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DISCOVER: Study of Ivacaftor in Cystic Fibrosis Subjects Aged 12 Years and Older Homozygous for the F508del-CFTR Mutation

Sponsor
Vertex Pharmaceuticals Incorporated (Industry)
Overall Status
Terminated
CT.gov ID
NCT00953706
Collaborator
Cystic Fibrosis Foundation (Other)
140
Enrollment
34
Locations
2
Arms
44
Duration (Months)
4.1
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study was to evaluate the safety and efficacy of ivacaftor in participants with cystic fibrosis (CF) who were aged 12 years or older and were homozygous for the F508del-CF transmembrane conductance regulator (CFTR) mutation. Ivacaftor is a potent and selective CFTR potentiator of wild-type, G551D, F508del, and R117H forms of human CFTR protein. Potentiators are pharmacological agents that increase the chloride ion transport properties of the channel in the presence of cyclic adenosine monophosphate (AMP)-dependent protein kinase A (PKA) activation.

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

This study investigated the effects of ivacaftor in participants with cystic fibrosis (CF)

=12 years of age with a forced expiratory volume in 1 second (FEV1) >=40 percent (%) predicted. This study was conducted in 2 parts.

  • Part A of this study was a randomized, double-blind, placebo-controlled, parallel-group evaluation of participants with CF who were aged 12 years or older and were homozygous for the F508del-CFTR mutation.

  • Part B of this study was an open-label extension of Part A, enrolling participants who completed Part A and met pre-specified endpoint criteria, and explored the safety and efficacy of ivacaftor over long-term treatment in participants with CF aged 12 years or older who were homozygous for the F508del-CFTR mutation.

Study Design

Study Type:
Interventional
Actual Enrollment :
140 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Safety and Efficacy of VX-770 in Subjects Aged 12 Years and Older With Cystic Fibrosis Who Are Homozygous for the F508del-CFTR Mutation
Study Start Date :
Sep 1, 2009
Actual Primary Completion Date :
Jul 1, 2010
Actual Study Completion Date :
May 1, 2013

Arms and Interventions

Arm Intervention/Treatment
Placebo Comparator: Placebo

Placebo matched to ivacaftor tablet orally every 12 hours (q12h) for 16 weeks during Part A (double-blind treatment period), followed by ivacaftor 150 mg tablet orally q12h for 96 weeks during Part B (open-label extension period).

Drug: Ivacaftor
Tablet
Other Names:
  • VX-770

    • Drug: Placebo
    Tablet
    Experimental: Ivacaftor

    Ivacaftor 150 milligram (mg) tablet orally q12h for 16 weeks during Part A (double-blind treatment period), followed by ivacaftor 150 mg tablet orally q12h for 96 weeks during Part B (open-label extension period).

    Drug: Ivacaftor
    Tablet
    Other Names:
  • VX-770

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Part A : Absolute Change From Part A Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) Through Week 16 [Part A baseline through Week 16]

      Spirometry (as measured by ppFEV1) is a standardized assessment to evaluate lung function that is the most widely used endpoint in cystic fibrosis studies. FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. ppFEV1 (predicted for age, gender, and height) was calculated using the Knudson method.

    Secondary Outcome Measures

    1. Part A : Absolute Change From Part A Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score Through Week 16 [Part A baseline through Week 16]

      The CFQ-R is a validated patient-reported outcome measuring health-related quality of life for participants with cystic fibrosis. Respiratory domain assessed respiratory symptoms (for example, coughing, congestion, wheezing), score range: 0-100; Higher scores indicating fewer symptoms and better health-related quality of life.

    2. Part A : Absolute Change From Part A Baseline in Sweat Chloride Concentration Through Week 16 [Part A baseline through Week 16]

      The sweat chloride (quantitative pilocarpine iontophoresis) test is a standard diagnostic tool for cystic fibrosis (CF), serving as an indicator of cystic fibrosis transmembrane conductance regulator (CFTR) activity.

    3. Part A : Rate of Change From Baseline in Weight Through Week 16 [Part A baseline through Week 16]

      As malnutrition is common in participants with cystic fibrosis (CF) because of increased energy expenditures due to lung disease and fat malabsorption, body weight is an important clinical measure of nutritional status.

    4. Part B : Absolute Change From Part A and Part B Baseline in ppFEV1 Through Week 64 [Change from Part A baseline: Part A Baseline, Week 64; Change from Part B baseline: Part B Baseline (Week 16), Week 64]

      ppFEV1 is defined in Outcome Measure 1.

    5. Part B : Rate of Change From Part A Baseline in ppFEV1 Through Week 64 [Part A baseline through Week 64]

      ppFEV1 is defined in Outcome Measure 1.

    6. Part B : Rate of Change From Part B Baseline in ppFEV1 Through Week 64 [Part B baseline through Week 64]

      ppFEV1 is defined in Outcome Measure 1.

    7. Part B : Absolute Change From Part A and Part B Baseline in CFQ-R Respiratory Domain Score Through Week 64 [Change from Part A baseline: Part A Baseline, Week 64; Change from Part B baseline: Part B Baseline (Week 16), Week 64]

      The CFQ-R is a validated patient-reported outcome measuring health-related quality of life for participants with cystic fibrosis. Respiratory domain assessed respiratory symptoms (for example, coughing, congestion, wheezing), score range: 0-100; Higher scores indicating fewer symptoms and better health-related quality of life.

    8. Part B : Absolute Change From Part A and Part B Baseline in Sweat Chloride Concentration Through Week 64 [Change from Part A baseline: Part A Baseline, Week 64; Change from Part B baseline: Part B Baseline (Week 16), Week 64]

      The sweat chloride (quantitative pilocarpine iontophoresis) test is a standard diagnostic tool for cystic fibrosis (CF), serving as an indicator of cystic fibrosis transmembrane conductance regulator (CFTR) activity.

    9. Part B : Absolute Change From Part A and Part B Baseline in Weight Through Week 64 [Change from Part A baseline: Part A Baseline, Week 64; Change from Part B baseline: Part B Baseline (Week 16), Week 64]

      As malnutrition is common in patients with cystic fibrosis (CF) because of increased energy expenditures due to lung disease and fat malabsorption, body weight is an important clinical measure of nutritional status.

    10. Part B : Number of Participants With Pulmonary Exacerbations [Part B baseline through Week 64]

      Pulmonary exacerbation was defined as new, or changed, antibiotic therapy (intravenous, inhaled, or oral) for any 4 or more of the following signs/symptoms: change in sputum; new or increased hemoptysis; increased cough; increased dyspnea; malaise, fatigue, or lethargy; temperature above 38 degrees Celsius; anorexia or weight loss; sinus pain or tenderness; change in sinus discharge; change in physical examination of the chest; decrease in pulmonary function by 10 percent (%); and radiographic changes indicative of pulmonary infection.

    11. Part B : Number of Pulmonary Exacerbation Events [Part B baseline through Week 64]

      Pulmonary exacerbation was defined as new, or changed, antibiotic therapy (intravenous, inhaled, or oral) for any 4 or more of the following signs/symptoms: change in sputum; new or increased hemoptysis; increased cough; increased dyspnea; malaise, fatigue, or lethargy; temperature above 38 degrees Celsius; anorexia or weight loss; sinus pain or tenderness; change in sinus discharge; change in physical examination of the chest; decrease in pulmonary function by 10 percent (%); and radiographic changes indicative of pulmonary infection.

    12. Part B : Number of Pulmonary Exacerbation Events Per Participant Per Year [Part B baseline through Week 64]

      Pulmonary exacerbation was defined as new, or changed, antibiotic therapy (intravenous, inhaled, or oral) for any 4 or more of the following signs/symptoms: change in sputum; new or increased hemoptysis; increased cough; increased dyspnea; malaise, fatigue, or lethargy; temperature above 38 degrees Celsius; anorexia or weight loss; sinus pain or tenderness; change in sinus discharge; change in physical examination of the chest; decrease in pulmonary function by 10 percent (%); and radiographic changes indicative of pulmonary infection.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    12 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Confirmed diagnosis of cystic fibrosis (CF) and homozygous for F508del-CFTR mutation

    • Forced expiratory volume in 1 second (FEV1) of at least 40% of predicted normal for age, gender, and height

    • Willing to use at least 2 highly effective birth control methods during the study

    • No clinically significant abnormalities that would have interfered with the study assessments, as judged by the investigator

    • Able to understand and comply with protocol requirements, restrictions, and instructions and likely to complete the study as planned, as judged by the investigator

    Exclusion Criteria:

    • History of any illness or condition that might confound the results of the study or pose an additional risk in administering study drug to the subject

    • Acute respiratory infection, pulmonary exacerbation, or changes in therapy for pulmonary disease within 4 weeks of Day 1 of the study

    • History of alcohol, medication or illicit drug abuse within one year prior to Day 1

    • Abnormal liver function >=3 x the upper limit of normal

    • Abnormal renal function at Screening

    • History of solid organ or hematological transplantation

    • Pregnant or breast-feeding (for women)

    • Ongoing participation in another therapeutic clinical study or prior participation in an investigational drug study within 30 days prior to screening

    • Previous participation in a VX-809 study

    • Used inhaled hypertonic saline treatment

    • Concomitant use of any inhibitors or inducers of cytochrome P450 3A4 (CYP3A4)

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of Alabama Birmingham Alabama United States 35294
    2 Providence Medical Center Anchorage Alaska United States 99508
    3 Kaiser Permanente Medical Care Program Oakland California United States 94611
    4 Connecticut Children's Medical Center Hartford Connecticut United States 06106
    5 University of Miami Miller School of Medicine Miami Florida United States 33136
    6 Nemours Children's Clinic Orlando Florida United States 32801
    7 St. Luke's CF clinic Boise Idaho United States 83712
    8 University of Chicago Chicago Illinois United States 60637
    9 Riley Hospital for Children Indianapolis Indiana United States 46202
    10 Maine Medical Center Portland Maine United States 04102
    11 Massachusetts General Hospital Boston Massachusetts United States 02114
    12 University of Massachussetts Medical School Worcester Massachusetts United States 01655
    13 Helen DeVos Children's Hospital; Spectrum Health Hospitals Grand Rapids Michigan United States 49503
    14 The Children's Mercy Hospital Kansas City Missouri United States 64108
    15 Dartmouth-Hitchcock Medical Center Lebanon New Hampshire United States 03756
    16 Monmouth Medical Center Long Branch New Jersey United States 07740
    17 Morristown Memorial Hospital Morristown New Jersey United States 07962
    18 Albany Medical College Albany New York United States 12208
    19 Women and Children's Hospital of Buffalo Buffalo New York United States 14222
    20 New York Medical College Hawthorne New York United States 10532
    21 The CF Center, Beth Israel Medical Center New York City New York United States 10003
    22 Columbia University Medical Center New York New York United States 10032
    23 Akron Children's Hospital Akron Ohio United States 44308
    24 Cincinnati Children's Hospital Cincinnati Ohio United States 45229
    25 Toldedo Children's Hospital Toledo Ohio United States 43606
    26 University of Oklahoma Health Sciences Center Oklahoma City Oklahoma United States 73104
    27 Hershey Medical Center Hershey Pennsylvania United States 17033
    28 St. Christopher's Hospital for Children Philadelphia Pennsylvania United States 19134
    29 Medical University of South Carolina Charleston South Carolina United States 29425
    30 University of Tennessee Memphis Tennessee United States 38103
    31 Cook Children's Medical Center Fort Worth Texas United States 76104
    32 Univeristy of Utah Salt Lake City Utah United States 84132
    33 Vermont Lung Center at the University of Vermont Colchester Vermont United States 05446
    34 Medical College of Virginia Richmond Virginia United States 23298

    Sponsors and Collaborators

    • Vertex Pharmaceuticals Incorporated
    • Cystic Fibrosis Foundation

    Investigators

    • Principal Investigator: Patrick A Flume, MD, Medical University of South Carolina

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Vertex Pharmaceuticals Incorporated
    ClinicalTrials.gov Identifier:
    NCT00953706
    Other Study ID Numbers:
    • VX08-770-104
    • 2009-010261-23
    First Posted:
    Aug 6, 2009
    Last Update Posted:
    Sep 11, 2015
    Last Verified:
    Aug 1, 2015
    Keywords provided by Vertex Pharmaceuticals Incorporated
    Fibrosis
    Pancreatic Diseases
    Digestive System Diseases
    Lung Diseases
    Respiratory Tract Diseases
    Genetic Diseases, Inborn
    Infant, Newborn, Diseases
    Pathologic Processes
    Additional relevant MeSH terms:
    Cystic Fibrosis
    Fibrosis
    Ivacaftor

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Placebo - Part A Ivacaftor - Part A Placebo/Ivacaftor - Part B Ivacaftor/Ivacaftor - Part B
    Arm/Group Description Placebo matched to ivacaftor tablet orally every 12 hours (q12h) for 16 weeks during Part A (double-blind treatment period). Ivacaftor 150 milligram (mg) tablet orally q12h for 16 weeks during Part A (double-blind treatment period). Participants who received placebo during Part A, received ivacaftor 150 mg tablet orally q12h for 96 weeks during Part B (open-label extension period). Participants who received ivacaftor during Part A, received ivacaftor 150 mg tablet orally q12h for 96 weeks during Part B (open-label extension period).
    Period Title: Part A (16-Week Double-Blind Treatment)
    STARTED 28 112 0 0
    COMPLETED 26 104 0 0
    NOT COMPLETED 2 8 0 0
    Period Title: Part A (16-Week Double-Blind Treatment)
    STARTED 0 0 5 33
    COMPLETED 0 0 0 0
    NOT COMPLETED 0 0 5 33

    Baseline Characteristics

    Arm/Group Title Placebo - Part A Ivacaftor - Part A Total
    Arm/Group Description Placebo matched to ivacaftor tablet orally every 12 hours (q12h) for 16 weeks during Part A (double-blind treatment period). Ivacaftor 150 milligram (mg) tablet orally q12h for 16 weeks during Part A (double-blind treatment period). Total of all reporting groups
    Overall Participants 28 112 140
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    25.0
    (8.35)
    22.8
    (10.26)
    23.2
    (9.91)
    Age, Customized (participants) [Number]
    12 to 17 Years
    6
    21.4%
    44
    39.3%
    50
    35.7%
    18 to 24 Years
    10
    35.7%
    32
    28.6%
    42
    30%
    25 to 39 Years
    12
    42.9%
    26
    23.2%
    38
    27.1%
    40 to 45 Years
    0
    0%
    5
    4.5%
    5
    3.6%
    > 45 Years
    0
    0%
    5
    4.5%
    5
    3.6%
    Sex: Female, Male (Count of Participants)
    Female
    12
    42.9%
    54
    48.2%
    66
    47.1%
    Male
    16
    57.1%
    58
    51.8%
    74
    52.9%
    Race/Ethnicity, Customized (participants) [Number]
    Hispanic or Latino
    1
    3.6%
    2
    1.8%
    3
    2.1%
    Not Hispanic or Latino
    27
    96.4%
    110
    98.2%
    137
    97.9%
    Race/Ethnicity, Customized (participants) [Number]
    Black or African American
    0
    0%
    1
    0.9%
    1
    0.7%
    White
    28
    100%
    111
    99.1%
    139
    99.3%
    Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1), Continuous (percent predicted of FEV1) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [percent predicted of FEV1]
    74.8
    (24.06)
    79.7
    (22.67)
    78.7
    (22.95)
    ppFEV1, Categorical (participants) [Number]
    < 70%
    15
    53.6%
    38
    33.9%
    53
    37.9%
    ≥ 70% to ≤ 90%
    5
    17.9%
    35
    31.3%
    40
    28.6%
    > 90%
    8
    28.6%
    39
    34.8%
    47
    33.6%
    Weight (kilograms) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [kilograms]
    63.2
    (14.96)
    58.2
    (13.49)
    59.2
    (13.89)
    Body Mass Index (kilogram per square meter) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [kilogram per square meter]
    22.2
    (4.48)
    21.2
    (3.25)
    21.4
    (3.54)
    Sweat Chloride (millimoles per liter) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [millimoles per liter]
    102.4
    (7.91)
    101.4
    (10.28)
    101.6
    (9.83)

    Outcome Measures

    1. Primary Outcome
    Title Part A : Absolute Change From Part A Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) Through Week 16
    Description Spirometry (as measured by ppFEV1) is a standardized assessment to evaluate lung function that is the most widely used endpoint in cystic fibrosis studies. FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. ppFEV1 (predicted for age, gender, and height) was calculated using the Knudson method.
    Time Frame Part A baseline through Week 16

    Outcome Measure Data

    Analysis Population Description
    Part A Full Analysis Set (FAS) included all randomized participants who received at least 1 dose of study drug during Part A. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure.
    Arm/Group Title Placebo - Part A Ivacaftor - Part A
    Arm/Group Description Placebo matched to ivacaftor tablet orally q12h for 16 weeks during Part A (double-blind treatment period). Ivacaftor 150 mg tablet orally q12h for 16 weeks during Part A (double-blind treatment period).
    Measure Participants 28 111
    Least Squares Mean (Standard Error) [percent predicted of FEV1]
    -0.2
    (1.1)
    1.5
    (0.5)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo - Part A, Ivacaftor - Part A
    Comments The primary analysis for the primary efficacy variable was based on a Mixed-Effects Model for Repeated Measures (MMRM). The model included absolute change from baseline in percent predicted forced expiratory volume in 1 second (FEV1) as the dependent variable, treatment (ivacaftor versus placebo) and visit as fixed effects, and participant as a random effect, with adjustment for age and continuous baseline value of percent predicted FEV1.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.1509
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 1.7
    Confidence Interval (2-Sided) 95%
    -0.6 to 4.1
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.2
    Estimation Comments
    2. Secondary Outcome
    Title Part A : Absolute Change From Part A Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score Through Week 16
    Description The CFQ-R is a validated patient-reported outcome measuring health-related quality of life for participants with cystic fibrosis. Respiratory domain assessed respiratory symptoms (for example, coughing, congestion, wheezing), score range: 0-100; Higher scores indicating fewer symptoms and better health-related quality of life.
    Time Frame Part A baseline through Week 16

    Outcome Measure Data

    Analysis Population Description
    Part A FAS. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure.
    Arm/Group Title Placebo - Part A Ivacaftor - Part A
    Arm/Group Description Placebo matched to ivacaftor tablet orally q12h for 16 weeks during Part A (double-blind treatment period). Ivacaftor 150 mg tablet orally q12h for 16 weeks during Part A (double-blind treatment period).
    Measure Participants 28 111
    Least Squares Mean (Standard Error) [units on a scale]
    -1.4
    (1.9)
    -0.1
    (1.0)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo - Part A, Ivacaftor - Part A
    Comments Analysis for the respiratory domain score endpoint was similar to that of the primary analysis of the primary efficacy endpoint. Estimates were from Mixed-Effects Model for Repeated Measures (MMRM) with the dependent variable being absolute change from baseline, fixed effects for categorical visit and treatment group, and adjustment for for age and baseline value for CFQ-R score, using unstructured covariance matrix
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.5408
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 1.3
    Confidence Interval (2-Sided) 95%
    -2.9 to 5.6
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.1
    Estimation Comments
    3. Secondary Outcome
    Title Part A : Absolute Change From Part A Baseline in Sweat Chloride Concentration Through Week 16
    Description The sweat chloride (quantitative pilocarpine iontophoresis) test is a standard diagnostic tool for cystic fibrosis (CF), serving as an indicator of cystic fibrosis transmembrane conductance regulator (CFTR) activity.
    Time Frame Part A baseline through Week 16

    Outcome Measure Data

    Analysis Population Description
    Part A FAS. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure.
    Arm/Group Title Placebo - Part A Ivacaftor - Part A
    Arm/Group Description Placebo matched to ivacaftor tablet orally q12h for 16 weeks during Part A (double-blind treatment period). Ivacaftor 150 mg tablet orally q12h for 16 weeks during Part A (double-blind treatment period).
    Measure Participants 28 111
    Least Squares Mean (Standard Error) [millimole per liter (mmol/L)]
    0.1
    (1.2)
    -2.7
    (0.6)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo - Part A, Ivacaftor - Part A
    Comments Analysis for this variable was similar to that of the primary analysis of the primary efficacy endpoint. Estimates were from Mixed-Effects Model for Repeated Measures (MMRM) with dependent variable being absolute change from baseline, fixed effects for categorical visit and treatment group, and adjustment for continuous age and baseline value for age, sweat chloride, using unstructured covariance matrix.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0384
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -2.9
    Confidence Interval (2-Sided) 95%
    -5.6 to -0.2
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.4
    Estimation Comments
    4. Secondary Outcome
    Title Part A : Rate of Change From Baseline in Weight Through Week 16
    Description As malnutrition is common in participants with cystic fibrosis (CF) because of increased energy expenditures due to lung disease and fat malabsorption, body weight is an important clinical measure of nutritional status.
    Time Frame Part A baseline through Week 16

    Outcome Measure Data

    Analysis Population Description
    Part A FAS. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure.
    Arm/Group Title Placebo - Part A Ivacaftor - Part A
    Arm/Group Description Placebo matched to ivacaftor tablet orally q12h for 16 weeks during Part A (double-blind treatment period). Ivacaftor 150 mg tablet orally q12h for 16 weeks during Part A (double-blind treatment period).
    Measure Participants 28 112
    Least Squares Mean (Standard Error) [kilograms per 112 days]
    0.9
    (0.4)
    0.8
    (0.2)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo - Part A, Ivacaftor - Part A
    Comments The analysis used the linear mixed model with treatment as fixed effects, visit (days on study) and treatment by visit interaction as random effects, with adjustment for age group (< 18 years and ≥ 18 years) and percent predicted forced expiratory volume (FEV1) severity (< 70%, ≥ 70% to ≤ 90%, > 90%) at screening, with random intercept and random slope. Rate of change in the study period is the slope of weight versus time (days) multiplied by the number of days in the study period (112 days).
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.7265
    Comments
    Method Mixed Models Analysis
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.2
    Confidence Interval (2-Sided) 95%
    -1.1 to 0.7
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.5
    Estimation Comments
    5. Secondary Outcome
    Title Part B : Absolute Change From Part A and Part B Baseline in ppFEV1 Through Week 64
    Description ppFEV1 is defined in Outcome Measure 1.
    Time Frame Change from Part A baseline: Part A Baseline, Week 64; Change from Part B baseline: Part B Baseline (Week 16), Week 64

    Outcome Measure Data

    Analysis Population Description
    Part B FAS included all participants who received at least 1 dose of study drug during Part B. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure.
    Arm/Group Title Placebo/Ivacaftor - Part B Ivacaftor/Ivacaftor - Part B
    Arm/Group Description Participants who received placebo during Part A, received ivacaftor 150 mg tablet orally q12h for 96 weeks during Part B (open-label extension period). Participants who received ivacaftor during Part A, received ivacaftor 150 mg tablet orally q12h for 96 weeks during Part B (open-label extension period).
    Measure Participants 4 27
    Change From Part A Baseline at Week 64
    8.9398
    (9.70300)
    2.7233
    (10.52046)
    Change From Part B Baseline at Week 64
    3.5593
    (7.95875)
    -5.0565
    (11.44783)
    6. Secondary Outcome
    Title Part B : Rate of Change From Part A Baseline in ppFEV1 Through Week 64
    Description ppFEV1 is defined in Outcome Measure 1.
    Time Frame Part A baseline through Week 64

    Outcome Measure Data

    Analysis Population Description
    Part B FAS.
    Arm/Group Title Placebo/Ivacaftor - Part B Ivacaftor/Ivacaftor - Part B
    Arm/Group Description Participants who received placebo during Part A, received ivacaftor 150 mg tablet orally q12h for 96 weeks during Part B (open-label extension period). Participants who received ivacaftor during Part A, received ivacaftor 150 mg tablet orally q12h for 96 weeks during Part B (open-label extension period).
    Measure Participants 5 33
    Least Squares Mean (Standard Error) [percent predicted of FEV1 per 448 days]
    5.7445
    (3.6810)
    -1.0738
    (1.5025)
    7. Secondary Outcome
    Title Part B : Rate of Change From Part B Baseline in ppFEV1 Through Week 64
    Description ppFEV1 is defined in Outcome Measure 1.
    Time Frame Part B baseline through Week 64

    Outcome Measure Data

    Analysis Population Description
    Part B FAS.
    Arm/Group Title Placebo/Ivacaftor - Part B Ivacaftor/Ivacaftor - Part B
    Arm/Group Description Participants who received placebo during Part A, received ivacaftor 150 mg tablet orally q12h for 96 weeks during Part B (open-label extension period). Participants who received ivacaftor during Part A, received ivacaftor 150 mg tablet orally q12h for 96 weeks during Part B (open-label extension period).
    Measure Participants 5 33
    Least Squares Mean (Standard Error) [percent predicted of FEV1 per 336 days]
    5.3409
    (4.5790)
    -5.2994
    (1.8871)
    8. Secondary Outcome
    Title Part B : Absolute Change From Part A and Part B Baseline in CFQ-R Respiratory Domain Score Through Week 64
    Description The CFQ-R is a validated patient-reported outcome measuring health-related quality of life for participants with cystic fibrosis. Respiratory domain assessed respiratory symptoms (for example, coughing, congestion, wheezing), score range: 0-100; Higher scores indicating fewer symptoms and better health-related quality of life.
    Time Frame Change from Part A baseline: Part A Baseline, Week 64; Change from Part B baseline: Part B Baseline (Week 16), Week 64

    Outcome Measure Data

    Analysis Population Description
    Part B FAS. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure.
    Arm/Group Title Placebo/Ivacaftor - Part B Ivacaftor/Ivacaftor - Part B
    Arm/Group Description Participants who received placebo during Part A, received ivacaftor 150 mg tablet orally q12h for 96 weeks during Part B (open-label extension period). Participants who received ivacaftor during Part A, received ivacaftor 150 mg tablet orally q12h for 96 weeks during Part B (open-label extension period).
    Measure Participants 4 26
    Change From Part A Baseline at Week 64
    2.10
    (11.443)
    1.50
    (15.778)
    Change From Part B Baseline at Week 64
    2.08
    (17.763)
    2.62
    (15.899)
    9. Secondary Outcome
    Title Part B : Absolute Change From Part A and Part B Baseline in Sweat Chloride Concentration Through Week 64
    Description The sweat chloride (quantitative pilocarpine iontophoresis) test is a standard diagnostic tool for cystic fibrosis (CF), serving as an indicator of cystic fibrosis transmembrane conductance regulator (CFTR) activity.
    Time Frame Change from Part A baseline: Part A Baseline, Week 64; Change from Part B baseline: Part B Baseline (Week 16), Week 64

    Outcome Measure Data

    Analysis Population Description
    Part B FAS. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure.
    Arm/Group Title Placebo/Ivacaftor - Part B Ivacaftor/Ivacaftor - Part B
    Arm/Group Description Participants who received placebo during Part A, received ivacaftor 150 mg tablet orally q12h for 96 weeks during Part B (open-label extension period). Participants who received ivacaftor during Part A, received ivacaftor 150 mg tablet orally q12h for 96 weeks during Part B (open-label extension period).
    Measure Participants 4 26
    Change From Part A Baseline at Week 64
    -7.13
    (15.612)
    -3.65
    (11.963)
    Change From Part B Baseline at Week 64
    -3.88
    (7.685)
    -2.44
    (11.037)
    10. Secondary Outcome
    Title Part B : Absolute Change From Part A and Part B Baseline in Weight Through Week 64
    Description As malnutrition is common in patients with cystic fibrosis (CF) because of increased energy expenditures due to lung disease and fat malabsorption, body weight is an important clinical measure of nutritional status.
    Time Frame Change from Part A baseline: Part A Baseline, Week 64; Change from Part B baseline: Part B Baseline (Week 16), Week 64

    Outcome Measure Data

    Analysis Population Description
    Part B FAS. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure.
    Arm/Group Title Placebo/Ivacaftor - Part B Ivacaftor/Ivacaftor - Part B
    Arm/Group Description Participants who received placebo during Part A, received ivacaftor 150 mg tablet orally q12h for 96 weeks during Part B (open-label extension period). Participants who received ivacaftor during Part A, received ivacaftor 150 mg tablet orally q12h for 96 weeks during Part B (open-label extension period).
    Measure Participants 4 27
    Change From Part A Baseline at Week 64
    3.00
    (3.550)
    2.35
    (5.600)
    Change From Part B Baseline at Week 64
    1.28
    (2.243)
    1.45
    (3.840)
    11. Secondary Outcome
    Title Part B : Number of Participants With Pulmonary Exacerbations
    Description Pulmonary exacerbation was defined as new, or changed, antibiotic therapy (intravenous, inhaled, or oral) for any 4 or more of the following signs/symptoms: change in sputum; new or increased hemoptysis; increased cough; increased dyspnea; malaise, fatigue, or lethargy; temperature above 38 degrees Celsius; anorexia or weight loss; sinus pain or tenderness; change in sinus discharge; change in physical examination of the chest; decrease in pulmonary function by 10 percent (%); and radiographic changes indicative of pulmonary infection.
    Time Frame Part B baseline through Week 64

    Outcome Measure Data

    Analysis Population Description
    Part B FAS.
    Arm/Group Title Placebo/Ivacaftor - Part B Ivacaftor/Ivacaftor - Part B
    Arm/Group Description Participants who received placebo during Part A, received ivacaftor 150 mg tablet orally q12h for 96 weeks during Part B (open-label extension period). Participants who received ivacaftor during Part A, received ivacaftor 150 mg tablet orally q12h for 96 weeks during Part B (open-label extension period).
    Measure Participants 5 33
    Number [participants]
    4
    14.3%
    16
    14.3%
    12. Secondary Outcome
    Title Part B : Number of Pulmonary Exacerbation Events
    Description Pulmonary exacerbation was defined as new, or changed, antibiotic therapy (intravenous, inhaled, or oral) for any 4 or more of the following signs/symptoms: change in sputum; new or increased hemoptysis; increased cough; increased dyspnea; malaise, fatigue, or lethargy; temperature above 38 degrees Celsius; anorexia or weight loss; sinus pain or tenderness; change in sinus discharge; change in physical examination of the chest; decrease in pulmonary function by 10 percent (%); and radiographic changes indicative of pulmonary infection.
    Time Frame Part B baseline through Week 64

    Outcome Measure Data

    Analysis Population Description
    Part B FAS.
    Arm/Group Title Placebo/Ivacaftor - Part B Ivacaftor/Ivacaftor - Part B
    Arm/Group Description Participants who received placebo during Part A, received ivacaftor 150 mg tablet orally q12h for 96 weeks during Part B (open-label extension period). Participants who received ivacaftor during Part A, received ivacaftor 150 mg tablet orally q12h for 96 weeks during Part B (open-label extension period).
    Measure Participants 5 33
    Number [events]
    6
    26
    13. Secondary Outcome
    Title Part B : Number of Pulmonary Exacerbation Events Per Participant Per Year
    Description Pulmonary exacerbation was defined as new, or changed, antibiotic therapy (intravenous, inhaled, or oral) for any 4 or more of the following signs/symptoms: change in sputum; new or increased hemoptysis; increased cough; increased dyspnea; malaise, fatigue, or lethargy; temperature above 38 degrees Celsius; anorexia or weight loss; sinus pain or tenderness; change in sinus discharge; change in physical examination of the chest; decrease in pulmonary function by 10 percent (%); and radiographic changes indicative of pulmonary infection.
    Time Frame Part B baseline through Week 64

    Outcome Measure Data

    Analysis Population Description
    Part B FAS.
    Arm/Group Title Placebo/Ivacaftor - Part B Ivacaftor/Ivacaftor - Part B
    Arm/Group Description Participants who received placebo during Part A, received ivacaftor 150 mg tablet orally q12h for 96 weeks during Part B (open-label extension period). Participants who received ivacaftor during Part A, received ivacaftor 150 mg tablet orally q12h for 96 weeks during Part B (open-label extension period).
    Measure Participants 5 33
    Number [events per participant per year]
    1.10
    0.82

    Adverse Events

    Time Frame Adverse events (serious and non-serious) were collected from signing of informed consent through 2 years after last dose (in Part B) of study drug (median treatment duration: 112 days for Part A and 381 days for Part B)
    Adverse Event Reporting Description
    Arm/Group Title Placebo - Part A Ivacaftor - Part A Placebo/Ivacaftor - Part B Ivacaftor/Ivacaftor - Part B
    Arm/Group Description Placebo matched to ivacaftor tablet orally q12h for 16 weeks during Part A (double-blind treatment period). Ivacaftor 150 milligram (mg) tablet orally q12h for 16 weeks during Part A (double-blind treatment period). Participants who received placebo during Part A, received ivacaftor 150 mg tablet orally q12h for 96 weeks during Part B (open-label extension period). Participants who received ivacaftor during Part A, received ivacaftor 150 mg tablet orally q12h for 96 weeks during Part B (open-label extension period).
    All Cause Mortality
    Placebo - Part A Ivacaftor - Part A Placebo/Ivacaftor - Part B Ivacaftor/Ivacaftor - Part B
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Placebo - Part A Ivacaftor - Part A Placebo/Ivacaftor - Part B Ivacaftor/Ivacaftor - Part B
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 6/28 (21.4%) 15/112 (13.4%) 2/5 (40%) 14/33 (42.4%)
    Congenital, familial and genetic disorders
    Cystic fibrosis lung 5/28 (17.9%) 6 10/112 (8.9%) 12 2/5 (40%) 4 13/33 (39.4%) 20
    Gastrointestinal disorders
    Abdominal pain 0/28 (0%) 0 1/112 (0.9%) 2 0/5 (0%) 0 0/33 (0%) 0
    General disorders
    Fatigue 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 0/33 (0%) 0
    Infections and infestations
    Bronchopneumonia 1/28 (3.6%) 1 0/112 (0%) 0 0/5 (0%) 0 0/33 (0%) 0
    Central line infection 0/28 (0%) 0 0/112 (0%) 0 0/5 (0%) 0 1/33 (3%) 1
    Lung infection 0/28 (0%) 0 0/112 (0%) 0 0/5 (0%) 0 1/33 (3%) 1
    Injury, poisoning and procedural complications
    Ankle fracture 0/28 (0%) 0 0/112 (0%) 0 0/5 (0%) 0 1/33 (3%) 1
    Pelvic fracture 0/28 (0%) 0 0/112 (0%) 0 0/5 (0%) 0 1/33 (3%) 1
    Traumatic brain injury 0/28 (0%) 0 0/112 (0%) 0 0/5 (0%) 0 1/33 (3%) 1
    Musculoskeletal and connective tissue disorders
    Myopathy 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 0/33 (0%) 0
    Nervous system disorders
    Cognitive disorder 1/28 (3.6%) 1 0/112 (0%) 0 0/5 (0%) 0 0/33 (0%) 0
    Psychiatric disorders
    Anxiety 0/28 (0%) 0 0/112 (0%) 0 0/5 (0%) 0 1/33 (3%) 1
    Depression 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 1/33 (3%) 1
    Suicidal ideation 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 0/33 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Haemoptysis 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 1/33 (3%) 3
    Hypoxia 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 0/33 (0%) 0
    Nasal polyps 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 0/33 (0%) 0
    Vascular disorders
    Venous thrombosis 1/28 (3.6%) 1 0/112 (0%) 0 0/5 (0%) 0 0/33 (0%) 0
    Other (Not Including Serious) Adverse Events
    Placebo - Part A Ivacaftor - Part A Placebo/Ivacaftor - Part B Ivacaftor/Ivacaftor - Part B
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 25/28 (89.3%) 98/112 (87.5%) 5/5 (100%) 30/33 (90.9%)
    Blood and lymphatic system disorders
    Anaemia 0/28 (0%) 0 3/112 (2.7%) 3 0/5 (0%) 0 1/33 (3%) 1
    Lymphadenopathy 0/28 (0%) 0 3/112 (2.7%) 3 0/5 (0%) 0 0/33 (0%) 0
    Cardiac disorders
    Supraventricular Extrasystoles 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 0/33 (0%) 0
    Congenital, familial and genetic disorders
    Cystic fibrosis lung 7/28 (25%) 8 19/112 (17%) 24 3/5 (60%) 6 11/33 (33.3%) 17
    Cystic Fibrosis Related Diabetes 0/28 (0%) 0 0/112 (0%) 0 0/5 (0%) 0 2/33 (6.1%) 2
    Ear and labyrinth disorders
    Middle Ear Effusion 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 0/33 (0%) 0
    Tinnitus 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 0/33 (0%) 0
    Eye disorders
    Conjunctivitis 0/28 (0%) 0 3/112 (2.7%) 3 0/5 (0%) 0 0/33 (0%) 0
    Lacrimation Increased 1/28 (3.6%) 1 1/112 (0.9%) 1 0/5 (0%) 0 0/33 (0%) 0
    Conjunctivitis Allergic 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 0/33 (0%) 0
    Eye Pruritus 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 0/33 (0%) 0
    Eyelid Oedema 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 0/33 (0%) 0
    Visual Impairment 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 0/33 (0%) 0
    Erythema Of Eyelid 0/28 (0%) 0 0/112 (0%) 0 0/5 (0%) 0 1/33 (3%) 1
    Gastrointestinal disorders
    Abdominal pain upper 1/28 (3.6%) 4 7/112 (6.3%) 8 0/5 (0%) 0 2/33 (6.1%) 3
    Diarrhoea 2/28 (7.1%) 2 6/112 (5.4%) 7 0/5 (0%) 0 1/33 (3%) 1
    Nausea 1/28 (3.6%) 1 10/112 (8.9%) 11 0/5 (0%) 0 3/33 (9.1%) 3
    Abdominal pain 1/28 (3.6%) 1 4/112 (3.6%) 5 3/5 (60%) 3 2/33 (6.1%) 2
    Vomiting 0/28 (0%) 0 4/112 (3.6%) 4 0/5 (0%) 0 0/33 (0%) 0
    Flatulence 0/28 (0%) 0 2/112 (1.8%) 2 0/5 (0%) 0 0/33 (0%) 0
    Abdominal discomfort 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 0/33 (0%) 0
    Aphthous stomatitis 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 0/33 (0%) 0
    Ascites 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 0/33 (0%) 0
    Constipation 0/28 (0%) 0 1/112 (0.9%) 1 1/5 (20%) 1 1/33 (3%) 2
    Dental Caries 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 0/33 (0%) 0
    Distal Ileal Obstruction Syndrome 0/28 (0%) 0 1/112 (0.9%) 2 0/5 (0%) 0 0/33 (0%) 0
    Dry Mouth 1/28 (3.6%) 1 0/112 (0%) 0 0/5 (0%) 0 0/33 (0%) 0
    Dyspepsia 1/28 (3.6%) 1 0/112 (0%) 0 0/5 (0%) 0 0/33 (0%) 0
    Frequent Bowel Movements 0/28 (0%) 0 1/112 (0.9%) 2 0/5 (0%) 0 0/33 (0%) 0
    Gastrointestinal Hypomotility 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 0/33 (0%) 0
    Gastrooesophageal Reflux Disease 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 1/33 (3%) 1
    Hiatus Hernia 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 1/33 (3%) 1
    Pancreatic Duct Dilatation 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 0/33 (0%) 0
    Peptic Ulcer 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 0/33 (0%) 0
    Regurgitation 1/28 (3.6%) 1 0/112 (0%) 0 0/5 (0%) 0 0/33 (0%) 0
    Tooth Impacted 1/28 (3.6%) 1 0/112 (0%) 0 0/5 (0%) 0 0/33 (0%) 0
    Toothache 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 1/33 (3%) 1
    Distal Intestinal Obstruction Syndrome 0/28 (0%) 0 0/112 (0%) 0 0/5 (0%) 0 1/33 (3%) 1
    Sensitivity Of Teeth 0/28 (0%) 0 0/112 (0%) 0 0/5 (0%) 0 1/33 (3%) 1
    General disorders
    Chills 2/28 (7.1%) 2 0/112 (0%) 0 0/5 (0%) 0 0/33 (0%) 0
    Fatigue 3/28 (10.7%) 3 8/112 (7.1%) 8 0/5 (0%) 0 1/33 (3%) 1
    Pyrexia 2/28 (7.1%) 2 9/112 (8%) 10 0/5 (0%) 0 2/33 (6.1%) 3
    Catheter Site Pain 1/28 (3.6%) 1 2/112 (1.8%) 2 0/5 (0%) 0 2/33 (6.1%) 2
    Application Site Pruritus 0/28 (0%) 0 1/112 (0.9%) 2 0/5 (0%) 0 0/33 (0%) 0
    Application Site Rash 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 0/33 (0%) 0
    Asthenia 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 0/33 (0%) 0
    Chest Pain 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 0/33 (0%) 0
    Feeling Abnormal 1/28 (3.6%) 2 0/112 (0%) 0 0/5 (0%) 0 0/33 (0%) 0
    Generalised Oedema 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 0/33 (0%) 0
    Influenza Like Illness 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 0/33 (0%) 0
    Thirst 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 0/33 (0%) 0
    Vessel Puncture Site Pain 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 0/33 (0%) 0
    Catheter Related Complication 0/28 (0%) 0 0/112 (0%) 0 0/5 (0%) 0 1/33 (3%) 1
    Infusion Site Pain 0/28 (0%) 0 0/112 (0%) 0 0/5 (0%) 0 1/33 (3%) 1
    Oedema Peripheral 0/28 (0%) 0 0/112 (0%) 0 0/5 (0%) 0 1/33 (3%) 1
    Pain 0/28 (0%) 0 0/112 (0%) 0 0/5 (0%) 0 1/33 (3%) 1
    Hepatobiliary disorders
    Cholelithiasis 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 0/33 (0%) 0
    Hepatosplenomegaly 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 0/33 (0%) 0
    Immune system disorders
    Allergy to Animal 1/28 (3.6%) 1 0/112 (0%) 0 0/5 (0%) 0 1/33 (3%) 1
    Seasonal Allergy 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 1/33 (3%) 1
    Hypersensitivity 0/28 (0%) 0 0/112 (0%) 0 1/5 (20%) 1 0/33 (0%) 0
    Infections and infestations
    Acute sinusitis 1/28 (3.6%) 1 0/112 (0%) 0 0/5 (0%) 0 1/33 (3%) 1
    Bronchitis 0/28 (0%) 0 0/112 (0%) 0 0/5 (0%) 0 3/33 (9.1%) 4
    Candidiasis 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 1/33 (3%) 1
    Clostridium Difficile colitis 0/28 (0%) 0 1/112 (0.9%) 2 0/5 (0%) 0 0/33 (0%) 0
    Ear infection 1/28 (3.6%) 1 1/112 (0.9%) 1 0/5 (0%) 0 1/33 (3%) 1
    Folliculitis 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 0/33 (0%) 0
    Hordeolum 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 0/33 (0%) 0
    Influenza 1/28 (3.6%) 1 0/112 (0%) 0 0/5 (0%) 0 0/33 (0%) 0
    Kidney infection 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 0/33 (0%) 0
    Laryngitis 1/28 (3.6%) 1 1/112 (0.9%) 1 0/5 (0%) 0 0/33 (0%) 0
    Nasopharyngitis 0/28 (0%) 0 4/112 (3.6%) 5 0/5 (0%) 0 0/33 (0%) 0
    Oral candidiasis 1/28 (3.6%) 1 1/112 (0.9%) 1 0/5 (0%) 0 1/33 (3%) 1
    Oral herpes 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 0/33 (0%) 0
    Orchitis 1/28 (3.6%) 1 0/112 (0%) 0 0/5 (0%) 0 0/33 (0%) 0
    Otitis media 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 0/33 (0%) 0
    Pharyngitis 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 0/33 (0%) 0
    Pharyngitis streptococcal 1/28 (3.6%) 1 1/112 (0.9%) 1 0/5 (0%) 0 0/33 (0%) 0
    Pneumonia staphylococcal 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 0/33 (0%) 0
    Respiratory monilliasis 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 0/33 (0%) 0
    Respiratory tract infection 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 0/33 (0%) 0
    Respiratory tract infection viral 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 0/33 (0%) 0
    Rhinitis 0/28 (0%) 0 5/112 (4.5%) 5 0/5 (0%) 0 0/33 (0%) 0
    Sinusitis 1/28 (3.6%) 1 8/112 (7.1%) 9 1/5 (20%) 1 4/33 (12.1%) 5
    Stenotrophomonas infection 1/28 (3.6%) 1 0/112 (0%) 0 0/5 (0%) 0 0/33 (0%) 0
    Tinea infection 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 0/33 (0%) 0
    Tooth abscess 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 0/33 (0%) 0
    Upper respiratory tract infection 2/28 (7.1%) 2 11/112 (9.8%) 13 1/5 (20%) 1 1/33 (3%) 2
    Urinary tract infection 1/28 (3.6%) 1 0/112 (0%) 0 0/5 (0%) 0 0/33 (0%) 0
    Viral upper respiratory tract infection 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 1/33 (3%) 2
    Vulvovaginal mycotic infection 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 2/33 (6.1%) 3
    Bacterial disease carrier 0/28 (0%) 0 0/112 (0%) 0 0/5 (0%) 0 1/33 (3%) 1
    Body tinea 0/28 (0%) 0 0/112 (0%) 0 0/5 (0%) 0 1/33 (3%) 1
    Cystitis 0/28 (0%) 0 0/112 (0%) 0 0/5 (0%) 0 1/33 (3%) 1
    Helicobacter gastritis 0/28 (0%) 0 0/112 (0%) 0 1/5 (20%) 1 0/33 (0%) 0
    Infectious mononucleosis 0/28 (0%) 0 0/112 (0%) 0 0/5 (0%) 0 1/33 (3%) 1
    Otitis externa 0/28 (0%) 0 0/112 (0%) 0 0/5 (0%) 0 1/33 (3%) 1
    Pneumonia 0/28 (0%) 0 0/112 (0%) 0 0/5 (0%) 0 1/33 (3%) 1
    Vaginitis bacterial 0/28 (0%) 0 0/112 (0%) 0 0/5 (0%) 0 1/33 (3%) 1
    Vulvovaginal candidiasis 0/28 (0%) 0 0/112 (0%) 0 0/5 (0%) 0 1/33 (3%) 1
    Injury, poisoning and procedural complications
    Contusion 0/28 (0%) 0 2/112 (1.8%) 3 0/5 (0%) 0 1/33 (3%) 1
    Skin Laceration 0/28 (0%) 0 2/112 (1.8%) 2 0/5 (0%) 0 2/33 (6.1%) 2
    Foreign Body Trauma 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 0/33 (0%) 0
    Joint Injury 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 0/33 (0%) 0
    Joint Sprain 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 0/33 (0%) 0
    Muscle Strain 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 1/33 (3%) 1
    Procedural Pain 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 0/33 (0%) 0
    Procedural Site Reaction 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 0/33 (0%) 0
    Thermal Burn 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 1/33 (3%) 1
    Traumatic Brain Injury 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 0/33 (0%) 0
    Animal Bite 0/28 (0%) 0 0/112 (0%) 0 0/5 (0%) 0 2/33 (6.1%) 2
    Arthropod Sting 0/28 (0%) 0 0/112 (0%) 0 1/5 (20%) 1 0/33 (0%) 0
    Excoriation 0/28 (0%) 0 0/112 (0%) 0 0/5 (0%) 0 1/33 (3%) 1
    Head Injury 0/28 (0%) 0 0/112 (0%) 0 0/5 (0%) 0 1/33 (3%) 1
    Road Traffic Accident 0/28 (0%) 0 0/112 (0%) 0 0/5 (0%) 0 1/33 (3%) 1
    Sunburn 0/28 (0%) 0 0/112 (0%) 0 0/5 (0%) 0 1/33 (3%) 1
    Wound 0/28 (0%) 0 0/112 (0%) 0 1/5 (20%) 1 0/33 (0%) 0
    Investigations
    Alanine aminotransferase increased 2/28 (7.1%) 3 1/112 (0.9%) 1 0/5 (0%) 0 2/33 (6.1%) 2
    Aspartate aminotransferase increased 2/28 (7.1%) 3 1/112 (0.9%) 1 0/5 (0%) 0 1/33 (3%) 1
    C-reactive protein increased 1/28 (3.6%) 1 6/112 (5.4%) 6 0/5 (0%) 0 0/33 (0%) 0
    Pulmonary function test decreased 2/28 (7.1%) 2 3/112 (2.7%) 4 0/5 (0%) 0 1/33 (3%) 2
    Blood glucose increased 1/28 (3.6%) 1 5/112 (4.5%) 5 0/5 (0%) 0 1/33 (3%) 1
    Bacteria sputum identified 1/28 (3.6%) 1 3/112 (2.7%) 4 0/5 (0%) 0 1/33 (3%) 1
    Prothrombin time prolonged 1/28 (3.6%) 1 3/112 (2.7%) 3 0/5 (0%) 0 0/33 (0%) 0
    Gamma-glutamyl transferase increased 1/28 (3.6%) 1 2/112 (1.8%) 2 0/5 (0%) 0 0/33 (0%) 0
    Glucose urine present 0/28 (0%) 0 3/112 (2.7%) 4 0/5 (0%) 0 1/33 (3%) 1
    Hepatic enzyme increased 1/28 (3.6%) 1 2/112 (1.8%) 2 0/5 (0%) 0 0/33 (0%) 0
    Blood immunoglobulin G increased 0/28 (0%) 0 2/112 (1.8%) 2 0/5 (0%) 0 0/33 (0%) 0
    Breath sounds abnormal 0/28 (0%) 0 2/112 (1.8%) 2 0/5 (0%) 0 1/33 (3%) 1
    Forced expiratory volume decreased 0/28 (0%) 0 2/112 (1.8%) 2 1/5 (20%) 1 1/33 (3%) 1
    Vitamin D decreased 0/28 (0%) 0 2/112 (1.8%) 2 0/5 (0%) 0 0/33 (0%) 0
    White blood cell count increased 0/28 (0%) 0 2/112 (1.8%) 2 0/5 (0%) 0 0/33 (0%) 0
    Acivated partial thromboplastin time prolonged 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 1/33 (3%) 1
    Antibiotic level above therapeutic 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 0/33 (0%) 0
    Bacterial culture positive 0/28 (0%) 0 1/112 (0.9%) 2 0/5 (0%) 0 0/33 (0%) 0
    Blood alkaline phosphatase increased 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 0/33 (0%) 0
    Blood glucose decreased 0/28 (0%) 0 1/112 (0.9%) 2 0/5 (0%) 0 0/33 (0%) 0
    Blood lactate dehydrogenase increased 1/28 (3.6%) 2 0/112 (0%) 0 0/5 (0%) 0 0/33 (0%) 0
    Bone density decreased 1/28 (3.6%) 1 0/112 (0%) 0 0/5 (0%) 0 0/33 (0%) 0
    Liver function test abnormal 1/28 (3.6%) 1 0/112 (0%) 0 0/5 (0%) 0 1/33 (3%) 1
    Neutrophil count increased 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 0/33 (0%) 0
    Platelet count decreased 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 0/33 (0%) 0
    Sputum culture positive 0/28 (0%) 0 1/112 (0.9%) 2 0/5 (0%) 0 0/33 (0%) 0
    Weight decreased 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 0/33 (0%) 0
    White blood cell count decreased 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 0/33 (0%) 0
    International normalised ratio increased 0/28 (0%) 0 0/112 (0%) 0 0/5 (0%) 0 1/33 (3%) 2
    Oxygen saturation decreased 0/28 (0%) 0 0/112 (0%) 0 0/5 (0%) 0 1/33 (3%) 1
    Sputum abnormal 0/28 (0%) 0 0/112 (0%) 0 0/5 (0%) 0 1/33 (3%) 1
    Weight increased 0/28 (0%) 0 0/112 (0%) 0 0/5 (0%) 0 1/33 (3%) 1
    Metabolism and nutrition disorders
    Hyperglycaemia 1/28 (3.6%) 1 2/112 (1.8%) 2 0/5 (0%) 0 1/33 (3%) 1
    Hypoglycaemia 0/28 (0%) 0 3/112 (2.7%) 3 0/5 (0%) 0 2/33 (6.1%) 2
    Gout 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 0/33 (0%) 0
    Vitamin D Deficiency 0/28 (0%) 0 0/112 (0%) 0 1/5 (20%) 1 1/33 (3%) 1
    Glucose Tolerance Impaired 0/28 (0%) 0 0/112 (0%) 0 0/5 (0%) 0 1/33 (3%) 1
    Hypovitaminosis 0/28 (0%) 0 0/112 (0%) 0 0/5 (0%) 0 1/33 (3%) 1
    Musculoskeletal and connective tissue disorders
    Musculoskeletal chest pain 2/28 (7.1%) 2 3/112 (2.7%) 3 0/5 (0%) 0 3/33 (9.1%) 3
    Arthralgia 0/28 (0%) 0 3/112 (2.7%) 5 0/5 (0%) 0 4/33 (12.1%) 4
    Back Pain 1/28 (3.6%) 2 2/112 (1.8%) 2 0/5 (0%) 0 2/33 (6.1%) 3
    Pain In Extremity 0/28 (0%) 0 3/112 (2.7%) 3 0/5 (0%) 0 2/33 (6.1%) 3
    Joint Swelling 0/28 (0%) 0 2/112 (1.8%) 2 0/5 (0%) 0 0/33 (0%) 0
    Arthritis 0/28 (0%) 0 1/112 (0.9%) 2 0/5 (0%) 0 0/33 (0%) 0
    Bone Pain 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 0/33 (0%) 0
    Clubbing 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 2/33 (6.1%) 2
    Muscular Weakness 1/28 (3.6%) 1 0/112 (0%) 0 0/5 (0%) 0 0/33 (0%) 0
    Myopathy 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 0/33 (0%) 0
    Neck Pain 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 0/33 (0%) 0
    Myalgia 0/28 (0%) 0 0/112 (0%) 0 0/5 (0%) 0 3/33 (9.1%) 4
    Arthropathy 0/28 (0%) 0 0/112 (0%) 0 0/5 (0%) 0 1/33 (3%) 1
    Musculoskeletal Pain 0/28 (0%) 0 0/112 (0%) 0 0/5 (0%) 0 1/33 (3%) 1
    Synovial Cyst 0/28 (0%) 0 0/112 (0%) 0 0/5 (0%) 0 1/33 (3%) 1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Focal Nodular Hyperplasia 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 0/33 (0%) 0
    Skin Papilloma 0/28 (0%) 0 0/112 (0%) 0 0/5 (0%) 0 1/33 (3%) 1
    Nervous system disorders
    Dizziness 2/28 (7.1%) 2 2/112 (1.8%) 3 0/5 (0%) 0 0/33 (0%) 0
    Headache 2/28 (7.1%) 3 11/112 (9.8%) 17 0/5 (0%) 0 1/33 (3%) 1
    Sinus Headache 0/28 (0%) 0 2/112 (1.8%) 2 0/5 (0%) 0 0/33 (0%) 0
    Burning Sensation 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 0/33 (0%) 0
    Dysgeusia 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 0/33 (0%) 0
    Hyperaesthesia 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 0/33 (0%) 0
    Migraine 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 1/33 (3%) 1
    Paraesthesia 1/28 (3.6%) 1 0/112 (0%) 0 0/5 (0%) 0 0/33 (0%) 0
    Presyncope 1/28 (3.6%) 1 0/112 (0%) 0 0/5 (0%) 0 0/33 (0%) 0
    Somnolence 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 0/33 (0%) 0
    Syncope 1/28 (3.6%) 1 0/112 (0%) 0 0/5 (0%) 0 0/33 (0%) 0
    Psychiatric disorders
    Anxiety 2/28 (7.1%) 2 1/112 (0.9%) 1 1/5 (20%) 1 2/33 (6.1%) 2
    Abnormal Dreams 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 0/33 (0%) 0
    Depression 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 2/33 (6.1%) 3
    Hallucination 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 0/33 (0%) 0
    Insomnia 1/28 (3.6%) 1 0/112 (0%) 0 0/5 (0%) 0 0/33 (0%) 0
    Adjustment Disorder 0/28 (0%) 0 0/112 (0%) 0 0/5 (0%) 0 1/33 (3%) 1
    Renal and urinary disorders
    Calculus Bladder 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 0/33 (0%) 0
    Chromaturia 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 0/33 (0%) 0
    Haematuria 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 0/33 (0%) 0
    Nephrolithiasis 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 1/33 (3%) 1
    Proteinuria 1/28 (3.6%) 1 0/112 (0%) 0 0/5 (0%) 0 0/33 (0%) 0
    Renal Cyst 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 0/33 (0%) 0
    Renal Failure Acute 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 0/33 (0%) 0
    Urinary Retention 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 0/33 (0%) 0
    Reproductive system and breast disorders
    Breast Tenderness 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 0/33 (0%) 0
    Dysmenorrhoea 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 0/33 (0%) 0
    Prostatic Cyst 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 0/33 (0%) 0
    Testicular Pain 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 0/33 (0%) 0
    Testicular Swelling 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 0/33 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Asthma 1/28 (3.6%) 2 1/112 (0.9%) 1 0/5 (0%) 0 1/33 (3%) 1
    Bronchospasm 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 0/33 (0%) 0
    Cough 4/28 (14.3%) 5 34/112 (30.4%) 43 0/5 (0%) 0 15/33 (45.5%) 17
    Dysphonia 0/28 (0%) 0 0/112 (0%) 0 1/5 (20%) 1 0/33 (0%) 0
    Dyspnoea 0/28 (0%) 0 5/112 (4.5%) 5 1/5 (20%) 1 2/33 (6.1%) 2
    Epistaxis 1/28 (3.6%) 1 1/112 (0.9%) 1 0/5 (0%) 0 2/33 (6.1%) 2
    Haemoptysis 1/28 (3.6%) 1 5/112 (4.5%) 10 2/5 (40%) 3 2/33 (6.1%) 2
    Increased viscosity of bronchial secretion 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 0/33 (0%) 0
    Nasal congestion 2/28 (7.1%) 2 13/112 (11.6%) 14 0/5 (0%) 0 2/33 (6.1%) 2
    Nasal mucosal disorder 0/28 (0%) 0 3/112 (2.7%) 3 0/5 (0%) 0 1/33 (3%) 1
    Nasal oedema 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 0/33 (0%) 0
    Nasal polyps 1/28 (3.6%) 1 3/112 (2.7%) 3 0/5 (0%) 0 0/33 (0%) 0
    Oropharyngeal pain 3/28 (10.7%) 3 10/112 (8.9%) 12 0/5 (0%) 0 1/33 (3%) 1
    Paranasal sinus hypersecretion 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 0/33 (0%) 0
    Pharyngeal disorder 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 0/33 (0%) 0
    Pharyngeal erythema 1/28 (3.6%) 1 2/112 (1.8%) 2 0/5 (0%) 0 0/33 (0%) 0
    Pleuritic pain 1/28 (3.6%) 1 1/112 (0.9%) 1 0/5 (0%) 0 1/33 (3%) 1
    Postnasal drip 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 0/33 (0%) 0
    Productive cough 1/28 (3.6%) 1 9/112 (8%) 9 0/5 (0%) 0 4/33 (12.1%) 5
    Rales 1/28 (3.6%) 1 3/112 (2.7%) 4 0/5 (0%) 0 2/33 (6.1%) 2
    Respiration abnormal 0/28 (0%) 0 2/112 (1.8%) 2 1/5 (20%) 1 1/33 (3%) 1
    Respiratory tract congestion 1/28 (3.6%) 1 3/112 (2.7%) 4 0/5 (0%) 0 1/33 (3%) 1
    Rhinorrhoea 2/28 (7.1%) 2 4/112 (3.6%) 5 0/5 (0%) 0 1/33 (3%) 1
    Sinus congestion 1/28 (3.6%) 1 2/112 (1.8%) 2 0/5 (0%) 0 2/33 (6.1%) 2
    Sputum discoloured 0/28 (0%) 0 1/112 (0.9%) 2 0/5 (0%) 0 0/33 (0%) 0
    Tachypnoea 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 0/33 (0%) 0
    Throat irritation 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 0/33 (0%) 0
    Upper respiratory tract congestion 0/28 (0%) 0 0/112 (0%) 0 0/5 (0%) 0 1/33 (3%) 1
    Wheezing 0/28 (0%) 0 3/112 (2.7%) 3 0/5 (0%) 0 0/33 (0%) 0
    Skin and subcutaneous tissue disorders
    Dermatitis contact 0/28 (0%) 0 6/112 (5.4%) 9 0/5 (0%) 0 2/33 (6.1%) 2
    Rash 0/28 (0%) 0 9/112 (8%) 9 0/5 (0%) 0 1/33 (3%) 1
    Pruritus 0/28 (0%) 0 3/112 (2.7%) 3 0/5 (0%) 0 0/33 (0%) 0
    Rash Papular 0/28 (0%) 0 3/112 (2.7%) 3 0/5 (0%) 0 0/33 (0%) 0
    Rash Vesicular 0/28 (0%) 0 2/112 (1.8%) 3 0/5 (0%) 0 0/33 (0%) 0
    Blister 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 0/33 (0%) 0
    Hyperhidrosis 1/28 (3.6%) 1 0/112 (0%) 0 0/5 (0%) 0 1/33 (3%) 1
    Night Sweats 1/28 (3.6%) 1 0/112 (0%) 0 0/5 (0%) 0 0/33 (0%) 0
    Photodermatosis 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 0/33 (0%) 0
    Photosensitivity Reaction 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 1/33 (3%) 1
    Rash Macular 0/28 (0%) 0 1/112 (0.9%) 2 0/5 (0%) 0 2/33 (6.1%) 3
    Urticaria 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 0/33 (0%) 0
    Red Man Syndrome 0/28 (0%) 0 0/112 (0%) 0 1/5 (20%) 1 1/33 (3%) 1
    Surgical and medical procedures
    wisdom teeth removal 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 0/33 (0%) 0
    Vascular disorders
    Hypotension 0/28 (0%) 0 1/112 (0.9%) 1 0/5 (0%) 0 0/33 (0%) 0

    Limitations/Caveats

    In Part B, the treatment duration was 96 weeks; however, due to early study termination all analysis were performed up to Week 64, as planned.

    More Information

    Certain Agreements

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

    The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.

    Results Point of Contact

    Name/Title Medical Monitor
    Organization Vertex
    Phone 617-444-6777
    Email medicalinfo@vrtx.com
    Responsible Party:
    Vertex Pharmaceuticals Incorporated
    ClinicalTrials.gov Identifier:
    NCT00953706
    Other Study ID Numbers:
    • VX08-770-104
    • 2009-010261-23
    First Posted:
    Aug 6, 2009
    Last Update Posted:
    Sep 11, 2015
    Last Verified:
    Aug 1, 2015