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

This study has been terminated.
(Following review of results obtained from a pre-specified 6-month analysis of Part B data the study was terminated on the basis of futility.)
Sponsor:
Collaborator:
Cystic Fibrosis Foundation Therapeutics
Information provided by (Responsible Party):
Vertex Pharmaceuticals Incorporated
ClinicalTrials.gov Identifier:
NCT00953706
First received: August 4, 2009
Last updated: July 29, 2015
Last verified: July 2015
Results First Received: February 27, 2012  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Cystic Fibrosis
Interventions: Drug: Ivacaftor
Drug: Placebo

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Placebo – Part A Placebo matched to ivacaftor tablet orally every 12 hours (q12h) for 16 weeks during Part A (double-blind treatment period).
Ivacaftor – Part A Ivacaftor 150 milligram (mg) tablet orally q12h for 16 weeks during Part A (double-blind treatment period).
Placebo/Ivacaftor – Part B Participants who received placebo during Part A, received ivacaftor 150 mg tablet orally q12h for 96 weeks during Part B (open-label extension period).
Ivacaftor/Ivacaftor – Part B Participants who received ivacaftor during Part A, received ivacaftor 150 mg tablet orally q12h for 96 weeks during Part B (open-label extension period).

Participant Flow for 2 periods

Period 1:   Part A (16-Week Double-Blind Treatment)
    Placebo – Part A     Ivacaftor – Part A     Placebo/Ivacaftor – Part B     Ivacaftor/Ivacaftor – Part B  
STARTED     28 [1]   112 [2]   0     0  
COMPLETED     26 [3]   104 [4]   0     0  
NOT COMPLETED     2     8     0     0  
Adverse Event                 2                 3                 0                 0  
Lost to Follow-up                 0                 1                 0                 0  
Noncompliance with Study Requirements                 0                 2                 0                 0  
Required Prohibited Medication                 0                 1                 0                 0  
Sponsor Decision                 0                 1                 0                 0  
[1] All subjects who received at least 1 dose of study drug (placebo)
[2] All subjects who received at least 1 dose of study drug (ivacaftor)
[3] Only 5 participants continued in Part B.
[4] Only 33 participants continued in Part B.

Period 2:   Part B (96-Week Open-Label Extension)
    Placebo – Part A     Ivacaftor – Part A     Placebo/Ivacaftor – Part B     Ivacaftor/Ivacaftor – Part B  
STARTED     0     0     5     33  
COMPLETED     0     0     0     0  
NOT COMPLETED     0     0     5     33  
Adverse Event                 0                 0                 0                 2  
Noncompliance with Study Requirements                 0                 0                 0                 1  
Required Prohibited Medication                 0                 0                 0                 1  
Study Termination by Sponsor                 0                 0                 4                 25  
Withdrawal by Subject                 0                 0                 1                 2  
Unspecified                 0                 0                 0                 2  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Placebo – Part A Placebo matched to ivacaftor tablet orally every 12 hours (q12h) for 16 weeks during Part A (double-blind treatment period).
Ivacaftor – Part A Ivacaftor 150 milligram (mg) tablet orally q12h for 16 weeks during Part A (double-blind treatment period).
Total Total of all reporting groups

Baseline Measures
    Placebo – Part A     Ivacaftor – Part A     Total  
Number of Participants  
[units: participants]
  28     112     140  
Age  
[units: years]
Mean (Standard Deviation)
  25.0  (8.35)     22.8  (10.26)     23.2  (9.91)  
Age, Customized  
[units: participants]
     
12 to 17 Years     6     44     50  
18 to 24 Years     10     32     42  
25 to 39 Years     12     26     38  
40 to 45 Years     0     5     5  
> 45 Years     0     5     5  
Gender  
[units: participants]
     
Female     12     54     66  
Male     16     58     74  
Race/Ethnicity, Customized  
[units: participants]
     
Hispanic or Latino     1     2     3  
Not Hispanic or Latino     27     110     137  
Race/Ethnicity, Customized  
[units: participants]
     
Black or African American     0     1     1  
White     28     111     139  
Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1), Continuous [1]
[units: percent predicted of FEV1]
Mean (Standard Deviation)
  74.8  (24.06)     79.7  (22.67)     78.7  (22.95)  
ppFEV1, Categorical [1]
[units: participants]
     
< 70%     15     38     53  
≥ 70% to ≤ 90%     5     35     40  
> 90%     8     39     47  
Weight  
[units: kilograms]
Mean (Standard Deviation)
  63.2  (14.96)     58.2  (13.49)     59.2  (13.89)  
Body Mass Index  
[units: kilogram per square meter]
Mean (Standard Deviation)
  22.2  (4.48)     21.2  (3.25)     21.4  (3.54)  
Sweat Chloride  
[units: millimoles per liter]
Mean (Standard Deviation)
  102.4  (7.91)     101.4  (10.28)     101.6  (9.83)  
[1] Percent predicted for age, gender, and height.



  Outcome Measures
  Show All Outcome Measures

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

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

3.  Secondary:   Part A : Absolute Change From Part A Baseline in Sweat Chloride Concentration Through Week 16   [ Time Frame: Part A baseline through Week 16 ]

4.  Secondary:   Part A : Rate of Change From Baseline in Weight Through Week 16   [ Time Frame: Part A baseline through Week 16 ]

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

6.  Secondary:   Part B : Rate of Decline From Part A Baseline in ppFEV1 Through Week 64   [ Time Frame: Part A baseline through Week 64 ]

7.  Secondary:   Part B : Rate of Decline From Part B Baseline in ppFEV1 Through Week 64   [ Time Frame: Part B baseline through Week 64 ]

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

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

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

11.  Secondary:   Part B : Number of Participants With Pulmonary Exacerbations   [ Time Frame: Part B baseline through Week 64 ]

12.  Secondary:   Part B : Number of Pulmonary Exacerbation Events   [ Time Frame: Part B baseline through Week 64 ]

13.  Secondary:   Part B : Number of Pulmonary Exacerbation Events Per Participant Per Year   [ Time Frame: Part B baseline through Week 64 ]


  Serious Adverse Events


  Other Adverse Events
  Hide Other 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)
Additional Description No text entered.

Frequency Threshold
Threshold above which other adverse events are reported   0%  

Reporting Groups
  Description
Placebo – Part A Placebo matched to ivacaftor tablet orally q12h for 16 weeks during Part A (double-blind treatment period).
Ivacaftor – Part A Ivacaftor 150 milligram (mg) tablet orally q12h for 16 weeks during Part A (double-blind treatment period).
Placebo/Ivacaftor – Part B Participants who received placebo during Part A, received ivacaftor 150 mg tablet orally q12h for 96 weeks during Part B (open-label extension period).
Ivacaftor/Ivacaftor – Part B Participants who received ivacaftor during Part A, received ivacaftor 150 mg tablet orally q12h for 96 weeks during Part B (open-label extension period).

Other Adverse Events
    Placebo – Part A     Ivacaftor – Part A     Placebo/Ivacaftor – Part B     Ivacaftor/Ivacaftor – Part B  
Total, other (not including serious) adverse events          
# participants affected / at risk     25/28 (89.29%)     98/112 (87.50%)     5/5 (100.00%)     30/33 (90.91%)  
Blood and lymphatic system disorders          
Anaemia † 1        
# participants affected / at risk     0/28 (0.00%)     3/112 (2.68%)     0/5 (0.00%)     1/33 (3.03%)  
# events     0     3     0     1  
Lymphadenopathy † 1        
# participants affected / at risk     0/28 (0.00%)     3/112 (2.68%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     3     0     0  
Cardiac disorders          
Supraventricular Extrasystoles † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     1     0     0  
Congenital, familial and genetic disorders          
Cystic fibrosis lung † 1 [3]        
# participants affected / at risk     7/28 (25.00%)     19/112 (16.96%)     3/5 (60.00%)     11/33 (33.33%)  
# events     8     24     6     17  
Cystic Fibrosis Related Diabetes † 1        
# participants affected / at risk     0/28 (0.00%)     0/112 (0.00%)     0/5 (0.00%)     2/33 (6.06%)  
# events     0     0     0     2  
Ear and labyrinth disorders          
Middle Ear Effusion † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     1     0     0  
Tinnitus † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     1     0     0  
Eye disorders          
Conjunctivitis † 1        
# participants affected / at risk     0/28 (0.00%)     3/112 (2.68%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     3     0     0  
Lacrimation Increased † 1        
# participants affected / at risk     1/28 (3.57%)     1/112 (0.89%)     0/5 (0.00%)     0/33 (0.00%)  
# events     1     1     0     0  
Conjunctivitis Allergic † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     1     0     0  
Eye Pruritus † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     1     0     0  
Eyelid Oedema † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     1     0     0  
Visual Impairment † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     1     0     0  
Erythema Of Eyelid † 1        
# participants affected / at risk     0/28 (0.00%)     0/112 (0.00%)     0/5 (0.00%)     1/33 (3.03%)  
# events     0     0     0     1  
Gastrointestinal disorders          
Abdominal pain upper † 1        
# participants affected / at risk     1/28 (3.57%)     7/112 (6.25%)     0/5 (0.00%)     2/33 (6.06%)  
# events     4     8     0     3  
Diarrhoea † 1        
# participants affected / at risk     2/28 (7.14%)     6/112 (5.36%)     0/5 (0.00%)     1/33 (3.03%)  
# events     2     7     0     1  
Nausea † 1        
# participants affected / at risk     1/28 (3.57%)     10/112 (8.93%)     0/5 (0.00%)     3/33 (9.09%)  
# events     1     11     0     3  
Abdominal pain † 1        
# participants affected / at risk     1/28 (3.57%)     4/112 (3.57%)     3/5 (60.00%)     2/33 (6.06%)  
# events     1     5     3     2  
Vomiting † 1        
# participants affected / at risk     0/28 (0.00%)     4/112 (3.57%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     4     0     0  
Flatulence † 1        
# participants affected / at risk     0/28 (0.00%)     2/112 (1.79%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     2     0     0  
Abdominal discomfort † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     1     0     0  
Aphthous stomatitis † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     1     0     0  
Ascites † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     1     0     0  
Constipation † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     1/5 (20.00%)     1/33 (3.03%)  
# events     0     1     1     2  
Dental Caries † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     1     0     0  
Distal Ileal Obstruction Syndrome † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     2     0     0  
Dry Mouth † 1        
# participants affected / at risk     1/28 (3.57%)     0/112 (0.00%)     0/5 (0.00%)     0/33 (0.00%)  
# events     1     0     0     0  
Dyspepsia † 1        
# participants affected / at risk     1/28 (3.57%)     0/112 (0.00%)     0/5 (0.00%)     0/33 (0.00%)  
# events     1     0     0     0  
Frequent Bowel Movements † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     2     0     0  
Gastrointestinal Hypomotility † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     1     0     0  
Gastrooesophageal Reflux Disease † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     1/33 (3.03%)  
# events     0     1     0     1  
Hiatus Hernia † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     1/33 (3.03%)  
# events     0     1     0     1  
Pancreatic Duct Dilatation † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     1     0     0  
Peptic Ulcer † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     1     0     0  
Regurgitation † 1        
# participants affected / at risk     1/28 (3.57%)     0/112 (0.00%)     0/5 (0.00%)     0/33 (0.00%)  
# events     1     0     0     0  
Tooth Impacted † 1        
# participants affected / at risk     1/28 (3.57%)     0/112 (0.00%)     0/5 (0.00%)     0/33 (0.00%)  
# events     1     0     0     0  
Toothache † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     1/33 (3.03%)  
# events     0     1     0     1  
Distal Intestinal Obstruction Syndrome † 1        
# participants affected / at risk     0/28 (0.00%)     0/112 (0.00%)     0/5 (0.00%)     1/33 (3.03%)  
# events     0     0     0     1  
Sensitivity Of Teeth † 1        
# participants affected / at risk     0/28 (0.00%)     0/112 (0.00%)     0/5 (0.00%)     1/33 (3.03%)  
# events     0     0     0     1  
General disorders          
Chills † 1        
# participants affected / at risk     2/28 (7.14%)     0/112 (0.00%)     0/5 (0.00%)     0/33 (0.00%)  
# events     2     0     0     0  
Fatigue † 1        
# participants affected / at risk     3/28 (10.71%)     8/112 (7.14%)     0/5 (0.00%)     1/33 (3.03%)  
# events     3     8     0     1  
Pyrexia † 1        
# participants affected / at risk     2/28 (7.14%)     9/112 (8.04%)     0/5 (0.00%)     2/33 (6.06%)  
# events     2     10     0     3  
Catheter Site Pain † 1        
# participants affected / at risk     1/28 (3.57%)     2/112 (1.79%)     0/5 (0.00%)     2/33 (6.06%)  
# events     1     2     0     2  
Application Site Pruritus † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     2     0     0  
Application Site Rash † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     1     0     0  
Asthenia † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     1     0     0  
Chest Pain † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     1     0     0  
Feeling Abnormal † 1        
# participants affected / at risk     1/28 (3.57%)     0/112 (0.00%)     0/5 (0.00%)     0/33 (0.00%)  
# events     2     0     0     0  
Generalised Oedema † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     1     0     0  
Influenza Like Illness † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     1     0     0  
Thirst † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     1     0     0  
Vessel Puncture Site Pain † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     1     0     0  
Catheter Related Complication † 1        
# participants affected / at risk     0/28 (0.00%)     0/112 (0.00%)     0/5 (0.00%)     1/33 (3.03%)  
# events     0     0     0     1  
Infusion Site Pain † 1        
# participants affected / at risk     0/28 (0.00%)     0/112 (0.00%)     0/5 (0.00%)     1/33 (3.03%)  
# events     0     0     0     1  
Oedema Peripheral † 1        
# participants affected / at risk     0/28 (0.00%)     0/112 (0.00%)     0/5 (0.00%)     1/33 (3.03%)  
# events     0     0     0     1  
Pain † 1        
# participants affected / at risk     0/28 (0.00%)     0/112 (0.00%)     0/5 (0.00%)     1/33 (3.03%)  
# events     0     0     0     1  
Hepatobiliary disorders          
Cholelithiasis † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     1     0     0  
Hepatosplenomegaly † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     1     0     0  
Immune system disorders          
Allergy to Animal † 1        
# participants affected / at risk     1/28 (3.57%)     0/112 (0.00%)     0/5 (0.00%)     1/33 (3.03%)  
# events     1     0     0     1  
Seasonal Allergy † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     1/33 (3.03%)  
# events     0     1     0     1  
Hypersensitivity † 1        
# participants affected / at risk     0/28 (0.00%)     0/112 (0.00%)     1/5 (20.00%)     0/33 (0.00%)  
# events     0     0     1     0  
Infections and infestations          
Acute sinusitis † 1        
# participants affected / at risk     1/28 (3.57%)     0/112 (0.00%)     0/5 (0.00%)     1/33 (3.03%)  
# events     1     0     0     1  
Bronchitis † 1        
# participants affected / at risk     0/28 (0.00%)     0/112 (0.00%)     0/5 (0.00%)     3/33 (9.09%)  
# events     0     0     0     4  
Candidiasis † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     1/33 (3.03%)  
# events     0     1     0     1  
Clostridium Difficile colitis † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     2     0     0  
Ear infection † 1        
# participants affected / at risk     1/28 (3.57%)     1/112 (0.89%)     0/5 (0.00%)     1/33 (3.03%)  
# events     1     1     0     1  
Folliculitis † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     1     0     0  
Hordeolum † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     1     0     0  
Influenza † 1        
# participants affected / at risk     1/28 (3.57%)     0/112 (0.00%)     0/5 (0.00%)     0/33 (0.00%)  
# events     1     0     0     0  
Kidney infection † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     1     0     0  
Laryngitis † 1        
# participants affected / at risk     1/28 (3.57%)     1/112 (0.89%)     0/5 (0.00%)     0/33 (0.00%)  
# events     1     1     0     0  
Nasopharyngitis † 1        
# participants affected / at risk     0/28 (0.00%)     4/112 (3.57%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     5     0     0  
Oral candidiasis † 1        
# participants affected / at risk     1/28 (3.57%)     1/112 (0.89%)     0/5 (0.00%)     1/33 (3.03%)  
# events     1     1     0     1  
Oral herpes † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     1     0     0  
Orchitis † 1        
# participants affected / at risk     1/28 (3.57%)     0/112 (0.00%)     0/5 (0.00%)     0/33 (0.00%)  
# events     1     0     0     0  
Otitis media † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     1     0     0  
Pharyngitis † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     1     0     0  
Pharyngitis streptococcal † 1        
# participants affected / at risk     1/28 (3.57%)     1/112 (0.89%)     0/5 (0.00%)     0/33 (0.00%)  
# events     1     1     0     0  
Pneumonia staphylococcal † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     1     0     0  
Respiratory monilliasis † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     1     0     0  
Respiratory tract infection † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     1     0     0  
Respiratory tract infection viral † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     1     0     0  
Rhinitis † 1        
# participants affected / at risk     0/28 (0.00%)     5/112 (4.46%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     5     0     0  
Sinusitis † 1        
# participants affected / at risk     1/28 (3.57%)     8/112 (7.14%)     1/5 (20.00%)     4/33 (12.12%)  
# events     1     9     1     5  
Stenotrophomonas infection † 1        
# participants affected / at risk     1/28 (3.57%)     0/112 (0.00%)     0/5 (0.00%)     0/33 (0.00%)  
# events     1     0     0     0  
Tinea infection † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     1     0     0  
Tooth abscess † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     1     0     0  
Upper respiratory tract infection † 1        
# participants affected / at risk     2/28 (7.14%)     11/112 (9.82%)     1/5 (20.00%)     1/33 (3.03%)  
# events     2     13     1     2  
Urinary tract infection † 1        
# participants affected / at risk     1/28 (3.57%)     0/112 (0.00%)     0/5 (0.00%)     0/33 (0.00%)  
# events     1     0     0     0  
Viral upper respiratory tract infection † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     1/33 (3.03%)  
# events     0     1     0     2  
Vulvovaginal mycotic infection † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     2/33 (6.06%)  
# events     0     1     0     3  
Bacterial disease carrier † 1        
# participants affected / at risk     0/28 (0.00%)     0/112 (0.00%)     0/5 (0.00%)     1/33 (3.03%)  
# events     0     0     0     1  
Body tinea † 1        
# participants affected / at risk     0/28 (0.00%)     0/112 (0.00%)     0/5 (0.00%)     1/33 (3.03%)  
# events     0     0     0     1  
Cystitis † 1        
# participants affected / at risk     0/28 (0.00%)     0/112 (0.00%)     0/5 (0.00%)     1/33 (3.03%)  
# events     0     0     0     1  
Helicobacter gastritis † 1        
# participants affected / at risk     0/28 (0.00%)     0/112 (0.00%)     1/5 (20.00%)     0/33 (0.00%)  
# events     0     0     1     0  
Infectious mononucleosis † 1        
# participants affected / at risk     0/28 (0.00%)     0/112 (0.00%)     0/5 (0.00%)     1/33 (3.03%)  
# events     0     0     0     1  
Otitis externa † 1        
# participants affected / at risk     0/28 (0.00%)     0/112 (0.00%)     0/5 (0.00%)     1/33 (3.03%)  
# events     0     0     0     1  
Pneumonia † 1        
# participants affected / at risk     0/28 (0.00%)     0/112 (0.00%)     0/5 (0.00%)     1/33 (3.03%)  
# events     0     0     0     1  
Vaginitis bacterial † 1        
# participants affected / at risk     0/28 (0.00%)     0/112 (0.00%)     0/5 (0.00%)     1/33 (3.03%)  
# events     0     0     0     1  
Vulvovaginal candidiasis † 1        
# participants affected / at risk     0/28 (0.00%)     0/112 (0.00%)     0/5 (0.00%)     1/33 (3.03%)  
# events     0     0     0     1  
Injury, poisoning and procedural complications          
Contusion † 1        
# participants affected / at risk     0/28 (0.00%)     2/112 (1.79%)     0/5 (0.00%)     1/33 (3.03%)  
# events     0     3     0     1  
Skin Laceration † 1        
# participants affected / at risk     0/28 (0.00%)     2/112 (1.79%)     0/5 (0.00%)     2/33 (6.06%)  
# events     0     2     0     2  
Foreign Body Trauma † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     1     0     0  
Joint Injury † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     1     0     0  
Joint Sprain † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     1     0     0  
Muscle Strain † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     1/33 (3.03%)  
# events     0     1     0     1  
Procedural Pain † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     1     0     0  
Procedural Site Reaction † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     1     0     0  
Thermal Burn † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     1/33 (3.03%)  
# events     0     1     0     1  
Traumatic Brain Injury † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     1     0     0  
Animal Bite † 1        
# participants affected / at risk     0/28 (0.00%)     0/112 (0.00%)     0/5 (0.00%)     2/33 (6.06%)  
# events     0     0     0     2  
Arthropod Sting † 1        
# participants affected / at risk     0/28 (0.00%)     0/112 (0.00%)     1/5 (20.00%)     0/33 (0.00%)  
# events     0     0     1     0  
Excoriation † 1        
# participants affected / at risk     0/28 (0.00%)     0/112 (0.00%)     0/5 (0.00%)     1/33 (3.03%)  
# events     0     0     0     1  
Head Injury † 1        
# participants affected / at risk     0/28 (0.00%)     0/112 (0.00%)     0/5 (0.00%)     1/33 (3.03%)  
# events     0     0     0     1  
Road Traffic Accident † 1        
# participants affected / at risk     0/28 (0.00%)     0/112 (0.00%)     0/5 (0.00%)     1/33 (3.03%)  
# events     0     0     0     1  
Sunburn † 1        
# participants affected / at risk     0/28 (0.00%)     0/112 (0.00%)     0/5 (0.00%)     1/33 (3.03%)  
# events     0     0     0     1  
Wound † 1        
# participants affected / at risk     0/28 (0.00%)     0/112 (0.00%)     1/5 (20.00%)     0/33 (0.00%)  
# events     0     0     1     0  
Investigations          
Alanine aminotransferase increased † 1        
# participants affected / at risk     2/28 (7.14%)     1/112 (0.89%)     0/5 (0.00%)     2/33 (6.06%)  
# events     3     1     0     2  
Aspartate aminotransferase increased † 1        
# participants affected / at risk     2/28 (7.14%)     1/112 (0.89%)     0/5 (0.00%)     1/33 (3.03%)  
# events     3     1     0     1  
C-reactive protein increased † 1        
# participants affected / at risk     1/28 (3.57%)     6/112 (5.36%)     0/5 (0.00%)     0/33 (0.00%)  
# events     1     6     0     0  
Pulmonary function test decreased † 1        
# participants affected / at risk     2/28 (7.14%)     3/112 (2.68%)     0/5 (0.00%)     1/33 (3.03%)  
# events     2     4     0     2  
Blood glucose increased † 1        
# participants affected / at risk     1/28 (3.57%)     5/112 (4.46%)     0/5 (0.00%)     1/33 (3.03%)  
# events     1     5     0     1  
Bacteria sputum identified † 1        
# participants affected / at risk     1/28 (3.57%)     3/112 (2.68%)     0/5 (0.00%)     1/33 (3.03%)  
# events     1     4     0     1  
Prothrombin time prolonged † 1        
# participants affected / at risk     1/28 (3.57%)     3/112 (2.68%)     0/5 (0.00%)     0/33 (0.00%)  
# events     1     3     0     0  
Gamma-glutamyl transferase increased † 1        
# participants affected / at risk     1/28 (3.57%)     2/112 (1.79%)     0/5 (0.00%)     0/33 (0.00%)  
# events     1     2     0     0  
Glucose urine present † 1        
# participants affected / at risk     0/28 (0.00%)     3/112 (2.68%)     0/5 (0.00%)     1/33 (3.03%)  
# events     0     4     0     1  
Hepatic enzyme increased † 1        
# participants affected / at risk     1/28 (3.57%)     2/112 (1.79%)     0/5 (0.00%)     0/33 (0.00%)  
# events     1     2     0     0  
Blood immunoglobulin G increased † 1        
# participants affected / at risk     0/28 (0.00%)     2/112 (1.79%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     2     0     0  
Breath sounds abnormal † 1        
# participants affected / at risk     0/28 (0.00%)     2/112 (1.79%)     0/5 (0.00%)     1/33 (3.03%)  
# events     0     2     0     1  
Forced expiratory volume decreased † 1        
# participants affected / at risk     0/28 (0.00%)     2/112 (1.79%)     1/5 (20.00%)     1/33 (3.03%)  
# events     0     2     1     1  
Vitamin D decreased † 1        
# participants affected / at risk     0/28 (0.00%)     2/112 (1.79%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     2     0     0  
White blood cell count increased † 1        
# participants affected / at risk     0/28 (0.00%)     2/112 (1.79%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     2     0     0  
Acivated partial thromboplastin time prolonged † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     1/33 (3.03%)  
# events     0     1     0     1  
Antibiotic level above therapeutic † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     1     0     0  
Bacterial culture positive † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     2     0     0  
Blood alkaline phosphatase increased † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     1     0     0  
Blood glucose decreased † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     2     0     0  
Blood lactate dehydrogenase increased † 1        
# participants affected / at risk     1/28 (3.57%)     0/112 (0.00%)     0/5 (0.00%)     0/33 (0.00%)  
# events     2     0     0     0  
Bone density decreased † 1        
# participants affected / at risk     1/28 (3.57%)     0/112 (0.00%)     0/5 (0.00%)     0/33 (0.00%)  
# events     1     0     0     0  
Liver function test abnormal † 1        
# participants affected / at risk     1/28 (3.57%)     0/112 (0.00%)     0/5 (0.00%)     1/33 (3.03%)  
# events     1     0     0     1  
Neutrophil count increased † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     1     0     0  
Platelet count decreased † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     1     0     0  
Sputum culture positive † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     2     0     0  
Weight decreased † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     1     0     0  
White blood cell count decreased † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     1     0     0  
International normalised ratio increased † 1        
# participants affected / at risk     0/28 (0.00%)     0/112 (0.00%)     0/5 (0.00%)     1/33 (3.03%)  
# events     0     0     0     2  
Oxygen saturation decreased † 1        
# participants affected / at risk     0/28 (0.00%)     0/112 (0.00%)     0/5 (0.00%)     1/33 (3.03%)  
# events     0     0     0     1  
Sputum abnormal † 1        
# participants affected / at risk     0/28 (0.00%)     0/112 (0.00%)     0/5 (0.00%)     1/33 (3.03%)  
# events     0     0     0     1  
Weight increased † 1        
# participants affected / at risk     0/28 (0.00%)     0/112 (0.00%)     0/5 (0.00%)     1/33 (3.03%)  
# events     0     0     0     1  
Metabolism and nutrition disorders          
Hyperglycaemia † 1        
# participants affected / at risk     1/28 (3.57%)     2/112 (1.79%)     0/5 (0.00%)     1/33 (3.03%)  
# events     1     2     0     1  
Hypoglycaemia † 1        
# participants affected / at risk     0/28 (0.00%)     3/112 (2.68%)     0/5 (0.00%)     2/33 (6.06%)  
# events     0     3     0     2  
Gout † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     1     0     0  
Vitamin D Deficiency † 1        
# participants affected / at risk     0/28 (0.00%)     0/112 (0.00%)     1/5 (20.00%)     1/33 (3.03%)  
# events     0     0     1     1  
Glucose Tolerance Impaired † 1        
# participants affected / at risk     0/28 (0.00%)     0/112 (0.00%)     0/5 (0.00%)     1/33 (3.03%)  
# events     0     0     0     1  
Hypovitaminosis † 1        
# participants affected / at risk     0/28 (0.00%)     0/112 (0.00%)     0/5 (0.00%)     1/33 (3.03%)  
# events     0     0     0     1  
Musculoskeletal and connective tissue disorders          
Musculoskeletal chest pain † 1        
# participants affected / at risk     2/28 (7.14%)     3/112 (2.68%)     0/5 (0.00%)     3/33 (9.09%)  
# events     2     3     0     3  
Arthralgia † 1        
# participants affected / at risk     0/28 (0.00%)     3/112 (2.68%)     0/5 (0.00%)     4/33 (12.12%)  
# events     0     5     0     4  
Back Pain † 1        
# participants affected / at risk     1/28 (3.57%)     2/112 (1.79%)     0/5 (0.00%)     2/33 (6.06%)  
# events     2     2     0     3  
Pain In Extremity † 1        
# participants affected / at risk     0/28 (0.00%)     3/112 (2.68%)     0/5 (0.00%)     2/33 (6.06%)  
# events     0     3     0     3  
Joint Swelling † 1        
# participants affected / at risk     0/28 (0.00%)     2/112 (1.79%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     2     0     0  
Arthritis † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     2     0     0  
Bone Pain † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     1     0     0  
Clubbing † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     2/33 (6.06%)  
# events     0     1     0     2  
Muscular Weakness † 1        
# participants affected / at risk     1/28 (3.57%)     0/112 (0.00%)     0/5 (0.00%)     0/33 (0.00%)  
# events     1     0     0     0  
Myopathy † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     1     0     0  
Neck Pain † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     1     0     0  
Myalgia † 1        
# participants affected / at risk     0/28 (0.00%)     0/112 (0.00%)     0/5 (0.00%)     3/33 (9.09%)  
# events     0     0     0     4  
Arthropathy † 1        
# participants affected / at risk     0/28 (0.00%)     0/112 (0.00%)     0/5 (0.00%)     1/33 (3.03%)  
# events     0     0     0     1  
Musculoskeletal Pain † 1        
# participants affected / at risk     0/28 (0.00%)     0/112 (0.00%)     0/5 (0.00%)     1/33 (3.03%)  
# events     0     0     0     1  
Synovial Cyst † 1        
# participants affected / at risk     0/28 (0.00%)     0/112 (0.00%)     0/5 (0.00%)     1/33 (3.03%)  
# events     0     0     0     1  
Neoplasms benign, malignant and unspecified (incl cysts and polyps)          
Focal Nodular Hyperplasia † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     1     0     0  
Skin Papilloma † 1        
# participants affected / at risk     0/28 (0.00%)     0/112 (0.00%)     0/5 (0.00%)     1/33 (3.03%)  
# events     0     0     0     1  
Nervous system disorders          
Dizziness † 1        
# participants affected / at risk     2/28 (7.14%)     2/112 (1.79%)     0/5 (0.00%)     0/33 (0.00%)  
# events     2     3     0     0  
Headache † 1        
# participants affected / at risk     2/28 (7.14%)     11/112 (9.82%)     0/5 (0.00%)     1/33 (3.03%)  
# events     3     17     0     1  
Sinus Headache † 1        
# participants affected / at risk     0/28 (0.00%)     2/112 (1.79%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     2     0     0  
Burning Sensation † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     1     0     0  
Dysgeusia † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     1     0     0  
Hyperaesthesia † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     1     0     0  
Migraine † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     1/33 (3.03%)  
# events     0     1     0     1  
Paraesthesia † 1        
# participants affected / at risk     1/28 (3.57%)     0/112 (0.00%)     0/5 (0.00%)     0/33 (0.00%)  
# events     1     0     0     0  
Presyncope † 1        
# participants affected / at risk     1/28 (3.57%)     0/112 (0.00%)     0/5 (0.00%)     0/33 (0.00%)  
# events     1     0     0     0  
Somnolence † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     1     0     0  
Syncope † 1        
# participants affected / at risk     1/28 (3.57%)     0/112 (0.00%)     0/5 (0.00%)     0/33 (0.00%)  
# events     1     0     0     0  
Psychiatric disorders          
Anxiety † 1        
# participants affected / at risk     2/28 (7.14%)     1/112 (0.89%)     1/5 (20.00%)     2/33 (6.06%)  
# events     2     1     1     2  
Abnormal Dreams † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     1     0     0  
Depression † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     2/33 (6.06%)  
# events     0     1     0     3  
Hallucination † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     1     0     0  
Insomnia † 1        
# participants affected / at risk     1/28 (3.57%)     0/112 (0.00%)     0/5 (0.00%)     0/33 (0.00%)  
# events     1     0     0     0  
Adjustment Disorder † 1        
# participants affected / at risk     0/28 (0.00%)     0/112 (0.00%)     0/5 (0.00%)     1/33 (3.03%)  
# events     0     0     0     1  
Renal and urinary disorders          
Calculus Bladder † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     1     0     0  
Chromaturia † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     1     0     0  
Haematuria † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     1     0     0  
Nephrolithiasis † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     1/33 (3.03%)  
# events     0     1     0     1  
Proteinuria † 1        
# participants affected / at risk     1/28 (3.57%)     0/112 (0.00%)     0/5 (0.00%)     0/33 (0.00%)  
# events     1     0     0     0  
Renal Cyst † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     1     0     0  
Renal Failure Acute † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     1     0     0  
Urinary Retention † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     1     0     0  
Reproductive system and breast disorders          
Breast Tenderness † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     1     0     0  
Dysmenorrhoea † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     1     0     0  
Prostatic Cyst † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     1     0     0  
Testicular Pain † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     1     0     0  
Testicular Swelling † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     1     0     0  
Respiratory, thoracic and mediastinal disorders          
Asthma † 1        
# participants affected / at risk     1/28 (3.57%)     1/112 (0.89%)     0/5 (0.00%)     1/33 (3.03%)  
# events     2     1     0     1  
Bronchospasm † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     1     0     0  
Cough † 1        
# participants affected / at risk     4/28 (14.29%)     34/112 (30.36%)     0/5 (0.00%)     15/33 (45.45%)  
# events     5     43     0     17  
Dysphonia † 1        
# participants affected / at risk     0/28 (0.00%)     0/112 (0.00%)     1/5 (20.00%)     0/33 (0.00%)  
# events     0     0     1     0  
Dyspnoea † 1        
# participants affected / at risk     0/28 (0.00%)     5/112 (4.46%)     1/5 (20.00%)     2/33 (6.06%)  
# events     0     5     1     2  
Epistaxis † 1        
# participants affected / at risk     1/28 (3.57%)     1/112 (0.89%)     0/5 (0.00%)     2/33 (6.06%)  
# events     1     1     0     2  
Haemoptysis † 1        
# participants affected / at risk     1/28 (3.57%)     5/112 (4.46%)     2/5 (40.00%)     2/33 (6.06%)  
# events     1     10     3     2  
Increased viscosity of bronchial secretion † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     1     0     0  
Nasal congestion † 1        
# participants affected / at risk     2/28 (7.14%)     13/112 (11.61%)     0/5 (0.00%)     2/33 (6.06%)  
# events     2     14     0     2  
Nasal mucosal disorder † 1        
# participants affected / at risk     0/28 (0.00%)     3/112 (2.68%)     0/5 (0.00%)     1/33 (3.03%)  
# events     0     3     0     1  
Nasal oedema † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     1     0     0  
Nasal polyps † 1        
# participants affected / at risk     1/28 (3.57%)     3/112 (2.68%)     0/5 (0.00%)     0/33 (0.00%)  
# events     1     3     0     0  
Oropharyngeal pain † 1        
# participants affected / at risk     3/28 (10.71%)     10/112 (8.93%)     0/5 (0.00%)     1/33 (3.03%)  
# events     3     12     0     1  
Paranasal sinus hypersecretion † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     1     0     0  
Pharyngeal disorder † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     1     0     0  
Pharyngeal erythema † 1        
# participants affected / at risk     1/28 (3.57%)     2/112 (1.79%)     0/5 (0.00%)     0/33 (0.00%)  
# events     1     2     0     0  
Pleuritic pain † 1        
# participants affected / at risk     1/28 (3.57%)     1/112 (0.89%)     0/5 (0.00%)     1/33 (3.03%)  
# events     1     1     0     1  
Postnasal drip † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     1     0     0  
Productive cough † 1        
# participants affected / at risk     1/28 (3.57%)     9/112 (8.04%)     0/5 (0.00%)     4/33 (12.12%)  
# events     1     9     0     5  
Rales † 1        
# participants affected / at risk     1/28 (3.57%)     3/112 (2.68%)     0/5 (0.00%)     2/33 (6.06%)  
# events     1     4     0     2  
Respiration abnormal † 1        
# participants affected / at risk     0/28 (0.00%)     2/112 (1.79%)     1/5 (20.00%)     1/33 (3.03%)  
# events     0     2     1     1  
Respiratory tract congestion † 1        
# participants affected / at risk     1/28 (3.57%)     3/112 (2.68%)     0/5 (0.00%)     1/33 (3.03%)  
# events     1     4     0     1  
Rhinorrhoea † 1        
# participants affected / at risk     2/28 (7.14%)     4/112 (3.57%)     0/5 (0.00%)     1/33 (3.03%)  
# events     2     5     0     1  
Sinus congestion † 1        
# participants affected / at risk     1/28 (3.57%)     2/112 (1.79%)     0/5 (0.00%)     2/33 (6.06%)  
# events     1     2     0     2  
Sputum discoloured † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     2     0     0  
Tachypnoea † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     1     0     0  
Throat irritation † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     1     0     0  
Upper respiratory tract congestion † 1        
# participants affected / at risk     0/28 (0.00%)     0/112 (0.00%)     0/5 (0.00%)     1/33 (3.03%)  
# events     0     0     0     1  
Wheezing † 1        
# participants affected / at risk     0/28 (0.00%)     3/112 (2.68%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     3     0     0  
Skin and subcutaneous tissue disorders          
Dermatitis contact † 1        
# participants affected / at risk     0/28 (0.00%)     6/112 (5.36%)     0/5 (0.00%)     2/33 (6.06%)  
# events     0     9     0     2  
Rash † 1        
# participants affected / at risk     0/28 (0.00%)     9/112 (8.04%)     0/5 (0.00%)     1/33 (3.03%)  
# events     0     9     0     1  
Pruritus † 1        
# participants affected / at risk     0/28 (0.00%)     3/112 (2.68%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     3     0     0  
Rash Papular † 1        
# participants affected / at risk     0/28 (0.00%)     3/112 (2.68%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     3     0     0  
Rash Vesicular † 1        
# participants affected / at risk     0/28 (0.00%)     2/112 (1.79%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     3     0     0  
Blister † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     1     0     0  
Hyperhidrosis † 1        
# participants affected / at risk     1/28 (3.57%)     0/112 (0.00%)     0/5 (0.00%)     1/33 (3.03%)  
# events     1     0     0     1  
Night Sweats † 1        
# participants affected / at risk     1/28 (3.57%)     0/112 (0.00%)     0/5 (0.00%)     0/33 (0.00%)  
# events     1     0     0     0  
Photodermatosis † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     1     0     0  
Photosensitivity Reaction † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     1/33 (3.03%)  
# events     0     1     0     1  
Rash Macular † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     2/33 (6.06%)  
# events     0     2     0     3  
Urticaria † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     1     0     0  
Red Man Syndrome † 1        
# participants affected / at risk     0/28 (0.00%)     0/112 (0.00%)     1/5 (20.00%)     1/33 (3.03%)  
# events     0     0     1     1  
Surgical and medical procedures          
wisdom teeth removal † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     1     0     0  
Vascular disorders          
Hypotension † 1        
# participants affected / at risk     0/28 (0.00%)     1/112 (0.89%)     0/5 (0.00%)     0/33 (0.00%)  
# events     0     1     0     0  
Events were collected by systematic assessment
1 Term from vocabulary, MedDRA (12.0)
[3] CF exacerbations were coded as "cystic fibrosis lung."



  Limitations and Caveats
  Hide Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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
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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.
The agreement is:
unchecked 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 less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.


Results Point of Contact:  
Name/Title: Medical Monitor
Organization: Vertex
phone: 617-444-6777
e-mail: medicalinfo@vrtx.com


No publications provided by Vertex Pharmaceuticals Incorporated

Publications automatically indexed to this study:

Responsible Party: Vertex Pharmaceuticals Incorporated
ClinicalTrials.gov Identifier: NCT00953706     History of Changes
Other Study ID Numbers: VX08-770-104, 2009-010261-23
Study First Received: August 4, 2009
Results First Received: February 27, 2012
Last Updated: July 29, 2015
Health Authority: United States: Food and Drug Administration