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Study of Ivacaftor in Subjects With Cystic Fibrosis (CF) Who Have a Non-G551D CF Transmembrane Conductance Regulator (CFTR) Gating Mutation (KONNECTION)

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ClinicalTrials.gov Identifier: NCT01614470
Recruitment Status : Completed
First Posted : June 8, 2012
Results First Posted : October 29, 2014
Last Update Posted : October 29, 2014
Sponsor:
Collaborator:
Cystic Fibrosis Foundation
Information provided by (Responsible Party):
Vertex Pharmaceuticals Incorporated

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Cystic Fibrosis
Interventions Drug: Ivacaftor
Drug: Placebo
Enrollment 39
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Part 1: Ivacaftor First, Then Placebo Part 1: Placebo First, Then Ivacaftor Part 2: Ivacaftor
Hide Arm/Group Description Ivacaftor 150 milligram (mg) tablet orally twice daily for 8 weeks in treatment period 1 followed by placebo matched to ivacaftor tablet orally twice daily for 8 weeks in treatment period 2. Washout out period of 4 to 8 weeks was maintained between each treatment period. Placebo matched to ivacaftor tablet orally twice daily for 8 weeks in treatment period 1 followed by ivacaftor 150 mg tablet orally twice daily for 8 weeks in treatment period 2. Washout out period of 4 to 8 weeks was maintained between each treatment period. Ivacaftor 150 mg tablet orally twice daily for 16 weeks.
Period Title: Part 1: Treatment Period 1 (8 Weeks)
Started 20 19 0
Completed 18 18 0
Not Completed 2 1 0
Reason Not Completed
Lost to Follow-up             1             0             0
Need to extend washout period             1             1             0
Period Title: Part 1: Washout Period (4 to 8 Weeks)
Started 18 18 0
Completed 18 18 0
Not Completed 0 0 0
Period Title: Part 1: Treatment Period 2 (8 Weeks)
Started 18 18 0
Completed 18 18 0
Not Completed 0 0 0
Period Title: Part 2: Open-label Period (16 Weeks)
Started 0 0 36
Completed 0 0 36
Not Completed 0 0 0
Arm/Group Title Part 1: Ivacaftor First, Then Placebo Part 1: Placebo First, Then Ivacaftor Total
Hide Arm/Group Description Ivacaftor 150 milligram (mg) tablet orally twice daily for 8 weeks in treatment period 1 followed by placebo matched to ivacaftor tablet orally twice daily for 8 weeks in treatment period 2. Washout out period of 4 to 8 weeks was maintained between each treatment period. Placebo matched to ivacaftor tablet orally twice daily for 8 weeks in treatment period 1 followed by ivacaftor 150 mg tablet orally twice daily for 8 weeks in treatment period 2. Washout out period of 4 to 8 weeks was maintained between each treatment period. Total of all reporting groups
Overall Number of Baseline Participants 20 19 39
Hide Baseline Analysis Population Description
Full Analysis Set (FAS) was defined as all randomized subjects who received at least 1 dose of study drug (ivacaftor or placebo).
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 20 participants 19 participants 39 participants
23.8  (13.25) 21.7  (12.92) 22.8  (12.96)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 20 participants 19 participants 39 participants
Female
7
  35.0%
10
  52.6%
17
  43.6%
Male
13
  65.0%
9
  47.4%
22
  56.4%
1.Primary Outcome
Title Part 1: Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 8
Hide Description FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Hankinson and Wang standards were used to calculate percent predicted FEV1 (for age, gender, and height). The Hankinson standard was used for male subjects 18 years and older and female subjects 16 years and older. The Wang standard was used for male subjects aged 6 to 17 years and for female subjects aged 6 to 15 years. Baseline was defined as the most recent non-missing measurement collected before initial administration of study drug during study Part 1.
Time Frame Part 1: Baseline (pre-dose Day 1), Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
FAS for Part 1: all randomized subjects who received at least 1 dose of study drug (ivacaftor or placebo). Here, "n" signifies those subjects who were evaluable for this measure at given time point for each group, respectively.
Arm/Group Title Part 1: Ivacaftor Part 1: Placebo
Hide Arm/Group Description:
Ivacaftor 150 mg tablet orally twice daily for 8 weeks in either treatment period 1 or treatment period 2.
Placebo matched to ivacaftor tablet orally twice daily for 8 weeks in either treatment period 1 or treatment period 2.
Overall Number of Participants Analyzed 38 37
Mean (Standard Deviation)
Unit of Measure: percent predicted of FEV1
Baseline (n=38, 37) 76.3659  (20.33450) 79.3361  (20.83991)
Change Through Week 8 (n=37, 37) 8.1308  (9.94676) -5.8738  (7.23722)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1: Ivacaftor, Part 1: Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares (LS) mean difference
Estimated Value 10.6780
Confidence Interval (2-Sided) 95%
7.2559 to 14.1000
Estimation Comments [Not Specified]
2.Primary Outcome
Title Part 2: Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through 24 Weeks of Treatment (Week 36 Visit)
Hide Description FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Hankinson and Wang standards were used to calculate percent predicted FEV1 (for age, gender, and height). The Hankinson standard was used for male subjects 18 years and older and female subjects 16 years and older. The Wang standard was used for male subjects aged 6 to 17 years and for female subjects aged 6 to 15 years. Absolute change in percent predicted FEV1 over 24 weeks of ivacaftor treatment (from Week 12 [Part 1: Treatment Period 2] through Week 36 [Part 2]) was reported for subjects who received ivacaftor in Part 1: Treatment Period 2, as per planned analysis. Baseline was defined as the most recent non-missing measurement collected before initial administration of study drug during Part 1: Treatment Period 2.
Time Frame Baseline (pre-dose Week 12), Week 36
Hide Outcome Measure Data
Hide Analysis Population Description
FAS for Part 2: all randomized subjects who received at least 1 dose of study drug (ivacaftor). Only subjects who were randomized to receive ivacaftor during Part 1: Treatment Period 2 were to be analyzed for this measure.
Arm/Group Title Part 1 Treatment Period 2: Ivacaftor, Part 2: Ivacaftor
Hide Arm/Group Description:
Ivacaftor 150 mg tablet orally twice daily for 24 weeks (8 weeks in Part 1: Treatment Period 2 and 16 weeks in Part 2).
Overall Number of Participants Analyzed 18
Mean (Standard Deviation)
Unit of Measure: percent predicted of FEV1
Baseline 74.8375  (19.36754)
Change Through Week 36 13.5307  (10.18174)
3.Secondary Outcome
Title Part 1: Change From Baseline in Body Mass Index (BMI) at Week 8
Hide Description BMI was defined as weight in kilogram (kg) divided by height in meters^2 (m^2). Baseline was defined as the most recent non-missing measurement collected before initial administration of study drug during study Part 1.
Time Frame Part 1: Baseline (pre-dose Day 1), Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
FAS for Part 1: all randomized subjects who received at least 1 dose of study drug (ivacaftor or placebo). Here, "n" signifies those subjects who were evaluable for this measure at given time point for each group, respectively.
Arm/Group Title Part 1: Ivacaftor Part 1: Placebo
Hide Arm/Group Description:
Ivacaftor 150 mg tablet orally twice daily for 8 weeks in either treatment period 1 or treatment period 2.
Placebo matched to ivacaftor tablet orally twice daily for 8 weeks in either treatment period 1 or treatment period 2.
Overall Number of Participants Analyzed 38 37
Mean (Standard Deviation)
Unit of Measure: kg/m^2
Baseline (n=38, 37) 22.241  (5.1880) 22.527  (4.9956)
Change at Week 8 (n=37, 37) 0.748  (0.5793) 0.043  (0.6980)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1: Ivacaftor, Part 1: Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 0.6624
Confidence Interval (2-Sided) 95%
0.3366 to 0.9881
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Part 2: Change From Baseline in Body Mass Index (BMI) at 24 Weeks of Treatment (Week 36 Visit)
Hide Description BMI was defined as weight in kg divided by height in m^2. Change in BMI over 24 weeks of ivacaftor treatment (from Week 12 [Part 1: Treatment Period 2] through Week 36 [Part 2]) was reported for subjects who received ivacaftor in Part 1: Treatment Period 2 as per planned analysis. Baseline was defined as the most recent non-missing measurement collected before initial administration of study drug during Part 1: Treatment Period 2.
Time Frame Baseline (pre-dose Week 12), Week 36
Hide Outcome Measure Data
Hide Analysis Population Description
FAS for Part 2: all randomized subjects who received at least 1 dose of study drug (ivacaftor). Only subjects who were randomized to receive ivacaftor during Part 1: Treatment Period 2 were to be analyzed for this measure.
Arm/Group Title Part 1 Treatment Period 2: Ivacaftor, Part 2: Ivacaftor
Hide Arm/Group Description:
Ivacaftor 150 mg tablet orally twice daily for 24 weeks (8 weeks in Part 1: Treatment Period 2 and 16 weeks in Part 2).
Overall Number of Participants Analyzed 18
Mean (Standard Deviation)
Unit of Measure: kg/m^2
Baseline 22.222  (6.2919)
Change at Week 36 1.263  (0.7588)
5.Secondary Outcome
Title Part 1: Change From Baseline in Sweat Chloride Through Week 8
Hide Description Sweat samples were collected using an approved Macroduct (Wescor, Logan, Utah) collection device. A volume of greater than or equal to (>=) 15 microliter was required for determination of sweat chloride. Baseline was defined as the most recent non-missing measurement collected before initial administration of study drug during study Part 1.
Time Frame Part 1: Baseline (pre-dose Day 1), Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
FAS for Part 1: all randomized subjects who received at least 1 dose of study drug (ivacaftor or placebo). Here, "n" signifies those subjects who were evaluable for this measure at given time point for each group, respectively.
Arm/Group Title Part 1: Ivacaftor Part 1: Placebo
Hide Arm/Group Description:
Ivacaftor 150 mg tablet orally twice daily for 8 weeks in either treatment period 1 or treatment period 2.
Placebo matched to ivacaftor tablet orally twice daily for 8 weeks in either treatment period 1 or treatment period 2.
Overall Number of Participants Analyzed 38 37
Mean (Standard Deviation)
Unit of Measure: millimole per liter (mmol/L)
Baseline (n=38, 37) 93.37  (18.099) 94.23  (20.581)
Change Through Week 8 (n=36, 36) -55.82  (24.890) -5.63  (9.833)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1: Ivacaftor, Part 1: Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -49.1667
Confidence Interval (2-Sided) 95%
-56.9527 to -41.3807
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Part 2: Change From Baseline in Sweat Chloride Through 24 Weeks of Treatment (Week 36 Visit)
Hide Description Sweat samples were collected using an approved Macroduct (Wescor, Logan, Utah) collection device. A volume of greater than or equal to (>=) 15 microliter was required for determination of sweat chloride. Change in sweat chloride over 24 weeks of ivacaftor treatment (from Week 12 [Part 1: Treatment Period 2] through Week 36 [Part 2]) was reported for subjects who received ivacaftor in Part 1: Treatment Period 2 as per planned analysis. Baseline was defined as the most recent non-missing measurement collected before initial administration of study drug during Part 1: Treatment Period 2.
Time Frame Baseline (pre-dose Week 12), Week 36
Hide Outcome Measure Data
Hide Analysis Population Description
FAS for Part 2: all randomized subjects who received at least 1 dose of study drug (ivacaftor). Only subjects who were randomized to receive ivacaftor during Part 1: Treatment Period 2 were to be analyzed for this measure. Here "n" signifies those subjects who were evaluable for this measure at given time point.
Arm/Group Title Part 1 Treatment Period 2: Ivacaftor, Part 2: Ivacaftor
Hide Arm/Group Description:
Ivacaftor 150 mg tablet orally twice daily for 24 weeks (8 weeks in Part 1: Treatment Period 2 and 16 weeks in Part 2).
Overall Number of Participants Analyzed 18
Mean (Standard Deviation)
Unit of Measure: mmol/L
Baseline (n=18) 92.03  (11.468)
Change Through Week 36 (n=17) -59.24  (32.566)
7.Secondary Outcome
Title Part 1: Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score Through Week 8
Hide Description The CFQ-R is a validated patient-reported outcome measuring health-related quality of life for subjects with cystic fibrosis. Respiratory domain assessed respiratory symptoms (for example, coughing, congestion, wheezing), score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life. Baseline was defined as the most recent non-missing measurement collected before initial administration of study drug during study Part 1.
Time Frame Part 1: Baseline (pre-dose Day 1), Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
FAS for Part 1: all randomized subjects who received at least 1 dose of study drug (ivacaftor or placebo). Here, "n" signifies those subjects who were evaluable for this measure at given time point for each group, respectively.
Arm/Group Title Part 1: Ivacaftor Part 1: Placebo
Hide Arm/Group Description:
Ivacaftor 150 mg tablet orally twice daily for 8 weeks in either treatment period 1 or treatment period 2.
Placebo matched to ivacaftor tablet orally twice daily for 8 weeks in either treatment period 1 or treatment period 2.
Overall Number of Participants Analyzed 38 37
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline (n=38, 37) 70.61  (17.409) 74.55  (20.616)
Change Through Week 8 (n=37, 37) 12.31  (16.891) -2.33  (20.648)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Part 1: Ivacaftor, Part 1: Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0004
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 9.6105
Confidence Interval (2-Sided) 95%
4.4874 to 14.7336
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Part 2: Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score Through 24 Weeks of Treatment (Week 36 Visit)
Hide Description The CFQ-R is a validated patient-reported outcome measuring health-related quality of life for subjects 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. Change in CFQ-R respiratory domain score over 24 weeks of ivacaftor treatment (from Week 12 [Part 1: Treatment Period 2] through Week 36 [Part 2]) was reported for subjects who received ivacaftor in Part 1: Treatment Period 2 as per planned analysis. Baseline was defined as the most recent non-missing measurement collected before initial administration of study drug during Part 1: Treatment Period 2.
Time Frame Baseline (pre-dose Week 12), Week 36
Hide Outcome Measure Data
Hide Analysis Population Description
FAS for Part 2: all randomized subjects who received at least 1 dose of study drug (ivacaftor). Only subjects who were randomized to receive ivacaftor during Part 1: Treatment Period 2 were to be analyzed for this measure.
Arm/Group Title Part 1 Treatment Period 2: Ivacaftor, Part 2: Ivacaftor
Hide Arm/Group Description:
Ivacaftor 150 mg tablet orally twice daily for 24 weeks (8 weeks in Part 1: Treatment Period 2 and 16 weeks in Part 2).
Overall Number of Participants Analyzed 18
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline 71.30  (19.526)
Change Through Week 36 11.42  (13.604)
9.Secondary Outcome
Title Part 1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Hide Description AE: any adverse change from subject's baseline (pre-treatment) condition, including any adverse experience, abnormal recording/clinical laboratory assessment which occurs during course of study, whether it is considered related to study drug or not. SAE: medical event or condition, which falls into any of following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, in-patient hospitalization/prolonged hospitalization, persistent/significant disability/incapacity, congenital anomaly/birth defect, important medical event.
Time Frame Part 1: From signing of informed consent up to Week 20
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Set for Part 1 included all subjects who received at least 1 dose of study drug (ivacaftor or placebo).
Arm/Group Title Part 1: Ivacaftor Part 1: Placebo
Hide Arm/Group Description:
Ivacaftor 150 mg tablet orally twice daily for 8 weeks in either treatment period 1 or treatment period 2.
Placebo matched to ivacaftor tablet orally twice daily for 8 weeks in either treatment period 1 or treatment period 2.
Overall Number of Participants Analyzed 38 37
Measure Type: Number
Unit of Measure: participants
AEs 28 31
SAEs 4 7
10.Secondary Outcome
Title Part 2: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Hide Description AE: any adverse change from subject's baseline (pre-treatment) condition, including any adverse experience, abnormal recording/clinical laboratory assessment which occurs during course of study, whether it is considered related to study drug or not. SAE: medical event or condition, which falls into any of following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, in-patient hospitalization/prolonged hospitalization, persistent/significant disability/incapacity, congenital anomaly/birth defect, important medical event.
Time Frame Part 2: Week 20 up to Week 40
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Set for Part 2 included all subjects who received at least 1 dose of study drug (ivacaftor).
Arm/Group Title Part 2: Ivacaftor
Hide Arm/Group Description:
Ivacaftor 150 mg tablet orally twice daily for 16 weeks.
Overall Number of Participants Analyzed 36
Measure Type: Number
Unit of Measure: participants
AEs 30
SAEs 3
Time Frame Part 1: From signing of informed consent up to Week 20; Part 2: Week 20 up to Week 40
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Part 1: Ivacaftor Part 1: Placebo Part 2: Ivacaftor
Hide Arm/Group Description Ivacaftor 150 mg tablet orally twice daily for 8 weeks in either treatment period 1 or treatment period 2. Placebo matched to ivacaftor tablet orally twice daily for 8 weeks in either treatment period 1 or treatment period 2. Ivacaftor 150 mg tablet orally twice daily for 16 weeks.
All-Cause Mortality
Part 1: Ivacaftor Part 1: Placebo Part 2: Ivacaftor
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Part 1: Ivacaftor Part 1: Placebo Part 2: Ivacaftor
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   4/38 (10.53%)   7/37 (18.92%)   3/36 (8.33%) 
Gastrointestinal disorders       
Distal Ileal Obstruction Syndrome  1  1/38 (2.63%)  0/37 (0.00%)  0/36 (0.00%) 
Appendiceal Mucocoele  1  0/38 (0.00%)  1/37 (2.70%)  0/36 (0.00%) 
Intussusception  1  0/38 (0.00%)  1/37 (2.70%)  0/36 (0.00%) 
Distal intestinal obstruction syndrome  1  0/38 (0.00%)  0/37 (0.00%)  1/36 (2.78%) 
Infections and infestations       
Infective pulmonary exacerbation of cystic fibrosis  1  2/38 (5.26%)  6/37 (16.22%)  2/36 (5.56%) 
Metabolism and nutrition disorders       
Dehydration  1  0/38 (0.00%)  0/37 (0.00%)  1/36 (2.78%) 
Musculoskeletal and connective tissue disorders       
Intervertebral Disc Protrusion  1  1/38 (2.63%)  0/37 (0.00%)  0/36 (0.00%) 
Nervous system disorders       
Convulsion  1  0/38 (0.00%)  0/37 (0.00%)  1/36 (2.78%) 
Dizziness  1  0/38 (0.00%)  0/37 (0.00%)  1/36 (2.78%) 
Respiratory, thoracic and mediastinal disorders       
Paranasal Cyst  1  0/38 (0.00%)  1/37 (2.70%)  0/36 (0.00%) 
Pneumothorax  1  0/38 (0.00%)  1/37 (2.70%)  0/36 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 15.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Part 1: Ivacaftor Part 1: Placebo Part 2: Ivacaftor
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   27/38 (71.05%)   30/37 (81.08%)   30/36 (83.33%) 
Blood and lymphatic system disorders       
Anaemia  1  1/38 (2.63%)  0/37 (0.00%)  0/36 (0.00%) 
Ear and labyrinth disorders       
Hyperacusis  1  0/38 (0.00%)  1/37 (2.70%)  0/36 (0.00%) 
Cerumen impaction  1  0/38 (0.00%)  0/37 (0.00%)  1/36 (2.78%) 
Hypoacusis  1  0/38 (0.00%)  0/37 (0.00%)  1/36 (2.78%) 
Endocrine disorders       
Thyroid disorder  1  1/38 (2.63%)  0/37 (0.00%)  0/36 (0.00%) 
Eye disorders       
Conjunctivitis allergic  1  0/38 (0.00%)  0/37 (0.00%)  1/36 (2.78%) 
Gastrointestinal disorders       
Constipation  1  2/38 (5.26%)  1/37 (2.70%)  2/36 (5.56%) 
Abdominal pain  1  1/38 (2.63%)  4/37 (10.81%)  3/36 (8.33%) 
Abdominal pain upper  1  1/38 (2.63%)  0/37 (0.00%)  2/36 (5.56%) 
Distal ileal obstruction syndrome  1  1/38 (2.63%)  1/37 (2.70%)  0/36 (0.00%) 
Nausea  1  1/38 (2.63%)  4/37 (10.81%)  1/36 (2.78%) 
Toothache  1  1/38 (2.63%)  0/37 (0.00%)  1/36 (2.78%) 
Vomiting  1  1/38 (2.63%)  1/37 (2.70%)  0/36 (0.00%) 
Cheilitis  1  0/38 (0.00%)  1/37 (2.70%)  0/36 (0.00%) 
Diarrhoea  1  0/38 (0.00%)  1/37 (2.70%)  1/36 (2.78%) 
Distal intestinal obstruction syndrome  1  0/38 (0.00%)  1/37 (2.70%)  0/36 (0.00%) 
Flatulence  1  0/38 (0.00%)  2/37 (5.41%)  0/36 (0.00%) 
Gastrooesophageal reflux disease  1  0/38 (0.00%)  2/37 (5.41%)  1/36 (2.78%) 
Abdominal distension  1  0/38 (0.00%)  0/37 (0.00%)  1/36 (2.78%) 
Anal fissure  1  0/38 (0.00%)  0/37 (0.00%)  1/36 (2.78%) 
Food poisoning  1  0/38 (0.00%)  0/37 (0.00%)  1/36 (2.78%) 
Gastritis  1  0/38 (0.00%)  0/37 (0.00%)  1/36 (2.78%) 
Haemorrhoids  1  0/38 (0.00%)  0/37 (0.00%)  1/36 (2.78%) 
Pancreatitis  1  0/38 (0.00%)  0/37 (0.00%)  1/36 (2.78%) 
General disorders       
Pyrexia  1  3/38 (7.89%)  1/37 (2.70%)  2/36 (5.56%) 
Fatigue  1  2/38 (5.26%)  0/37 (0.00%)  1/36 (2.78%) 
Chest pain  1  1/38 (2.63%)  0/37 (0.00%)  0/36 (0.00%) 
Exercise tolerance decreased  1  1/38 (2.63%)  0/37 (0.00%)  0/36 (0.00%) 
Malaise  1  1/38 (2.63%)  0/37 (0.00%)  0/36 (0.00%) 
Medical device site reaction  1  1/38 (2.63%)  0/37 (0.00%)  0/36 (0.00%) 
Oedema peripheral  1  0/38 (0.00%)  1/37 (2.70%)  1/36 (2.78%) 
Infusion site thrombosis  1  0/38 (0.00%)  0/37 (0.00%)  1/36 (2.78%) 
Injection site pain  1  0/38 (0.00%)  0/37 (0.00%)  1/36 (2.78%) 
Non-cardiac chest pain  1  0/38 (0.00%)  0/37 (0.00%)  1/36 (2.78%) 
Hepatobiliary disorders       
Biliary colic  1  0/38 (0.00%)  0/37 (0.00%)  1/36 (2.78%) 
Immune system disorders       
Hypersensitivity  1  0/38 (0.00%)  0/37 (0.00%)  1/36 (2.78%) 
Seasonal allergy  1  0/38 (0.00%)  0/37 (0.00%)  1/36 (2.78%) 
Infections and infestations       
Infective pulmonary exacerbation of cystic fibrosis  1  7/38 (18.42%)  6/37 (16.22%)  4/36 (11.11%) 
Rhinitis  1  3/38 (7.89%)  2/37 (5.41%)  0/36 (0.00%) 
Influenza  1  2/38 (5.26%)  2/37 (5.41%)  0/36 (0.00%) 
Conjunctivitis infective  1  1/38 (2.63%)  0/37 (0.00%)  0/36 (0.00%) 
Respiratory tract infection viral  1  1/38 (2.63%)  0/37 (0.00%)  0/36 (0.00%) 
Sinusitis  1  1/38 (2.63%)  2/37 (5.41%)  2/36 (5.56%) 
Upper respiratory tract infection  1  1/38 (2.63%)  2/37 (5.41%)  3/36 (8.33%) 
Urinary tract infection  1  1/38 (2.63%)  0/37 (0.00%)  0/36 (0.00%) 
Bacterial disease carrier  1  0/38 (0.00%)  1/37 (2.70%)  0/36 (0.00%) 
Bronchitis  1  0/38 (0.00%)  1/37 (2.70%)  0/36 (0.00%) 
Gastroenteritis  1  0/38 (0.00%)  1/37 (2.70%)  1/36 (2.78%) 
Tonsillitis  1  0/38 (0.00%)  1/37 (2.70%)  0/36 (0.00%) 
Vulvovaginal mycotic infection  1  0/38 (0.00%)  1/37 (2.70%)  1/36 (2.78%) 
Gastrointestinal viral infection  1  0/38 (0.00%)  0/37 (0.00%)  1/36 (2.78%) 
Impetigo  1  0/38 (0.00%)  0/37 (0.00%)  1/36 (2.78%) 
Lower respiratory tract infection  1  0/38 (0.00%)  0/37 (0.00%)  1/36 (2.78%) 
Pharyngitis streptococcal  1  0/38 (0.00%)  0/37 (0.00%)  1/36 (2.78%) 
Injury, poisoning and procedural complications       
Contusion  1  1/38 (2.63%)  0/37 (0.00%)  0/36 (0.00%) 
Ligament sprain  1  0/38 (0.00%)  1/37 (2.70%)  1/36 (2.78%) 
Arthropod bite  1  0/38 (0.00%)  0/37 (0.00%)  1/36 (2.78%) 
Sunburn  1  0/38 (0.00%)  0/37 (0.00%)  1/36 (2.78%) 
Vaccination complication  1  0/38 (0.00%)  0/37 (0.00%)  1/36 (2.78%) 
Investigations       
Alanine aminotransferase increased  1  1/38 (2.63%)  0/37 (0.00%)  0/36 (0.00%) 
Blood creatinine increased  1  1/38 (2.63%)  0/37 (0.00%)  0/36 (0.00%) 
C-reactive protein increased  1  1/38 (2.63%)  1/37 (2.70%)  0/36 (0.00%) 
Gamma-glutamyltransferase increased  1  1/38 (2.63%)  0/37 (0.00%)  0/36 (0.00%) 
Neutrophil count increased  1  1/38 (2.63%)  0/37 (0.00%)  0/36 (0.00%) 
Respiratory rate increased  1  1/38 (2.63%)  0/37 (0.00%)  0/36 (0.00%) 
White blood cell count increased  1  1/38 (2.63%)  0/37 (0.00%)  0/36 (0.00%) 
Hepatic enzyme increased  1  0/38 (0.00%)  1/37 (2.70%)  0/36 (0.00%) 
Pulmonary function test decreased  1  0/38 (0.00%)  1/37 (2.70%)  1/36 (2.78%) 
Breath sounds abnormal  1  0/38 (0.00%)  0/37 (0.00%)  1/36 (2.78%) 
Weight decreased  1  0/38 (0.00%)  0/37 (0.00%)  1/36 (2.78%) 
Metabolism and nutrition disorders       
Hypoglycaemia  1  0/38 (0.00%)  1/37 (2.70%)  1/36 (2.78%) 
Decreased appetite  1  0/38 (0.00%)  0/37 (0.00%)  1/36 (2.78%) 
Musculoskeletal and connective tissue disorders       
Arthralgia  1  2/38 (5.26%)  0/37 (0.00%)  1/36 (2.78%) 
Back pain  1  1/38 (2.63%)  0/37 (0.00%)  0/36 (0.00%) 
Torticollis  1  1/38 (2.63%)  0/37 (0.00%)  0/36 (0.00%) 
Osteochondrosis  1  0/38 (0.00%)  1/37 (2.70%)  0/36 (0.00%) 
Musculoskeletal pain  1  0/38 (0.00%)  0/37 (0.00%)  1/36 (2.78%) 
Pain in jaw  1  0/38 (0.00%)  0/37 (0.00%)  1/36 (2.78%) 
Tendonitis  1  0/38 (0.00%)  0/37 (0.00%)  1/36 (2.78%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Oral papilloma  1  1/38 (2.63%)  0/37 (0.00%)  0/36 (0.00%) 
Malignant melanoma  1  0/38 (0.00%)  0/37 (0.00%)  1/36 (2.78%) 
Nervous system disorders       
Headache  1  3/38 (7.89%)  5/37 (13.51%)  4/36 (11.11%) 
Dysgeusia  1  1/38 (2.63%)  0/37 (0.00%)  0/36 (0.00%) 
Sinus headache  1  1/38 (2.63%)  0/37 (0.00%)  0/36 (0.00%) 
Lethargy  1  0/38 (0.00%)  1/37 (2.70%)  1/36 (2.78%) 
Benign intracranial hypertension  1  0/38 (0.00%)  0/37 (0.00%)  1/36 (2.78%) 
Psychiatric disorders       
Anxiety  1  0/38 (0.00%)  0/37 (0.00%)  1/36 (2.78%) 
Reproductive system and breast disorders       
Metrorrhagia  1  1/38 (2.63%)  0/37 (0.00%)  0/36 (0.00%) 
Vulvovaginal discomfort  1  0/38 (0.00%)  1/37 (2.70%)  0/36 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Cough  1  6/38 (15.79%)  7/37 (18.92%)  5/36 (13.89%) 
Sputum increased  1  3/38 (7.89%)  3/37 (8.11%)  2/36 (5.56%) 
Dysphonia  1  1/38 (2.63%)  0/37 (0.00%)  1/36 (2.78%) 
Epistaxis  1  1/38 (2.63%)  0/37 (0.00%)  1/36 (2.78%) 
Haemoptysis  1  1/38 (2.63%)  2/37 (5.41%)  1/36 (2.78%) 
Lung hyperinflation  1  1/38 (2.63%)  1/37 (2.70%)  1/36 (2.78%) 
Nasal congestion  1  1/38 (2.63%)  1/37 (2.70%)  0/36 (0.00%) 
Oropharyngeal pain  1  1/38 (2.63%)  3/37 (8.11%)  3/36 (8.33%) 
Rales  1  1/38 (2.63%)  3/37 (8.11%)  1/36 (2.78%) 
Respiration abnormal  1  1/38 (2.63%)  0/37 (0.00%)  0/36 (0.00%) 
Rhinorrhoea  1  1/38 (2.63%)  2/37 (5.41%)  0/36 (0.00%) 
Wheezing  1  1/38 (2.63%)  0/37 (0.00%)  2/36 (5.56%) 
Asthma  1  0/38 (0.00%)  1/37 (2.70%)  3/36 (8.33%) 
Bronchospasm  1  0/38 (0.00%)  1/37 (2.70%)  0/36 (0.00%) 
Nasal mucosal disorder  1  0/38 (0.00%)  1/37 (2.70%)  0/36 (0.00%) 
Paranasal sinus hypersecretion  1  0/38 (0.00%)  1/37 (2.70%)  1/36 (2.78%) 
Productive cough  1  0/38 (0.00%)  2/37 (5.41%)  0/36 (0.00%) 
Pulmonary congestion  1  0/38 (0.00%)  1/37 (2.70%)  1/36 (2.78%) 
Respiratory tract congestion  1  0/38 (0.00%)  2/37 (5.41%)  0/36 (0.00%) 
Sinus congestion  1  0/38 (0.00%)  2/37 (5.41%)  2/36 (5.56%) 
Sputum discoloured  1  0/38 (0.00%)  1/37 (2.70%)  2/36 (5.56%) 
Nasal polyps  1  0/38 (0.00%)  0/37 (0.00%)  1/36 (2.78%) 
Nasal turbinate hypertrophy  1  0/38 (0.00%)  0/37 (0.00%)  1/36 (2.78%) 
Pneumonitis  1  0/38 (0.00%)  0/37 (0.00%)  1/36 (2.78%) 
Vocal cord inflammation  1  0/38 (0.00%)  0/37 (0.00%)  1/36 (2.78%) 
Skin and subcutaneous tissue disorders       
Dermatitis contact  1  1/38 (2.63%)  0/37 (0.00%)  0/36 (0.00%) 
Dry skin  1  1/38 (2.63%)  1/37 (2.70%)  0/36 (0.00%) 
Pruritus  1  1/38 (2.63%)  1/37 (2.70%)  0/36 (0.00%) 
Rash  1  1/38 (2.63%)  2/37 (5.41%)  1/36 (2.78%) 
Rash papular  1  1/38 (2.63%)  0/37 (0.00%)  0/36 (0.00%) 
Acne  1  0/38 (0.00%)  1/37 (2.70%)  1/36 (2.78%) 
Urticaria  1  0/38 (0.00%)  1/37 (2.70%)  0/36 (0.00%) 
Vascular disorders       
Orthostatic hypotension  1  1/38 (2.63%)  0/37 (0.00%)  0/36 (0.00%) 
Hypertension  1  0/38 (0.00%)  0/37 (0.00%)  1/36 (2.78%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 15.1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
PI is free to publish results of the study after (1) the first multi-center publication, (2) if the sponsor elects not to publish the results, or (3) 18 months after close of the study, whichever occurs first. Proposed publications are to be submitted to the sponsor for review and comment for a period of at least 45 days (which may be extended under certain circumstances related to protection of intellectual property); the sponsor cannot require changes to the proposed publications.
Results Point of Contact
Name/Title: Medical Monitor
Organization: Vertex Pharmaceuticals Incorporated
Phone: 617-341-6777
Responsible Party: Vertex Pharmaceuticals Incorporated
ClinicalTrials.gov Identifier: NCT01614470     History of Changes
Other Study ID Numbers: VX12-770-111
First Submitted: June 5, 2012
First Posted: June 8, 2012
Results First Submitted: October 23, 2014
Results First Posted: October 29, 2014
Last Update Posted: October 29, 2014