Study to Evaluate Safety and Efficacy of VX-661 in Combination With Ivacaftor in Subjects With Cystic Fibrosis, Homozygous for the F508del-CFTR Mutation With an Open-Label Expansion
Sponsor
Vertex Pharmaceuticals Incorporated (Industry)
Overall Status
Completed
CT.gov ID
NCT02070744
Collaborator
(none)
40
23
5
26.9
1.7
0.1
Study Details
Study Description
Brief Summary
The objective of this study was to evaluate the safety and efficacy of VX-661in combination with ivacaftor in participants with cystic fibrosis (CF) who are homozygous for F508del cystic fibrosis transmembrane conductance regulator (CFTR) mutation
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
40 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Care Provider, Investigator)
Primary Purpose:
Treatment
Official Title:
A Phase 2, Randomized, Multicenter, Double Blind, Placebo Controlled Study to Evaluate Safety, Efficacy, Pharmacokinetics, and Pharmacodynamics of VX-661 in Combination With Ivacaftor for 12 Weeks in Subjects With Cystic Fibrosis, Homozygous for the F508del CFTR Mutation With an Open-Label Extension
Study Start Date
:
Mar 1, 2014
Actual Primary Completion Date
:
May 27, 2016
Actual Study Completion Date
:
May 27, 2016
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: PC Phase: VX-661 50 mg q12h + IVA 150 mg q12h Participants received VX-661 50 milligram (mg) tablet plus Ivacaftor (IVA) 150 mg tablet every 12 hours (q12h) for 12 weeks. |
Drug: VX-661
Tablet, oral use
Drug: Ivacaftor
Film coated tablet, oral use
|
| Placebo Comparator: PC Phase: VX 661 placebo q12h + IVA placebo q12h Participants received placebo matched to VX-661 tablet plus placebo matched to IVA tablet q12h for 12 weeks. |
Drug: Placebo matched to VX-661
Tablet, oral use
Drug: Placebo matched to Ivacaftor
Film coated tablet, oral use
|
| Experimental: PC Phase: VX-661 100 mg qd + IVA 150 mg q12h Participants received two VX-661 50 mg tablets once daily (qd) plus IVA 150 mg tablet q12h for 12 weeks. |
Drug: VX-661
Tablet, oral use
Drug: Ivacaftor
Film coated tablet, oral use
|
| Placebo Comparator: PC Phase: VX -661 placebo qd + IVA placebo q12h Participants received two placebo matched to VX-661 tablets qd plus placebo matched to IVA tablet q12h for 12 weeks. |
Drug: Placebo matched to VX-661
Tablet, oral use
Drug: Placebo matched to Ivacaftor
Film coated tablet, oral use
|
| Experimental: OLE Phase: VX-661 100 mg qd + IVA 150 mg q12h Participants who completed 12 week PC phase underwent a washout period of at least 4 weeks before entering the OLE phase and received two VX-661 50 mg tablets qd plus IVA 150 mg tablet q12h for 48 weeks in OLE phase. |
Drug: VX-661
Tablet, oral use
Drug: Ivacaftor
Film coated tablet, oral use
|
Outcome Measures
Primary Outcome Measures
- PC Phase: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [Baseline (PC Phase) up to 112 days]
AE: Any untoward medical occurrence in a participant during the study; the event does not necessarily have a causal relationship with the treatment. This includes any newly occurring event or previous condition that has increased in severity or frequency after the informed consent form is signed. AE includes serious as well as Non-serious AEs. SAE (subset of AE): medical event or condition, which falls into any of the following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, Inpatient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. AEs with start date or increased severity on or after the first dose of study drug through the end of study participation considered treatment-emergent. Baseline was defined as Day 1 of PC Phase.
- OLE Phase: Number of Participants With Treatment-Emergent AEs and SAEs [Baseline (OLE Phase) up to 364 days]
AE: Any untoward medical occurrence in a participant during the study; the event does not necessarily have a causal relationship with the treatment. This includes any newly occurring event or previous condition that has increased in severity or frequency after the informed consent form is signed. AE includes serious as well as Non-serious AEs. SAE (subset of AE): medical event or condition, which falls into any of the following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, Inpatient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. AEs with start date or increased severity on or after the first dose of study drug through the end of study participation considered treatment-emergent. Baseline was defined as Day 1 of the OLE Phase.
Secondary Outcome Measures
- PC Phase: Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 12 [Baseline (PC Phase), Through Week 12]
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Baseline was defined as Day 1 of PC Phase.
- OLE Phase: Absolute Change From Baseline in Percent Predicted FEV1 Through Week 40 [Baseline (OLE Phase), Through Week 40]
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Baseline was defined as Day 1 of the OLE Phase.
- PC Phase: Relative Change From Baseline in Percent Predicted FEV1 Through Week 12 [Baseline (PC Phase), Through Week 12]
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Baseline was defined as Day 1 of PC Phase.
- OLE Phase: Relative Change From Baseline in Percent Predicted FEV1 Through Week 40 [Baseline (OLE Phase), Through Week 40]
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Baseline was defined as Day 1 of the OLE Phase.
- PC Phase: Absolute Change From Baseline in Sweat Chloride Through Week 12 [Baseline (PC Phase), Through Week 12]
Sweat samples were collected using an approved collection device. Baseline was defined as Day 1 of PC Phase.
- OLE Phase: Absolute Change From Baseline in Sweat Chloride Through Week 40 [Baseline (OLE Phase), Through Week 40]
Sweat samples were collected using an approved collection device. Baseline was defined as Day 1 of the OLE Phase.
- PC Phase: Absolute Change From Baseline in Body Weight at Week 12 [Baseline (PC Phase), Week 12]
Baseline was defined as Day 1 of PC Phase.
- OLE Phase: Absolute Change From Baseline in Body Weight at Week 40 [Baseline (OLE Phase), Week 40]
Baseline was defined as Day 1 of the OLE Phase.
- PC Phase: Absolute Change From Baseline Body Mass Index (BMI) at Week 12 [Baseline (PC Phase), Week 12]
BMI was calculated using following formula: BMI = Weight in kg/height in square meter (m^2). Baseline was defined as Day 1 of PC Phase.
- OLE Phase: Absolute Change From Baseline BMI at Week 40 [Baseline (OLE Phase), Week 40]
BMI was calculated using following formula: BMI = Weight in kg/height in m^2. Baseline was defined as Day 1 of the OLE Phase.
- PC Phase: Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score Through Week 12 [Baseline (PC Phase), Through Week 12]
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 (for example, coughing, congestion, wheezing), score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life. Baseline was defined as Day 1 of PC Phase.
- OLE Phase: Absolute Change From Baseline in CFQ-R Respiratory Domain Score Through Week 40 [Baseline (OLE Phase), Through Week 40]
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 (for example, coughing, congestion, wheezing), score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life. Baseline was defined as Day 1 of the OLE Phase.
- PC Phase: Maximum Plasma Concentration (Cmax) of VX-661 and IVA [Pre-dose, 2, 3, 4, 6, 9 and 12 hours post-dose on Day 85]
- PC Phase: Area Under the Concentration Versus Time Curve From Time 0 to 24 Hours (AUC0-24h) of VX-661 [Pre-dose, 2, 3, 4, 6, 9 and 12 hours post-dose on Day 85]
Pharmacokinetic (PK) sampling was performed up to 12 hours post-dose on Day 85. For Arm VX-661 50 mg q12h + IVA 150 mg q12h (VX-661 q12h regimen), area under the concentration versus time curve from time 0 to 12 hours (AUC0-12h) was multiplied by 2 to obtain AUC0-24h.
- PC Phase: Area Under the Concentration Versus Time Curve From Time 0 to 12 Hours (AUC0-12h) of IVA [Pre-dose, 2, 3, 4, 6, 9 and 12 hours post-dose on Day 85]
- PC Phase: Time to Reach Cmax (Tmax) of VX-661 and IVA [Pre-dose, 2, 3, 4, 6, 9 and 12 hours post-dose on Day 85]
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Homozygous for the F508del CFTR mutation
-
FEV1 ≥40% and ≤90% of predicted normal for age, sex, and height
-
Stable CF disease as judged by the investigator
Exclusion Criteria:
-
History of any comorbidity that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering study drug to the participant
-
Pregnant and nursing females: Females of childbearing potential must have a negative pregnancy test at screening and Day 1 of the PC Phase and Day -7 or Day 1 of the OLE Phase (whichever was applicable)
-
Sexually active participants of reproductive potential who are not willing to follow the contraception requirements
-
The participant or a close relative of the participant is the investigator or sub investigator, research assistant, pharmacist, study coordinator, or other staff directly involved with the conduct of the study.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Birmingham | Alabama | United States | ||
| 2 | Palo Alto | California | United States | ||
| 3 | Stanford | California | United States | ||
| 4 | Altamonte Springs | Florida | United States | ||
| 5 | Miami | Florida | United States | ||
| 6 | Orlando | Florida | United States | ||
| 7 | Tampa | Florida | United States | ||
| 8 | Boise | Idaho | United States | ||
| 9 | Chicago | Illinois | United States | ||
| 10 | Boston | Massachusetts | United States | ||
| 11 | New Brunswick | New Jersey | United States | ||
| 12 | New York | New York | United States | ||
| 13 | Durham | North Carolina | United States | ||
| 14 | Cincinnati | Ohio | United States | ||
| 15 | Oklahoma City | Oklahoma | United States | ||
| 16 | Pittsburgh | Pennsylvania | United States | ||
| 17 | Charleston | South Carolina | United States | ||
| 18 | Memphis | Tennessee | United States | ||
| 19 | Houston | Texas | United States | ||
| 20 | Burlington | Vermont | United States | ||
| 21 | Colchester | Vermont | United States | ||
| 22 | Seattle | Washington | United States | ||
| 23 | Milwaukee | Wisconsin | United States |
Sponsors and Collaborators
- Vertex Pharmaceuticals Incorporated
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Vertex Pharmaceuticals Incorporated
ClinicalTrials.gov Identifier:
NCT02070744
Other Study ID Numbers:
- VX13-661-103
First Posted:
Feb 25, 2014
Last Update Posted:
Apr 13, 2018
Last Verified:
Mar 1, 2018
Keywords provided by Vertex Pharmaceuticals Incorporated
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | The study consisted of 2 phases: a randomized, double-blind, placebo-controlled (PC) phase in which participants received either VX-661 in combination with Ivacaftor (IVA), or matched placebo and an open-label extension (OLE) phase in which participants received VX-661 in combination with IVA. |
| Arm/Group Title | PC Phase: VX-661 50 mg q12h + IVA 150 mg q12h | PC Phase: VX-661 Placebo q12h + IVA Placebo q12h | PC Phase: VX-661 100 mg qd + IVA 150 mg q12h | PC Phase: VX -661 Placebo qd + IVA Placebo q12h | OLE Phase: VX-661 100 mg qd + IVA 150 mg q12h |
|---|---|---|---|---|---|
| Arm/Group Description | Participants received VX-661 50 milligram (mg) tablet plus IVA 150 mg tablet every 12 hours (q12h) for 12 weeks. | Participants received placebo matched to VX-661 tablet plus placebo matched to IVA tablet q12h for 12 weeks. | Participants received two VX-661 50 mg tablets once daily (qd) plus IVA 150 mg tablet q12h for 12 weeks. | Participants received two placebo matched to VX-661 tablets qd plus placebo matched to IVA tablet q12h for 12 weeks. | Participants who completed 12 week PC phase underwent a washout period of at least 4 weeks before entering the OLE phase and received two VX-661 50 mg tablets qd plus IVA 150 mg tablet q12h for 48 weeks in OLE phase. |
| Period Title: PC Phase (12 Weeks) | |||||
| STARTED | 6 | 5 | 15 | 14 | 0 |
| Treated | 6 | 5 | 15 | 13 | 0 |
| COMPLETED | 6 | 5 | 15 | 13 | 0 |
| NOT COMPLETED | 0 | 0 | 0 | 1 | 0 |
| Period Title: PC Phase (12 Weeks) | |||||
| STARTED | 0 | 0 | 0 | 0 | 27 |
| COMPLETED | 0 | 0 | 0 | 0 | 24 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 3 |
Baseline Characteristics
| Arm/Group Title | PC Phase: VX-661 50 mg q12h + IVA 150 mg q12h | PC Phase: VX-661 Placebo q12h + IVA Placebo q12h | PC Phase: VX-661 100 mg qd + IVA 150 mg q12h | PC Phase: VX -661 Placebo qd + IVA Placebo q12h | Total |
|---|---|---|---|---|---|
| Arm/Group Description | Participants received VX-661 50 mg tablet plus IVA 150 mg tablet q12h for 12 weeks. | Participants received placebo matched to VX-661 tablet plus placebo matched to IVA tablet q12h for 12 weeks. | Participants received two VX-661 50 mg tablets qd plus IVA 150 mg tablet q12h for 12 weeks. | Participants received two placebo matched to VX-661 tablets qd plus placebo matched to IVA tablet q12h for 12 weeks. | Total of all reporting groups |
| Overall Participants | 6 | 5 | 15 | 13 | 39 |
| Age (years) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [years] |
33.0
(10.6)
|
24.2
(2.2)
|
27.3
(5.2)
|
30.3
(10.8)
|
28.8
(8.3)
|
| Sex: Female, Male (Count of Participants) | |||||
| Female |
2
33.3%
|
2
40%
|
7
46.7%
|
3
23.1%
|
14
35.9%
|
| Male |
4
66.7%
|
3
60%
|
8
53.3%
|
10
76.9%
|
25
64.1%
|
Outcome Measures
| Title | PC Phase: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) |
|---|---|
| Description | AE: Any untoward medical occurrence in a participant during the study; the event does not necessarily have a causal relationship with the treatment. This includes any newly occurring event or previous condition that has increased in severity or frequency after the informed consent form is signed. AE includes serious as well as Non-serious AEs. SAE (subset of AE): medical event or condition, which falls into any of the following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, Inpatient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. AEs with start date or increased severity on or after the first dose of study drug through the end of study participation considered treatment-emergent. Baseline was defined as Day 1 of PC Phase. |
| Time Frame | Baseline (PC Phase) up to 112 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Set was defined as all participants who received at least 1 dose of study drug in PC Phase. |
| Arm/Group Title | PC Phase: VX-661 50 mg q12h + IVA 150 mg q12h | PC Phase: VX-661 Placebo q12h + IVA Placebo q12h | PC Phase: VX-661 100 mg qd + IVA 150 mg q12h | PC Phase: VX -661 Placebo qd + IVA Placebo q12h |
|---|---|---|---|---|
| Arm/Group Description | Participants received VX-661 50 mg tablet plus IVA 150 mg tablet q12h for 12 weeks. | Participants received placebo matched to VX-661 tablet plus placebo matched to IVA tablet q12h for 12 weeks. | Participants received two VX-661 50 mg tablets qd plus IVA 150 mg tablet q12h for 12 weeks. | Participants received two placebo matched to VX-661 tablets qd plus placebo matched to IVA tablet q12h for 12 weeks. |
| Measure Participants | 6 | 5 | 15 | 13 |
| Participants with AEs |
6
100%
|
5
100%
|
15
100%
|
13
100%
|
| Participants with SAEs |
1
16.7%
|
2
40%
|
4
26.7%
|
5
38.5%
|
| Title | OLE Phase: Number of Participants With Treatment-Emergent AEs and SAEs |
|---|---|
| Description | AE: Any untoward medical occurrence in a participant during the study; the event does not necessarily have a causal relationship with the treatment. This includes any newly occurring event or previous condition that has increased in severity or frequency after the informed consent form is signed. AE includes serious as well as Non-serious AEs. SAE (subset of AE): medical event or condition, which falls into any of the following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, Inpatient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. AEs with start date or increased severity on or after the first dose of study drug through the end of study participation considered treatment-emergent. Baseline was defined as Day 1 of the OLE Phase. |
| Time Frame | Baseline (OLE Phase) up to 364 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Set was defined as all participants who received at least 1 dose of study drug in OLE Phase. |
| Arm/Group Title | OLE Phase: VX-661 100 mg qd + IVA 150 mg q12h |
|---|---|
| Arm/Group Description | Participants who completed 12 week PC phase underwent a washout period of at least 4 weeks before entering the OLE phase and received two VX-661 50 mg tablets qd plus IVA 150 mg tablet q12h for 48 weeks in OLE phase. |
| Measure Participants | 27 |
| Participants with AEs |
25
416.7%
|
| Participants with SAEs |
6
100%
|
| Title | PC Phase: Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 12 |
|---|---|
| Description | FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Baseline was defined as Day 1 of PC Phase. |
| Time Frame | Baseline (PC Phase), Through Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS was defined as all randomized participants who received at least 1 dose of study drug in PC Phase. |
| Arm/Group Title | PC Phase: VX-661 50 mg q12h + IVA 150 mg q12h | PC Phase: VX-661 Placebo q12h + IVA Placebo q12h | PC Phase: VX-661 100 mg qd + IVA 150 mg q12h | PC Phase: VX -661 Placebo qd + IVA Placebo q12h |
|---|---|---|---|---|
| Arm/Group Description | Participants received VX-661 50 mg tablet plus IVA 150 mg tablet q12h for 12 weeks. | Participants received placebo matched to VX-661 tablet plus placebo matched to IVA tablet q12h for 12 weeks. | Participants received two VX-661 50 mg tablets qd plus IVA 150 mg tablet q12h for 12 weeks. | Participants received two placebo matched to VX-661 tablets qd plus placebo matched to IVA tablet q12h for 12 weeks. |
| Measure Participants | 6 | 5 | 15 | 13 |
| Least Squares Mean (95% Confidence Interval) [Percent predicted of FEV1] |
0.9
|
-0.1
|
3.0
|
1.9
|
| Title | OLE Phase: Absolute Change From Baseline in Percent Predicted FEV1 Through Week 40 |
|---|---|
| Description | FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Baseline was defined as Day 1 of the OLE Phase. |
| Time Frame | Baseline (OLE Phase), Through Week 40 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis population was defined as all participants who received at least 1 dose of study drug in OLE phase. |
| Arm/Group Title | OLE Phase:VX-661 100 mg qd + IVA 150 mg q12h |
|---|---|
| Arm/Group Description | Participants who completed 12 week PC phase underwent a washout period of at least 4 weeks before entering the OLE phase and received two VX-661 50 mg tablets qd plus IVA 150 mg tablet q12h for 48 weeks in OLE phase. |
| Measure Participants | 27 |
| Least Squares Mean (95% Confidence Interval) [Percent predicted of FEV1] |
2.7
|
| Title | PC Phase: Relative Change From Baseline in Percent Predicted FEV1 Through Week 12 |
|---|---|
| Description | FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Baseline was defined as Day 1 of PC Phase. |
| Time Frame | Baseline (PC Phase), Through Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS was defined as all randomized participants who received at least 1 dose of study drug in PC Phase. |
| Arm/Group Title | PC Phase: VX-661 50 mg + IVA 150 mg | PC Phase: VX-661 Placebo q12h + IVA Placebo q12h | PC Phase: VX-661 100 mg qd + IVA 150 mg q12h | PC Phase: VX -661 Placebo qd + IVA Placebo q12h |
|---|---|---|---|---|
| Arm/Group Description | Participants received VX-661 50 mg tablet plus IVA 150 mg tablet q12h for 12 weeks. | Participants received placebo matched to VX-661 tablet plus placebo matched to IVA tablet q12h for 12 weeks. | Participants received two VX-661 50 mg tablets qd plus IVA 150 mg tablet q12h for 12 weeks. | Participants received two placebo matched to VX-661 tablets qd plus placebo matched to IVA tablet q12h for 12 weeks. |
| Measure Participants | 6 | 5 | 15 | 13 |
| Least Squares Mean (95% Confidence Interval) [Percent change] |
2.6
|
1.0
|
6.0
|
4.2
|
| Title | OLE Phase: Relative Change From Baseline in Percent Predicted FEV1 Through Week 40 |
|---|---|
| Description | FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Baseline was defined as Day 1 of the OLE Phase. |
| Time Frame | Baseline (OLE Phase), Through Week 40 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis population was defined as all participants who received at least 1 dose of study drug in the OLE Phase. |
| Arm/Group Title | OLE Phase: VX-661 100 mg qd + IVA 150 mg q12h |
|---|---|
| Arm/Group Description | Participants who completed 12 week PC phase underwent a washout period of at least 4 weeks before entering the OLE phase and received two VX-661 50 mg tablets qd plus IVA 150 mg tablet q12h for 48 weeks in OLE phase. |
| Measure Participants | 27 |
| Least Squares Mean (95% Confidence Interval) [Percent change] |
6.1
|
| Title | PC Phase: Absolute Change From Baseline in Sweat Chloride Through Week 12 |
|---|---|
| Description | Sweat samples were collected using an approved collection device. Baseline was defined as Day 1 of PC Phase. |
| Time Frame | Baseline (PC Phase), Through Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS was defined as all randomized participants who received at least 1 dose of study drug in PC Phase. Here, "Number of participants analyzed" signifies those participants who were evaluable for this outcome measure. |
| Arm/Group Title | PC Phase: VX-661 50 mg q12h + IVA 150 mg q12h | PC Phase: VX-661 Placebo q12h + IVA Placebo q12h | PC Phase: VX-661 100 mg qd + IVA 150 mg q12h | PC Phase: VX -661 Placebo qd + IVA Placebo q12h |
|---|---|---|---|---|
| Arm/Group Description | Participants received VX-661 50 mg tablet plus IVA 150 mg tablet q12h for 12 weeks. | Participants received placebo matched to VX-661 tablet plus placebo matched to IVA tablet q12h for 12 weeks. | Participants received two VX-661 50 mg tablets qd plus IVA 150 mg tablet q12h for 12 weeks. | Participants received two placebo matched to VX-661 tablets qd plus placebo matched to IVA tablet q12h for 12 weeks. |
| Measure Participants | 5 | 5 | 13 | 13 |
| Least Squares Mean (95% Confidence Interval) [Millimole per liter (mmol/L)] |
-10.6
|
2.9
|
-4.7
|
0.8
|
| Title | OLE Phase: Absolute Change From Baseline in Sweat Chloride Through Week 40 |
|---|---|
| Description | Sweat samples were collected using an approved collection device. Baseline was defined as Day 1 of the OLE Phase. |
| Time Frame | Baseline (OLE Phase), Through Week 40 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis population was defined as all participants who received at least 1 dose of study drug in the OLE Phase. Here, "Number of participants analyzed" signifies those participants who were evaluable for this outcome measure. |
| Arm/Group Title | OLE Phase: VX-661 100 mg qd + IVA 150 mg q12h |
|---|---|
| Arm/Group Description | Participants who completed 12 week PC phase underwent a washout period of at least 4 weeks before entering the OLE phase and received two VX-661 50 mg tablets qd plus IVA 150 mg tablet q12h for 48 weeks in OLE phase. |
| Measure Participants | 25 |
| Least Squares Mean (95% Confidence Interval) [mmol/L] |
-6.6
|
| Title | PC Phase: Absolute Change From Baseline in Body Weight at Week 12 |
|---|---|
| Description | Baseline was defined as Day 1 of PC Phase. |
| Time Frame | Baseline (PC Phase), Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS was defined as all randomized participants who received at least 1 dose of study drug in PC Phase. |
| Arm/Group Title | PC Phase: VX-661 50 mg q12h + IVA 150 mg q12h | PC Phase: VX-661 Placebo q12h + IVA Placebo q12h | PC Phase: VX-661 100 mg qd + IVA 150 mg q12h | PC Phase: VX -661 Placebo qd + IVA Placebo q12h |
|---|---|---|---|---|
| Arm/Group Description | Participants received VX-661 50 mg tablet plus IVA 150 mg tablet q12h for 12 weeks. | Participants received placebo matched to VX-661 tablet plus placebo matched to IVA tablet q12h for 12 weeks. | Participants received two VX-661 50 mg tablets qd plus IVA 150 mg tablet q12h for 12 weeks. | Participants received two placebo matched to VX-661 tablets qd plus placebo matched to IVA tablet q12h for 12 weeks. |
| Measure Participants | 6 | 5 | 15 | 13 |
| Least Squares Mean (95% Confidence Interval) [kilogram (kg)] |
1.0
|
1.6
|
0.5
|
0.3
|
| Title | OLE Phase: Absolute Change From Baseline in Body Weight at Week 40 |
|---|---|
| Description | Baseline was defined as Day 1 of the OLE Phase. |
| Time Frame | Baseline (OLE Phase), Week 40 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis population was defined as all participants who received at least 1 dose of study drug in the OLE Phase. |
| Arm/Group Title | OLE Phase: VX-661 100 mg qd + IVA 150 mg q12h |
|---|---|
| Arm/Group Description | Participants who completed 12 week PC phase underwent a washout period of at least 4 weeks before entering the OLE phase and received two VX-661 50 mg tablets qd plus IVA 150 mg tablet q12h for 48 weeks in OLE phase. |
| Measure Participants | 27 |
| Least Squares Mean (95% Confidence Interval) [kg] |
1.0
|
| Title | PC Phase: Absolute Change From Baseline Body Mass Index (BMI) at Week 12 |
|---|---|
| Description | BMI was calculated using following formula: BMI = Weight in kg/height in square meter (m^2). Baseline was defined as Day 1 of PC Phase. |
| Time Frame | Baseline (PC Phase), Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS was defined as all randomized participants who received at least 1 dose of study drug in PC Phase. |
| Arm/Group Title | PC Phase: VX-661 50 mg q12h + IVA 150 mg q12h | PC Phase: VX-661 Placebo q12h + IVA Placebo q12h | PC Phase: VX-661 100 mg qd + IVA 150 mg q12h | PC Phase: VX -661 Placebo qd + IVA Placebo q12h |
|---|---|---|---|---|
| Arm/Group Description | Participants received VX-661 50 mg tablet plus IVA 150 mg tablet q12h for 12 weeks. | Participants received placebo matched to VX-661 tablet plus placebo matched to IVA tablet q12h for 12 weeks. | Participants received two VX-661 50 mg tablets qd plus IVA 150 mg tablet q12h for 12 weeks. | Participants received two placebo matched to VX-661 tablets qd plus placebo matched to IVA tablet q12h for 12 weeks. |
| Measure Participants | 6 | 5 | 15 | 13 |
| Least Squares Mean (95% Confidence Interval) [Kilogram per square meter (kg/m^2)] |
0.38
|
0.54
|
0.18
|
0.11
|
| Title | OLE Phase: Absolute Change From Baseline BMI at Week 40 |
|---|---|
| Description | BMI was calculated using following formula: BMI = Weight in kg/height in m^2. Baseline was defined as Day 1 of the OLE Phase. |
| Time Frame | Baseline (OLE Phase), Week 40 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis population was defined as all participants who received at least 1 dose of study drug in the OLE Phase. |
| Arm/Group Title | OLE Phase: VX-661 100 mg qd + IVA 150 mg q12h |
|---|---|
| Arm/Group Description | Participants who completed 12 week PC phase underwent a washout period of at least 4 weeks before entering the OLE phase and received two VX-661 50 mg tablets qd plus IVA 150 mg tablet q12h for 48 weeks in OLE phase. |
| Measure Participants | 27 |
| Least Squares Mean (95% Confidence Interval) [kg/m^2] |
0.33
|
| Title | PC Phase: Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score Through Week 12 |
|---|---|
| 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 (for example, coughing, congestion, wheezing), score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life. Baseline was defined as Day 1 of PC Phase. |
| Time Frame | Baseline (PC Phase), Through Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS was defined as all randomized participants who received at least 1 dose of study drug in PC Phase. |
| Arm/Group Title | PC Phase: VX-661 50 mg q12h + IVA 150 mg q12h | PC Phase: VX-661 Placebo q12h + IVA Placebo q12h | PC Phase: VX-661 100 mg qd + IVA 150 mg q12h | PC Phase: VX -661 Placebo qd + IVA Placebo q12h |
|---|---|---|---|---|
| Arm/Group Description | Participants received VX-661 50 mg tablet plus IVA 150 mg tablet q12h for 12 weeks. | Participants received placebo matched to VX-661 tablet plus placebo matched to IVA tablet q12h for 12 weeks. | Participants received two VX-661 50 mg tablets qd plus IVA 150 mg tablet q12h for 12 weeks. | Participants received two placebo matched to VX-661 tablets qd plus placebo matched to IVA tablet q12h for 12 weeks. |
| Measure Participants | 6 | 5 | 15 | 13 |
| Least Squares Mean (95% Confidence Interval) [units on a scale] |
5.6
|
-4.6
|
1.0
|
0.4
|
| Title | OLE Phase: Absolute Change From Baseline in CFQ-R Respiratory Domain Score Through Week 40 |
|---|---|
| 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 (for example, coughing, congestion, wheezing), score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life. Baseline was defined as Day 1 of the OLE Phase. |
| Time Frame | Baseline (OLE Phase), Through Week 40 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis population was defined as all participants who received at least 1 dose of study drug in the OLE Phase. |
| Arm/Group Title | OLE Phase: VX-661 100 mg qd + IVA 150 mg q12h |
|---|---|
| Arm/Group Description | Participants who completed 12 week PC phase underwent a washout period of at least 4 weeks before entering the OLE phase and received two VX-661 50 mg tablets qd plus IVA 150 mg tablet q12h for 48 weeks in OLE phase. |
| Measure Participants | 27 |
| Least Squares Mean (95% Confidence Interval) [units on a scale] |
-0.6
|
| Title | PC Phase: Maximum Plasma Concentration (Cmax) of VX-661 and IVA |
|---|---|
| Description | |
| Time Frame | Pre-dose, 2, 3, 4, 6, 9 and 12 hours post-dose on Day 85 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis population included all participants who received a dose of VX-661 and IVA, whether the participant completed dosing or not and if the dataset(s) supported the noncompartmental analyses. |
| Arm/Group Title | PC Phase: VX-661 50 mg q12h + IVA 150 mg q12h | PC Phase: VX-661 100 mg qd + IVA 150 mg q12h |
|---|---|---|
| Arm/Group Description | Participants received VX-661 50 mg tablet plus IVA 150 mg tablet q12h for 12 weeks. | Participants received two VX-661 50 mg tablets qd plus IVA 150 mg tablet q12h for 12 weeks. |
| Measure Participants | 6 | 15 |
| VX-661 |
4890
(3150)
|
6460
(1240)
|
| IVA |
1490
(1150)
|
1210
(585)
|
| Title | PC Phase: Area Under the Concentration Versus Time Curve From Time 0 to 24 Hours (AUC0-24h) of VX-661 |
|---|---|
| Description | Pharmacokinetic (PK) sampling was performed up to 12 hours post-dose on Day 85. For Arm VX-661 50 mg q12h + IVA 150 mg q12h (VX-661 q12h regimen), area under the concentration versus time curve from time 0 to 12 hours (AUC0-12h) was multiplied by 2 to obtain AUC0-24h. |
| Time Frame | Pre-dose, 2, 3, 4, 6, 9 and 12 hours post-dose on Day 85 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis population included all participants who received a dose of VX-661 and IVA, whether the participant completed dosing or not and if the dataset(s) supported the noncompartmental analyses. Here, "Number of participants analyzed" signifies those participants who were evaluable for this outcome measure. |
| Arm/Group Title | PC Phase: VX-661 50 mg q12h + IVA 150 mg q12h | PC Phase: VX-661 100 mg qd + IVA 150 mg q12h |
|---|---|---|
| Arm/Group Description | Participants received VX-661 50 mg tablet plus IVA 150 mg tablet q12h for 12 weeks. | Participants received two VX-661 50 mg tablets qd plus IVA 150 mg tablet q12h for 12 weeks. |
| Measure Participants | 5 | 15 |
| Mean (Standard Deviation) [Hour*nanogram per milliliter (hr*ng/mL)] |
84900
(55900)
|
75500
(20300)
|
| Title | PC Phase: Area Under the Concentration Versus Time Curve From Time 0 to 12 Hours (AUC0-12h) of IVA |
|---|---|
| Description | |
| Time Frame | Pre-dose, 2, 3, 4, 6, 9 and 12 hours post-dose on Day 85 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis population included all participants who received a dose of VX-661 and IVA, whether the participant completed dosing or not and if the dataset(s) supported the noncompartmental analyses. Here, "Number of participants analyzed" signifies those participants who were evaluable for this outcome measure. |
| Arm/Group Title | PC Phase: VX-661 50 mg q12h + IVA 150 mg q12h | PC Phase: VX-661 100 mg qd + IVA 150 mg q12h |
|---|---|---|
| Arm/Group Description | Participants received VX-661 50 mg tablet plus IVA 150 mg tablet q12h for 12 weeks. | Participants received two VX-661 50 mg tablets qd plus IVA 150 mg tablet q12h for 12 weeks. |
| Measure Participants | 5 | 15 |
| Mean (Standard Deviation) [hr*ng/mL] |
14700
(11600)
|
10100
(4890)
|
| Title | PC Phase: Time to Reach Cmax (Tmax) of VX-661 and IVA |
|---|---|
| Description | |
| Time Frame | Pre-dose, 2, 3, 4, 6, 9 and 12 hours post-dose on Day 85 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis population included all participants who received a dose of VX-661 and IVA, whether the participant completed dosing or not and if the dataset(s) supported the noncompartmental analyses. |
| Arm/Group Title | PC Phase: VX-661 50 mg q12h + IVA 150 mg q12h | PC Phase: VX-661 100 mg qd + IVA 150 mg q12h |
|---|---|---|
| Arm/Group Description | Participants received VX-661 50 mg tablet plus IVA 150 mg tablet q12h for 12 weeks. | Participants received two VX-661 50 mg tablets qd plus IVA 150 mg tablet q12h for 12 weeks. |
| Measure Participants | 6 | 15 |
| VX-661 |
2.48
|
3.23
|
| IVA |
3.59
|
4.00
|
Adverse Events
| Time Frame | Baseline (Day 1 of PC Phase) up to 112 days (Placebo control phase); Baseline (Day 1 of OLE Phase) up to 364 days (OLE phase) | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Safety Set was defined as all participants who received at least 1 dose of study drug in PC Phase and OLE Phase. | |||||||||
| Arm/Group Title | PC Phase: VX-661 50 mg q12h + IVA 150 mg q12h | PC Phase: VX 661 Placebo q12h + IVA Placebo q12h | PC Phase: VX-661 100 mg qd + IVA 150 mg q12h | PC Phase: VX -661 Placebo qd + IVA Placebo q12h | OLE Phase: VX-661 100 mg qd + IVA 150 mg q12h | |||||
| Arm/Group Description | Participants received VX-661 50 mg tablet plus IVA 150 mg tablet q12h for 12 weeks. | Participants received placebo matched to VX-661 tablet plus placebo matched to IVA tablet q12h for 12 weeks. | Participants received two VX-661 50 mg tablets qd plus IVA 150 mg tablet q12h for 12 weeks. | Participants received two placebo matched to VX-661 tablets qd plus placebo matched to IVA tablet q12h for 12 weeks. | Participants who completed 12 week PC phase underwent a washout period of at least 4 weeks before entering the OLE phase and received two VX-661 50 mg tablets qd plus IVA 150 mg tablet q12h for 48 weeks in OLE phase. | |||||
All Cause Mortality |
||||||||||
| PC Phase: VX-661 50 mg q12h + IVA 150 mg q12h | PC Phase: VX 661 Placebo q12h + IVA Placebo q12h | PC Phase: VX-661 100 mg qd + IVA 150 mg q12h | PC Phase: VX -661 Placebo qd + IVA Placebo q12h | OLE Phase: VX-661 100 mg qd + IVA 150 mg q12h | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/6 (0%) | 0/5 (0%) | 0/15 (0%) | 0/13 (0%) | 0/27 (0%) | |||||
Serious Adverse Events |
||||||||||
| PC Phase: VX-661 50 mg q12h + IVA 150 mg q12h | PC Phase: VX 661 Placebo q12h + IVA Placebo q12h | PC Phase: VX-661 100 mg qd + IVA 150 mg q12h | PC Phase: VX -661 Placebo qd + IVA Placebo q12h | OLE Phase: VX-661 100 mg qd + IVA 150 mg q12h | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/6 (16.7%) | 2/5 (40%) | 4/15 (26.7%) | 5/13 (38.5%) | 6/27 (22.2%) | |||||
| Congenital, familial and genetic disorders | ||||||||||
| Cystic fibrosis related diabetes | 0/6 (0%) | 0/5 (0%) | 0/15 (0%) | 0/13 (0%) | 1/27 (3.7%) | |||||
| Gastrointestinal disorders | ||||||||||
| Intestinal obstruction | 0/6 (0%) | 0/5 (0%) | 0/15 (0%) | 1/13 (7.7%) | 0/27 (0%) | |||||
| Infections and infestations | ||||||||||
| Infective pulmonary exacerbation of cystic fibrosis | 0/6 (0%) | 2/5 (40%) | 4/15 (26.7%) | 4/13 (30.8%) | 5/27 (18.5%) | |||||
| Chronic sinusitis | 1/6 (16.7%) | 0/5 (0%) | 0/15 (0%) | 0/13 (0%) | 0/27 (0%) | |||||
| Pneumonia | 0/6 (0%) | 0/5 (0%) | 0/15 (0%) | 1/13 (7.7%) | 0/27 (0%) | |||||
| Metabolism and nutrition disorders | ||||||||||
| Dehydration | 0/6 (0%) | 0/5 (0%) | 0/15 (0%) | 0/13 (0%) | 1/27 (3.7%) | |||||
| Renal and urinary disorders | ||||||||||
| Nephrolithiasis | 0/6 (0%) | 0/5 (0%) | 0/15 (0%) | 0/13 (0%) | 1/27 (3.7%) | |||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||
| Pneumothorax | 0/6 (0%) | 0/5 (0%) | 0/15 (0%) | 1/13 (7.7%) | 0/27 (0%) | |||||
Other (Not Including Serious) Adverse Events |
||||||||||
| PC Phase: VX-661 50 mg q12h + IVA 150 mg q12h | PC Phase: VX 661 Placebo q12h + IVA Placebo q12h | PC Phase: VX-661 100 mg qd + IVA 150 mg q12h | PC Phase: VX -661 Placebo qd + IVA Placebo q12h | OLE Phase: VX-661 100 mg qd + IVA 150 mg q12h | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 6/6 (100%) | 5/5 (100%) | 15/15 (100%) | 13/13 (100%) | 25/27 (92.6%) | |||||
| Ear and labyrinth disorders | ||||||||||
| Tinnitus | 1/6 (16.7%) | 0/5 (0%) | 0/15 (0%) | 0/13 (0%) | 0/27 (0%) | |||||
| Gastrointestinal disorders | ||||||||||
| Diarrhoea | 1/6 (16.7%) | 0/5 (0%) | 3/15 (20%) | 1/13 (7.7%) | 0/27 (0%) | |||||
| Nausea | 0/6 (0%) | 0/5 (0%) | 2/15 (13.3%) | 0/13 (0%) | 2/27 (7.4%) | |||||
| Dyspepsia | 1/6 (16.7%) | 1/5 (20%) | 0/15 (0%) | 0/13 (0%) | 0/27 (0%) | |||||
| Abdominal distension | 0/6 (0%) | 0/5 (0%) | 1/15 (6.7%) | 0/13 (0%) | 0/27 (0%) | |||||
| Abdominal pain | 0/6 (0%) | 0/5 (0%) | 1/15 (6.7%) | 0/13 (0%) | 0/27 (0%) | |||||
| Abdominal pain upper | 0/6 (0%) | 0/5 (0%) | 1/15 (6.7%) | 0/13 (0%) | 0/27 (0%) | |||||
| Haemorrhoids | 0/6 (0%) | 0/5 (0%) | 0/15 (0%) | 1/13 (7.7%) | 0/27 (0%) | |||||
| Peptic ulcer | 0/6 (0%) | 0/5 (0%) | 0/15 (0%) | 1/13 (7.7%) | 0/27 (0%) | |||||
| Gastrooesophageal reflux disease | 0/6 (0%) | 0/5 (0%) | 0/15 (0%) | 0/13 (0%) | 3/27 (11.1%) | |||||
| Constipation | 0/6 (0%) | 0/5 (0%) | 0/15 (0%) | 0/13 (0%) | 2/27 (7.4%) | |||||
| Flatulence | 0/6 (0%) | 0/5 (0%) | 0/15 (0%) | 0/13 (0%) | 2/27 (7.4%) | |||||
| General disorders | ||||||||||
| Fatigue | 1/6 (16.7%) | 1/5 (20%) | 1/15 (6.7%) | 0/13 (0%) | 2/27 (7.4%) | |||||
| Peripheral swelling | 0/6 (0%) | 0/5 (0%) | 1/15 (6.7%) | 0/13 (0%) | 0/27 (0%) | |||||
| Non-cardiac chest pain | 0/6 (0%) | 1/5 (20%) | 0/15 (0%) | 0/13 (0%) | 0/27 (0%) | |||||
| Oedema peripheral | 0/6 (0%) | 0/5 (0%) | 0/15 (0%) | 1/13 (7.7%) | 0/27 (0%) | |||||
| Vaccination site discomfort | 0/6 (0%) | 0/5 (0%) | 0/15 (0%) | 1/13 (7.7%) | 0/27 (0%) | |||||
| Pyrexia | 0/6 (0%) | 0/5 (0%) | 0/15 (0%) | 0/13 (0%) | 2/27 (7.4%) | |||||
| Infections and infestations | ||||||||||
| Infective pulmonary exacerbation of cystic fibrosis | 1/6 (16.7%) | 3/5 (60%) | 5/15 (33.3%) | 4/13 (30.8%) | 13/27 (48.1%) | |||||
| Nasopharyngitis | 0/6 (0%) | 0/5 (0%) | 2/15 (13.3%) | 0/13 (0%) | 3/27 (11.1%) | |||||
| Upper respiratory tract infection | 0/6 (0%) | 1/5 (20%) | 1/15 (6.7%) | 0/13 (0%) | 2/27 (7.4%) | |||||
| Bacterial vaginosis | 0/6 (0%) | 0/5 (0%) | 1/15 (6.7%) | 0/13 (0%) | 0/27 (0%) | |||||
| Acute sinusitis | 0/6 (0%) | 1/5 (20%) | 0/15 (0%) | 0/13 (0%) | 0/27 (0%) | |||||
| Bronchitis | 0/6 (0%) | 0/5 (0%) | 0/15 (0%) | 1/13 (7.7%) | 0/27 (0%) | |||||
| Chronic sinusitis | 0/6 (0%) | 0/5 (0%) | 0/15 (0%) | 1/13 (7.7%) | 0/27 (0%) | |||||
| Oral candidiasis | 0/6 (0%) | 0/5 (0%) | 0/15 (0%) | 1/13 (7.7%) | 2/27 (7.4%) | |||||
| Viral upper respiratory tract infection | 0/6 (0%) | 0/5 (0%) | 0/15 (0%) | 1/13 (7.7%) | 0/27 (0%) | |||||
| Vulvovaginal mycotic infection | 0/6 (0%) | 0/5 (0%) | 0/15 (0%) | 1/13 (7.7%) | 0/27 (0%) | |||||
| Tooth infection | 0/6 (0%) | 0/5 (0%) | 0/15 (0%) | 0/13 (0%) | 2/27 (7.4%) | |||||
| Injury, poisoning and procedural complications | ||||||||||
| Arthropod bite | 0/6 (0%) | 0/5 (0%) | 1/15 (6.7%) | 0/13 (0%) | 0/27 (0%) | |||||
| Muscle strain | 1/6 (16.7%) | 0/5 (0%) | 0/15 (0%) | 0/13 (0%) | 0/27 (0%) | |||||
| Investigations | ||||||||||
| Pulmonary function test decreased | 1/6 (16.7%) | 1/5 (20%) | 2/15 (13.3%) | 1/13 (7.7%) | 0/27 (0%) | |||||
| Weight decreased | 0/6 (0%) | 0/5 (0%) | 2/15 (13.3%) | 1/13 (7.7%) | 3/27 (11.1%) | |||||
| Alanine aminotransferase increased | 0/6 (0%) | 1/5 (20%) | 1/15 (6.7%) | 0/13 (0%) | 2/27 (7.4%) | |||||
| Aspartate aminotransferase increased | 0/6 (0%) | 1/5 (20%) | 1/15 (6.7%) | 0/13 (0%) | 2/27 (7.4%) | |||||
| C-reactive protein increased | 0/6 (0%) | 0/5 (0%) | 1/15 (6.7%) | 1/13 (7.7%) | 0/27 (0%) | |||||
| Heart rate increased | 0/6 (0%) | 1/5 (20%) | 1/15 (6.7%) | 0/13 (0%) | 0/27 (0%) | |||||
| Blood bilirubin unconjugated increased | 0/6 (0%) | 0/5 (0%) | 1/15 (6.7%) | 0/13 (0%) | 0/27 (0%) | |||||
| Blood triglycerides increased | 0/6 (0%) | 0/5 (0%) | 1/15 (6.7%) | 0/13 (0%) | 0/27 (0%) | |||||
| Breath sounds abnormal | 1/6 (16.7%) | 0/5 (0%) | 0/15 (0%) | 0/13 (0%) | 0/27 (0%) | |||||
| Gamma-glutamyltransferase increased | 0/6 (0%) | 0/5 (0%) | 1/15 (6.7%) | 0/13 (0%) | 0/27 (0%) | |||||
| Urine output decreased | 1/6 (16.7%) | 0/5 (0%) | 0/15 (0%) | 0/13 (0%) | 0/27 (0%) | |||||
| Forced expiratory volume decreased | 0/6 (0%) | 1/5 (20%) | 0/15 (0%) | 2/13 (15.4%) | 0/27 (0%) | |||||
| Vitamin D decreased | 0/6 (0%) | 0/5 (0%) | 0/15 (0%) | 2/13 (15.4%) | 0/27 (0%) | |||||
| Activated partial thromboplastin time prolonged | 0/6 (0%) | 0/5 (0%) | 0/15 (0%) | 1/13 (7.7%) | 0/27 (0%) | |||||
| Oxygen saturation decreased | 0/6 (0%) | 1/5 (20%) | 0/15 (0%) | 0/13 (0%) | 0/27 (0%) | |||||
| Prothrombin time prolonged | 0/6 (0%) | 0/5 (0%) | 0/15 (0%) | 1/13 (7.7%) | 0/27 (0%) | |||||
| Vitamin A decreased | 0/6 (0%) | 0/5 (0%) | 0/15 (0%) | 1/13 (7.7%) | 0/27 (0%) | |||||
| Vitamin K decreased | 0/6 (0%) | 0/5 (0%) | 0/15 (0%) | 1/13 (7.7%) | 0/27 (0%) | |||||
| White blood cells urine positive | 0/6 (0%) | 0/5 (0%) | 0/15 (0%) | 1/13 (7.7%) | 0/27 (0%) | |||||
| Metabolism and nutrition disorders | ||||||||||
| Decreased appetite | 0/6 (0%) | 0/5 (0%) | 1/15 (6.7%) | 0/13 (0%) | 0/27 (0%) | |||||
| Gout | 0/6 (0%) | 0/5 (0%) | 1/15 (6.7%) | 0/13 (0%) | 0/27 (0%) | |||||
| Iron deficiency | 1/6 (16.7%) | 0/5 (0%) | 0/15 (0%) | 0/13 (0%) | 0/27 (0%) | |||||
| Hypoglycaemia | 0/6 (0%) | 0/5 (0%) | 0/15 (0%) | 1/13 (7.7%) | 0/27 (0%) | |||||
| Vitamin E deficiency | 0/6 (0%) | 0/5 (0%) | 0/15 (0%) | 1/13 (7.7%) | 0/27 (0%) | |||||
| Musculoskeletal and connective tissue disorders | ||||||||||
| Back pain | 1/6 (16.7%) | 0/5 (0%) | 0/15 (0%) | 2/13 (15.4%) | 0/27 (0%) | |||||
| Arthralgia | 0/6 (0%) | 0/5 (0%) | 1/15 (6.7%) | 0/13 (0%) | 3/27 (11.1%) | |||||
| Arthritis | 0/6 (0%) | 0/5 (0%) | 1/15 (6.7%) | 0/13 (0%) | 0/27 (0%) | |||||
| Muscle spasms | 1/6 (16.7%) | 0/5 (0%) | 0/15 (0%) | 0/13 (0%) | 0/27 (0%) | |||||
| Musculoskeletal pain | 1/6 (16.7%) | 0/5 (0%) | 0/15 (0%) | 0/13 (0%) | 0/27 (0%) | |||||
| Pain in extremity | 0/6 (0%) | 0/5 (0%) | 1/15 (6.7%) | 0/13 (0%) | 0/27 (0%) | |||||
| Myalgia | 0/6 (0%) | 0/5 (0%) | 0/15 (0%) | 1/13 (7.7%) | 2/27 (7.4%) | |||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||
| Lipoma | 0/6 (0%) | 0/5 (0%) | 1/15 (6.7%) | 0/13 (0%) | 0/27 (0%) | |||||
| Nervous system disorders | ||||||||||
| Headache | 1/6 (16.7%) | 0/5 (0%) | 2/15 (13.3%) | 1/13 (7.7%) | 4/27 (14.8%) | |||||
| Dizziness | 0/6 (0%) | 0/5 (0%) | 1/15 (6.7%) | 1/13 (7.7%) | 0/27 (0%) | |||||
| Hyposmia | 1/6 (16.7%) | 0/5 (0%) | 0/15 (0%) | 0/13 (0%) | 0/27 (0%) | |||||
| Lethargy | 0/6 (0%) | 0/5 (0%) | 0/15 (0%) | 1/13 (7.7%) | 0/27 (0%) | |||||
| Sinus headache | 0/6 (0%) | 1/5 (20%) | 0/15 (0%) | 0/13 (0%) | 0/27 (0%) | |||||
| Somnolence | 0/6 (0%) | 0/5 (0%) | 0/15 (0%) | 1/13 (7.7%) | 0/27 (0%) | |||||
| Psychiatric disorders | ||||||||||
| Disorientation | 0/6 (0%) | 0/5 (0%) | 0/15 (0%) | 1/13 (7.7%) | 0/27 (0%) | |||||
| Reproductive system and breast disorders | ||||||||||
| Menorrhagia | 0/6 (0%) | 0/5 (0%) | 1/15 (6.7%) | 0/13 (0%) | 0/27 (0%) | |||||
| Testicular pain | 1/6 (16.7%) | 0/5 (0%) | 0/15 (0%) | 0/13 (0%) | 0/27 (0%) | |||||
| Amenorrhoea | 0/6 (0%) | 1/5 (20%) | 0/15 (0%) | 0/13 (0%) | 0/27 (0%) | |||||
| Breast tenderness | 0/6 (0%) | 0/5 (0%) | 0/15 (0%) | 1/13 (7.7%) | 0/27 (0%) | |||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||
| Cough | 3/6 (50%) | 2/5 (40%) | 4/15 (26.7%) | 5/13 (38.5%) | 10/27 (37%) | |||||
| Dyspnoea | 1/6 (16.7%) | 2/5 (40%) | 2/15 (13.3%) | 1/13 (7.7%) | 3/27 (11.1%) | |||||
| Haemoptysis | 0/6 (0%) | 0/5 (0%) | 3/15 (20%) | 3/13 (23.1%) | 3/27 (11.1%) | |||||
| Respiration abnormal | 1/6 (16.7%) | 1/5 (20%) | 2/15 (13.3%) | 0/13 (0%) | 3/27 (11.1%) | |||||
| Nasal congestion | 1/6 (16.7%) | 0/5 (0%) | 1/15 (6.7%) | 3/13 (23.1%) | 2/27 (7.4%) | |||||
| Lower respiratory tract congestion | 1/6 (16.7%) | 0/5 (0%) | 1/15 (6.7%) | 0/13 (0%) | 0/27 (0%) | |||||
| Sputum increased | 0/6 (0%) | 2/5 (40%) | 1/15 (6.7%) | 2/13 (15.4%) | 4/27 (14.8%) | |||||
| Oropharyngeal pain | 0/6 (0%) | 0/5 (0%) | 1/15 (6.7%) | 1/13 (7.7%) | 2/27 (7.4%) | |||||
| Sputum discoloured | 0/6 (0%) | 1/5 (20%) | 1/15 (6.7%) | 0/13 (0%) | 0/27 (0%) | |||||
| Epistaxis | 1/6 (16.7%) | 0/5 (0%) | 0/15 (0%) | 0/13 (0%) | 0/27 (0%) | |||||
| Nasal oedema | 1/6 (16.7%) | 0/5 (0%) | 0/15 (0%) | 0/13 (0%) | 0/27 (0%) | |||||
| Painful respiration | 0/6 (0%) | 0/5 (0%) | 1/15 (6.7%) | 0/13 (0%) | 0/27 (0%) | |||||
| Paranasal sinus hypersecretion | 1/6 (16.7%) | 0/5 (0%) | 0/15 (0%) | 0/13 (0%) | 0/27 (0%) | |||||
| Productive cough | 1/6 (16.7%) | 0/5 (0%) | 0/15 (0%) | 0/13 (0%) | 0/27 (0%) | |||||
| Sinus congestion | 1/6 (16.7%) | 0/5 (0%) | 0/15 (0%) | 0/13 (0%) | 5/27 (18.5%) | |||||
| Wheezing | 0/6 (0%) | 0/5 (0%) | 1/15 (6.7%) | 0/13 (0%) | 2/27 (7.4%) | |||||
| Rales | 0/6 (0%) | 1/5 (20%) | 0/15 (0%) | 1/13 (7.7%) | 0/27 (0%) | |||||
| Pleurisy | 0/6 (0%) | 0/5 (0%) | 0/15 (0%) | 1/13 (7.7%) | 0/27 (0%) | |||||
| Pleuritic pain | 0/6 (0%) | 0/5 (0%) | 0/15 (0%) | 1/13 (7.7%) | 0/27 (0%) | |||||
| Pneumothorax | 0/6 (0%) | 0/5 (0%) | 0/15 (0%) | 1/13 (7.7%) | 0/27 (0%) | |||||
| Respiratory tract congestion | 0/6 (0%) | 0/5 (0%) | 0/15 (0%) | 1/13 (7.7%) | 3/27 (11.1%) | |||||
| Upper respiratory tract congestion | 0/6 (0%) | 0/5 (0%) | 0/15 (0%) | 1/13 (7.7%) | 0/27 (0%) | |||||
| Skin and subcutaneous tissue disorders | ||||||||||
| Acne | 0/6 (0%) | 0/5 (0%) | 1/15 (6.7%) | 0/13 (0%) | 0/27 (0%) | |||||
| Dermatitis allergic | 0/6 (0%) | 0/5 (0%) | 1/15 (6.7%) | 0/13 (0%) | 0/27 (0%) | |||||
| Rash | 1/6 (16.7%) | 0/5 (0%) | 0/15 (0%) | 0/13 (0%) | 0/27 (0%) | |||||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
PI is free to publish results of the study after (1) the first multi-center publication, (2) if the sponsor elects not to publish the results, or (3) 18 months after close of the study, whichever occurs first. Proposed publications are to be submitted to the sponsor for review and comment for a period of at least 45 days (which may be extended under certain circumstances related to protection of intellectual property); the sponsor cannot require changes to the proposed publications.
Results Point of Contact
| Name/Title | Medical Monitor |
|---|---|
| Organization | Vertex Pharmaceuticals Incorporated |
| Phone | 617-341-6777 |
| medicalinfo@vrtx.com |
Responsible Party:
Vertex Pharmaceuticals Incorporated
ClinicalTrials.gov Identifier:
NCT02070744
Other Study ID Numbers:
- VX13-661-103
First Posted:
Feb 25, 2014
Last Update Posted:
Apr 13, 2018
Last Verified:
Mar 1, 2018