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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 (TRAFFIC)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01807923
Recruitment Status : Completed
First Posted : March 8, 2013
Results First Posted : August 31, 2015
Last Update Posted : August 31, 2015
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: Lumacaftor Plus Ivacaftor Combination
Drug: Ivacaftor
Drug: Placebo
Enrollment 559
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 187 185 187
Completed 182 179 176
Not Completed 5 6 11
Reason Not Completed
Adverse Event             2             1             2
Withdrawal of Consent (not due to AE)             0             3             2
Physician Decision             0             0             1
Not Eligible (Genotype)             0             0             1
Randomized But Not Treated             3             2             5
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 184 183 182 549
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 184 participants 183 participants 182 participants 549 participants
25.0  (10.80) 24.7  (9.71) 25.5  (10.09) 25.1  (10.20)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 184 participants 183 participants 182 participants 549 participants
Female
84
  45.7%
86
  47.0%
84
  46.2%
254
  46.3%
Male
100
  54.3%
97
  53.0%
98
  53.8%
295
  53.7%
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 180 176 172
Least Squares Mean (Standard Error)
Unit of Measure: percent predicted of FEV1
-0.44  (0.524) 3.59  (0.525) 2.16  (0.530)
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 <0.0001
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares (LS) Mean Difference
Estimated Value 4.03
Confidence Interval (2-Sided) 95%
2.62 to 5.44
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 0.0003
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 2.60
Confidence Interval (2-Sided) 95%
1.18 to 4.01
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 180 176 172
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-0.34  (0.913) 6.39  (0.914) 3.99  (0.923)
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 <0.0001
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 6.73
Confidence Interval (2-Sided) 95%
4.27 to 9.19
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 0.0006
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 4.33
Confidence Interval (2-Sided) 95%
1.86 to 6.80
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 184 178 176
Least Squares Mean (Standard Error)
Unit of Measure: kilogram per square meter (kg/m^2)
0.19  (0.070) 0.35  (0.070) 0.32  (0.071)
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 0.1122
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.16
Confidence Interval (2-Sided) 95%
-0.04 to 0.35
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 0.1938
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.13
Confidence Interval (2-Sided) 95%
-0.07 to 0.32
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 184 176 172
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
1.10  (1.161) 4.98  (1.178) 2.60  (1.192)
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 0.0168
Comments This test is considered nominally significant because a hierarchical procedure was used and was broken prior to this test.
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 3.88
Confidence Interval (2-Sided) 95%
0.70 to 7.05
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 0.3569
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 1.50
Confidence Interval (2-Sided) 95%
-1.69 to 4.69
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 184 183 182
Measure Type: Number
Unit of Measure: percentage of participants
22.3 46.4 36.8
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 2.9378
Confidence Interval (2-Sided) 95%
1.8786 to 4.5941
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 0.0023
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 2.0592
Confidence Interval (2-Sided) 95%
1.2920 to 3.2819
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 184 183 182
Measure Type: Number
Unit of Measure: pulmonary exacerbation events per year
1.07 0.77 0.71
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 0.0491
Comments [Not Specified]
Method Negative Binomial Regression
Comments [Not Specified]
Method of Estimation Estimation Parameter Event Rate Ratio
Estimated Value 0.7186
Confidence Interval (2-Sided) 95%
0.5170 to 0.9987
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 0.0169
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 0.6643
Confidence Interval (2-Sided) 95%
0.4749 to 0.9291
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 184 178 176
Least Squares Mean (Standard Error)
Unit of Measure: kilograms (kg)
0.93  (0.202) 1.34  (0.205) 1.23  (0.205)
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 0.1565
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.40
Confidence Interval (2-Sided) 95%
-0.16 to 0.96
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 0.2992
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.30
Confidence Interval (2-Sided) 95%
-0.26 to 0.86
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 69 65 58
Least Squares Mean (Standard Error)
Unit of Measure: z-score
0.0153  (0.04886) 0.1132  (0.05081) 0.0933  (0.05431)
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 0.1539
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.0980
Confidence Interval (2-Sided) 95%
-0.0370 to 0.2330
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 0.2713
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.0781
Confidence Interval (2-Sided) 95%
-0.0615 to 0.2176
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. 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 184 183 182
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 0.0396
Comments [Not Specified]
Method Cox Proportional Hazard Regression
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.692
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 0.0385
Comments [Not Specified]
Method Cox Proportional Hazard Regression
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.691
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 184 183 182
Measure Type: Number
Unit of Measure: percentage of participants
39.7 30.1 30.2
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 0.0552
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.6565
Confidence Interval (2-Sided) 95%
0.4266 to 1.0103
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 0.0512
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.6438
Confidence Interval (2-Sided) 95%
0.4142 to 1.0005
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 179 175 170
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
0.0006  (0.00739) 0.0066  (0.00746) 0.0100  (0.00757)
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 0.5604
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.0060
Confidence Interval (2-Sided) 95%
-0.0142 to 0.0262
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 0.3613
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.0095
Confidence Interval (2-Sided) 95%
-0.0109 to 0.0298
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 180 173 171
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
1.4  (1.03) 3.5  (1.04) 2.8  (1.04)
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 0.1342
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 2.1
Confidence Interval (2-Sided) 95%
-0.7 to 4.9
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 0.3071
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 1.4
Confidence Interval (2-Sided) 95%
-1.3 to 4.2
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 184 183 182
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
Effectiveness (n = 163, 156, 144) -5.30  (1.643) 0.19  (1.666) 0.50  (1.726)
Side Effects (n = 162, 154, 143) 2.23  (1.119) -1.94  (1.141) -2.51  (1.179)
Convenience (n = 163, 154, 144) 4.37  (1.504) 4.98  (1.540) 7.45  (1.579)
Global Satisfaction (n= 163, 154, 144) -10.49  (1.863) -5.00  (1.906) -3.77  (1.956)
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 0.0160
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 5.49
Confidence Interval (2-Sided) 95%
1.03 to 9.96
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 0.0126
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 5.80
Confidence Interval (2-Sided) 95%
1.25 to 10.35
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 0.0074
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -4.18
Confidence Interval (2-Sided) 95%
-7.23 to -1.13
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 0.0029
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -4.74
Confidence Interval (2-Sided) 95%
-7.85 to -1.63
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 0.7721
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.61
Confidence Interval (2-Sided) 95%
-3.50 to 4.71
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 0.1472
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 3.08
Confidence Interval (2-Sided) 95%
-1.09 to 7.25
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 0.0345
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 5.49
Confidence Interval (2-Sided) 95%
0.40 to 10.58
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 0.0109
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 6.72
Confidence Interval (2-Sided) 95%
1.55 to 11.89
Estimation Comments [Not Specified]
14.Secondary Outcome
Title Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Treatment-Emergent 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 Nonserious 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.
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 184 183 182
Measure Type: Number
Unit of Measure: participants
Participants With Treatment-Emergent AEs 174 175 174
Participants With Treatment-Emergent SAEs 49 33 33
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,ave is average of individual 3 to 6 hours post-dose observed concentrations across Day 15, and Weeks 4 and 8 and Ctrough, ave 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 180 181
Mean (Standard Deviation)
Unit of Measure: microgram per milliliter (mcg/mL)
LUM, Day 1: C3-6h (n = 180, 175) 27.5  (12.5) 18.4  (8.55)
LUM, Day 15: Ctrough (n = 172, 175) 7.56  (5.33) 14.1  (6.99)
LUM, Day 15: C3-6 (n = 167, 171) 26.1  (11.5) 23.6  (8.54)
LUM, Week 4: Ctrough (n = 172, 178) 7.75  (5.05) 13.4  (6.70)
LUM, Week 4: C3-6 (n = 170, 171) 28.4  (11.2) 24.2  (8.66)
LUM, Week 8: Ctrough (n = 173, 174) 7.43  (5.60) 13.4  (6.68)
LUM, Week 8: C3-6 (n = 165, 171) 28.2  (11.2) 24.4  (8.80)
LUM, Week 16: Ctrough (n = 165, 164) 6.95  (4.99) 13.5  (7.49)
M-28 LUM, Day 1: C3-6h (n = 180, 175) 0.220  (0.107) 0.179  (0.0811)
M-28 LUM, Day 15: Ctrough (n = 172, 175) 1.25  (0.614) 1.48  (0.590)
M-28 LUM, Day 15: C3-6 (n = 167, 171) 1.37  (0.606) 1.49  (0.576)
M-28 LUM, Week 4: Ctrough (n = 172, 178) 1.31  (0.646) 1.48  (0.642)
M-28 LUM, Week 4: C3-6 (n = 170, 171) 1.39  (0.635) 1.49  (0.615)
M-28 LUM, Week 8: Ctrough (n = 173, 174) 1.32  (0.684) 1.53  (0.674)
M-28 LUM, Week 8: C3-6 (n = 165, 171) 1.42  (0.658) 1.56  (0.669)
M-28 LUM, Week 16: Ctrough (n = 165, 164) 1.30  (0.769) 1.57  (0.757)
IVA, Day 1: C3-6h (n = 180, 175) 1.29  (0.624) 1.24  (0.630)
IVA, Day 15: Ctrough (n = 172, 176) 0.151  (0.123) 0.115  (0.123)
IVA, Day 15: C3-6 (n = 167, 171) 0.557  (0.311) 0.413  (0.199)
IVA, Week 4: Ctrough (n = 172, 178) 0.142  (0.107) 0.105  (0.083)
IVA, Week 4: C3-6 (n = 170, 171) 0.638  (0.325) 0.456  (0.235)
IVA, Week 8: Ctrough (n = 173, 174) 0.130  (0.101) 0.0894  (0.0726)
IVA, Week 8: C3-6 (n = 165, 171) 0.648  (0.364) 0.470  (0.295)
IVA, Week 16: Ctrough (n = 165, 164) 0.133  (0.131) 0.0834  (0.0622)
M-1 IVA, Day 1: C3-6h (n = 180, 175) 2.46  (1.29) 2.41  (1.35)
M-1 IVA, Day 15: Ctrough (n = 172, 176) 0.665  (0.578) 0.511  (0.530)
M-1 IVA, Day 15: C3-6 (n = 167, 171) 1.94  (0.981) 1.71  (0.867)
M-1 IVA, Week 4: Ctrough (n = 172, 178) 0.628  (0.492) 0.450  (0.345)
M-1 IVA, Week 4: C3-6 (n = 170, 171) 2.21  (1.01) 1.76  (0.932)
M-1 IVA, Week 8: Ctrough (n = 173, 174) 0.584  (0.451) 0.404  (0.381)
M-1 IVA, Week 8: C3-6 (n = 165, 171) 2.17  (1.06) 1.78  (0.975)
M-1 IVA, Week 16: Ctrough (n = 165, 164) 0.589  (0.519) 0.396  (0.319)
M-6 IVA, Day 1: C3-6h (n = 180, 175) 0.976  (0.877) 0.927  (0.875)
M-6 IVA, Day 15: Ctrough (n = 172, 176) 1.68  (1.31) 1.67  (1.40)
M-6 IVA, Day 15: C3-6 (n = 167, 171) 3.03  (1.96) 2.87  (1.81)
M-6 IVA, Week 4: Ctrough (n = 172, 178) 1.66  (1.36) 1.46  (0.938)
M-6 IVA, Week 4: C3-6 (n = 170, 171) 3.07  (1.92) 2.49  (1.53)
M-6 IVA, Week 8: Ctrough (n = 173, 174) 1.52  (1.12) 1.31  (0.946)
M-6 IVA, Week 8: C3-6 (n = 165, 171) 2.96  (1.86) 2.36  (1.57)
M-6 IVA, Week 16: Ctrough (n = 165, 164) 1.40  (1.11) 1.33  (1.02)
LUM: Ctrough,ave (n = 179, 181) 7.49  (3.93) 13.5  (5.52)
LUM: C3-6h,ave (n = 179, 181) 27.7  (8.63) 24.0  (7.29)
M-28 LUM: Ctrough,ave (n = 179, 181) 1.31  (0.628) 1.51  (0.614)
M-28 LUM: C3-6h,ave (n = 179, 181) 1.39  (0.596) 1.51  (0.585)
IVA: Ctrough,ave (n = 179, 181) 0.137  (0.0773) 0.0989  (0.0644)
IVA: C3-6h,ave (n = 179, 181) 0.614  (0.271) 0.445  (0.193)
M1-IVA: Ctrough,ave (n = 179, 181) 0.606  (0.350) 0.441  (0.293)
M1-IVA: C3-6h,ave (n = 179, 181) 2.11  (0.817) 1.74  (0.726)
M6-IVA: Ctrough,ave (n = 179, 181) 1.57  (0.992) 1.44  (0.861)
M6-IVA: C3-6h,ave (n = 179, 181) 3.04  (1.55) 2.57  (1.34)
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   49/184 (26.63%)   33/183 (18.03%)   33/182 (18.13%) 
Cardiac disorders       
Pericarditis  1  0/184 (0.00%)  1/183 (0.55%)  0/182 (0.00%) 
Gastrointestinal disorders       
Distal intestinal obstruction syndrome  1  2/184 (1.09%)  2/183 (1.09%)  2/182 (1.10%) 
Constipation  1  1/184 (0.54%)  0/183 (0.00%)  1/182 (0.55%) 
Abdominal adhesions  1  0/184 (0.00%)  1/183 (0.55%)  0/182 (0.00%) 
Dysphagia  1  0/184 (0.00%)  1/183 (0.55%)  0/182 (0.00%) 
Inguinal hernia  1  0/184 (0.00%)  1/183 (0.55%)  0/182 (0.00%) 
Lower gastrointestinal haemorrhage  1  0/184 (0.00%)  0/183 (0.00%)  1/182 (0.55%) 
Small intestinal obstruction  1  0/184 (0.00%)  1/183 (0.55%)  0/182 (0.00%) 
Vomiting  1  0/184 (0.00%)  1/183 (0.55%)  0/182 (0.00%) 
General disorders       
Implant site thrombosis  1  0/184 (0.00%)  2/183 (1.09%)  0/182 (0.00%) 
Device dislocation  1  0/184 (0.00%)  1/183 (0.55%)  0/182 (0.00%) 
Hepatobiliary disorders       
Hepatitis cholestatic  1  0/184 (0.00%)  1/183 (0.55%)  0/182 (0.00%) 
Immune system disorders       
Drug hypersensitivity  1  0/184 (0.00%)  0/183 (0.00%)  1/182 (0.55%) 
Infections and infestations       
Infective pulmonary exacerbation of cystic fibrosis  1  41/184 (22.28%)  19/183 (10.38%)  17/182 (9.34%) 
Influenza  1  1/184 (0.54%)  2/183 (1.09%)  0/182 (0.00%) 
Tracheobronchitis  1  1/184 (0.54%)  1/183 (0.55%)  1/182 (0.55%) 
Pneumonia  1  0/184 (0.00%)  2/183 (1.09%)  0/182 (0.00%) 
Appendicitis  1  1/184 (0.54%)  0/183 (0.00%)  0/182 (0.00%) 
Bronchopneumonia  1  1/184 (0.54%)  0/183 (0.00%)  0/182 (0.00%) 
Catheter site cellulitis  1  0/184 (0.00%)  1/183 (0.55%)  0/182 (0.00%) 
Clostridium difficile infection  1  0/184 (0.00%)  1/183 (0.55%)  0/182 (0.00%) 
Gastroenteritis  1  0/184 (0.00%)  1/183 (0.55%)  0/182 (0.00%) 
Infective exacerbation of bronchiectasis  1  1/184 (0.54%)  0/183 (0.00%)  0/182 (0.00%) 
Kidney infection  1  0/184 (0.00%)  0/183 (0.00%)  1/182 (0.55%) 
Lung infection  1  1/184 (0.54%)  0/183 (0.00%)  0/182 (0.00%) 
Pneumonia mycoplasmal  1  0/184 (0.00%)  1/183 (0.55%)  0/182 (0.00%) 
Respiratory tract infection viral  1  0/184 (0.00%)  1/183 (0.55%)  0/182 (0.00%) 
Urinary tract infection  1  0/184 (0.00%)  0/183 (0.00%)  1/182 (0.55%) 
Injury, poisoning and procedural complications       
Post procedural haematoma  1  0/184 (0.00%)  0/183 (0.00%)  1/182 (0.55%) 
Investigations       
Forced expiratory volume decreased  1  0/184 (0.00%)  1/183 (0.55%)  1/182 (0.55%) 
Alanine aminotransferase increased  1  0/184 (0.00%)  0/183 (0.00%)  1/182 (0.55%) 
Aspartate aminotransferase increased  1  0/184 (0.00%)  0/183 (0.00%)  1/182 (0.55%) 
Blood alkaline phosphatase increased  1  1/184 (0.54%)  0/183 (0.00%)  0/182 (0.00%) 
Gamma-glutamyltransferase increased  1  0/184 (0.00%)  0/183 (0.00%)  1/182 (0.55%) 
Metabolism and nutrition disorders       
Diabetes mellitus inadequate control  1  1/184 (0.54%)  0/183 (0.00%)  0/182 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Colon cancer metastatic  1  1/184 (0.54%)  0/183 (0.00%)  0/182 (0.00%) 
Renal cancer  1  1/184 (0.54%)  0/183 (0.00%)  0/182 (0.00%) 
Seminoma  1  0/184 (0.00%)  0/183 (0.00%)  1/182 (0.55%) 
Nervous system disorders       
Epilepsy  1  0/184 (0.00%)  0/183 (0.00%)  1/182 (0.55%) 
Renal and urinary disorders       
Nephrolithiasis  1  0/184 (0.00%)  0/183 (0.00%)  1/182 (0.55%) 
Respiratory, thoracic and mediastinal disorders       
Haemoptysis  1  2/184 (1.09%)  0/183 (0.00%)  5/182 (2.75%) 
Cough  1  0/184 (0.00%)  2/183 (1.09%)  1/182 (0.55%) 
Bronchospasm  1  0/184 (0.00%)  1/183 (0.55%)  0/182 (0.00%) 
Dyspnoea  1  0/184 (0.00%)  1/183 (0.55%)  0/182 (0.00%) 
Lung disorder  1  0/184 (0.00%)  0/183 (0.00%)  1/182 (0.55%) 
Pneumomediastinum  1  0/184 (0.00%)  0/183 (0.00%)  1/182 (0.55%) 
Pneumothorax  1  0/184 (0.00%)  0/183 (0.00%)  1/182 (0.55%) 
Skin and subcutaneous tissue disorders       
Rash  1  0/184 (0.00%)  0/183 (0.00%)  1/182 (0.55%) 
Vascular disorders       
Deep vein thrombosis  1  1/184 (0.54%)  0/183 (0.00%)  0/182 (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   173/184 (94.02%)   175/183 (95.63%)   172/182 (94.51%) 
Blood and lymphatic system disorders       
Eosinophilia  1  1/184 (0.54%)  2/183 (1.09%)  0/182 (0.00%) 
Lymphadenopathy  1  1/184 (0.54%)  2/183 (1.09%)  0/182 (0.00%) 
Lymph node pain  1  1/184 (0.54%)  0/183 (0.00%)  0/182 (0.00%) 
Neutropenia  1  0/184 (0.00%)  0/183 (0.00%)  1/182 (0.55%) 
Thrombocytosis  1  0/184 (0.00%)  0/183 (0.00%)  1/182 (0.55%) 
Cardiac disorders       
Palpitations  1  1/184 (0.54%)  1/183 (0.55%)  0/182 (0.00%) 
Atrial fibrillation  1  1/184 (0.54%)  0/183 (0.00%)  0/182 (0.00%) 
Atrioventricular block second degree  1  1/184 (0.54%)  0/183 (0.00%)  0/182 (0.00%) 
Defect conduction intraventricular  1  0/184 (0.00%)  0/183 (0.00%)  1/182 (0.55%) 
Pericarditis  1  0/184 (0.00%)  1/183 (0.55%)  0/182 (0.00%) 
Tachycardia  1  0/184 (0.00%)  1/183 (0.55%)  0/182 (0.00%) 
Congenital, familial and genetic disorders       
Cystic fibrosis related diabetes  1  0/184 (0.00%)  2/183 (1.09%)  0/182 (0.00%) 
Ear and labyrinth disorders       
Vertigo  1  1/184 (0.54%)  4/183 (2.19%)  0/182 (0.00%) 
Ear pain  1  1/184 (0.54%)  2/183 (1.09%)  1/182 (0.55%) 
Cerumen impaction  1  0/184 (0.00%)  2/183 (1.09%)  0/182 (0.00%) 
Tympanic membrane disorder  1  1/184 (0.54%)  0/183 (0.00%)  1/182 (0.55%) 
Tympanic membrane hyperaemia  1  0/184 (0.00%)  1/183 (0.55%)  1/182 (0.55%) 
Ear canal erythema  1  0/184 (0.00%)  1/183 (0.55%)  0/182 (0.00%) 
Ear congestion  1  1/184 (0.54%)  0/183 (0.00%)  0/182 (0.00%) 
Endocrine disorders       
Hypothyroidism  1  0/184 (0.00%)  1/183 (0.55%)  0/182 (0.00%) 
Eye disorders       
Vision blurred  1  1/184 (0.54%)  1/183 (0.55%)  2/182 (1.10%) 
Asthenopia  1  1/184 (0.54%)  0/183 (0.00%)  1/182 (0.55%) 
Blepharospasm  1  0/184 (0.00%)  1/183 (0.55%)  1/182 (0.55%) 
Astigmatism  1  0/184 (0.00%)  1/183 (0.55%)  0/182 (0.00%) 
Conjunctivitis allergic  1  1/184 (0.54%)  0/183 (0.00%)  0/182 (0.00%) 
Eye disorder  1  0/184 (0.00%)  1/183 (0.55%)  0/182 (0.00%) 
Eye pruritus  1  0/184 (0.00%)  1/183 (0.55%)  0/182 (0.00%) 
Visual acuity reduced  1  0/184 (0.00%)  0/183 (0.00%)  1/182 (0.55%) 
Gastrointestinal disorders       
Diarrhoea  1  13/184 (7.07%)  16/183 (8.74%)  24/182 (13.19%) 
Abdominal pain  1  12/184 (6.52%)  11/183 (6.01%)  23/182 (12.64%) 
Nausea  1  11/184 (5.98%)  9/183 (4.92%)  14/182 (7.69%) 
Constipation  1  11/184 (5.98%)  6/183 (3.28%)  7/182 (3.85%) 
Abdominal pain upper  1  10/184 (5.43%)  7/183 (3.83%)  5/182 (2.75%) 
Flatulence  1  1/184 (0.54%)  9/183 (4.92%)  11/182 (6.04%) 
Vomiting  1  2/184 (1.09%)  8/183 (4.37%)  7/182 (3.85%) 
Abdominal distension  1  4/184 (2.17%)  2/183 (1.09%)  5/182 (2.75%) 
Gastrooesophageal reflux disease  1  2/184 (1.09%)  3/183 (1.64%)  6/182 (3.30%) 
Dyspepsia  1  2/184 (1.09%)  3/183 (1.64%)  4/182 (2.20%) 
Abdominal discomfort  1  1/184 (0.54%)  3/183 (1.64%)  3/182 (1.65%) 
Enteritis  1  2/184 (1.09%)  0/183 (0.00%)  3/182 (1.65%) 
Steatorrhoea  1  0/184 (0.00%)  1/183 (0.55%)  3/182 (1.65%) 
Dry mouth  1  1/184 (0.54%)  1/183 (0.55%)  1/182 (0.55%) 
Frequent bowel movements  1  1/184 (0.54%)  1/183 (0.55%)  1/182 (0.55%) 
Toothache  1  1/184 (0.54%)  0/183 (0.00%)  2/182 (1.10%) 
Abdominal pain lower  1  1/184 (0.54%)  0/183 (0.00%)  1/182 (0.55%) 
Distal intestinal obstruction syndrome  1  0/184 (0.00%)  2/183 (1.09%)  0/182 (0.00%) 
Faeces soft  1  0/184 (0.00%)  1/183 (0.55%)  1/182 (0.55%) 
Gastrointestinal motility disorder  1  1/184 (0.54%)  1/183 (0.55%)  0/182 (0.00%) 
Malabsorption  1  0/184 (0.00%)  1/183 (0.55%)  1/182 (0.55%) 
Abdominal tenderness  1  0/184 (0.00%)  1/183 (0.55%)  0/182 (0.00%) 
Anal fissure  1  1/184 (0.54%)  0/183 (0.00%)  0/182 (0.00%) 
Chapped lips  1  0/184 (0.00%)  1/183 (0.55%)  0/182 (0.00%) 
Colonic haematoma  1  0/184 (0.00%)  1/183 (0.55%)  0/182 (0.00%) 
Defaecation urgency  1  1/184 (0.54%)  0/183 (0.00%)  0/182 (0.00%) 
Faecaloma  1  1/184 (0.54%)  0/183 (0.00%)  0/182 (0.00%) 
Gastric dilatation  1  0/184 (0.00%)  0/183 (0.00%)  1/182 (0.55%) 
Gastritis  1  0/184 (0.00%)  1/183 (0.55%)  0/182 (0.00%) 
Gastrointestinal pain  1  1/184 (0.54%)  0/183 (0.00%)  0/182 (0.00%) 
Gastrointestinal sounds abnormal  1  0/184 (0.00%)  1/183 (0.55%)  0/182 (0.00%) 
Gingival swelling  1  0/184 (0.00%)  1/183 (0.55%)  0/182 (0.00%) 
Gingivitis ulcerative  1  0/184 (0.00%)  0/183 (0.00%)  1/182 (0.55%) 
Haemorrhoids  1  0/184 (0.00%)  0/183 (0.00%)  1/182 (0.55%) 
Oesophagitis  1  1/184 (0.54%)  0/183 (0.00%)  0/182 (0.00%) 
Rectal haemorrhage  1  0/184 (0.00%)  1/183 (0.55%)  0/182 (0.00%) 
Rectal tenesmus  1  1/184 (0.54%)  0/183 (0.00%)  0/182 (0.00%) 
Tongue coated  1  1/184 (0.54%)  0/183 (0.00%)  0/182 (0.00%) 
General disorders       
Fatigue  1  19/184 (10.33%)  17/183 (9.29%)  17/182 (9.34%) 
Pyrexia  1  12/184 (6.52%)  12/183 (6.56%)  17/182 (9.34%) 
Asthenia  1  3/184 (1.63%)  5/183 (2.73%)  3/182 (1.65%) 
Pain  1  2/184 (1.09%)  4/183 (2.19%)  3/182 (1.65%) 
Chest discomfort  1  1/184 (0.54%)  3/183 (1.64%)  3/182 (1.65%) 
Malaise  1  1/184 (0.54%)  2/183 (1.09%)  3/182 (1.65%) 
Chills  1  1/184 (0.54%)  0/183 (0.00%)  2/182 (1.10%) 
Drug intolerance  1  0/184 (0.00%)  0/183 (0.00%)  3/182 (1.65%) 
Chest pain  1  2/184 (1.09%)  0/183 (0.00%)  0/182 (0.00%) 
Influenza like illness  1  1/184 (0.54%)  0/183 (0.00%)  1/182 (0.55%) 
Drug interaction  1  0/184 (0.00%)  0/183 (0.00%)  1/182 (0.55%) 
Exercise tolerance decreased  1  0/184 (0.00%)  0/183 (0.00%)  1/182 (0.55%) 
Feeling abnormal  1  1/184 (0.54%)  0/183 (0.00%)  0/182 (0.00%) 
Feeling cold  1  0/184 (0.00%)  1/183 (0.55%)  0/182 (0.00%) 
Feeling hot  1  0/184 (0.00%)  0/183 (0.00%)  1/182 (0.55%) 
Hyperthermia  1  0/184 (0.00%)  0/183 (0.00%)  1/182 (0.55%) 
Implant site thrombosis  1  0/184 (0.00%)  0/183 (0.00%)  1/182 (0.55%) 
Local swelling  1  1/184 (0.54%)  0/183 (0.00%)  0/182 (0.00%) 
Medical device pain  1  1/184 (0.54%)  0/183 (0.00%)  0/182 (0.00%) 
Oedema peripheral  1  1/184 (0.54%)  0/183 (0.00%)  0/182 (0.00%) 
Hepatobiliary disorders       
Cholelithiasis  1  1/184 (0.54%)  0/183 (0.00%)  0/182 (0.00%) 
Hepatitis  1  1/184 (0.54%)  0/183 (0.00%)  0/182 (0.00%) 
Immune system disorders       
Allergy to arthropod sting  1  0/184 (0.00%)  1/183 (0.55%)  1/182 (0.55%) 
Seasonal allergy  1  1/184 (0.54%)  0/183 (0.00%)  1/182 (0.55%) 
Anaphylactic reaction  1  1/184 (0.54%)  0/183 (0.00%)  0/182 (0.00%) 
Hypersensitivity  1  1/184 (0.54%)  0/183 (0.00%)  0/182 (0.00%) 
Milk allergy  1  0/184 (0.00%)  0/183 (0.00%)  1/182 (0.55%) 
Infections and infestations       
Infective pulmonary exacerbation of cystic fibrosis  1  58/184 (31.52%)  57/183 (31.15%)  54/182 (29.67%) 
Nasopharyngitis  1  20/184 (10.87%)  9/183 (4.92%)  26/182 (14.29%) 
Upper respiratory tract infection  1  10/184 (5.43%)  16/183 (8.74%)  17/182 (9.34%) 
Viral upper respiratory tract infection  1  12/184 (6.52%)  15/183 (8.20%)  13/182 (7.14%) 
Rhinitis  1  12/184 (6.52%)  16/183 (8.74%)  8/182 (4.40%) 
Sinusitis  1  12/184 (6.52%)  7/183 (3.83%)  5/182 (2.75%) 
Influenza  1  3/184 (1.63%)  8/183 (4.37%)  8/182 (4.40%) 
Bronchitis  1  7/184 (3.80%)  9/183 (4.92%)  2/182 (1.10%) 
Respiratory tract infection  1  3/184 (1.63%)  2/183 (1.09%)  6/182 (3.30%) 
Pharyngitis  1  2/184 (1.09%)  4/183 (2.19%)  4/182 (2.20%) 
Vulvovaginal mycotic infection  1  4/184 (2.17%)  2/183 (1.09%)  3/182 (1.65%) 
Oral candidiasis  1  3/184 (1.63%)  2/183 (1.09%)  3/182 (1.65%) 
Urinary tract infection  1  3/184 (1.63%)  2/183 (1.09%)  3/182 (1.65%) 
Upper respiratory tract infection bacterial  1  2/184 (1.09%)  2/183 (1.09%)  3/182 (1.65%) 
Viral infection  1  4/184 (2.17%)  2/183 (1.09%)  1/182 (0.55%) 
Gastroenteritis viral  1  1/184 (0.54%)  2/183 (1.09%)  2/182 (1.10%) 
Lower respiratory tract infection bacterial  1  3/184 (1.63%)  1/183 (0.55%)  1/182 (0.55%) 
Respiratory tract infection viral  1  1/184 (0.54%)  2/183 (1.09%)  2/182 (1.10%) 
Gastroenteritis  1  0/184 (0.00%)  1/183 (0.55%)  3/182 (1.65%) 
H1N1 influenza  1  1/184 (0.54%)  1/183 (0.55%)  2/182 (1.10%) 
Oral herpes  1  1/184 (0.54%)  1/183 (0.55%)  2/182 (1.10%) 
Otitis media  1  0/184 (0.00%)  3/183 (1.64%)  1/182 (0.55%) 
Acute sinusitis  1  1/184 (0.54%)  1/183 (0.55%)  1/182 (0.55%) 
Bronchopulmonary aspergillosis allergic  1  1/184 (0.54%)  2/183 (1.09%)  0/182 (0.00%) 
Fungal skin infection  1  2/184 (1.09%)  1/183 (0.55%)  0/182 (0.00%) 
Laryngitis  1  1/184 (0.54%)  2/183 (1.09%)  0/182 (0.00%) 
Sputum purulent  1  0/184 (0.00%)  2/183 (1.09%)  1/182 (0.55%) 
Bacterial disease carrier  1  1/184 (0.54%)  1/183 (0.55%)  0/182 (0.00%) 
Bronchitis bacterial  1  0/184 (0.00%)  1/183 (0.55%)  1/182 (0.55%) 
Chronic sinusitis  1  0/184 (0.00%)  1/183 (0.55%)  1/182 (0.55%) 
Clostridium difficile colitis  1  1/184 (0.54%)  0/183 (0.00%)  1/182 (0.55%) 
Herpes zoster  1  0/184 (0.00%)  1/183 (0.55%)  1/182 (0.55%) 
Lower respiratory tract infection viral  1  0/184 (0.00%)  2/183 (1.09%)  0/182 (0.00%) 
Mycobacterium abscessus infection  1  2/184 (1.09%)  0/183 (0.00%)  0/182 (0.00%) 
Pharyngitis streptococcal  1  1/184 (0.54%)  0/183 (0.00%)  1/182 (0.55%) 
Tonsillitis  1  1/184 (0.54%)  1/183 (0.55%)  0/182 (0.00%) 
Vulvovaginal candidiasis  1  2/184 (1.09%)  0/183 (0.00%)  0/182 (0.00%) 
Acute tonsillitis  1  1/184 (0.54%)  0/183 (0.00%)  0/182 (0.00%) 
Body tinea  1  1/184 (0.54%)  0/183 (0.00%)  0/182 (0.00%) 
Bronchopulmonary aspergillosis  1  0/184 (0.00%)  1/183 (0.55%)  0/182 (0.00%) 
Conjunctivitis bacterial  1  1/184 (0.54%)  0/183 (0.00%)  0/182 (0.00%) 
Ear infection  1  0/184 (0.00%)  0/183 (0.00%)  1/182 (0.55%) 
Eye infection  1  1/184 (0.54%)  0/183 (0.00%)  0/182 (0.00%) 
Folliculitis  1  0/184 (0.00%)  0/183 (0.00%)  1/182 (0.55%) 
Genital infection fungal  1  0/184 (0.00%)  1/183 (0.55%)  0/182 (0.00%) 
Giardiasis  1  0/184 (0.00%)  0/183 (0.00%)  1/182 (0.55%) 
Herpes dermatitis  1  0/184 (0.00%)  0/183 (0.00%)  1/182 (0.55%) 
Herpes simplex  1  0/184 (0.00%)  1/183 (0.55%)  0/182 (0.00%) 
Lower respiratory tract infection  1  1/184 (0.54%)  0/183 (0.00%)  0/182 (0.00%) 
Lung infection  1  0/184 (0.00%)  1/183 (0.55%)  0/182 (0.00%) 
Lung infection pseudomonal  1  1/184 (0.54%)  0/183 (0.00%)  0/182 (0.00%) 
Oral fungal infection  1  1/184 (0.54%)  0/183 (0.00%)  0/182 (0.00%) 
Oropharyngeal candidiasis  1  0/184 (0.00%)  0/183 (0.00%)  1/182 (0.55%) 
Otitis externa  1  0/184 (0.00%)  0/183 (0.00%)  1/182 (0.55%) 
Overgrowth bacterial  1  1/184 (0.54%)  0/183 (0.00%)  0/182 (0.00%) 
Pseudomonas bronchitis  1  0/184 (0.00%)  1/183 (0.55%)  0/182 (0.00%) 
Soft tissue infection  1  0/184 (0.00%)  1/183 (0.55%)  0/182 (0.00%) 
Stoma site infection  1  0/184 (0.00%)  0/183 (0.00%)  1/182 (0.55%) 
Subcutaneous abscess  1  0/184 (0.00%)  1/183 (0.55%)  0/182 (0.00%) 
Tinea pedis  1  0/184 (0.00%)  1/183 (0.55%)  0/182 (0.00%) 
Tinea versicolour  1  0/184 (0.00%)  0/183 (0.00%)  1/182 (0.55%) 
Tooth infection  1  1/184 (0.54%)  0/183 (0.00%)  0/182 (0.00%) 
Tracheitis  1  0/184 (0.00%)  1/183 (0.55%)  0/182 (0.00%) 
Vestibular neuronitis  1  0/184 (0.00%)  1/183 (0.55%)  0/182 (0.00%) 
Viral rhinitis  1  0/184 (0.00%)  1/183 (0.55%)  0/182 (0.00%) 
Viral tonsillitis  1  1/184 (0.54%)  0/183 (0.00%)  0/182 (0.00%) 
Injury, poisoning and procedural complications       
Muscle strain  1  0/184 (0.00%)  3/183 (1.64%)  2/182 (1.10%) 
Joint injury  1  1/184 (0.54%)  1/183 (0.55%)  2/182 (1.10%) 
Ligament sprain  1  0/184 (0.00%)  1/183 (0.55%)  2/182 (1.10%) 
Procedural pain  1  1/184 (0.54%)  0/183 (0.00%)  2/182 (1.10%) 
Concussion  1  0/184 (0.00%)  0/183 (0.00%)  2/182 (1.10%) 
Excoriation  1  2/184 (1.09%)  0/183 (0.00%)  0/182 (0.00%) 
Facial bones fracture  1  2/184 (1.09%)  0/183 (0.00%)  0/182 (0.00%) 
Stoma site pain  1  0/184 (0.00%)  2/183 (1.09%)  0/182 (0.00%) 
Sunburn  1  1/184 (0.54%)  1/183 (0.55%)  0/182 (0.00%) 
Arthropod bite  1  0/184 (0.00%)  1/183 (0.55%)  0/182 (0.00%) 
Back injury  1  1/184 (0.54%)  0/183 (0.00%)  0/182 (0.00%) 
Contusion  1  0/184 (0.00%)  1/183 (0.55%)  0/182 (0.00%) 
Fall  1  1/184 (0.54%)  0/183 (0.00%)  0/182 (0.00%) 
Foot fracture  1  0/184 (0.00%)  0/183 (0.00%)  1/182 (0.55%) 
Foreign body in eye  1  0/184 (0.00%)  0/183 (0.00%)  1/182 (0.55%) 
Laceration  1  0/184 (0.00%)  1/183 (0.55%)  0/182 (0.00%) 
Meniscus injury  1  1/184 (0.54%)  0/183 (0.00%)  0/182 (0.00%) 
Muscle rupture  1  0/184 (0.00%)  0/183 (0.00%)  1/182 (0.55%) 
Post procedural complication  1  0/184 (0.00%)  0/183 (0.00%)  1/182 (0.55%) 
Radius fracture  1  0/184 (0.00%)  0/183 (0.00%)  1/182 (0.55%) 
Respiratory fume inhalation disorder  1  0/184 (0.00%)  0/183 (0.00%)  1/182 (0.55%) 
Skeletal injury  1  1/184 (0.54%)  0/183 (0.00%)  0/182 (0.00%) 
Stoma site erythema  1  0/184 (0.00%)  1/183 (0.55%)  0/182 (0.00%) 
Vaccination complication  1  0/184 (0.00%)  0/183 (0.00%)  1/182 (0.55%) 
Vascular procedure complication  1  1/184 (0.54%)  0/183 (0.00%)  0/182 (0.00%) 
Investigations       
Blood creatine phosphokinase increased  1  10/184 (5.43%)  10/183 (5.46%)  13/182 (7.14%) 
Bacterial test positive  1  9/184 (4.89%)  4/183 (2.19%)  7/182 (3.85%) 
Alanine aminotransferase increased  1  5/184 (2.72%)  4/183 (2.19%)  3/182 (1.65%) 
Forced expiratory volume decreased  1  7/184 (3.80%)  3/183 (1.64%)  1/182 (0.55%) 
Weight decreased  1  5/184 (2.72%)  2/183 (1.09%)  4/182 (2.20%) 
Liver function test abnormal  1  6/184 (3.26%)  3/183 (1.64%)  1/182 (0.55%) 
Pulmonary function test decreased  1  6/184 (3.26%)  4/183 (2.19%)  0/182 (0.00%) 
Aspartate aminotransferase increased  1  3/184 (1.63%)  3/183 (1.64%)  3/182 (1.65%) 
Blood creatinine increased  1  4/184 (2.17%)  3/183 (1.64%)  1/182 (0.55%) 
White blood cell count increased  1  1/184 (0.54%)  2/183 (1.09%)  2/182 (1.10%) 
Blood glucose decreased  1  3/184 (1.63%)  0/183 (0.00%)  1/182 (0.55%) 
Hepatic enzyme increased  1  0/184 (0.00%)  2/183 (1.09%)  2/182 (1.10%) 
Vitamin D decreased  1  1/184 (0.54%)  1/183 (0.55%)  2/182 (1.10%) 
Breath sounds abnormal  1  1/184 (0.54%)  2/183 (1.09%)  0/182 (0.00%) 
Fungal test positive  1  1/184 (0.54%)  1/183 (0.55%)  1/182 (0.55%) 
Staphylococcus test positive  1  0/184 (0.00%)  1/183 (0.55%)  2/182 (1.10%) 
Transaminases increased  1  1/184 (0.54%)  1/183 (0.55%)  1/182 (0.55%) 
Blood alkaline phosphatase increased  1  2/184 (1.09%)  0/183 (0.00%)  0/182 (0.00%) 
Blood glucose increased  1  1/184 (0.54%)  1/183 (0.55%)  0/182 (0.00%) 
Blood immunoglobulin E increased  1  1/184 (0.54%)  1/183 (0.55%)  0/182 (0.00%) 
Blood phosphorus increased  1  1/184 (0.54%)  0/183 (0.00%)  1/182 (0.55%) 
Body temperature increased  1  0/184 (0.00%)  1/183 (0.55%)  1/182 (0.55%) 
Atypical mycobacterium test positive  1  0/184 (0.00%)  0/183 (0.00%)  1/182 (0.55%) 
Blood bicarbonate decreased  1  1/184 (0.54%)  0/183 (0.00%)  0/182 (0.00%) 
Blood calcium increased  1  0/184 (0.00%)  1/183 (0.55%)  0/182 (0.00%) 
Blood lactate dehydrogenase increased  1  1/184 (0.54%)  0/183 (0.00%)  0/182 (0.00%) 
Blood phosphorus abnormal  1  0/184 (0.00%)  1/183 (0.55%)  0/182 (0.00%) 
Blood potassium increased  1  0/184 (0.00%)  0/183 (0.00%)  1/182 (0.55%) 
Blood sodium decreased  1  0/184 (0.00%)  0/183 (0.00%)  1/182 (0.55%) 
Blood urea increased  1  1/184 (0.54%)  0/183 (0.00%)  0/182 (0.00%) 
C-reactive protein increased  1  0/184 (0.00%)  1/183 (0.55%)  0/182 (0.00%) 
Chest X-ray abnormal  1  0/184 (0.00%)  0/183 (0.00%)  1/182 (0.55%) 
Forced expiratory volume increased  1  0/184 (0.00%)  0/183 (0.00%)  1/182 (0.55%) 
Gamma-glutamyltransferase increased  1  1/184 (0.54%)  0/183 (0.00%)  0/182 (0.00%) 
Glucose tolerance test abnormal  1  1/184 (0.54%)  0/183 (0.00%)  0/182 (0.00%) 
Glucose urine present  1  1/184 (0.54%)  0/183 (0.00%)  0/182 (0.00%) 
Haemoglobin increased  1  0/184 (0.00%)  0/183 (0.00%)  1/182 (0.55%) 
Heart rate increased  1  0/184 (0.00%)  1/183 (0.55%)  0/182 (0.00%) 
Neutrophil count increased  1  0/184 (0.00%)  1/183 (0.55%)  0/182 (0.00%) 
Platelet count decreased  1  0/184 (0.00%)  1/183 (0.55%)  0/182 (0.00%) 
Pseudomonas test positive  1  1/184 (0.54%)  0/183 (0.00%)  0/182 (0.00%) 
Red blood cell count increased  1  0/184 (0.00%)  0/183 (0.00%)  1/182 (0.55%) 
Sputum abnormal  1  1/184 (0.54%)  0/183 (0.00%)  0/182 (0.00%) 
Urine calcium increased  1  0/184 (0.00%)  0/183 (0.00%)  1/182 (0.55%) 
Vitamin E decreased  1  0/184 (0.00%)  1/183 (0.55%)  0/182 (0.00%) 
White blood cell count decreased  1  0/184 (0.00%)  0/183 (0.00%)  1/182 (0.55%) 
White blood cells urine positive  1  0/184 (0.00%)  1/183 (0.55%)  0/182 (0.00%) 
Metabolism and nutrition disorders       
Decreased appetite  1  4/184 (2.17%)  6/183 (3.28%)  6/182 (3.30%) 
Hypoglycaemia  1  3/184 (1.63%)  6/183 (3.28%)  2/182 (1.10%) 
Dehydration  1  3/184 (1.63%)  0/183 (0.00%)  1/182 (0.55%) 
Hyperglycaemia  1  2/184 (1.09%)  1/183 (0.55%)  1/182 (0.55%) 
Gout  1  2/184 (1.09%)  1/183 (0.55%)  0/182 (0.00%) 
Diabetes mellitus  1  1/184 (0.54%)  0/183 (0.00%)  1/182 (0.55%) 
Hyponatraemia  1  0/184 (0.00%)  0/183 (0.00%)  2/182 (1.10%) 
Glucose tolerance impaired  1  0/184 (0.00%)  1/183 (0.55%)  0/182 (0.00%) 
Hyperkalaemia  1  0/184 (0.00%)  0/183 (0.00%)  1/182 (0.55%) 
Hypokalaemia  1  1/184 (0.54%)  0/183 (0.00%)  0/182 (0.00%) 
Iron deficiency  1  1/184 (0.54%)  0/183 (0.00%)  0/182 (0.00%) 
Magnesium deficiency  1  0/184 (0.00%)  0/183 (0.00%)  1/182 (0.55%) 
Vitamin K deficiency  1  0/184 (0.00%)  1/183 (0.55%)  0/182 (0.00%) 
Musculoskeletal and connective tissue disorders       
Musculoskeletal chest pain  1  6/184 (3.26%)  7/183 (3.83%)  3/182 (1.65%) 
Myalgia  1  4/184 (2.17%)  3/183 (1.64%)  7/182 (3.85%) 
Back pain  1  5/184 (2.72%)  3/183 (1.64%)  5/182 (2.75%) 
Arthralgia  1  4/184 (2.17%)  1/183 (0.55%)  2/182 (1.10%) 
Pain in extremity  1  4/184 (2.17%)  0/183 (0.00%)  1/182 (0.55%) 
Musculoskeletal pain  1  0/184 (0.00%)  1/183 (0.55%)  3/182 (1.65%) 
Flank pain  1  0/184 (0.00%)  2/183 (1.09%)  1/182 (0.55%) 
Muscle spasms  1  2/184 (1.09%)  1/183 (0.55%)  0/182 (0.00%) 
Joint swelling  1  2/184 (1.09%)  0/183 (0.00%)  0/182 (0.00%) 
Musculoskeletal stiffness  1  0/184 (0.00%)  1/183 (0.55%)  1/182 (0.55%) 
Tendon pain  1  1/184 (0.54%)  0/183 (0.00%)  1/182 (0.55%) 
Arthropathy  1  0/184 (0.00%)  0/183 (0.00%)  1/182 (0.55%) 
Intervertebral disc protrusion  1  1/184 (0.54%)  0/183 (0.00%)  0/182 (0.00%) 
Musculoskeletal discomfort  1  1/184 (0.54%)  0/183 (0.00%)  0/182 (0.00%) 
Neck pain  1  1/184 (0.54%)  0/183 (0.00%)  0/182 (0.00%) 
Tendon disorder  1  0/184 (0.00%)  0/183 (0.00%)  1/182 (0.55%) 
Tendonitis  1  1/184 (0.54%)  0/183 (0.00%)  0/182 (0.00%) 
Nervous system disorders       
Headache  1  25/184 (13.59%)  28/183 (15.30%)  29/182 (15.93%) 
Dizziness  1  5/184 (2.72%)  5/183 (2.73%)  5/182 (2.75%) 
Sinus headache  1  2/184 (1.09%)  3/183 (1.64%)  3/182 (1.65%) 
Migraine  1  3/184 (1.63%)  0/183 (0.00%)  3/182 (1.65%) 
Lethargy  1  1/184 (0.54%)  2/183 (1.09%)  2/182 (1.10%) 
Dysgeusia  1  2/184 (1.09%)  0/183 (0.00%)  2/182 (1.10%) 
Poor quality sleep  1  0/184 (0.00%)  0/183 (0.00%)  3/182 (1.65%) 
Dysarthria  1  0/184 (0.00%)  1/183 (0.55%)  1/182 (0.55%) 
Paraesthesia  1  0/184 (0.00%)  2/183 (1.09%)  0/182 (0.00%) 
Syncope  1  1/184 (0.54%)  0/183 (0.00%)  1/182 (0.55%) 
Tremor  1  0/184 (0.00%)  0/183 (0.00%)  2/182 (1.10%) 
Amnesia  1  0/184 (0.00%)  0/183 (0.00%)  1/182 (0.55%) 
Ataxia  1  1/184 (0.54%)  0/183 (0.00%)  0/182 (0.00%) 
Cognitive disorder  1  0/184 (0.00%)  0/183 (0.00%)  1/182 (0.55%) 
Dysaesthesia  1  0/184 (0.00%)  1/183 (0.55%)  0/182 (0.00%) 
Epilepsy  1  0/184 (0.00%)  0/183 (0.00%)  1/182 (0.55%) 
Hypoaesthesia  1  1/184 (0.54%)  0/183 (0.00%)  0/182 (0.00%) 
Memory impairment  1  0/184 (0.00%)  1/183 (0.55%)  0/182 (0.00%) 
Neuropathy peripheral  1  1/184 (0.54%)  0/183 (0.00%)  0/182 (0.00%) 
Presyncope  1  1/184 (0.54%)  0/183 (0.00%)  0/182 (0.00%) 
Sciatica  1  1/184 (0.54%)  0/183 (0.00%)  0/182 (0.00%) 
Somnolence  1  1/184 (0.54%)  0/183 (0.00%)  0/182 (0.00%) 
Tension headache  1  0/184 (0.00%)  0/183 (0.00%)  1/182 (0.55%) 
Psychiatric disorders       
Insomnia  1  6/184 (3.26%)  2/183 (1.09%)  3/182 (1.65%) 
Anxiety  1  2/184 (1.09%)  2/183 (1.09%)  2/182 (1.10%) 
Depression  1  4/184 (2.17%)  1/183 (0.55%)  1/182 (0.55%) 
Depressed mood  1  0/184 (0.00%)  0/183 (0.00%)  3/182 (1.65%) 
Irritability  1  1/184 (0.54%)  1/183 (0.55%)  0/182 (0.00%) 
Attention deficit/hyperactivity disorder  1  0/184 (0.00%)  1/183 (0.55%)  0/182 (0.00%) 
Bradyphrenia  1  1/184 (0.54%)  0/183 (0.00%)  0/182 (0.00%) 
Depressive symptom  1  0/184 (0.00%)  1/183 (0.55%)  0/182 (0.00%) 
Disorientation  1  0/184 (0.00%)  0/183 (0.00%)  1/182 (0.55%) 
Disturbance in social behaviour  1  0/184 (0.00%)  0/183 (0.00%)  1/182 (0.55%) 
Emotional disorder  1  1/184 (0.54%)  0/183 (0.00%)  0/182 (0.00%) 
Libido decreased  1  1/184 (0.54%)  0/183 (0.00%)  0/182 (0.00%) 
Middle insomnia  1  1/184 (0.54%)  0/183 (0.00%)  0/182 (0.00%) 
Sleep disorder  1  0/184 (0.00%)  0/183 (0.00%)  1/182 (0.55%) 
Suicidal ideation  1  0/184 (0.00%)  1/183 (0.55%)  0/182 (0.00%) 
Renal and urinary disorders       
Nephrolithiasis  1  1/184 (0.54%)  2/183 (1.09%)  0/182 (0.00%) 
Urine odour abnormal  1  2/184 (1.09%)  0/183 (0.00%)  0/182 (0.00%) 
Calculus urinary  1  0/184 (0.00%)  0/183 (0.00%)  1/182 (0.55%) 
Haematuria  1  0/184 (0.00%)  0/183 (0.00%)  1/182 (0.55%) 
Leukocyturia  1  1/184 (0.54%)  0/183 (0.00%)  0/182 (0.00%) 
Nephropathy  1  0/184 (0.00%)  0/183 (0.00%)  1/182 (0.55%) 
Nephropathy toxic  1  0/184 (0.00%)  0/183 (0.00%)  1/182 (0.55%) 
Pollakiuria  1  0/184 (0.00%)  0/183 (0.00%)  1/182 (0.55%) 
Renal failure acute  1  0/184 (0.00%)  0/183 (0.00%)  1/182 (0.55%) 
Urine abnormality  1  0/184 (0.00%)  0/183 (0.00%)  1/182 (0.55%) 
Reproductive system and breast disorders       
Dysmenorrhoea  1  2/184 (1.09%)  1/183 (0.55%)  2/182 (1.10%) 
Metrorrhagia  1  0/184 (0.00%)  2/183 (1.09%)  3/182 (1.65%) 
Amenorrhoea  1  0/184 (0.00%)  0/183 (0.00%)  3/182 (1.65%) 
Menorrhagia  1  0/184 (0.00%)  2/183 (1.09%)  1/182 (0.55%) 
Menstruation irregular  1  0/184 (0.00%)  2/183 (1.09%)  1/182 (0.55%) 
Polymenorrhoea  1  0/184 (0.00%)  1/183 (0.55%)  1/182 (0.55%) 
Erectile dysfunction  1  1/184 (0.54%)  0/183 (0.00%)  0/182 (0.00%) 
Gynaecomastia  1  0/184 (0.00%)  1/183 (0.55%)  0/182 (0.00%) 
Penile erythema  1  1/184 (0.54%)  0/183 (0.00%)  0/182 (0.00%) 
Testicular pain  1  0/184 (0.00%)  0/183 (0.00%)  1/182 (0.55%) 
Respiratory, thoracic and mediastinal disorders       
Cough  1  66/184 (35.87%)  52/183 (28.42%)  47/182 (25.82%) 
Haemoptysis  1  23/184 (12.50%)  22/183 (12.02%)  26/182 (14.29%) 
Sputum increased  1  23/184 (12.50%)  15/183 (8.20%)  25/182 (13.74%) 
Dyspnoea  1  14/184 (7.61%)  21/183 (11.48%)  17/182 (9.34%) 
Respiration abnormal  1  9/184 (4.89%)  26/183 (14.21%)  14/182 (7.69%) 
Nasal congestion  1  25/184 (13.59%)  9/183 (4.92%)  11/182 (6.04%) 
Oropharyngeal pain  1  10/184 (5.43%)  24/183 (13.11%)  11/182 (6.04%) 
Rhinorrhoea  1  5/184 (2.72%)  6/183 (3.28%)  10/182 (5.49%) 
Wheezing  1  6/184 (3.26%)  5/183 (2.73%)  5/182 (2.75%) 
Rales  1  7/184 (3.80%)  4/183 (2.19%)  4/182 (2.20%) 
Productive cough  1  1/184 (0.54%)  6/183 (3.28%)  7/182 (3.85%) 
Respiratory tract congestion  1  5/184 (2.72%)  3/183 (1.64%)  4/182 (2.20%) 
Epistaxis  1  4/184 (2.17%)  4/183 (2.19%)  2/182 (1.10%) 
Asthma  1  3/184 (1.63%)  0/183 (0.00%)  6/182 (3.30%) 
Bronchospasm  1  1/184 (0.54%)  3/183 (1.64%)  5/182 (2.75%) 
Sinus congestion  1  1/184 (0.54%)  7/183 (3.83%)  1/182 (0.55%) 
Paranasal sinus hypersecretion  1  1/184 (0.54%)  4/183 (2.19%)  3/182 (1.65%) 
Sputum discoloured  1  3/184 (1.63%)  2/183 (1.09%)  1/182 (0.55%) 
Nasal inflammation  1  1/184 (0.54%)  3/183 (1.64%)  1/182 (0.55%) 
Rhinitis allergic  1  2/184 (1.09%)  1/183 (0.55%)  2/182 (1.10%) 
Rhonchi  1  2/184 (1.09%)  2/183 (1.09%)  1/182 (0.55%) 
Upper-airway cough syndrome  1  2/184 (1.09%)  1/183 (0.55%)  2/182 (1.10%) 
Dysphonia  1  2/184 (1.09%)  1/183 (0.55%)  1/182 (0.55%) 
Dyspnoea exertional  1  0/184 (0.00%)  3/183 (1.64%)  1/182 (0.55%) 
Increased upper airway secretion  1  1/184 (0.54%)  1/183 (0.55%)  2/182 (1.10%) 
Increased viscosity of bronchial secretion  1  2/184 (1.09%)  0/183 (0.00%)  2/182 (1.10%) 
Painful respiration  1  2/184 (1.09%)  1/183 (0.55%)  1/182 (0.55%) 
Pharyngeal erythema  1  1/184 (0.54%)  2/183 (1.09%)  1/182 (0.55%) 
Pleuritic pain  1  2/184 (1.09%)  0/183 (0.00%)  2/182 (1.10%) 
Lung hyperinflation  1  1/184 (0.54%)  1/183 (0.55%)  1/182 (0.55%) 
Throat irritation  1  2/184 (1.09%)  0/183 (0.00%)  1/182 (0.55%) 
Bronchial hyperreactivity  1  0/184 (0.00%)  1/183 (0.55%)  1/182 (0.55%) 
Nasal polyps  1  1/184 (0.54%)  0/183 (0.00%)  1/182 (0.55%) 
Obstructive airways disorder  1  1/184 (0.54%)  1/183 (0.55%)  0/182 (0.00%) 
Paranasal cyst  1  1/184 (0.54%)  0/183 (0.00%)  1/182 (0.55%) 
Pulmonary congestion  1  0/184 (0.00%)  2/183 (1.09%)  0/182 (0.00%) 
Allergic cough  1  1/184 (0.54%)  0/183 (0.00%)  0/182 (0.00%) 
Bronchial obstruction  1  0/184 (0.00%)  0/183 (0.00%)  1/182 (0.55%) 
Bronchiectasis  1  1/184 (0.54%)  0/183 (0.00%)  0/182 (0.00%) 
Hypoxia  1  0/184 (0.00%)  1/183 (0.55%)  0/182 (0.00%) 
Nasal obstruction  1  0/184 (0.00%)  1/183 (0.55%)  0/182 (0.00%) 
Nasal oedema  1  1/184 (0.54%)  0/183 (0.00%)  0/182 (0.00%) 
Nasal septum deviation  1  0/184 (0.00%)  0/183 (0.00%)  1/182 (0.55%) 
Nasal turbinate hypertrophy  1  0/184 (0.00%)  1/183 (0.55%)  0/182 (0.00%) 
Pharyngeal exudate  1  0/184 (0.00%)  0/183 (0.00%)  1/182 (0.55%) 
Prolonged expiration  1  0/184 (0.00%)  1/183 (0.55%)  0/182 (0.00%) 
Pulmonary pain  1  0/184 (0.00%)  1/183 (0.55%)  0/182 (0.00%) 
Respiratory failure  1  1/184 (0.54%)  0/183 (0.00%)  0/182 (0.00%) 
Respiratory tract irritation  1  0/184 (0.00%)  0/183 (0.00%)  1/182 (0.55%) 
Rhinalgia  1  0/184 (0.00%)  0/183 (0.00%)  1/182 (0.55%) 
Sneezing  1  1/184 (0.54%)  0/183 (0.00%)  0/182 (0.00%) 
Throat tightness  1  0/184 (0.00%)  1/183 (0.55%)  0/182 (0.00%) 
Upper respiratory tract inflammation  1  0/184 (0.00%)  0/183 (0.00%)  1/182 (0.55%) 
Skin and subcutaneous tissue disorders       
Rash  1  2/184 (1.09%)  8/183 (4.37%)  6/182 (3.30%) 
Pruritus  1  1/184 (0.54%)  5/183 (2.73%)  4/182 (2.20%) 
Acne  1  5/184 (2.72%)  1/183 (0.55%)  1/182 (0.55%) 
Hyperhidrosis  1  0/184 (0.00%)  1/183 (0.55%)  2/182 (1.10%) 
Night sweats  1  0/184 (0.00%)  2/183 (1.09%)  1/182 (0.55%) 
Urticaria  1  2/184 (1.09%)  1/183 (0.55%)  0/182 (0.00%) 
Alopecia  1  1/184 (0.54%)  0/183 (0.00%)  1/182 (0.55%) 
Dermatitis allergic  1  2/184 (1.09%)  0/183 (0.00%)  0/182 (0.00%) 
Photosensitivity reaction  1  0/184 (0.00%)  0/183 (0.00%)  2/182 (1.10%) 
Pruritus allergic  1  1/184 (0.54%)  1/183 (0.55%)  0/182 (0.00%) 
Pruritus generalised  1  1/184 (0.54%)  0/183 (0.00%)  1/182 (0.55%) 
Rash macular  1  1/184 (0.54%)  1/183 (0.55%)  0/182 (0.00%) 
Chloasma  1  0/184 (0.00%)  1/183 (0.55%)  0/182 (0.00%) 
Cold sweat  1  1/184 (0.54%)  0/183 (0.00%)  0/182 (0.00%) 
Dermatitis acneiform  1  0/184 (0.00%)  0/183 (0.00%)  1/182 (0.55%) 
Drug eruption  1  1/184 (0.54%)  0/183 (0.00%)  0/182 (0.00%) 
Dry skin  1  0/184 (0.00%)  0/183 (0.00%)  1/182 (0.55%) 
Eczema  1  0/184 (0.00%)  0/183 (0.00%)  1/182 (0.55%) 
Erythema  1  0/184 (0.00%)  0/183 (0.00%)  1/182 (0.55%) 
Erythema nodosum  1  0/184 (0.00%)  0/183 (0.00%)  1/182 (0.55%) 
Macule  1  0/184 (0.00%)  1/183 (0.55%)  0/182 (0.00%) 
Rash generalised  1  1/184 (0.54%)  0/183 (0.00%)  0/182 (0.00%) 
Rash maculo-papular  1  0/184 (0.00%)  0/183 (0.00%)  1/182 (0.55%) 
Red man syndrome  1  1/184 (0.54%)  0/183 (0.00%)  0/182 (0.00%) 
Swelling face  1  0/184 (0.00%)  0/183 (0.00%)  1/182 (0.55%) 
Vascular disorders       
Hypertension  1  0/184 (0.00%)  2/183 (1.09%)  2/182 (1.10%) 
Flushing  1  0/184 (0.00%)  1/183 (0.55%)  1/182 (0.55%) 
Hot flush  1  0/184 (0.00%)  0/183 (0.00%)  2/182 (1.10%) 
Deep vein thrombosis  1  1/184 (0.54%)  0/183 (0.00%)  0/182 (0.00%) 
Hypotension  1  1/184 (0.54%)  0/183 (0.00%)  0/182 (0.00%) 
Poor venous access  1  0/184 (0.00%)  0/183 (0.00%)  1/182 (0.55%) 
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: NCT01807923    
Other Study ID Numbers: VX12-809-103
First Submitted: March 4, 2013
First Posted: March 8, 2013
Results First Submitted: August 1, 2015
Results First Posted: August 31, 2015
Last Update Posted: August 31, 2015