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A Study of Lumacaftor in Combination With Ivacaftor in Cystic Fibrosis Subjects Aged 12 Years and Older Who Are Homozygous for the F508del-CFTR Mutation (TRANSPORT)

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ClinicalTrials.gov Identifier: NCT01807949
Recruitment Status : Completed
First Posted : March 8, 2013
Results First Posted : September 1, 2015
Last Update Posted : September 27, 2016
Sponsor:
Information provided by (Responsible Party):
Vertex Pharmaceuticals Incorporated

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Cystic Fibrosis, Homozygous for the F508del CFTR Mutation
Interventions Drug: Placebo
Drug: Lumacaftor Plus Ivacaftor Combination
Drug: Ivacaftor
Enrollment 563
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Placebo LUM 600 mg qd/IVA 250 mg q12h LUM 400 mg q12h/ IVA 250 mg q12h
Hide Arm/Group Description Placebo matched to lumacaftor (LUM, VX-809) and ivacaftor (IVA, VX-770) tablet every 12 hours (q12h), up to Week 24. LUM 600 milligram (mg) plus IVA 250 mg fixed-dose combination (FDC) tablet in the morning and IVA 250 mg film-coated tablet in the evening, up to Week 24. LUM 400 mg plus IVA 250 mg FDC tablet in the morning and in the evening, up to Week 24.
Period Title: Overall Study
Started 187 187 189
Completed 185 180 180
Not Completed 2 7 9
Reason Not Completed
Adverse Event             1             2             2
Withdrawal by Subject             1             2             2
Non-Compliance             0             0             1
Undefined             0             1             2
Randomized But Not Treated             0             2             2
Arm/Group Title Placebo LUM 600 mg qd/IVA 250 mg q12h LUM 400 mg q12h/ IVA 250 mg q12h Total
Hide Arm/Group Description Placebo matched to LUM and IVA tablet q12h, up to Week 24. LUM 600 mg plus IVA 250 mg FDC tablet in the morning and IVA 250 mg film-coated tablet in the evening, up to Week 24. LUM 400 mg plus IVA 250 mg FDC tablet in the morning and in the evening, up to Week 24. Total of all reporting groups
Overall Number of Baseline Participants 187 185 187 559
Hide Baseline Analysis Population Description
Full Analysis Set (FAS) included all randomized participants who received any amount of study drug.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 187 participants 185 participants 187 participants 559 participants
25.7  (10.02) 24.3  (8.31) 25.0  (9.03) 25.0  (9.16)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 187 participants 185 participants 187 participants 559 participants
Female
97
  51.9%
96
  51.9%
98
  52.4%
291
  52.1%
Male
90
  48.1%
89
  48.1%
89
  47.6%
268
  47.9%
1.Primary Outcome
Title Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) at Week 24
Hide Description Absolute change from baseline at week 24 was assessed as the average treatment effect at Week 16 and at Week 24. FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Hankinson and Wang standards were used to calculate percent predicted FEV1 (for age, gender, race, and height). The Hankinson standard was used for male participants 18 years and older and female participants 16 years and older. The Wang standard was used for male participants aged 12 to 17 years and for female participants aged 12 to 15 years.
Time Frame Baseline, Week 16 and 24
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS) included all randomized participants who received any amount of study drug. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure.
Arm/Group Title Placebo LUM 600 mg qd/IVA 250 mg q12h LUM 400 mg q12h/ IVA 250 mg q12h
Hide Arm/Group Description:
Placebo matched to LUM and IVA tablet q12h, up to Week 24.
LUM 600 mg plus IVA 250 mg FDC tablet in the morning and IVA 250 mg film-coated tablet in the evening, up to Week 24.
LUM 400 mg plus IVA 250 mg FDC tablet in the morning and in the evening, up to Week 24.
Overall Number of Participants Analyzed 183 181 180
Least Squares Mean (Standard Error)
Unit of Measure: percent predicted of FEV1
-0.15  (0.539) 2.46  (0.540) 2.85  (0.540)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, LUM 600 mg qd/IVA 250 mg q12h
Comments Analysis was performed using mixed-effects model for repeated measures (MMRM) model including treatment, visit, and treatment-by-visit interaction as fixed effects with adjustments for sex (male versus female), age group at baseline (less than [<] 18 versus greater than equal to [>=]18 years old), and percent predicted FEV1 severity at Screening (<70 versus >=70).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0004
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares (LS) Mean Difference
Estimated Value 2.62
Confidence Interval (2-Sided) 95%
1.18 to 4.06
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, LUM 400 mg q12h/ IVA 250 mg q12h
Comments Analysis was performed using MMRM model, as described in Statistical Analysis 1.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 3.00
Confidence Interval (2-Sided) 95%
1.56 to 4.44
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Relative Change From Baseline in Percent Predicted FEV1 at Week 24
Hide Description Assessed as the average treatment effect at Week 16 and at Week 24. FEV1 and percent predicted FEV1 are defined in Outcome Measure (OM) 1.
Time Frame Baseline, Week 16 and 24
Hide Outcome Measure Data
Hide Analysis Population Description
FAS. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure.
Arm/Group Title Placebo LUM 600 mg qd/IVA 250 mg q12h LUM 400 mg q12h/ IVA 250 mg q12h
Hide Arm/Group Description:
Placebo matched to LUM and IVA tablet q12h, up to Week 24.
LUM 600 mg plus IVA 250 mg FDC tablet in the morning and IVA 250 mg film-coated tablet in the evening, up to Week 24.
LUM 400 mg plus IVA 250 mg FDC tablet in the morning and in the evening, up to Week 24.
Overall Number of Participants Analyzed 183 181 180
Least Squares Mean (Standard Error)
Unit of Measure: percent change
0.00  (0.960) 4.42  (0.961) 5.25  (0.961)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, LUM 600 mg qd/IVA 250 mg q12h
Comments Analysis was performed using MMRM model including treatment, visit, and treatment-by-visit interaction as fixed effects with adjustments for sex (male versus female), age group at baseline (<18 versus >=18 years old), and percent predicted FEV1 severity at Screening (<70 versus >=70).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0007
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 4.42
Confidence Interval (2-Sided) 95%
1.86 to 6.98
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, LUM 400 mg q12h/ IVA 250 mg q12h
Comments Analysis was performed using MMRM model, as described in Statistical Analysis 1.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 5.25
Confidence Interval (2-Sided) 95%
2.69 to 7.81
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Absolute Change From Baseline in Body Mass Index (BMI) at Week 24
Hide Description BMI was defined as weight in kilogram (kg) divided by height*height in square meter (m^2).
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
FAS. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure.
Arm/Group Title Placebo LUM 600 mg qd/IVA 250 mg q12h LUM 400 mg q12h/ IVA 250 mg q12h
Hide Arm/Group Description:
Placebo matched to LUM and IVA tablet q12h, up to Week 24.
LUM 600 mg plus IVA 250 mg FDC tablet in the morning and IVA 250 mg film-coated tablet in the evening, up to Week 24.
LUM 400 mg plus IVA 250 mg FDC tablet in the morning and in the evening, up to Week 24.
Overall Number of Participants Analyzed 183 180 180
Least Squares Mean (Standard Error)
Unit of Measure: kilogram per square meter (kg/m^2)
0.07  (0.066) 0.48  (0.066) 0.43  (0.066)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, LUM 600 mg qd/IVA 250 mg q12h
Comments Analysis was performed using MMRM model including treatment, visit, and treatment-by-visit interaction as fixed effects with adjustments for sex (male versus female), age group at baseline (<18 versus >=18 years old), percent predicted FEV1 severity at Screening (<70 versus >=70), and baseline BMI.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.41
Confidence Interval (2-Sided) 95%
0.23 to 0.59
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, LUM 400 mg q12h/ IVA 250 mg q12h
Comments Analysis was performed using MMRM model, as described in Statistical Analysis 1.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0001
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.36
Confidence Interval (2-Sided) 95%
0.17 to 0.54
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score at Week 24
Hide 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), the scaled score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life.
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
FAS. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure.
Arm/Group Title Placebo LUM 600 mg qd/IVA 250 mg q12h LUM 400 mg q12h/ IVA 250 mg q12h
Hide Arm/Group Description:
Placebo matched to LUM and IVA tablet q12h, up to Week 24.
LUM 600 mg plus IVA 250 mg FDC tablet in the morning and IVA 250 mg film-coated tablet in the evening, up to Week 24.
LUM 400 mg plus IVA 250 mg FDC tablet in the morning and in the evening, up to Week 24.
Overall Number of Participants Analyzed 185 180 179
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
2.81  (1.153) 5.02  (1.166) 5.66  (1.169)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, LUM 600 mg qd/IVA 250 mg q12h
Comments Analysis was performed using MMRM model including treatment, visit, and treatment-by-visit interaction as fixed effects with adjustments for sex (male versus female), age group at baseline (<18 versus >=18 years old), percent predicted FEV1 severity at Screening (<70 versus >=70), and baseline CFQ-R respiratory domain score.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1651
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 2.21
Confidence Interval (2-Sided) 95%
-0.91 to 5.33
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, LUM 400 mg q12h/ IVA 250 mg q12h
Comments Analysis was performed using MMRM model, as described in Statistical Analysis 1.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0736
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 2.85
Confidence Interval (2-Sided) 95%
-0.27 to 5.98
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Percentage of Participants With Response Based on Percent Predicted FEV1
Hide Description A participant was considered as a responder if the participant had >=5% increase from baseline in average percent predicted FEV1 at Week 16 and at Week 24 (relative change). FEV1 and percent predicted FEV1 are defined in OM 1. A participant with a missing average relative change from baseline in percent predicted FEV1 at Week 16 and at Week 24 was considered as a non-responder.
Time Frame Week 16 and 24
Hide Outcome Measure Data
Hide Analysis Population Description
FAS.
Arm/Group Title Placebo LUM 600 mg qd/IVA 250 mg q12h LUM 400 mg q12h/ IVA 250 mg q12h
Hide Arm/Group Description:
Placebo matched to LUM and IVA tablet q12h, up to Week 24.
LUM 600 mg plus IVA 250 mg FDC tablet in the morning and IVA 250 mg film-coated tablet in the evening, up to Week 24.
LUM 400 mg plus IVA 250 mg FDC tablet in the morning and in the evening, up to Week 24.
Overall Number of Participants Analyzed 187 185 187
Measure Type: Number
Unit of Measure: percentage of participants
22.5 45.9 41.2
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, LUM 600 mg qd/IVA 250 mg q12h
Comments Odds Ratio (OR) and 95% confidence intervals (Cis) are Mantel-Haenszel estimates. P values are from a Cochran-Mantel-Haenszel test stratified by sex (male versus female), age group at baseline (<18 versus >=18 years old), and percent predicted FEV1 severity at Screening (<70 versus >=70).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments This test is considered nominally significant because a hierarchical procedure was used and was broken prior to this test.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.9568
Confidence Interval (2-Sided) 95%
1.8829 to 4.6431
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, LUM 400 mg q12h/ IVA 250 mg q12h
Comments Analysis was performed as described in Statistical Analysis 1.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0001
Comments This test is considered nominally significant because a hierarchical procedure was used and was broken prior to this test.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.3834
Confidence Interval (2-Sided) 95%
1.5234 to 3.7286
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Number of Pulmonary Exacerbation Events
Hide Description The total number of days on study is equal to the Week 24 date or the last dose date (whichever occurred last) minus the first dose date plus 1. The total number of years (48 weeks) on study is equal to the number of days on study divided by 336. Pulmonary exacerbation events per year (48 weeks) are reported.
Time Frame through Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
FAS.
Arm/Group Title Placebo LUM 600 mg qd/IVA 250 mg q12h LUM 400 mg q12h/ IVA 250 mg q12h
Hide Arm/Group Description:
Placebo matched to LUM and IVA tablet q12h, up to Week 24.
LUM 600 mg plus IVA 250 mg FDC tablet in the morning and IVA 250 mg film-coated tablet in the evening, up to Week 24.
LUM 400 mg plus IVA 250 mg FDC tablet in the morning and in the evening, up to Week 24.
Overall Number of Participants Analyzed 187 185 187
Measure Type: Number
Unit of Measure: pulmonary exacerbation events per year
1.18 0.82 0.67
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, LUM 600 mg qd/IVA 250 mg q12h
Comments Analysis was performed using regression analysis for a negative binomial distribution with sex (male versus female), age group at baseline (<18 versus >=18 years old), and percent predicted FEV1 severity at Screening (<70 versus >=70) as covariates with the logarithm of time on study as the offset.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0116
Comments This test is considered nominally significant because a hierarchical procedure was used and was broken prior to this test.
Method Negative Binomial Regression
Comments [Not Specified]
Method of Estimation Estimation Parameter Event Rate Ratio
Estimated Value 0.6912
Confidence Interval (2-Sided) 95%
0.5187 to 0.9209
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, LUM 400 mg q12h/ IVA 250 mg q12h
Comments Analysis was performed as described in Statistical Analysis 1.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0002
Comments This test is considered nominally significant because a hierarchical procedure was used and was broken prior to this test.
Method Negative Binomial Regression
Comments [Not Specified]
Method of Estimation Estimation Parameter Event Rate Ratio
Estimated Value 0.5659
Confidence Interval (2-Sided) 95%
0.4191 to 0.7641
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Absolute Change From Baseline in Weight at Week 24
Hide Description [Not Specified]
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
FAS. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure.
Arm/Group Title Placebo LUM 600 mg qd/IVA 250 mg q12h LUM 400 mg q12h/ IVA 250 mg q12h
Hide Arm/Group Description:
Placebo matched to LUM and IVA tablet q12h, up to Week 24.
LUM 600 mg plus IVA 250 mg FDC tablet in the morning and IVA 250 mg film-coated tablet in the evening, up to Week 24.
LUM 400 mg plus IVA 250 mg FDC tablet in the morning and in the evening, up to Week 24.
Overall Number of Participants Analyzed 183 180 180
Least Squares Mean (Standard Error)
Unit of Measure: kilograms (kg)
0.44  (0.187) 1.57  (0.188) 1.38  (0.187)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, LUM 600 mg qd/IVA 250 mg q12h
Comments Analysis was performed using MMRM model including treatment, visit, and treatment-by-visit interaction as fixed effects with adjustments for sex (male versus female), age group at baseline (<18 versus >=18 years old), percent predicted FEV1 severity at Screening (<70 versus >=70), and baseline weight.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 1.13
Confidence Interval (2-Sided) 95%
0.62 to 1.64
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, LUM 400 mg q12h/ IVA 250 mg q12h
Comments Analysis was performed as described in Statistical Analysis 1.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0003
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.95
Confidence Interval (2-Sided) 95%
0.43 to 1.46
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Absolute Change From Baseline in BMI-for-age Z-score at Week 24
Hide Description Z-Score is a statistical measure to evaluate how a single data point compares to a standard. It describes whether a mean was above or below the standard and how unusual the measurement is with range from -infinity to +infinity; 0: same mean, >0: a greater mean, and <0: a lesser mean than the standard. BMI-for-age z-score was calculated by using centers for disease control and prevention (CDC) growth charts for the pediatric population.
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
FAS. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure. Only participants who were <20 years of age were analyzed.
Arm/Group Title Placebo LUM 600 mg qd/IVA 250 mg q12h LUM 400 mg q12h/ IVA 250 mg q12h
Hide Arm/Group Description:
Placebo matched to LUM and IVA tablet q12h, up to Week 24.
LUM 600 mg plus IVA 250 mg FDC tablet in the morning and IVA 250 mg film-coated tablet in the evening, up to Week 24.
LUM 400 mg plus IVA 250 mg FDC tablet in the morning and in the evening, up to Week 24.
Overall Number of Participants Analyzed 53 54 58
Least Squares Mean (Standard Error)
Unit of Measure: z-score
-0.0674  (0.04706) 0.1640  (0.04652) 0.1544  (0.04513)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, LUM 600 mg qd/IVA 250 mg q12h
Comments Analysis was performed using MMRM model including treatment, visit, and treatment-by-visit interaction as fixed effects with adjustments for sex (male versus female), age group at baseline (<18 versus >=18 years old), percent predicted FEV1 severity at Screening (<70 versus >=70), and baseline BMI z-score.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0005
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.2313
Confidence Interval (2-Sided) 95%
0.1037 to 0.3589
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, LUM 400 mg q12h/ IVA 250 mg q12h
Comments Analysis was performed as described in Statistical Analysis 1.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0006
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.2217
Confidence Interval (2-Sided) 95%
0.0961 to 0.3473
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Time-to-First Pulmonary Exacerbation
Hide Description Time to first pulmonary exacerbation was assessed using Cox Regression method. For participants who completed 24 weeks of treatment, participants without a pulmonary exacerbation before treatment completion were considered censored at the time of treatment completion or at the Week 24 Visit (whichever occurred last). For participants who prematurely discontinued study treatment, participants without a pulmonary exacerbation through the Week 24 Visit were considered censored at the time of the Week 24 Visit.
Time Frame through Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
FAS.
Arm/Group Title Placebo LUM 600 mg qd/IVA 250 mg q12h LUM 400 mg q12h/ IVA 250 mg q12h
Hide Arm/Group Description:
Placebo matched to LUM and IVA tablet q12h, up to Week 24.
LUM 600 mg plus IVA 250 mg FDC tablet in the morning and IVA 250 mg film-coated tablet in the evening, up to Week 24.
LUM 400 mg plus IVA 250 mg FDC tablet in the morning and in the evening, up to Week 24.
Overall Number of Participants Analyzed 187 185 187
Median (Full Range)
Unit of Measure: days
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
[1]
Median time was not reached as less than 50% of participants had the event of interest.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, LUM 600 mg qd/IVA 250 mg q12h
Comments Analysis was performed using Cox proportional hazard regression, time is the time-to-first event or censoring, with adjustment for sex (male versus female), age group at baseline (<18 versus >=18 years old), and percent predicted FEV1 severity at Screening (<70 versus >=70).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0384
Comments [Not Specified]
Method Cox Proportional Hazard Regression
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.716
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, LUM 400 mg q12h/ IVA 250 mg q12h
Comments Analysis was performed as described in Statistical Analysis 1.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0003
Comments [Not Specified]
Method Cox Proportional Hazard Regression
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.533
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Percentage of Participants With At Least 1 Pulmonary Exacerbation Event
Hide Description [Not Specified]
Time Frame through Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
FAS.
Arm/Group Title Placebo LUM 600 mg qd/IVA 250 mg q12h LUM 400 mg q12h/ IVA 250 mg q12h
Hide Arm/Group Description:
Placebo matched to LUM and IVA tablet q12h, up to Week 24.
LUM 600 mg plus IVA 250 mg FDC tablet in the morning and IVA 250 mg film-coated tablet in the evening, up to Week 24.
LUM 400 mg plus IVA 250 mg FDC tablet in the morning and in the evening, up to Week 24.
Overall Number of Participants Analyzed 187 185 187
Measure Type: Number
Unit of Measure: percentage of participants
47.1 36.8 28.9
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, LUM 600 mg qd/IVA 250 mg q12h
Comments OR and 95% confidence intervals (CIs) are Mantel-Haenszel estimates. P values are from a Cochran-Mantel-Haenszel test stratified by sex (male versus female), age group at baseline (<18 versus >=18 years old), and percent predicted FEV1 severity at Screening (<70 versus >=70).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0393
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.6373
Confidence Interval (2-Sided) 95%
0.4160 to 0.9764
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, LUM 400 mg q12h/ IVA 250 mg q12h
Comments Analysis was performed as described in Statistical Analysis 1.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0002
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.4429
Confidence Interval (2-Sided) 95%
0.2863 to 0.6851
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Absolute Change From Baseline in Euro Quality of Life Scale (EuroQol) 5-Dimension-3 Level (EQ-5D-3L) Index Score at Week 24
Hide Description EQ-5D-3L: participant rated questionnaire to assess health-related quality of life. It consists of EQ-5D descriptive system and EQ-5D Visual Analog Scale (VAS). EQ-5D-3L descriptive system comprises the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 3 levels: no problems (1), some problems (2), and extreme problems (3). The 5 dimensional 3-level systems are converted into a single index utility score. Values for theoretically possible health states are calculated using a regression model and weighted according to the social preferences of the Unites States (US) general population. For this population, the possible EQ-5D-3L index scores ranges from -0.11 (that is, 3 for all 5 dimensions) to 1.0 (that is, 1 for all 5 dimensions), where higher scores indicate a better health state.
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
FAS. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure.
Arm/Group Title Placebo LUM 600 mg qd/IVA 250 mg q12h LUM 400 mg q12h/ IVA 250 mg q12h
Hide Arm/Group Description:
Placebo matched to LUM and IVA tablet q12h, up to Week 24.
LUM 600 mg plus IVA 250 mg FDC tablet in the morning and IVA 250 mg film-coated tablet in the evening, up to Week 24.
LUM 400 mg plus IVA 250 mg FDC tablet in the morning and in the evening, up to Week 24.
Overall Number of Participants Analyzed 183 178 176
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
0.0117  (0.00673) 0.0090  (0.00682) 0.0108  (0.00683)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, LUM 600 mg qd/IVA 250 mg q12h
Comments Analysis was performed using MMRM model including treatment, visit, and treatment-by-visit interaction as fixed effects with adjustments for sex (male versus female), age group at baseline (<18 versus >=18 years old), percent predicted FEV1 severity at Screening (<70 versus >=70), and baseline EQ-5D-3L index score.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7679
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.0028
Confidence Interval (2-Sided) 95%
-0.0211 to 0.0156
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, LUM 400 mg q12h/ IVA 250 mg q12h
Comments Analysis was performed as described in Statistical Analysis 1.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9214
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.0009
Confidence Interval (2-Sided) 95%
-0.0192 to 0.0174
Estimation Comments [Not Specified]
12.Secondary Outcome
Title Absolute Change From Baseline in EQ-5D-3L VAS Score at Week 24
Hide Description The EQ-5D-3L VAS records the participant's self-rated health on a vertical, visual analogue scale where the best state a participant can imagine is marked 100 and the worst state a participant can imagine is marked 0, higher scores indicates a better health state.
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
FAS. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure.
Arm/Group Title Placebo LUM 600 mg qd/IVA 250 mg q12h LUM 400 mg q12h/ IVA 250 mg q12h
Hide Arm/Group Description:
Placebo matched to LUM and IVA tablet q12h, up to Week 24.
LUM 600 mg plus IVA 250 mg FDC tablet in the morning and IVA 250 mg film-coated tablet in the evening, up to Week 24.
LUM 400 mg plus IVA 250 mg FDC tablet in the morning and in the evening, up to Week 24.
Overall Number of Participants Analyzed 182 177 177
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
3.3  (1.07) 5.7  (1.08) 6.6  (1.08)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, LUM 600 mg qd/IVA 250 mg q12h
Comments Analysis was performed using MMRM model including treatment, visit, and treatment-by-visit interaction as fixed effects with adjustments for sex (male versus female), age group at baseline (<18 versus >=18 years old), percent predicted FEV1 severity at Screening (<70 versus >=70), and baseline EQ-5D-3L VAS score.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1034
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 2.4
Confidence Interval (2-Sided) 95%
-0.5 to 5.3
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, LUM 400 mg q12h/ IVA 250 mg q12h
Comments Analysis was performed as described in Statistical Analysis 1.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0262
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 3.3
Confidence Interval (2-Sided) 95%
0.4 to 6.2
Estimation Comments [Not Specified]
13.Secondary Outcome
Title Absolute Change From Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Domain Scores at Week 24
Hide Description The TSQM is a 14-item self-administered questionnaire which measures participants' experiences with their medication on four dimensions: effectiveness, side effects, convenience and global satisfaction. For each dimension, responses are added and transformed to a scale from 0 to 100, where higher scores indicate greater satisfaction.
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
FAS. Here, "n" signifies participants who were evaluable for specified category for each arm, respectively.
Arm/Group Title Placebo LUM 600 mg qd/IVA 250 mg q12h LUM 400 mg q12h/ IVA 250 mg q12h
Hide Arm/Group Description:
Placebo matched to LUM and IVA tablet q12h, up to Week 24.
LUM 600 mg plus IVA 250 mg FDC tablet in the morning and IVA 250 mg film-coated tablet in the evening, up to Week 24.
LUM 400 mg plus IVA 250 mg FDC tablet in the morning and in the evening, up to Week 24.
Overall Number of Participants Analyzed 187 185 187
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
Effectiveness (n = 159, 161, 161) -8.49  (1.814) 0.15  (1.807) 3.12  (1.793)
Side Effects (n = 157, 159, 161) 2.03  (1.144) -1.14  (1.137) -2.26  (1.121)
Convenience (n = 158, 160, 161) 4.57  (1.525) 4.57  (1.523) 4.88  (1.501)
Global Satisfaction (n= 158, 160, 161) -9.62  (1.841) -4.98  (1.845) -2.46  (1.814)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, LUM 600 mg qd/IVA 250 mg q12h
Comments Effectiveness: analysis was performed using MMRM model including treatment, visit, and treatment-by-visit interaction as fixed effects with adjustments for sex (male versus female), age group at baseline (<18 versus >=18 years old), percent predicted FEV1 severity at Screening (<70 versus >=70), and baseline TSQM effectiveness score.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0005
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 8.64
Confidence Interval (2-Sided) 95%
3.77 to 13.51
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, LUM 400 mg q12h/ IVA 250 mg q12h
Comments Effectiveness: analysis was performed as described in Statistical Analysis 1.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 11.61
Confidence Interval (2-Sided) 95%
6.75 to 16.48
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, LUM 600 mg qd/IVA 250 mg q12h
Comments Side Effects: analysis was performed using MMRM model including treatment, visit, and treatment-by-visit interaction as fixed effects with adjustments for sex (male versus female), age group at baseline (<18 versus >=18 years old), percent predicted FEV1 severity at Screening (<70 versus >=70), and baseline TSQM side effects score.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0403
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -3.18
Confidence Interval (2-Sided) 95%
-6.21 to -0.14
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, LUM 400 mg q12h/ IVA 250 mg q12h
Comments Side Effects: analysis was performed as described in Statistical Analysis 1.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0054
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -4.29
Confidence Interval (2-Sided) 95%
-7.31 to -1.28
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, LUM 600 mg qd/IVA 250 mg q12h
Comments Convenience: analysis was performed using MMRM model including treatment, visit, and treatment-by-visit interaction as fixed effects with adjustments for sex (male versus female), age group at baseline (<18 versus >=18 years old), percent predicted FEV1 severity at Screening (<70 versus >=70), and baseline TSQM convenience score.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.0000
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.00
Confidence Interval (2-Sided) 95%
-4.07 to 4.07
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, LUM 400 mg q12h/ IVA 250 mg q12h
Comments Convenience: analysis was performed as described in Statistical Analysis 1.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8777
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.32
Confidence Interval (2-Sided) 95%
-3.74 to 4.37
Estimation Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo, LUM 600 mg qd/IVA 250 mg q12h
Comments Global Satisfaction: analysis was performed using MMRM model including treatment, visit, and treatment-by-visit interaction as fixed effects with adjustments for sex (male versus female), age group at baseline (<18 versus >=18 years old), percent predicted FEV1 severity at Screening (<70 versus >=70), and baseline TSQM global satisfaction score.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0668
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 4.64
Confidence Interval (2-Sided) 95%
-0.32 to 9.61
Estimation Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo, LUM 400 mg q12h/ IVA 250 mg q12h
Comments Global Satisfaction: analysis was performed as described in Statistical Analysis 1.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0045
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 7.16
Confidence Interval (2-Sided) 95%
2.23 to 12.08
Estimation Comments [Not Specified]
14.Secondary Outcome
Title Number of Participants With Treatment-Emergent Adverse Events (AEs) and Treatment-Emergent Serious Adverse Events (SAEs)
Hide 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, in-patient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. Any AE that increased in severity or that was newly developed at or after the initial dosing of study drug to 28 days after the last dose of study drug is considered treatment-emergent.
Time Frame up to Week 28
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Set (SS) included all randomized participants who received any amount of study drug. Participants were analyzed as per actual treatment received.
Arm/Group Title Placebo LUM 600 mg qd/IVA 250 mg q12h LUM 400 mg q12h/ IVA 250 mg q12h
Hide Arm/Group Description:
Placebo matched to LUM and IVA tablet q12h, up to Week 24.
LUM 600 mg plus IVA 250 mg FDC tablet in the morning and IVA 250 mg film-coated tablet in the evening, up to Week 24.
LUM 400 mg plus IVA 250 mg FDC tablet in the morning and in the evening, up to Week 24.
Overall Number of Participants Analyzed 186 186 187
Measure Type: Number
Unit of Measure: participants
Participants With Treatment-Emergent AEs 181 181 177
Participants With Treatment-Emergent SAEs 57 51 31
15.Secondary Outcome
Title Pre-dose Concentration (Ctrough), Average Pre-dose Concentration (Ctrough,Avg), 3 to 6 Hours Post-dose Concentration (C3-6h), and Average 3 to 6 Hours Post-dose Concentration (C3-6h,Avg)
Hide Description Ctrough, Ctrough,avg, C3-6h, and C3-6h,avg for lumacaftor, M28 lumacaftor (lumacaftor metabolite), ivacaftor, M1 ivacaftor (ivacaftor metabolite), and M6 ivacaftor (ivacaftor metabolite) were calculated. C3-6h,avg is average of individual 3 to 6 hours post-dose observed concentrations across Day 15, and Weeks 4 and 8 and Ctrough,avg is average of individual pre-dose observed concentrations across Weeks 4, 8, and 16. This outcome was not planned to be assessed in Placebo arm.
Time Frame For C3-6h: 3 to 6 hours after morning dose on Day 1 and 15, Week 4 and 8; For C3-6h,avg 3 to 6 hours after morning dose on Day 15, Week 4 and 8; For Ctrough and Ctrough,avg: before morning dose on Week 4, 8, and 16
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) population included all randomized participants who received at least one dose of study drug and had a PK assessment. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure and "n" signifies participants evaluable for specified category for each arm, respectively.
Arm/Group Title LUM 600 mg qd/IVA 250 mg q12h LUM 400 mg q12h/ IVA 250 mg q12h
Hide Arm/Group Description:
LUM 600 mg plus IVA 250 mg FDC tablet in the morning and IVA 250 mg film-coated tablet in the evening, up to Week 24.
LUM 400 mg plus IVA 250 mg FDC tablet in the morning and in the evening, up to Week 24.
Overall Number of Participants Analyzed 182 182
Mean (Standard Deviation)
Unit of Measure: microgram per milliliter (mcg/mL)
LUM, Day 1: C3-6h (n = 181, 180) 30.8  (12.6) 20.2  (8.33)
LUM, Day 15: C3-6h (n = 174, 176) 30.4  (11.2) 23.9  (8.87)
LUM, Week 4: Ctrough (n = 174, 179) 8.11  (5.21) 13.2  (6.28)
LUM, Week 4: C3-6h (n = 164, 168) 29.2  (12.1) 24.5  (8.75)
LUM, Week 8: Ctrough (n = 177, 177) 7.87  (5.71) 12.4  (6.87)
LUM, Week 8: C3-6h (n = 174, 170) 30.4  (11.6) 24.9  (9.79)
LUM, Week 16: Ctrough (n = 171, 173) 7.53  (6.05) 12.2  (6.87)
M-28 LUM, Day 1: C3-6h (n = 181, 180) 0.226  (0.103) 0.181  (0.0790)
M-28 LUM, Day 15: C3-6h (n = 174, 176) 1.43  (0.588) 1.39  (0.606)
M-28 LUM, Week 4: Ctrough (n = 174, 179) 1.32  (0.680) 1.42  (0.661)
M-28 LUM, Week 4: C3-6h (n = 164, 168) 1.39  (0.657) 1.45  (0.675)
M-28 LUM, Week 8: Ctrough (n = 177, 177) 1.34  (0.714) 1.44  (0.722)
M-28 LUM, Week 8: C3-6h (n = 174, 170) 1.41  (0.702) 1.48  (0.711)
M-28 LUM, Week 16: Ctrough (n = 171, 173) 1.27  (0.763) 1.43  (0.775)
IVA, Day 1: C3-6h (n = 181, 180) 1.34  (0.643) 1.36  (0.647)
IVA, Day 15: C3-6h (n = 174, 176) 0.647  (0.492) 0.469  (0.282)
IVA, Week 4: Ctrough (n = 174, 179) 0.164  (0.207) 0.108  (0.112)
IVA, Week 4: C3-6h (n = 164, 168) 0.636  (0.380) 0.473  (0.239)
IVA, Week 8: Ctrough (n = 177, 177) 0.182  (0.293) 0.102  (0.130)
IVA, Week 8: C3-6h (n = 174, 170) 0.710  (0.567) 0.513  (0.277)
IVA, Week 16: Ctrough (n = 171, 173) 0.163  (0.237) 0.113  (0.218)
M-1 IVA, Day 1: C3-6h (n = 181, 180) 2.51  (1.30) 2.65  (1.29)
M-1 IVA, Day 15: C3-6h (n = 174, 176) 2.21  (1.08) 1.85  (0.860)
M-1 IVA, Week 4: Ctrough (n = 174, 179) 0.676  (0.612) 0.501  (0.455)
M-1 IVA, Week 4: C3-6h (n = 164, 168) 2.11  (1.12) 1.88  (0.953)
M-1 IVA, Week 8: Ctrough (n = 177, 177) 0.672  (0.704) 0.463  (0.495)
M-1 IVA, Week 8: C3-6h (n = 174, 170) 2.15  (1.19) 1.91  (0.910)
M-1 IVA, Week 16: Ctrough (n = 171, 173) 0.643  (0.594) 0.465  (0.449)
M-6 IVA, Day 1: C3-6h (n = 181, 180) 0.993  (0.820) 0.996  (0.797)
M-6 IVA, Day 15: C3-6h (n = 174, 176) 3.62  (2.18) 2.99  (1.68)
M-6 IVA, Week 4: Ctrough (n = 174, 179) 1.73  (1.34) 1.64  (1.20)
M-6 IVA, Week 4: C3-6h (n = 164, 168) 3.07  (1.84) 2.64  (1.45)
M-6 IVA, Week 8: Ctrough (n = 177, 177) 1.60  (1.22) 1.47  (1.17)
M-6 IVA, Week 8: C3-6h (n = 174, 170) 3.00  (2.01) 2.56  (1.48)
M-6 IVA, Week 16: Ctrough (n = 171, 173) 1.51  (1.29) 1.42  (1.05)
LUM: Ctrough,avg (n = 179, 182) 7.81  (4.26) 12.7  (5.60)
LUM: C3-6h,avg (n = 182, 181) 29.9  (9.19) 24.3  (7.72)
M-28 LUM: Ctrough,avg (n = 179, 182) 1.31  (0.672) 1.42  (0.676)
M-28 LUM: C3-6h,avg (n = 182, 181) 1.41  (0.620) 1.43  (0.640)
IVA: Ctrough,avg (n = 179, 182) 0.170  (0.196) 0.110  (0.124)
IVA: C3-6h,avg (n = 182, 181) 0.668  (0.392) 0.484  (0.210)
M1-IVA: Ctrough,avg (n = 179, 182) 0.660  (0.504) 0.484  (0.391)
M1-IVA: C3-6h,avg (n = 182, 181) 2.14  (0.951) 1.87  (0.710)
M6-IVA: Ctrough,avg (n = 179, 182) 1.60  (1.08) 1.50  (0.897)
M6-IVA: C3-6h,avg (n = 182, 181) 3.18  (1.65) 2.70  (1.23)
Time Frame up to Week 28
Adverse Event Reporting Description Participants were analyzed as per actual treatment received. Other adverse events includes only non-serious AEs.
 
Arm/Group Title Placebo LUM 600 mg qd/IVA 250 mg q12h LUM 400 mg q12h/ IVA 250 mg q12h
Hide Arm/Group Description Placebo matched to LUM and IVA tablet q12h, up to Week 24. LUM 600 mg plus IVA 250 mg FDC tablet in the morning and IVA 250 mg film-coated tablet in the evening, up to Week 24. LUM 400 mg plus IVA 250 mg FDC tablet in the morning and in the evening, up to Week 24.
All-Cause Mortality
Placebo LUM 600 mg qd/IVA 250 mg q12h LUM 400 mg q12h/ IVA 250 mg q12h
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Hide Serious Adverse Events
Placebo LUM 600 mg qd/IVA 250 mg q12h LUM 400 mg q12h/ IVA 250 mg q12h
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   57/186 (30.65%)   51/186 (27.42%)   31/187 (16.58%) 
Gastrointestinal disorders       
Distal intestinal obstruction syndrome  1  3/186 (1.61%)  0/186 (0.00%)  0/187 (0.00%) 
Constipation  1  1/186 (0.54%)  1/186 (0.54%)  0/187 (0.00%) 
Abdominal pain  1  1/186 (0.54%)  0/186 (0.00%)  0/187 (0.00%) 
Colitis  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
Ileus  1  0/186 (0.00%)  0/186 (0.00%)  1/187 (0.53%) 
General disorders       
Medical device complication  1  0/186 (0.00%)  2/186 (1.08%)  0/187 (0.00%) 
Pyrexia  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
Hepatobiliary disorders       
Cholestasis  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
Hepatitis  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
Infections and infestations       
Infective pulmonary exacerbation of cystic fibrosis  1  48/186 (25.81%)  36/186 (19.35%)  24/187 (12.83%) 
Bronchitis  1  2/186 (1.08%)  1/186 (0.54%)  0/187 (0.00%) 
Bronchopneumonia  1  0/186 (0.00%)  1/186 (0.54%)  1/187 (0.53%) 
Bronchopulmonary aspergillosis allergic  1  0/186 (0.00%)  2/186 (1.08%)  0/187 (0.00%) 
Appendicitis  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
Bronchopulmonary aspergillosis  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
Conjunctivitis  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
Gastroenteritis viral  1  0/186 (0.00%)  0/186 (0.00%)  1/187 (0.53%) 
Influenza  1  1/186 (0.54%)  0/186 (0.00%)  0/187 (0.00%) 
Lung infection pseudomonal  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
Pneumonia  1  0/186 (0.00%)  0/186 (0.00%)  1/187 (0.53%) 
Respiratory tract infection fungal  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
Viraemia  1  1/186 (0.54%)  0/186 (0.00%)  0/187 (0.00%) 
Viral infection  1  1/186 (0.54%)  0/186 (0.00%)  0/187 (0.00%) 
Injury, poisoning and procedural complications       
Post procedural haematoma  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
Suture related complication  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
Investigations       
Blood creatine phosphokinase increased  1  0/186 (0.00%)  0/186 (0.00%)  2/187 (1.07%) 
Liver function test abnormal  1  0/186 (0.00%)  1/186 (0.54%)  1/187 (0.53%) 
Bacterial test positive  1  0/186 (0.00%)  0/186 (0.00%)  1/187 (0.53%) 
Electrocardiogram T wave inversion  1  0/186 (0.00%)  0/186 (0.00%)  1/187 (0.53%) 
Hepatic enzyme increased  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
Musculoskeletal and connective tissue disorders       
Arthralgia  1  1/186 (0.54%)  0/186 (0.00%)  0/187 (0.00%) 
Nervous system disorders       
Convulsion  1  0/186 (0.00%)  0/186 (0.00%)  1/187 (0.53%) 
Hepatic encephalopathy  1  0/186 (0.00%)  0/186 (0.00%)  1/187 (0.53%) 
Psychiatric disorders       
Suicidal ideation  1  1/186 (0.54%)  0/186 (0.00%)  0/187 (0.00%) 
Suicide attempt  1  1/186 (0.54%)  0/186 (0.00%)  0/187 (0.00%) 
Renal and urinary disorders       
Nephrolithiasis  1  2/186 (1.08%)  1/186 (0.54%)  0/187 (0.00%) 
Proteinuria  1  1/186 (0.54%)  0/186 (0.00%)  0/187 (0.00%) 
Renal failure acute  1  1/186 (0.54%)  0/186 (0.00%)  0/187 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Haemoptysis  1  1/186 (0.54%)  4/186 (2.15%)  0/187 (0.00%) 
Bronchospasm  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
Dyspnoea  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
Pulmonary cavitation  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
Skin and subcutaneous tissue disorders       
Rash  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
Vascular disorders       
Axillary vein thrombosis  1  1/186 (0.54%)  0/186 (0.00%)  0/187 (0.00%) 
Deep vein thrombosis  1  1/186 (0.54%)  0/186 (0.00%)  0/187 (0.00%) 
Hypertension  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 17.0
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Placebo LUM 600 mg qd/IVA 250 mg q12h LUM 400 mg q12h/ IVA 250 mg q12h
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   181/186 (97.31%)   179/186 (96.24%)   175/187 (93.58%) 
Blood and lymphatic system disorders       
Increased tendency to bruise  1  2/186 (1.08%)  0/186 (0.00%)  0/187 (0.00%) 
Eosinophilia  1  1/186 (0.54%)  0/186 (0.00%)  0/187 (0.00%) 
Leukopenia  1  0/186 (0.00%)  0/186 (0.00%)  1/187 (0.53%) 
Lymphadenopathy  1  1/186 (0.54%)  0/186 (0.00%)  0/187 (0.00%) 
Neutropenia  1  0/186 (0.00%)  0/186 (0.00%)  1/187 (0.53%) 
Cardiac disorders       
Palpitations  1  1/186 (0.54%)  1/186 (0.54%)  1/187 (0.53%) 
Tachycardia  1  1/186 (0.54%)  0/186 (0.00%)  1/187 (0.53%) 
Atrioventricular block first degree  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
Cyanosis  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
Sinus arrhythmia  1  0/186 (0.00%)  0/186 (0.00%)  1/187 (0.53%) 
Sinus bradycardia  1  0/186 (0.00%)  0/186 (0.00%)  1/187 (0.53%) 
Ventricular extrasystoles  1  0/186 (0.00%)  0/186 (0.00%)  1/187 (0.53%) 
Congenital, familial and genetic disorders       
Cystic fibrosis related diabetes  1  5/186 (2.69%)  0/186 (0.00%)  2/187 (1.07%) 
Talipes  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
Ear and labyrinth disorders       
Tinnitus  1  1/186 (0.54%)  1/186 (0.54%)  3/187 (1.60%) 
Ear pain  1  0/186 (0.00%)  1/186 (0.54%)  3/187 (1.60%) 
Ear discomfort  1  1/186 (0.54%)  1/186 (0.54%)  1/187 (0.53%) 
Tympanic membrane disorder  1  0/186 (0.00%)  2/186 (1.08%)  0/187 (0.00%) 
Vertigo  1  1/186 (0.54%)  0/186 (0.00%)  1/187 (0.53%) 
Middle ear effusion  1  1/186 (0.54%)  0/186 (0.00%)  0/187 (0.00%) 
Vertigo positional  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
Endocrine disorders       
Cushingoid  1  1/186 (0.54%)  0/186 (0.00%)  0/187 (0.00%) 
Early menarche  1  0/186 (0.00%)  0/186 (0.00%)  1/187 (0.53%) 
Eye disorders       
Vision blurred  1  0/186 (0.00%)  1/186 (0.54%)  2/187 (1.07%) 
Blepharospasm  1  0/186 (0.00%)  0/186 (0.00%)  2/187 (1.07%) 
Eye pruritus  1  1/186 (0.54%)  1/186 (0.54%)  0/187 (0.00%) 
Blindness transient  1  1/186 (0.54%)  0/186 (0.00%)  0/187 (0.00%) 
Conjunctival hyperaemia  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
Eye irritation  1  1/186 (0.54%)  0/186 (0.00%)  0/187 (0.00%) 
Eye pain  1  1/186 (0.54%)  0/186 (0.00%)  0/187 (0.00%) 
Eye swelling  1  0/186 (0.00%)  0/186 (0.00%)  1/187 (0.53%) 
Ocular hyperaemia  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
Periorbital oedema  1  1/186 (0.54%)  0/186 (0.00%)  0/187 (0.00%) 
Photopsia  1  0/186 (0.00%)  0/186 (0.00%)  1/187 (0.53%) 
Visual acuity reduced  1  0/186 (0.00%)  0/186 (0.00%)  1/187 (0.53%) 
Gastrointestinal disorders       
Nausea  1  17/186 (9.14%)  20/186 (10.75%)  32/187 (17.11%) 
Diarrhoea  1  18/186 (9.68%)  20/186 (10.75%)  21/187 (11.23%) 
Abdominal pain  1  19/186 (10.22%)  15/186 (8.06%)  10/187 (5.35%) 
Flatulence  1  10/186 (5.38%)  11/186 (5.91%)  13/187 (6.95%) 
Abdominal pain upper  1  8/186 (4.30%)  15/186 (8.06%)  7/187 (3.74%) 
Vomiting  1  9/186 (4.84%)  12/186 (6.45%)  9/187 (4.81%) 
Constipation  1  8/186 (4.30%)  5/186 (2.69%)  6/187 (3.21%) 
Abdominal distension  1  2/186 (1.08%)  6/186 (3.23%)  5/187 (2.67%) 
Frequent bowel movements  1  2/186 (1.08%)  1/186 (0.54%)  7/187 (3.74%) 
Dyspepsia  1  1/186 (0.54%)  3/186 (1.61%)  5/187 (2.67%) 
Gastrooesophageal reflux disease  1  1/186 (0.54%)  1/186 (0.54%)  6/187 (3.21%) 
Abdominal discomfort  1  0/186 (0.00%)  3/186 (1.61%)  3/187 (1.60%) 
Steatorrhoea  1  2/186 (1.08%)  2/186 (1.08%)  1/187 (0.53%) 
Eructation  1  1/186 (0.54%)  1/186 (0.54%)  2/187 (1.07%) 
Mouth ulceration  1  1/186 (0.54%)  1/186 (0.54%)  0/187 (0.00%) 
Post-tussive vomiting  1  1/186 (0.54%)  1/186 (0.54%)  0/187 (0.00%) 
Abdominal pain lower  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
Abdominal tenderness  1  1/186 (0.54%)  0/186 (0.00%)  0/187 (0.00%) 
Abnormal faeces  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
Aerophagia  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
Distal intestinal obstruction syndrome  1  1/186 (0.54%)  0/186 (0.00%)  0/187 (0.00%) 
Dry mouth  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
Epigastric discomfort  1  0/186 (0.00%)  0/186 (0.00%)  1/187 (0.53%) 
Faecaloma  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
Faeces discoloured  1  1/186 (0.54%)  0/186 (0.00%)  0/187 (0.00%) 
Faeces soft  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
Food poisoning  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
Gastritis  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
Gastrointestinal disorder  1  1/186 (0.54%)  0/186 (0.00%)  0/187 (0.00%) 
Gastrointestinal motility disorder  1  1/186 (0.54%)  0/186 (0.00%)  0/187 (0.00%) 
Gastrointestinal pain  1  1/186 (0.54%)  0/186 (0.00%)  0/187 (0.00%) 
Gastrointestinal sounds abnormal  1  0/186 (0.00%)  0/186 (0.00%)  1/187 (0.53%) 
Gastrointestinal tract irritation  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
Haematochezia  1  0/186 (0.00%)  0/186 (0.00%)  1/187 (0.53%) 
Haemorrhoids  1  1/186 (0.54%)  0/186 (0.00%)  0/187 (0.00%) 
Lip pain  1  0/186 (0.00%)  0/186 (0.00%)  1/187 (0.53%) 
Lip ulceration  1  1/186 (0.54%)  0/186 (0.00%)  0/187 (0.00%) 
Odynophagia  1  1/186 (0.54%)  0/186 (0.00%)  0/187 (0.00%) 
Oesophageal pain  1  0/186 (0.00%)  0/186 (0.00%)  1/187 (0.53%) 
Oral pain  1  1/186 (0.54%)  0/186 (0.00%)  0/187 (0.00%) 
Retching  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
Tongue discolouration  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
Tongue disorder  1  0/186 (0.00%)  0/186 (0.00%)  1/187 (0.53%) 
Tooth development disorder  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
Tooth impacted  1  0/186 (0.00%)  0/186 (0.00%)  1/187 (0.53%) 
Umbilical hernia  1  1/186 (0.54%)  0/186 (0.00%)  0/187 (0.00%) 
General disorders       
Pyrexia  1  22/186 (11.83%)  22/186 (11.83%)  16/187 (8.56%) 
Fatigue  1  10/186 (5.38%)  13/186 (6.99%)  17/187 (9.09%) 
Chest discomfort  1  4/186 (2.15%)  4/186 (2.15%)  4/187 (2.14%) 
Pain  1  2/186 (1.08%)  1/186 (0.54%)  5/187 (2.67%) 
Malaise  1  1/186 (0.54%)  4/186 (2.15%)  2/187 (1.07%) 
Chills  1  2/186 (1.08%)  1/186 (0.54%)  3/187 (1.60%) 
Chest pain  1  1/186 (0.54%)  0/186 (0.00%)  3/187 (1.60%) 
Thirst  1  0/186 (0.00%)  2/186 (1.08%)  2/187 (1.07%) 
Influenza like illness  1  2/186 (1.08%)  0/186 (0.00%)  1/187 (0.53%) 
Medical device pain  1  1/186 (0.54%)  0/186 (0.00%)  2/187 (1.07%) 
Sensation of foreign body  1  1/186 (0.54%)  2/186 (1.08%)  0/187 (0.00%) 
Application site pruritus  1  0/186 (0.00%)  1/186 (0.54%)  1/187 (0.53%) 
Application site rash  1  0/186 (0.00%)  1/186 (0.54%)  1/187 (0.53%) 
Asthenia  1  1/186 (0.54%)  1/186 (0.54%)  0/187 (0.00%) 
Device occlusion  1  0/186 (0.00%)  1/186 (0.54%)  1/187 (0.53%) 
Energy increased  1  2/186 (1.08%)  0/186 (0.00%)  0/187 (0.00%) 
Feeling jittery  1  0/186 (0.00%)  1/186 (0.54%)  1/187 (0.53%) 
Infusion site pain  1  2/186 (1.08%)  0/186 (0.00%)  0/187 (0.00%) 
Local swelling  1  2/186 (1.08%)  0/186 (0.00%)  0/187 (0.00%) 
Oedema peripheral  1  2/186 (1.08%)  0/186 (0.00%)  0/187 (0.00%) 
Vessel puncture site bruise  1  0/186 (0.00%)  1/186 (0.54%)  1/187 (0.53%) 
Adverse drug reaction  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
Application site irritation  1  1/186 (0.54%)  0/186 (0.00%)  0/187 (0.00%) 
Application site reaction  1  0/186 (0.00%)  0/186 (0.00%)  1/187 (0.53%) 
Device leakage  1  1/186 (0.54%)  0/186 (0.00%)  0/187 (0.00%) 
Device malfunction  1  1/186 (0.54%)  0/186 (0.00%)  0/187 (0.00%) 
Discomfort  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
Feeling hot  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
Infusion site bruising  1  1/186 (0.54%)  0/186 (0.00%)  0/187 (0.00%) 
Injection site erythema  1  1/186 (0.54%)  0/186 (0.00%)  0/187 (0.00%) 
Injection site pain  1  1/186 (0.54%)  0/186 (0.00%)  0/187 (0.00%) 
Injection site warmth  1  1/186 (0.54%)  0/186 (0.00%)  0/187 (0.00%) 
Medical device complication  1  0/186 (0.00%)  0/186 (0.00%)  1/187 (0.53%) 
Non-cardiac chest pain  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
Thrombosis in device  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
Vessel puncture site pain  1  0/186 (0.00%)  0/186 (0.00%)  1/187 (0.53%) 
Hepatobiliary disorders       
Biliary colic  1  0/186 (0.00%)  0/186 (0.00%)  1/187 (0.53%) 
Cholecystitis acute  1  1/186 (0.54%)  0/186 (0.00%)  0/187 (0.00%) 
Hepatic pain  1  0/186 (0.00%)  0/186 (0.00%)  1/187 (0.53%) 
Immune system disorders       
Seasonal allergy  1  1/186 (0.54%)  0/186 (0.00%)  1/187 (0.53%) 
Drug hypersensitivity  1  0/186 (0.00%)  0/186 (0.00%)  1/187 (0.53%) 
Food allergy  1  1/186 (0.54%)  0/186 (0.00%)  0/187 (0.00%) 
Infections and infestations       
Infective pulmonary exacerbation of cystic fibrosis  1  74/186 (39.78%)  58/186 (31.18%)  50/187 (26.74%) 
Nasopharyngitis  1  20/186 (10.75%)  14/186 (7.53%)  22/187 (11.76%) 
Upper respiratory tract infection  1  10/186 (5.38%)  8/186 (4.30%)  20/187 (10.70%) 
Viral upper respiratory tract infection  1  13/186 (6.99%)  13/186 (6.99%)  10/187 (5.35%) 
Sinusitis  1  7/186 (3.76%)  17/186 (9.14%)  11/187 (5.88%) 
Rhinitis  1  6/186 (3.23%)  14/186 (7.53%)  8/187 (4.28%) 
Influenza  1  3/186 (1.61%)  6/186 (3.23%)  11/187 (5.88%) 
Gastroenteritis  1  5/186 (2.69%)  4/186 (2.15%)  4/187 (2.14%) 
Pharyngitis  1  4/186 (2.15%)  3/186 (1.61%)  3/187 (1.60%) 
Viral infection  1  4/186 (2.15%)  4/186 (2.15%)  0/187 (0.00%) 
Vulvovaginal mycotic infection  1  0/186 (0.00%)  5/186 (2.69%)  3/187 (1.60%) 
Respiratory tract infection viral  1  1/186 (0.54%)  3/186 (1.61%)  2/187 (1.07%) 
Bronchitis  1  1/186 (0.54%)  2/186 (1.08%)  2/187 (1.07%) 
Ear infection  1  3/186 (1.61%)  1/186 (0.54%)  1/187 (0.53%) 
Oral candidiasis  1  1/186 (0.54%)  2/186 (1.08%)  2/187 (1.07%) 
Respiratory tract infection  1  2/186 (1.08%)  2/186 (1.08%)  1/187 (0.53%) 
Respiratory tract infection bacterial  1  0/186 (0.00%)  2/186 (1.08%)  3/187 (1.60%) 
Gastroenteritis viral  1  1/186 (0.54%)  1/186 (0.54%)  2/187 (1.07%) 
Upper respiratory tract infection bacterial  1  0/186 (0.00%)  3/186 (1.61%)  1/187 (0.53%) 
Urinary tract infection  1  1/186 (0.54%)  2/186 (1.08%)  1/187 (0.53%) 
Vulvovaginal candidiasis  1  2/186 (1.08%)  1/186 (0.54%)  1/187 (0.53%) 
Acute sinusitis  1  2/186 (1.08%)  0/186 (0.00%)  1/187 (0.53%) 
Bronchopulmonary aspergillosis allergic  1  1/186 (0.54%)  2/186 (1.08%)  0/187 (0.00%) 
Laryngitis  1  0/186 (0.00%)  2/186 (1.08%)  1/187 (0.53%) 
Lower respiratory tract infection bacterial  1  1/186 (0.54%)  2/186 (1.08%)  0/187 (0.00%) 
Bronchopulmonary aspergillosis  1  1/186 (0.54%)  1/186 (0.54%)  0/187 (0.00%) 
Clostridium difficile infection  1  0/186 (0.00%)  0/186 (0.00%)  2/187 (1.07%) 
Conjunctivitis  1  0/186 (0.00%)  1/186 (0.54%)  1/187 (0.53%) 
Gingivitis  1  0/186 (0.00%)  1/186 (0.54%)  1/187 (0.53%) 
Infectious mononucleosis  1  1/186 (0.54%)  0/186 (0.00%)  1/187 (0.53%) 
Oral fungal infection  1  1/186 (0.54%)  0/186 (0.00%)  1/187 (0.53%) 
Oral herpes  1  1/186 (0.54%)  1/186 (0.54%)  0/187 (0.00%) 
Otitis externa  1  2/186 (1.08%)  0/186 (0.00%)  0/187 (0.00%) 
Rash pustular  1  1/186 (0.54%)  0/186 (0.00%)  1/187 (0.53%) 
Acarodermatitis  1  0/186 (0.00%)  0/186 (0.00%)  1/187 (0.53%) 
Asymptomatic bacteriuria  1  1/186 (0.54%)  0/186 (0.00%)  0/187 (0.00%) 
Bacterial disease carrier  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
Bronchitis viral  1  1/186 (0.54%)  0/186 (0.00%)  0/187 (0.00%) 
Cellulitis  1  0/186 (0.00%)  0/186 (0.00%)  1/187 (0.53%) 
Chronic sinusitis  1  0/186 (0.00%)  0/186 (0.00%)  1/187 (0.53%) 
Clostridium difficile colitis  1  1/186 (0.54%)  0/186 (0.00%)  0/187 (0.00%) 
Cystitis  1  1/186 (0.54%)  0/186 (0.00%)  0/187 (0.00%) 
Device related infection  1  1/186 (0.54%)  0/186 (0.00%)  0/187 (0.00%) 
Epididymitis  1  0/186 (0.00%)  0/186 (0.00%)  1/187 (0.53%) 
Eye infection  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
Eyelid infection  1  1/186 (0.54%)  0/186 (0.00%)  0/187 (0.00%) 
Fungal infection  1  0/186 (0.00%)  0/186 (0.00%)  1/187 (0.53%) 
Genital herpes  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
Gynaecological chlamydia infection  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
Herpes simplex  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
Herpes zoster  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
Hordeolum  1  0/186 (0.00%)  0/186 (0.00%)  1/187 (0.53%) 
Infected bites  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
Infusion site infection  1  1/186 (0.54%)  0/186 (0.00%)  0/187 (0.00%) 
Localised infection  1  0/186 (0.00%)  0/186 (0.00%)  1/187 (0.53%) 
Lower respiratory tract infection  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
Lower respiratory tract infection viral  1  0/186 (0.00%)  0/186 (0.00%)  1/187 (0.53%) 
Lung infection  1  1/186 (0.54%)  0/186 (0.00%)  0/187 (0.00%) 
Lung infection pseudomonal  1  1/186 (0.54%)  0/186 (0.00%)  0/187 (0.00%) 
Nipple infection  1  0/186 (0.00%)  0/186 (0.00%)  1/187 (0.53%) 
Otitis media  1  0/186 (0.00%)  0/186 (0.00%)  1/187 (0.53%) 
Pharyngitis bacterial  1  0/186 (0.00%)  0/186 (0.00%)  1/187 (0.53%) 
Pneumonia  1  0/186 (0.00%)  0/186 (0.00%)  1/187 (0.53%) 
Pseudomonas bronchitis  1  1/186 (0.54%)  0/186 (0.00%)  0/187 (0.00%) 
Tinea versicolour  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
Tonsillitis  1  0/186 (0.00%)  0/186 (0.00%)  1/187 (0.53%) 
Tooth abscess  1  1/186 (0.54%)  0/186 (0.00%)  0/187 (0.00%) 
Tooth infection  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
Vaginitis bacterial  1  0/186 (0.00%)  0/186 (0.00%)  1/187 (0.53%) 
Injury, poisoning and procedural complications       
Ligament sprain  1  2/186 (1.08%)  3/186 (1.61%)  3/187 (1.60%) 
Muscle strain  1  2/186 (1.08%)  1/186 (0.54%)  3/187 (1.60%) 
Laceration  1  1/186 (0.54%)  3/186 (1.61%)  1/187 (0.53%) 
Procedural pain  1  1/186 (0.54%)  1/186 (0.54%)  2/187 (1.07%) 
Joint injury  1  1/186 (0.54%)  1/186 (0.54%)  1/187 (0.53%) 
Sunburn  1  1/186 (0.54%)  1/186 (0.54%)  1/187 (0.53%) 
Arthropod bite  1  1/186 (0.54%)  0/186 (0.00%)  1/187 (0.53%) 
Concussion  1  0/186 (0.00%)  1/186 (0.54%)  1/187 (0.53%) 
Limb injury  1  1/186 (0.54%)  0/186 (0.00%)  1/187 (0.53%) 
Vaccination complication  1  1/186 (0.54%)  0/186 (0.00%)  1/187 (0.53%) 
Alcohol poisoning  1  1/186 (0.54%)  0/186 (0.00%)  0/187 (0.00%) 
Animal bite  1  0/186 (0.00%)  0/186 (0.00%)  1/187 (0.53%) 
Ankle fracture  1  1/186 (0.54%)  0/186 (0.00%)  0/187 (0.00%) 
Arthropod sting  1  1/186 (0.54%)  0/186 (0.00%)  0/187 (0.00%) 
Contusion  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
Foreign body  1  0/186 (0.00%)  0/186 (0.00%)  1/187 (0.53%) 
Iliotibial band syndrome  1  0/186 (0.00%)  0/186 (0.00%)  1/187 (0.53%) 
Joint dislocation  1  1/186 (0.54%)  0/186 (0.00%)  0/187 (0.00%) 
Ligament injury  1  0/186 (0.00%)  0/186 (0.00%)  1/187 (0.53%) 
Rib fracture  1  0/186 (0.00%)  0/186 (0.00%)  1/187 (0.53%) 
Road traffic accident  1  0/186 (0.00%)  0/186 (0.00%)  1/187 (0.53%) 
Splinter  1  0/186 (0.00%)  0/186 (0.00%)  1/187 (0.53%) 
Stoma site irritation  1  0/186 (0.00%)  0/186 (0.00%)  1/187 (0.53%) 
Thermal burn  1  1/186 (0.54%)  0/186 (0.00%)  0/187 (0.00%) 
Traumatic haematoma  1  1/186 (0.54%)  0/186 (0.00%)  0/187 (0.00%) 
Investigations       
Blood creatine phosphokinase increased  1  10/186 (5.38%)  4/186 (2.15%)  12/187 (6.42%) 
Pulmonary function test decreased  1  14/186 (7.53%)  5/186 (2.69%)  3/187 (1.60%) 
Aspartate aminotransferase increased  1  5/186 (2.69%)  3/186 (1.61%)  5/187 (2.67%) 
Bacterial test positive  1  1/186 (0.54%)  4/186 (2.15%)  7/187 (3.74%) 
Alanine aminotransferase increased  1  4/186 (2.15%)  2/186 (1.08%)  4/187 (2.14%) 
Weight decreased  1  2/186 (1.08%)  3/186 (1.61%)  2/187 (1.07%) 
Forced expiratory volume decreased  1  4/186 (2.15%)  0/186 (0.00%)  2/187 (1.07%) 
Hepatic enzyme increased  1  0/186 (0.00%)  4/186 (2.15%)  2/187 (1.07%) 
Blood glucose increased  1  1/186 (0.54%)  3/186 (1.61%)  1/187 (0.53%) 
Sputum abnormal  1  2/186 (1.08%)  0/186 (0.00%)  2/187 (1.07%) 
Blood alkaline phosphatase increased  1  2/186 (1.08%)  0/186 (0.00%)  1/187 (0.53%) 
Blood creatinine increased  1  1/186 (0.54%)  1/186 (0.54%)  1/187 (0.53%) 
Blood glucose decreased  1  0/186 (0.00%)  1/186 (0.54%)  2/187 (1.07%) 
Body temperature increased  1  0/186 (0.00%)  2/186 (1.08%)  1/187 (0.53%) 
Gamma-glutamyltransferase increased  1  1/186 (0.54%)  1/186 (0.54%)  1/187 (0.53%) 
Blood lactate dehydrogenase increased  1  1/186 (0.54%)  1/186 (0.54%)  0/187 (0.00%) 
Eosinophil count increased  1  0/186 (0.00%)  1/186 (0.54%)  1/187 (0.53%) 
Fungal test positive  1  1/186 (0.54%)  0/186 (0.00%)  1/187 (0.53%) 
Haemoglobin decreased  1  1/186 (0.54%)  0/186 (0.00%)  1/187 (0.53%) 
Atypical mycobacterium test positive  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
Blood bicarbonate decreased  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
Blood calcium increased  1  1/186 (0.54%)  0/186 (0.00%)  0/187 (0.00%) 
Blood immunoglobulin E increased  1  1/186 (0.54%)  0/186 (0.00%)  0/187 (0.00%) 
Blood iron decreased  1  1/186 (0.54%)  0/186 (0.00%)  0/187 (0.00%) 
Blood pressure increased  1  0/186 (0.00%)  0/186 (0.00%)  1/187 (0.53%) 
Blood sodium decreased  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
Blood sodium increased  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
Blood urine present  1  1/186 (0.54%)  0/186 (0.00%)  0/187 (0.00%) 
Breath sounds abnormal  1  0/186 (0.00%)  0/186 (0.00%)  1/187 (0.53%) 
C-reactive protein increased  1  1/186 (0.54%)  0/186 (0.00%)  0/187 (0.00%) 
Coagulation test abnormal  1  0/186 (0.00%)  0/186 (0.00%)  1/187 (0.53%) 
Crystal urine present  1  1/186 (0.54%)  0/186 (0.00%)  0/187 (0.00%) 
Electrocardiogram PR shortened  1  1/186 (0.54%)  0/186 (0.00%)  0/187 (0.00%) 
Electrocardiogram T wave abnormal  1  0/186 (0.00%)  0/186 (0.00%)  1/187 (0.53%) 
Glycosylated haemoglobin increased  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
Haemophilus test positive  1  0/186 (0.00%)  0/186 (0.00%)  1/187 (0.53%) 
Liver function test abnormal  1  0/186 (0.00%)  0/186 (0.00%)  1/187 (0.53%) 
Lymphocyte count decreased  1  0/186 (0.00%)  0/186 (0.00%)  1/187 (0.53%) 
Mean cell haemoglobin decreased  1  0/186 (0.00%)  0/186 (0.00%)  1/187 (0.53%) 
Mean cell volume increased  1  1/186 (0.54%)  0/186 (0.00%)  0/187 (0.00%) 
Neutrophil count increased  1  0/186 (0.00%)  0/186 (0.00%)  1/187 (0.53%) 
Oxygen saturation decreased  1  0/186 (0.00%)  0/186 (0.00%)  1/187 (0.53%) 
Red blood cell count decreased  1  1/186 (0.54%)  0/186 (0.00%)  0/187 (0.00%) 
Serum ferritin decreased  1  1/186 (0.54%)  0/186 (0.00%)  0/187 (0.00%) 
Transaminases increased  1  0/186 (0.00%)  0/186 (0.00%)  1/187 (0.53%) 
Vitamin D decreased  1  1/186 (0.54%)  0/186 (0.00%)  0/187 (0.00%) 
Weight increased  1  0/186 (0.00%)  0/186 (0.00%)  1/187 (0.53%) 
White blood cell count decreased  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
White blood cell count increased  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
Metabolism and nutrition disorders       
Decreased appetite  1  5/186 (2.69%)  7/186 (3.76%)  12/187 (6.42%) 
Hypoglycaemia  1  5/186 (2.69%)  4/186 (2.15%)  2/187 (1.07%) 
Hyperglycaemia  1  1/186 (0.54%)  2/186 (1.08%)  3/187 (1.60%) 
Gout  1  1/186 (0.54%)  2/186 (1.08%)  0/187 (0.00%) 
Dehydration  1  0/186 (0.00%)  1/186 (0.54%)  1/187 (0.53%) 
Vitamin D deficiency  1  0/186 (0.00%)  2/186 (1.08%)  0/187 (0.00%) 
Diabetes mellitus inadequate control  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
Glucose tolerance impaired  1  0/186 (0.00%)  0/186 (0.00%)  1/187 (0.53%) 
Hypokalaemia  1  1/186 (0.54%)  0/186 (0.00%)  0/187 (0.00%) 
Hypomagnesaemia  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
Hyponatraemia  1  1/186 (0.54%)  0/186 (0.00%)  0/187 (0.00%) 
Increased appetite  1  1/186 (0.54%)  0/186 (0.00%)  0/187 (0.00%) 
Vitamin A deficiency  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
Vitamin E deficiency  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
Musculoskeletal and connective tissue disorders       
Back pain  1  6/186 (3.23%)  5/186 (2.69%)  9/187 (4.81%) 
Myalgia  1  8/186 (4.30%)  6/186 (3.23%)  3/187 (1.60%) 
Arthralgia  1  7/186 (3.76%)  2/186 (1.08%)  6/187 (3.21%) 
Musculoskeletal chest pain  1  1/186 (0.54%)  8/186 (4.30%)  1/187 (0.53%) 
Flank pain  1  2/186 (1.08%)  3/186 (1.61%)  3/187 (1.60%) 
Pain in extremity  1  2/186 (1.08%)  3/186 (1.61%)  2/187 (1.07%) 
Musculoskeletal pain  1  1/186 (0.54%)  2/186 (1.08%)  3/187 (1.60%) 
Muscle spasms  1  2/186 (1.08%)  1/186 (0.54%)  0/187 (0.00%) 
Muscle twitching  1  0/186 (0.00%)  1/186 (0.54%)  2/187 (1.07%) 
Neck pain  1  0/186 (0.00%)  1/186 (0.54%)  2/187 (1.07%) 
Joint swelling  1  2/186 (1.08%)  0/186 (0.00%)  0/187 (0.00%) 
Muscle tightness  1  0/186 (0.00%)  2/186 (1.08%)  0/187 (0.00%) 
Tendonitis  1  1/186 (0.54%)  0/186 (0.00%)  1/187 (0.53%) 
Arthritis  1  1/186 (0.54%)  0/186 (0.00%)  0/187 (0.00%) 
Arthropathy  1  0/186 (0.00%)  0/186 (0.00%)  1/187 (0.53%) 
Bone cyst  1  1/186 (0.54%)  0/186 (0.00%)  0/187 (0.00%) 
Chondritis  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
Foot deformity  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
Hypermobility syndrome  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
Intervertebral disc protrusion  1  1/186 (0.54%)  0/186 (0.00%)  0/187 (0.00%) 
Muscle contracture  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
Muscular weakness  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
Musculoskeletal discomfort  1  0/186 (0.00%)  0/186 (0.00%)  1/187 (0.53%) 
Musculoskeletal stiffness  1  0/186 (0.00%)  0/186 (0.00%)  1/187 (0.53%) 
Pubic pain  1  0/186 (0.00%)  0/186 (0.00%)  1/187 (0.53%) 
Rhabdomyolysis  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
Temporomandibular joint syndrome  1  0/186 (0.00%)  0/186 (0.00%)  1/187 (0.53%) 
Tendon pain  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
Nervous system disorders       
Headache  1  33/186 (17.74%)  30/186 (16.13%)  29/187 (15.51%) 
Sinus headache  1  7/186 (3.76%)  15/186 (8.06%)  7/187 (3.74%) 
Dizziness  1  5/186 (2.69%)  7/186 (3.76%)  3/187 (1.60%) 
Lethargy  1  3/186 (1.61%)  3/186 (1.61%)  2/187 (1.07%) 
Migraine  1  2/186 (1.08%)  1/186 (0.54%)  1/187 (0.53%) 
Dysgeusia  1  1/186 (0.54%)  2/186 (1.08%)  0/187 (0.00%) 
Hypoaesthesia  1  1/186 (0.54%)  1/186 (0.54%)  1/187 (0.53%) 
Tremor  1  1/186 (0.54%)  1/186 (0.54%)  1/187 (0.53%) 
Amnesia  1  1/186 (0.54%)  0/186 (0.00%)  1/187 (0.53%) 
Intercostal neuralgia  1  1/186 (0.54%)  0/186 (0.00%)  1/187 (0.53%) 
Paraesthesia  1  1/186 (0.54%)  0/186 (0.00%)  1/187 (0.53%) 
Parosmia  1  1/186 (0.54%)  1/186 (0.54%)  0/187 (0.00%) 
Ageusia  1  0/186 (0.00%)  0/186 (0.00%)  1/187 (0.53%) 
Cervicogenic headache  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
Convulsion  1  0/186 (0.00%)  0/186 (0.00%)  1/187 (0.53%) 
Coordination abnormal  1  0/186 (0.00%)  0/186 (0.00%)  1/187 (0.53%) 
Disturbance in attention  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
Epilepsy  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
Hyperaesthesia  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
Hypertonia  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
Hyposmia  1  1/186 (0.54%)  0/186 (0.00%)  0/187 (0.00%) 
Loss of consciousness  1  1/186 (0.54%)  0/186 (0.00%)  0/187 (0.00%) 
Muscle contractions involuntary  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
Nerve compression  1  1/186 (0.54%)  0/186 (0.00%)  0/187 (0.00%) 
Presyncope  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
Syncope  1  0/186 (0.00%)  0/186 (0.00%)  1/187 (0.53%) 
Psychiatric disorders       
Insomnia  1  7/186 (3.76%)  5/186 (2.69%)  2/187 (1.07%) 
Anxiety  1  2/186 (1.08%)  2/186 (1.08%)  2/187 (1.07%) 
Depression  1  3/186 (1.61%)  1/186 (0.54%)  1/187 (0.53%) 
Libido decreased  1  0/186 (0.00%)  0/186 (0.00%)  1/187 (0.53%) 
Mental disorder  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
Mood altered  1  0/186 (0.00%)  0/186 (0.00%)  1/187 (0.53%) 
Nervousness  1  0/186 (0.00%)  0/186 (0.00%)  1/187 (0.53%) 
Nightmare  1  1/186 (0.54%)  0/186 (0.00%)  0/187 (0.00%) 
Sleep disorder  1  1/186 (0.54%)  0/186 (0.00%)  0/187 (0.00%) 
Renal and urinary disorders       
Nephrolithiasis  1  1/186 (0.54%)  2/186 (1.08%)  1/187 (0.53%) 
Pollakiuria  1  0/186 (0.00%)  1/186 (0.54%)  1/187 (0.53%) 
Proteinuria  1  1/186 (0.54%)  1/186 (0.54%)  0/187 (0.00%) 
Calculus ureteric  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
Haematuria  1  0/186 (0.00%)  0/186 (0.00%)  1/187 (0.53%) 
Renal colic  1  1/186 (0.54%)  0/186 (0.00%)  0/187 (0.00%) 
Urinary incontinence  1  0/186 (0.00%)  0/186 (0.00%)  1/187 (0.53%) 
Urine odour abnormal  1  0/186 (0.00%)  0/186 (0.00%)  1/187 (0.53%) 
Reproductive system and breast disorders       
Menstruation irregular  1  0/186 (0.00%)  3/186 (1.61%)  3/187 (1.60%) 
Dysmenorrhoea  1  0/186 (0.00%)  2/186 (1.08%)  3/187 (1.60%) 
Metrorrhagia  1  1/186 (0.54%)  2/186 (1.08%)  1/187 (0.53%) 
Menorrhagia  1  0/186 (0.00%)  1/186 (0.54%)  2/187 (1.07%) 
Polymenorrhoea  1  0/186 (0.00%)  1/186 (0.54%)  2/187 (1.07%) 
Amenorrhoea  1  0/186 (0.00%)  2/186 (1.08%)  0/187 (0.00%) 
Breast tenderness  1  1/186 (0.54%)  0/186 (0.00%)  0/187 (0.00%) 
Endometriosis  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
Haemorrhagic ovarian cyst  1  0/186 (0.00%)  0/186 (0.00%)  1/187 (0.53%) 
Oligomenorrhoea  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
Uterine spasm  1  0/186 (0.00%)  0/186 (0.00%)  1/187 (0.53%) 
Vaginal haemorrhage  1  0/186 (0.00%)  0/186 (0.00%)  1/187 (0.53%) 
Vulvovaginal pain  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
Vulvovaginal pruritus  1  1/186 (0.54%)  0/186 (0.00%)  0/187 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Cough  1  82/186 (44.09%)  69/186 (37.10%)  56/187 (29.95%) 
Sputum increased  1  47/186 (25.27%)  40/186 (21.51%)  29/187 (15.51%) 
Dyspnoea  1  15/186 (8.06%)  32/186 (17.20%)  31/187 (16.58%) 
Haemoptysis  1  26/186 (13.98%)  28/186 (15.05%)  20/187 (10.70%) 
Nasal congestion  1  19/186 (10.22%)  24/186 (12.90%)  13/187 (6.95%) 
Oropharyngeal pain  1  20/186 (10.75%)  20/186 (10.75%)  13/187 (6.95%) 
Respiration abnormal  1  13/186 (6.99%)  14/186 (7.53%)  18/187 (9.63%) 
Rhinorrhoea  1  10/186 (5.38%)  11/186 (5.91%)  11/187 (5.88%) 
Productive cough  1  14/186 (7.53%)  11/186 (5.91%)  5/187 (2.67%) 
Sinus congestion  1  11/186 (5.91%)  8/186 (4.30%)  8/187 (4.28%) 
Respiratory tract congestion  1  6/186 (3.23%)  8/186 (4.30%)  9/187 (4.81%) 
Wheezing  1  9/186 (4.84%)  7/186 (3.76%)  6/187 (3.21%) 
Paranasal sinus hypersecretion  1  5/186 (2.69%)  8/186 (4.30%)  6/187 (3.21%) 
Dysphonia  1  4/186 (2.15%)  3/186 (1.61%)  7/187 (3.74%) 
Sputum discoloured  1  6/186 (3.23%)  3/186 (1.61%)  3/187 (1.60%) 
Rales  1  6/186 (3.23%)  2/186 (1.08%)  2/187 (1.07%) 
Asthma  1  2/186 (1.08%)  4/186 (2.15%)  2/187 (1.07%) 
Epistaxis  1  2/186 (1.08%)  5/186 (2.69%)  1/187 (0.53%) 
Upper-airway cough syndrome  1  2/186 (1.08%)  2/186 (1.08%)  3/187 (1.60%) 
Bronchial obstruction  1  2/186 (1.08%)  1/186 (0.54%)  1/187 (0.53%) 
Painful respiration  1  1/186 (0.54%)  0/186 (0.00%)  3/187 (1.60%) 
Increased viscosity of bronchial secretion  1  3/186 (1.61%)  0/186 (0.00%)  0/187 (0.00%) 
Nasal discharge discolouration  1  0/186 (0.00%)  1/186 (0.54%)  2/187 (1.07%) 
Pleuritic pain  1  1/186 (0.54%)  1/186 (0.54%)  1/187 (0.53%) 
Rhinitis allergic  1  2/186 (1.08%)  1/186 (0.54%)  0/187 (0.00%) 
Sneezing  1  0/186 (0.00%)  1/186 (0.54%)  2/187 (1.07%) 
Throat irritation  1  1/186 (0.54%)  2/186 (1.08%)  0/187 (0.00%) 
Bronchospasm  1  0/186 (0.00%)  2/186 (1.08%)  0/187 (0.00%) 
Dyspnoea exertional  1  1/186 (0.54%)  0/186 (0.00%)  1/187 (0.53%) 
Nasal polyps  1  2/186 (1.08%)  0/186 (0.00%)  0/187 (0.00%) 
Sputum decreased  1  0/186 (0.00%)  2/186 (1.08%)  0/187 (0.00%) 
Bronchial hyperreactivity  1  0/186 (0.00%)  0/186 (0.00%)  1/187 (0.53%) 
Bronchial secretion retention  1  1/186 (0.54%)  0/186 (0.00%)  0/187 (0.00%) 
Hiccups  1  0/186 (0.00%)  0/186 (0.00%)  1/187 (0.53%) 
Hyperventilation  1  0/186 (0.00%)  0/186 (0.00%)  1/187 (0.53%) 
Increased bronchial secretion  1  1/186 (0.54%)  0/186 (0.00%)  0/187 (0.00%) 
Lung disorder  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
Lung hyperinflation  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
Nasal discomfort  1  1/186 (0.54%)  0/186 (0.00%)  0/187 (0.00%) 
Pharyngeal erythema  1  1/186 (0.54%)  0/186 (0.00%)  0/187 (0.00%) 
Pharyngeal exudate  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
Pharyngeal oedema  1  0/186 (0.00%)  0/186 (0.00%)  1/187 (0.53%) 
Pleurisy  1  1/186 (0.54%)  0/186 (0.00%)  0/187 (0.00%) 
Pneumonitis  1  0/186 (0.00%)  0/186 (0.00%)  1/187 (0.53%) 
Pulmonary pain  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
Respiratory disorder  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
Respiratory gas exchange disorder  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
Respiratory tract irritation  1  0/186 (0.00%)  0/186 (0.00%)  1/187 (0.53%) 
Rhonchi  1  0/186 (0.00%)  0/186 (0.00%)  1/187 (0.53%) 
Sinus disorder  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
Upper respiratory tract congestion  1  0/186 (0.00%)  0/186 (0.00%)  1/187 (0.53%) 
Upper respiratory tract inflammation  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
Skin and subcutaneous tissue disorders       
Rash  1  5/186 (2.69%)  8/186 (4.30%)  18/187 (9.63%) 
Acne  1  4/186 (2.15%)  8/186 (4.30%)  1/187 (0.53%) 
Hyperhidrosis  1  2/186 (1.08%)  5/186 (2.69%)  3/187 (1.60%) 
Pruritus  1  3/186 (1.61%)  2/186 (1.08%)  2/187 (1.07%) 
Alopecia  1  1/186 (0.54%)  1/186 (0.54%)  3/187 (1.60%) 
Night sweats  1  1/186 (0.54%)  1/186 (0.54%)  2/187 (1.07%) 
Urticaria  1  2/186 (1.08%)  2/186 (1.08%)  0/187 (0.00%) 
Eczema  1  1/186 (0.54%)  2/186 (1.08%)  0/187 (0.00%) 
Dry skin  1  1/186 (0.54%)  0/186 (0.00%)  1/187 (0.53%) 
Erythema  1  1/186 (0.54%)  1/186 (0.54%)  0/187 (0.00%) 
Onychoclasis  1  2/186 (1.08%)  0/186 (0.00%)  0/187 (0.00%) 
Rash pruritic  1  0/186 (0.00%)  1/186 (0.54%)  1/187 (0.53%) 
Red man syndrome  1  2/186 (1.08%)  0/186 (0.00%)  0/187 (0.00%) 
Skin odour abnormal  1  0/186 (0.00%)  1/186 (0.54%)  1/187 (0.53%) 
Blister  1  1/186 (0.54%)  0/186 (0.00%)  0/187 (0.00%) 
Cutaneous lupus erythematosus  1  0/186 (0.00%)  0/186 (0.00%)  1/187 (0.53%) 
Dermatitis  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
Drug eruption  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
Hair texture abnormal  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
Hyperkeratosis  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
Ingrowing nail  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
Lividity  1  0/186 (0.00%)  0/186 (0.00%)  1/187 (0.53%) 
Papule  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
Pruritus allergic  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
Pruritus generalised  1  0/186 (0.00%)  0/186 (0.00%)  1/187 (0.53%) 
Rash erythematous  1  0/186 (0.00%)  0/186 (0.00%)  1/187 (0.53%) 
Rash macular  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
Rash papular  1  1/186 (0.54%)  0/186 (0.00%)  0/187 (0.00%) 
Skin lesion  1  0/186 (0.00%)  0/186 (0.00%)  1/187 (0.53%) 
Swelling face  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
Vascular disorders       
Flushing  1  1/186 (0.54%)  2/186 (1.08%)  0/187 (0.00%) 
Hot flush  1  0/186 (0.00%)  0/186 (0.00%)  2/187 (1.07%) 
Deep vein thrombosis  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
Hypertension  1  0/186 (0.00%)  0/186 (0.00%)  1/187 (0.53%) 
Orthostatic hypotension  1  1/186 (0.54%)  0/186 (0.00%)  0/187 (0.00%) 
Peripheral coldness  1  0/186 (0.00%)  0/186 (0.00%)  1/187 (0.53%) 
Phlebitis  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
Subclavian vein thrombosis  1  0/186 (0.00%)  1/186 (0.54%)  0/187 (0.00%) 
Venous thrombosis limb  1  1/186 (0.54%)  0/186 (0.00%)  0/187 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 17.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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
Layout table for Results Point of Contact information
Name/Title: Medical Monitor
Organization: Vertex Pharmaceuticals Incorporated
Phone: 617-341-6777
EMail: medicalinfo@vrtx.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Vertex Pharmaceuticals Incorporated
ClinicalTrials.gov Identifier: NCT01807949    
Other Study ID Numbers: VX12-809-104
First Submitted: March 4, 2013
First Posted: March 8, 2013
Results First Submitted: August 1, 2015
Results First Posted: September 1, 2015
Last Update Posted: September 27, 2016