
Measure Participants	64
Least Squares Mean (95% Confidence Interval) [mmol/L]	-16.2

6. Secondary Outcome

Title	Part A: Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score for 115/116 FAS (TEZ/IVA Group)
Description	The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with CF. Respiratory domain assessed respiratory symptoms, score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life.
Time Frame	From Parent Study 115 Baseline at Week 96 (Study 116)

Outcome Measure Data

Analysis Population Description

115/116 FAS (TEZ/IVA group). As pre-specified in the SAP, model-based efficacy analysis for participants from parent Study 115 was planned only for the TEZ/IVA treatment group.

Arm/Group Title	TEZ/IVA
Arm/Group Description	Participants who were administered TEZ/IVA in parent Study 115 received TEZ/IVA (either TEZ 50 mg qd/IVA 75 mg q12h or TEZ 100 mg qd/IVA 150 mg q12h based on body weight for participants aged 6 through 11 years at enrollment and TEZ 100 mg qd/IVA 150 mg q12h for participants aged >=12 years at enrollment) for 96 weeks in Part A of Study 116. Doses were adjusted upward for changes in body weight and/or age.
Measure Participants	53
Least Squares Mean (95% Confidence Interval) [units on a scale]	6.4

7. Secondary Outcome

Title	Part A: Absolute Change in CFQ-R Respiratory Domain Score for 113B/116 FAS
Description	The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with CF. Respiratory domain assessed respiratory symptoms, score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life.
Time Frame	From Parent Study 113B Baseline at Week 96 (Study 116)

Outcome Measure Data

Analysis Population Description

113B/116 FAS.

Arm/Group Title	TEZ/IVA
Arm/Group Description	Participants from parent Study 113B received TEZ/IVA (either TEZ 50 mg qd/IVA 75 mg q12h or TEZ 100 mg qd/IVA 150 mg q12h based on body weight for participants aged 6 through 11 years at enrollment and TEZ 100 mg qd/IVA 150 mg q12h for participants aged >=12 years at enrollment) for 96 weeks in Part A of Study 116. Doses were adjusted upward for changes in body weight and/or age.
Measure Participants	64
Least Squares Mean (95% Confidence Interval) [units on a scale]	6.0

8. Secondary Outcome

Title	Part A: Absolute Change in Body Mass Index (BMI) for 115/116 FAS (TEZ/IVA Group)
Description	BMI was defined as weight in kilograms (kg) divided by squared height in meters (m^2).
Time Frame	From Parent Study 115 Baseline at Week 96 (Study 116)

Outcome Measure Data

Analysis Population Description

115/116 FAS (TEZ/IVA group). As pre-specified in the SAP, model-based efficacy analysis for participants from parent Study 115 was planned only for the TEZ/IVA treatment group.

Arm/Group Title	TEZ/IVA
Arm/Group Description	Participants who were administered TEZ/IVA in parent study 115 received TEZ/IVA (either TEZ 50 mg qd/IVA 75 mg q12h or TEZ 100 mg qd/IVA 150 mg q12h based on body weight for participants aged 6 through 11 years at enrollment and TEZ 100 mg qd/IVA 150 mg q12h for participants aged >=12 years at enrollment) for 96 weeks in Part A of Study 116. Doses were adjusted upward for changes in body weight and/or age.
Measure Participants	53
Least Squares Mean (95% Confidence Interval) [kilogram per meter square (kg/m^2)]	1.25

9. Secondary Outcome

Title	Part A: Absolute Change in BMI for 113B/116 FAS
Description	BMI was defined as weight in kg divided by m^2.
Time Frame	From Parent Study 113B Baseline at Week 96 (Study 116)

Outcome Measure Data

Analysis Population Description

113B/116 FAS.

Arm/Group Title	TEZ/IVA
Arm/Group Description	Participants from parent Study 113B received TEZ/IVA (either TEZ 50 mg qd/IVA 75 mg q12h or TEZ 100 mg qd/IVA 150 mg q12h based on body weight for participants aged 6 through 11 years at enrollment and TEZ 100 mg qd/IVA 150 mg q12h for participants aged >=12 years at enrollment) for 96 weeks in Part A of Study 116. Doses were adjusted upward for changes in body weight and/or age.
Measure Participants	64
Least Squares Mean (95% Confidence Interval) [kg/m^2]	1.19

Adverse Events

Time Frame	Part A: Day 1 up to Week 100
Arm/Group Title	TEZ/IVA
Arm/Group Description	Participants from parent Studies 113B and 115 received TEZ/IVA (either TEZ 50 mg qd/IVA 75 mg q12h or TEZ 100 mg qd/IVA 150 mg q12h based on body weight for participants aged 6 through 11 years at enrollment and TEZ 100 mg qd/IVA 150 mg q12h for participants aged >=12 years at enrollment) for 96 weeks in Part A of Study 116. Doses were adjusted upward for changes in body weight and/or age.
All Cause Mortality
	TEZ/IVA
	Affected / at Risk (%)	# Events
Total	0/130 (0%)
Serious Adverse Events
	TEZ/IVA
	Affected / at Risk (%)	# Events
Total	31/130 (23.8%)
Blood and lymphatic system disorders
Immune thrombocytopenia	1/130 (0.8%)
Congenital, familial and genetic disorders
Cystic fibrosis related diabetes	1/130 (0.8%)
Gastrointestinal disorders
Abdominal pain	2/130 (1.5%)
Constipation	1/130 (0.8%)
Diarrhoea	1/130 (0.8%)
Distal intestinal obstruction syndrome	1/130 (0.8%)
Intestinal obstruction	1/130 (0.8%)
Small intestinal obstruction	1/130 (0.8%)
Vomiting	1/130 (0.8%)
General disorders
Asthenia	1/130 (0.8%)
Pyrexia	1/130 (0.8%)
Infections and infestations
Bacterial disease carrier	1/130 (0.8%)
Chronic sinusitis	1/130 (0.8%)
Device related sepsis	1/130 (0.8%)
Gastroenteritis	1/130 (0.8%)
Infective pulmonary exacerbation of cystic fibrosis	15/130 (11.5%)
Influenza	1/130 (0.8%)
Pertussis	1/130 (0.8%)
Respiratory tract infection bacterial	1/130 (0.8%)
Sinusitis	1/130 (0.8%)
Upper respiratory tract infection bacterial	1/130 (0.8%)
Injury, poisoning and procedural complications
Radius fracture	1/130 (0.8%)
Investigations
Alanine aminotransferase increased	1/130 (0.8%)
Aspartate aminotransferase increased	1/130 (0.8%)
Bacterial test positive	3/130 (2.3%)
Blood lactate dehydrogenase increased	1/130 (0.8%)
Gamma-glutamyltransferase increased	1/130 (0.8%)
Pulmonary function test decreased	1/130 (0.8%)
Stenotrophomonas test positive	1/130 (0.8%)
Metabolism and nutrition disorders
Weight gain poor	1/130 (0.8%)
Psychiatric disorders
Anxiety disorder	1/130 (0.8%)
Hallucination	1/130 (0.8%)
Personality change	1/130 (0.8%)
Respiratory, thoracic and mediastinal disorders
Asthma	1/130 (0.8%)
Haemoptysis	1/130 (0.8%)
Nasal polyps	1/130 (0.8%)
Sinus disorder	1/130 (0.8%)
Sinus polyp	1/130 (0.8%)
Skin and subcutaneous tissue disorders
Dermatitis contact	1/130 (0.8%)
Other (Not Including Serious) Adverse Events
	TEZ/IVA
	Affected / at Risk (%)	# Events
Total	128/130 (98.5%)
Ear and labyrinth disorders
Ear pain	8/130 (6.2%)
Gastrointestinal disorders
Abdominal pain	20/130 (15.4%)
Abdominal pain upper	8/130 (6.2%)
Constipation	10/130 (7.7%)
Diarrhoea	8/130 (6.2%)
Nausea	8/130 (6.2%)
Vomiting	21/130 (16.2%)
General disorders
Fatigue	7/130 (5.4%)
Pyrexia	26/130 (20%)
Infections and infestations
Bacterial disease carrier	7/130 (5.4%)
Ear infection	8/130 (6.2%)
Gastroenteritis	9/130 (6.9%)
Infective pulmonary exacerbation of cystic fibrosis	57/130 (43.8%)
Influenza	13/130 (10%)
Nasopharyngitis	24/130 (18.5%)
Otitis media	8/130 (6.2%)
Pharyngitis	8/130 (6.2%)
Pharyngitis streptococcal	8/130 (6.2%)
Rhinitis	11/130 (8.5%)
Upper respiratory tract infection	31/130 (23.8%)
Viral upper respiratory tract infection	10/130 (7.7%)
Investigations
Alanine aminotransferase increased	12/130 (9.2%)
Aspartate aminotransferase increased	8/130 (6.2%)
Bacterial test positive	19/130 (14.6%)
Forced expiratory volume decreased	7/130 (5.4%)
Pseudomonas test positive	11/130 (8.5%)
Nervous system disorders
Headache	20/130 (15.4%)
Respiratory, thoracic and mediastinal disorders
Cough	73/130 (56.2%)
Nasal congestion	24/130 (18.5%)
Nasal polyps	7/130 (5.4%)
Oropharyngeal pain	24/130 (18.5%)
Productive cough	22/130 (16.9%)
Rhinorrhoea	14/130 (10.8%)
Skin and subcutaneous tissue disorders
Rash	7/130 (5.4%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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