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Safety, Tolerability, Pharmacokinetics, and Preliminary Pharmacodynamics of QBW251 in Healthy Subjects and Cystic Fibrosis Patients

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ClinicalTrials.gov Identifier: NCT02190604
Recruitment Status : Terminated
First Posted : July 15, 2014
Results First Posted : July 19, 2017
Last Update Posted : July 19, 2017
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Condition Cystic Fibrosis
Interventions Drug: Placebo
Drug: QBW251
Enrollment 153
Recruitment Details For Cohort 6 continuing into the food effect part of the study the subjects remained on the same treatment assignment that was required during the fed state. Therefore no randomization f the subject occurred during the food effect arm. Only 5 of the 6 subjects went into the fed cohort.
Pre-assignment Details In parts 1 and 2, participants (Healthy Volunteers) were randomized 3:1 to receive QBW251X or placebo. In part 3, participants (cystic fibrosis (CF) patients) were randomized 3:1 to receive QBW251X or placebo.
Arm/Group Title Part 1 Cohort 1: QBW251 Part 1 Cohort 2: QBW251 Part 1 Cohort 3: QBW251 Part 1 Cohort 4: QBW251 Part 1 Cohort 5: QBW251 Part 1 Cohort 6: QBW251 (Fasting/Fed), Same Subjects Part 1 Cohort 7: QBW251 Part 1 Cohort 8: QBW251 Part 1 Placebo Part 2 Cohort 1: QBW251 Part 2 Cohort 2: QBW251 Part 2 Cohort 3: QBW251 Part 2 Cohort 4: QBW251 Part 2 Cohort 5: QBW251 Part 2 Placebo Part 3 Cohort 1: QBW251 Part 3 Cohort 2: QBW251 Part 3 Cohort 3: QBW251 Part 3 Placebo
Hide Arm/Group Description Single dose of QBW251 10 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15). Single dose of QBW251 25 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15). Single dose of QBW251 75 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15). Single dose of QBW251 150 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15). Single dose of QBW251 300 mg in healthy volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15). Single dose of QBW251 500 mg (fed). single dose with food for a preliminary assessment of the effect of food on the absorption of QBW251 in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15). Single dose of QBW251 750 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15). Single dose of QBW251 1000 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15). Placebo to QBW251 in all cohorts of part 1 in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15). Multiple doses of QBW25 150 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36). Multiple doses of QBW251 400 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36). Multiple doses of QBW251 750 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36). Multiple doses of QBW251 450 mg bid in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36). Multiple doses of QBW251 750 mg bid in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36). Placebo to QBW251 in all cohorts of part 2 in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36). 150 mg b.i.d. Multiple doses. Patients having a class III, IV, V, or VI mutation on one allele and any other CFTR mutation on the other allele in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42. 450 mg b.i.d. Multiple doses. Patients having a class III, IV, V, or VI mutation on one allele and any other CFTR mutation on the other allele in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42. 450 mg b.i.d. Multiple doses. Patients who are homozygous for the F508del mutation in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42. Placebo to QBW251 in all cohorts of part 3 in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.
Period Title: Part 1 and 2 (Healthy Volunteers)
Started 6 6 6 6 6 6 6 6 16 6 6 6 6 6 10 0 0 0 0
Completed 6 6 6 6 6 6 6 6 16 6 6 6 6 5 8 0 0 0 0
Not Completed 0 0 0 0 0 0 0 0 0 0 0 0 0 1 2 0 0 0 0
Reason Not Completed
Adverse Event             0             0             0             0             0             0             0             0             0             0             0             0             0             0             2             0             0             0             0
Lost to Follow-up             0             0             0             0             0             0             0             0             0             0             0             0             0             1             0             0             0             0             0
Period Title: Part 3 (Patients)
Started 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 6 12 19 12
Completed 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 6 12 19 12
Not Completed 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
Arm/Group Title Part 1 Cohort 1: QBW251 Part 1 Cohort 2: QBW251 Part 1 Cohort 3: QBW251 Part 1 Cohort 4: QBW251 Part 1 Cohort 6: QBW251 Part 1 Cohort 6: QBW251 (Fastin / Fed), Same Subjects Part 1 Cohort 7: QBW251 Part 1 Cohort 8: QBW251 Part 1 Placebo Part 2 Cohort 1: QBW251 Part 2 Cohort 2: QBW251 Part 2 Cohort 3: QBW251 Part 2 Cohort 4: QBW251 Part 2 Cohort 5: QBW251 Part 2 Placebo Part 3 Cohort 1: QBW251 Part 3 Cohort 2: QBW251 Part 3 Cohort 3: QBW251 Part 3 Placebo Total
Hide Arm/Group Description Single dose of QBW251 10 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15). Single dose of QBW251 25 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15). Single dose of QBW251 75 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15). Single dose of QBW251 150 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15). Single dose of QBW251 500 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15). Single dose of QBW251 500 mg (fed). single dose with food for a preliminary assessment of the effect of food on the absorption of QBW251 in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15). Single dose of QBW251 750 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15). Single dose of QBW251 1000 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15). Placebo to QBW251 in all cohorts of part 1 in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15). Multiple doses of QBW25 150 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36). Multiple doses of QBW251 400 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36). Multiple doses of QBW251 750 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36). Multiple doses of QBW251 450 mg bid in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36). Multiple doses of QBW251 750 mg bid in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36). Placebo to QBW251 in all cohorts of part 2 in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36). 150 mg b.i.d. Multiple doses. Patients having a class III, IV, V, or VI mutation on one allele and any other CFTR mutation on the other allele in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42. 450 mg b.i.d. Multiple doses. Patients having a class III, IV, V, or VI mutation on one allele and any other CFTR mutation on the other allele in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42. 450 mg b.i.d. Multiple doses. Patients who are homozygous for the F508del mutation in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42. Placebo to QBW251 in all cohorts of part 3 in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42. Total of all reporting groups
Overall Number of Baseline Participants 6 6 6 6 6 6 6 6 16 6 6 6 6 6 10 6 12 19 12 153
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 6 participants 6 participants 6 participants 6 participants 6 participants 6 participants 6 participants 6 participants 16 participants 6 participants 6 participants 6 participants 6 participants 6 participants 10 participants 6 participants 12 participants 19 participants 12 participants 153 participants
Part 1, HV (n= 64) 36.3  (8.69) 35  (14.25) 43.5  (3.39) 33.3  (9.61) 44.2  (8.23) 43.6  (9.07) 28.2  (9.28) 33.2  (9.47) 30.3  (9.18) NA [1]   (NA) NA [1]   (NA) NA [1]   (NA) NA [1]   (NA) NA [1]   (NA) NA [1]   (NA) NA [1]   (NA) NA [1]   (NA) NA [1]   (NA) NA [1]   (NA) 34.4  (9.92)
Part 2, HV (n=40) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) 30.3  (5.13) 30.5  (5.89) 29.2  (11.62) 31.7  (13.22) 27.8  (5) 29  (6.22) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) NA [2]   (NA) 29.7  (7.82)
Part 3, CF patients (n=49) NA [3]   (NA) NA [3]   (NA) NA [3]   (NA) NA [3]   (NA) NA [3]   (NA) NA [3]   (NA) NA [3]   (NA) NA [3]   (NA) NA [3]   (NA) NA [3]   (NA) NA [3]   (NA) NA [3]   (NA) NA [3]   (NA) NA [3]   (NA) NA [3]   (NA) 39.3  (5.47) 32.7  (13.77) 27  (5.44) 27.9  (6.37) 30.1  (9.18)
[1]
This row is for Part 1 HV
[2]
This row is for Part 2 HV
[3]
This row is for Part 3 HV
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 6 participants 6 participants 6 participants 6 participants 6 participants 6 participants 6 participants 16 participants 6 participants 6 participants 6 participants 6 participants 6 participants 10 participants 6 participants 12 participants 19 participants 12 participants 153 participants
Female
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  16.7%
5
  41.7%
9
  47.4%
4
  33.3%
19
  12.4%
Male
6
 100.0%
6
 100.0%
6
 100.0%
6
 100.0%
6
 100.0%
6
 100.0%
6
 100.0%
6
 100.0%
16
 100.0%
6
 100.0%
6
 100.0%
6
 100.0%
6
 100.0%
6
 100.0%
10
 100.0%
5
  83.3%
7
  58.3%
10
  52.6%
8
  66.7%
134
  87.6%
1.Primary Outcome
Title Part 1 and 2:Number of Participants (Healthy Volunteers) With Reported Adverse Events Receiving QBW251
Hide Description All adverse events (in healthy volunteers) reported.
Time Frame Day 1 to Day 36
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All treated subjects were included in the data analysis. Subjects were analyzed according to the study treatment(s) received.
Arm/Group Title Part 1 Cohort 4: QBW251 Part 1 Cohort 5: QBW251 Part 1 Cohort 6: QBW251 Part 1 Cohort 6: QBW251(Fed) Part 1 Cohort 7: QBW251 Part 1 Cohort 8: QBW251 Part 1 Placebo Part 2 Cohort 1: QBW251 Part 2 Cohort 2: QBW251 Part 2 Cohort 3: QBW251 Part 2 Cohort 4: QBW251 Part 2 Cohort 5: QBW251 Part 2 Placebo Part 1 Cohort 1: QBW251 Part 1 Cohort 2: QBW251 Part 1 Cohort 3: QBW251
Hide Arm/Group Description:
Single dose of QBW251 150 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
Single dose of QBW251 300 mg in healthy volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
Single dose of QBW251 500 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
Single dose of QBW251 500 mg (fed). single dose with food for a preliminary assessment of the effect of food on the absorption of QBW251 in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
Single dose of QBW251 750 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
Single dose of QBW251 1000 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
Placebo to QBW251 in all cohorts of part 1 in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
Multiple doses of QBW25 150 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
Multiple doses of QBW251 400 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
Multiple doses of QBW251 750 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
Multiple doses of QBW251 450 mg bid in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
Multiple doses of QBW251 750 mg bid in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
Placebo to QBW251 in all cohorts of part 2 in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
Single dose of QBW251 10 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15
Single dose of QBW251 25 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
Single dose of QBW251 75 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
Overall Number of Participants Analyzed 6 6 6 5 6 6 16 6 6 6 6 6 10 6 6 6
Measure Type: Number
Unit of Measure: Participants
Adverse events 1 2 2 1 1 4 8 3 6 3 6 4 7 3 2 0
Serious adverse events 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
Death 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
2.Primary Outcome
Title Part 3: Change in Lung Clearance Index (LCI) From Baseline to Day 15
Hide Description Change in Lung Clearance Index (LCI) will be conducted according to international standards in cystic fibrosis patients. Lung clearance index (LCI) is a measure of ventilation inhomogeneity that is derived from a multiple-breath washout test, A reduction in mean change from baseline for LCI2.5 indicates improvement.
Time Frame Baseline and Day 15
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Pharmacodynamics (PD) analysis set: All randomized patients were included in the PD analysis
Arm/Group Title Part 3 Cohort 1: QBW251 Part 3 Cohort 2: QBW251 Part 3 Cohort 3: QBW251 Part 3 Placebo
Hide Arm/Group Description:
150 mg b.i.d. Multiple doses. Patients having a class III, IV, V, or VI mutation on one allele and any other CFTR mutation on the other allele in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.
450 mg b.i.d. Multiple doses. Patients having a class III, IV, V, or VI mutation on one allele and any other CFTR mutation on the other allele in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.
450 mg b.i.d. Multiple doses. Patients who are homozygous for the F508del mutation in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.
Placebo to QBW251 in all cohorts of part 3 in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.
Overall Number of Participants Analyzed 5 11 17 11
Mean (Standard Deviation)
Unit of Measure: Ratio
0.27  (0.769) -0.85  (1.798) -0.13  (2.276) 0.28  (1.959)
3.Primary Outcome
Title Part 3: Number of Participants (Patients) With Reported Adverse Events Receiving QBW251
Hide Description All adverse events and serious adverse events (in patients) reported.
Time Frame Day 1 to Day 56
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set: All randomized patients were included in the safety analysis
Arm/Group Title Part 3 Cohort 1: QBW251 Part 3 Cohort 2: QBW251 Part 3 Cohort 3: QBW251 Part 3 Placebo
Hide Arm/Group Description:
150 mg b.i.d. Multiple doses. Patients having a class III, IV, V, or VI mutation on one allele and any other CFTR mutation on the other allele in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.
450 mg b.i.d. Multiple doses. Patients having a class III, IV, V, or VI mutation on one allele and any other CFTR mutation on the other allele in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.
450 mg b.i.d. Multiple doses. Patients who are homozygous for the F508del mutation in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.
Placebo to QBW251 in all cohorts of part 3 in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.
Overall Number of Participants Analyzed 6 12 19 12
Measure Type: Number
Unit of Measure: Participants
Adverse Events (AE) 6 8 18 8
Serious Adverse Events (SAE) 1 1 1 0
4.Secondary Outcome
Title Part 3:Change in Forced Expiratory Volume in 1 Second (FEV1) at Day 15
Hide Description Forced Expiratory Volume in 1 second (FEV1) will be measured via spirometer according to international standards. Forced Expiratory Volume in 1 second (FEV1) is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation
Time Frame Baseline and Day 15
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Pharmacodynamics (PD) analysis set: All randomized patients were included in the PD analysis
Arm/Group Title Part 3 Cohort 1: QBW251 Part 3 Cohort 2: QBW251 Part 3 Cohort 3: QBW251 Part 3 Placebo
Hide Arm/Group Description:
150 mg b.i.d. Multiple doses. Patients having a class III, IV, V, or VI mutation on one allele and any other CFTR mutation on the other allele in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.
450 mg b.i.d. Multiple doses. Patients having a class III, IV, V, or VI mutation on one allele and any other CFTR mutation on the other allele in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.
450 mg b.i.d. Multiple doses. Patients who are homozygous for the F508del mutation in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.
Placebo to QBW251 in all cohorts of part 3 in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.
Overall Number of Participants Analyzed 5 11 16 12
Least Squares Mean (Standard Error)
Unit of Measure: Liters
0.58  (2.476) 5.99  (1.648) -1.16  (1.059) -1.46  (1.229)
5.Secondary Outcome
Title Part 3: Change in Cystic Fibrosis Questionnaire-Revised Reported Outcomes
Hide Description Change in Cystic Fibrosis Questionnaire data will be obtained from patient reported outcomes (CFQ-R PRO). Respiratory Domain, cores range from 0 to 100, with higher scores indicating better health, a change of 4 is considered clinically relevant
Time Frame Baseline and Day 14
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Pharmacodynamics (PD) analysis set: All randomized patients were included in the PD analysis
Arm/Group Title Part 3 Cohort 1: QBW251 Part 3 Cohort 2: QBW251 Part 3 Cohort 3: QBW251 Part 3 Placebo
Hide Arm/Group Description:
150 mg b.i.d. Multiple doses. Patients having a class III, IV, V, or VI mutation on one allele and any other CFTR mutation on the other allele in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.
450 mg b.i.d. Multiple doses. Patients having a class III, IV, V, or VI mutation on one allele and any other CFTR mutation on the other allele in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.
450 mg b.i.d. Multiple doses. Patients who are homozygous for the F508del mutation in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.
Placebo to QBW251 in all cohorts of part 3 in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.
Overall Number of Participants Analyzed 5 11 19 12
Least Squares Mean (Standard Error)
Unit of Measure: Units on a scale
16.06  (6.872) 5.04  (4.617) -2.62  (2.853) -2.06  (4.415)
6.Secondary Outcome
Title Part 1: AUC0-t in Healthy Volunteers
Hide Description Pharmacokinetics of QBW251 in plasma: area under the plasma concentration versus time curve from time zero to time of last measurable concentration (AUC0-t). In part one of the study a single dose was administered and samples were collected up to 5 days. As a result the AUC0-t goes from Day 1 to Day 5 (for some lower doses QBW251 concentrations were not measured up to Day 5 as the concentrations were low due to the low dose administered)
Time Frame Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose (i.e. Days 2-5)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All subjects with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received study drug, and experienced no protocol deviations with relevant impact on PK data were included in the PK data analysis.
Arm/Group Title Part 1 Cohort 1: QBW251 Part 1 Cohort 2: QBW251 Part 1 Cohort 3: QBW251 Part 1 Cohort 4: QBW251 Part 1 Cohort 5: QBW251 Part 1 Cohort 6: QBW251 Part 1 Cohort 6: QBW251(Fed) Part 1 Cohort 7: QBW251 Part 1 Cohort 8: QBW251 Part 1 Placebo
Hide Arm/Group Description:
Single dose of QBW251 10 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
Single dose of QBW251 25 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
Single dose of QBW251 75 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
Single dose of QBW251 150 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
Single dose of QBW251 300 mg in healthy volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
Single dose of QBW251 500 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
Single dose of QBW251 500 mg (fed). single dose with food for a preliminary assessment of the effect of food on the absorption of QBW251 in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
Single dose of QBW251 750 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
Single dose of QBW251 1000 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
Placebo to QBW251 in all cohorts of part 1 in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
Overall Number of Participants Analyzed 6 6 6 6 6 6 5 6 6 16
Mean (Standard Deviation)
Unit of Measure: hr*ng/mL
52.5  (28.1) 73.7  (51.8) 692  (389) 1650  (907) 5470  (1070) 9450  (1740) 7470  (2190) 20200  (11500) 35900  (9100) NA [1]   (NA)
[1]
Not calculated
7.Secondary Outcome
Title Part 1: Maximum Concentration (Cmax) in Healthy Volunteers
Hide Description Pharmacokinetics of QBW251 in plasma: observed maximum plasma concentration following administration of QBW251. In this analysis Cmax will be reported using blood samples taken on Days 1- 5 are from healthy volunteers
Time Frame Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose (i.e. Days 1 - 5)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All subjects with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received study drug, and experienced no protocol deviations with relevant impact on PK data were included in the PK data analysis
Arm/Group Title Part 1 Cohort 1: QBW251 Part 1 Cohort 2: QBW251 Part 1 Cohort 3: QBW251 Part 1 Cohort 4: QBW251 Part 1 Cohort 5: QBW251 Part 1 Cohort 6: QBW251 Part 1 Cohort 6: QBW251(Fed) Part 1 Cohort 7: QBW251 Part 1 Cohort 8: QBW251
Hide Arm/Group Description:
Single dose of QBW251 10 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
Single dose of QBW251 25 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
Single dose of QBW251 75 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
Single dose of QBW251 150 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
Single dose of QBW251 300 mg in healthy volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
Single dose of QBW251 500 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
Single dose of QBW251 500 mg (fed). single dose with food for a preliminary assessment of the effect of food on the absorption of QBW251 in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
Single dose of QBW251 750 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
Single dose of QBW251 1000 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
Overall Number of Participants Analyzed 6 6 6 6 6 6 5 6 6
Mean (Standard Deviation)
Unit of Measure: ug/L
21.1  (11.9) 24.7  (15.9) 186  (82.3) 459  (267) 1110  (330) 1910  (413) 1090  (449) 2680  (1000) 4540  (930)
8.Secondary Outcome
Title Part 1: Time to Maximum Concentration (Tmax) in Healthy Volunteers
Hide Description Pharmacokinetics of QBW251 in plasma: time to reach the maximum concentration after administration of QBW251. In this analysis Tmax will be reported using blood samples taken on Days 1 - 5 from healthy volunteers. In this part of the study a single dose was administered and samples were collected up to 5 days. As a result the Tmax is one value as the concentration-time curve goes to Day 5 (for some lower does QBW251 concentrations were not measured up to Day 5 as the concentrations were low due to the low dose administered).
Time Frame Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose (i.e. Days 1 - 5)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All subjects with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received study drug, and experienced no protocol deviations with relevant impact on PK data were included in the PK data analysis
Arm/Group Title Part 1 Cohort 1: QBW251 Part 1 Cohort 2: QBW251 Part 1 Cohort 3: QBW251 Part 1 Cohort 4: QBW251 Part 1 Cohort 5: QBW251 Part 1 Cohort 6: QBW251 Part 1 Cohort 6: QBW251(Fed) Part 1 Cohort 7: QBW251 Part 1 Cohort 8: QBW251
Hide Arm/Group Description:
Single dose of QBW251 10 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
Single dose of QBW251 25 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
Single dose of QBW251 75 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
Single dose of QBW251 150 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
Single dose of QBW251 300 mg in healthy volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
Single dose of QBW251 500 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
Single dose of QBW251 500 mg (fed). single dose with food for a preliminary assessment of the effect of food on the absorption of QBW251 in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
Single dose of QBW251 750 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
Single dose of QBW251 1000 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
Overall Number of Participants Analyzed 6 6 6 6 6 6 5 6 6
Mean (Standard Deviation)
Unit of Measure: hr
0.756  (0.268) 1.25  (0.612) 1.33  (0.516) 1.50  (0.548) 1.50  (0.837) 2.17  (1.17) 3.40  (0.894) 2.52  (0.850) 1.83  (0.753)
9.Secondary Outcome
Title Part 1: T1/2 in Healthy Volunteers
Hide Description Pharmacokinetics of QBW251 in plasma: terminal elimination half-life. In this analysis T1/2 will be reported using blood samples taken on Days 1 - 5 from healthy volunteers. In part one of the study a single dose was administered and samples were collected up to 5 days. As a result the T1/2 goes from Day 1 to Day 5 (for some lower doses QBW251 concentrations were not measured up to Day 5 as the concentrations were low due to the low dose administered).
Time Frame Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose (i.e. Days 1 - 5)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All subjects with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received study drug, and experienced no protocol deviations with relevant impact on PK data were included in the PK data analysis
Arm/Group Title Part 1 Cohort 1: QBW251 Part 1 Cohort 2: QBW251 Part 1 Cohort 3: QBW251 Part 1 Cohort 4: QBW251 Part 1 Cohort 5: QBW251 Part 1 Cohort 6: QBW251 Part 1 Cohort 6: QBW251(Fed) Part 1 Cohort 7: QBW251 Part 1 Cohort 8: QBW251
Hide Arm/Group Description:
Single dose of QBW251 10 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
Single dose of QBW251 25 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
Single dose of QBW251 75 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
Single dose of QBW251 150 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
Single dose of QBW251 300 mg in healthy volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
Single dose of QBW251 500 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
Single dose of QBW251 500 mg (fed). single dose with food for a preliminary assessment of the effect of food on the absorption of QBW251 in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
Single dose of QBW251 750 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
Single dose of QBW251 1000 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
Overall Number of Participants Analyzed 6 6 6 6 6 6 5 6 6
Mean (Standard Deviation)
Unit of Measure: hr
NA [1]   (NA) NA [1]   (NA) 10.3  (4.24) 10.1  (3.35) 12.0  (2.26) 12.7  (1.99) 15.6  (5.03) 12.8  (3.85) 10.7  (2.19)
[1]
There were not enough time points to calculated the T1/2
10.Secondary Outcome
Title Part 1: AUCinf in Healthy Volunteers
Hide Description Pharmacokinetics of QBW251 in plasma: area under the plasma concentration time curve from time zero to infinity. In this analysis AUCinf will be reported using blood samples taken on Days 1 - 5 from healthy volunteers. In part one of the study a single dose was administered and samples were collected up to 5 days. As a result the AUCinf goes from Day 1 to Day 5 (for some lower doses QBW251 concentrations were not measured up to Day 5 as the concentrations were low due to the low dose administered)
Time Frame Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose (i.e. Days 1 - 5)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All subjects with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received study drug, and experienced no protocol deviations with relevant impact on PK data were included in the PK data analysis
Arm/Group Title Part 1 Cohort 1: QBW251 Part 1 Cohort 2: QBW251 Part 1 Cohort 3: QBW251 Part 1 Cohort 4: QBW251 Part 1 Cohort 5: QBW251 Part 1 Cohort 6: QBW251 Part 1 Cohort 6: QBW251(Fed) Part 1 Cohort 7: QBW251 Part 1 Cohort 8: QBW251
Hide Arm/Group Description:
Single dose of QBW251 10 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
Single dose of QBW251 25 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
Single dose of QBW251 75 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
Single dose of QBW251 150 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
Single dose of QBW251 300 mg in healthy volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
Single dose of QBW251 500 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
Single dose of QBW251 500 mg (fed). single dose with food for a preliminary assessment of the effect of food on the absorption of QBW251 in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
Single dose of QBW251 750 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
Single dose of QBW251 1000 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
Overall Number of Participants Analyzed 6 6 6 6 6 6 5 6 6
Mean (Standard Deviation)
Unit of Measure: hr*ng/mL
NA [1]   (NA) NA [1]   (NA) 731  (387) 1680  (903) 5510  (1080) 9480  (1740) 7540  (2220) 20300  (11500) 36000  (9120)
[1]
Not calculated due to insufficient data
11.Secondary Outcome
Title Part 1: CL/F in Healthy Volunteers
Hide Description Pharmacokinetics of QBW251 in plasma: apparent systemic clearance from plasma following extravascular administration. In this analysis CL/F will be reported using blood samples taken on Days 1 - 5 from healthy volunteers. In part one of the study a single dose was administered and samples were collected up to 5 days. As a result the CL/F goes from Day 1 to Day 5 (for some lower doses QBW251 concentrations were not measured up to Day 5 as the concentrations were low due to the low dose administered)
Time Frame Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose (i.e. Days 1 - 5)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All subjects with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received study drug, and experienced no protocol deviations with relevant impact on PK data were included in the PK data analysis
Arm/Group Title Part 1 Cohort 1: QBW251 Part 1 Cohort 2: QBW251 Part 1 Cohort 3: QBW251 Part 1 Cohort 4: QBW251 Part 1 Cohort 5: QBW251 Part 1 Cohort 6: QBW251 Part 1 Cohort 6: QBW251(Fed) Part 1 Cohort 7: QBW251 Part 1 Cohort 8: QBW251
Hide Arm/Group Description:
Single dose of QBW251 10 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
Single dose of QBW251 25 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
Single dose of QBW251 75 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
Single dose of QBW251 150 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
Single dose of QBW251 300 mg in healthy volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
Single dose of QBW251 500 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
Single dose of QBW251 500 mg (fed). single dose with food for a preliminary assessment of the effect of food on the absorption of QBW251 in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
Single dose of QBW251 750 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
Single dose of QBW251 1000 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
Overall Number of Participants Analyzed 6 6 6 6 6 6 5 6 6
Mean (Standard Deviation)
Unit of Measure: L/hr
NA [1]   (NA) NA [1]   (NA) 123  (49.0) 114  (63.9) 56.2  (11.0) 54.5  (11.9) 71.6  (22.6) 45.9  (19.9) 29.7  (9.00)
[1]
Not calculated due to insufficient data
12.Secondary Outcome
Title Part 1: Vz/F in Healthy Volunteers
Hide Description Pharmacokinetics of QBW251 in plasma: apparent volume of distribution during the terminal elimination phase following extravascular administration. In this analysis Vz/F will be reported using blood samples taken on Days 1 - 5 from healthy volunteers.
Time Frame Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose (i.e. Days 1 - 5)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All subjects with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received study drug, and experienced no protocol deviations with relevant impact on PK data were included in the PK data analysis
Arm/Group Title Part 1 Cohort 1: QBW251 Part 1 Cohort 2: QBW251 Part 1 Cohort 3: QBW251 Part 1 Cohort 4: QBW251 Part 1 Cohort 5: QBW251 Part 1 Cohort 6: QBW251 Part 1 Cohort 6: QBW251(Fed) Part 1 Cohort 7: QBW251 Part 1 Cohort 8: QBW251
Hide Arm/Group Description:
Single dose of QBW251 10 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
Single dose of QBW251 25 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
Single dose of QBW251 75 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
Single dose of QBW251 150 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
Single dose of QBW251 300 mg in healthy volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
Single dose of QBW251 500 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
Single dose of QBW251 500 mg (fed). single dose with food for a preliminary assessment of the effect of food on the absorption of QBW251 in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
Single dose of QBW251 750 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
Single dose of QBW251 1000 mg in Healthy Volunteers. Each treatment period was comprised of a baseline period (Day -1), an inpatient dosing period (Days 1 to 3), three follow-up visits (Days 4, 5, and 8), and one end-of-treatment-period evaluation performed 14 days after the dose of study drug (Day 15).
Overall Number of Participants Analyzed 6 6 6 6 6 6 5 6 6
Mean (Standard Deviation)
Unit of Measure: Liters
NA [1]   (NA) NA [1]   (NA) 1700  (772) 1490  (622) 957  (151) 995  (235) 1580  (587) 827  (375) 447  (112)
[1]
Not calculated due to insufficient data
13.Secondary Outcome
Title Part 2: AUCtau in Healthy Volunteers
Hide Description Pharmacokinetics of QBW251 in plasma after multiple doses: the area under the plasma concentration-time curve from time zero to end of the dosing interval tau. In this analysis AUCtau will be reported. Samples taken on Days 1 and 14 from healthy volunteers
Time Frame Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose Day 1 and 14; ( If B ID dosing, 12 hours samples will be pre-dosed)
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Hide Analysis Population Description
Pharmacokinetics analysis: All subjects with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received study drug, and experienced no protocol deviations with relevant impact on PK data were included in the PK data analysis
Arm/Group Title Part 2 Cohort 1: QBW251 Part 2 Cohort 2: QBW251 Part 2 Cohort 3: QBW251 Part 2 Cohort 4: QBW251 Part 2 Cohort 5: QBW251
Hide Arm/Group Description:
Multiple doses of QBW25 150 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
Multiple doses of QBW251 400 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
Multiple doses of QBW251 750 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
Multiple doses of QBW251 450 mg bid in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
Multiple doses of QBW251 750 mg bid in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
Overall Number of Participants Analyzed 6 6 6 6 6
Mean (Standard Deviation)
Unit of Measure: hr*ng/mL
Day1 1800  (794) 6170  (1250) 16100  (8170) 7160  (1960) 18800  (6360)
Day 14 2060  (708) 7620  (1470) 28300  (5570) 12100  (4930) 80300  (56300)
14.Secondary Outcome
Title Part 2: Maximum Concentration (Cmax) in Healthy Volunteers
Hide Description Pharmacokinetics of QBW251 in plasma after multiple doses: observed maximum plasma concentration following QBW251 at steady state. In this analysis Cmax will be reported using blood samples taken on Days 1 and 14 from healthy volunteers.
Time Frame Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose Day 1 and 14; ( If B ID dosing, 12 hours samples will be pre-dosed)
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Hide Analysis Population Description
Pharmacokinetics analysis: All subjects with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received study drug, and experienced no protocol deviations with relevant impact on PK data were included in the PK data analysis
Arm/Group Title Part 2 Cohort 1: QBW251 Part 2 Cohort 2: QBW251 Part 2 Cohort 3: QBW251 Part 2 Cohort 4: QBW251 Part 2 Cohort 5: QBW251
Hide Arm/Group Description:
Multiple doses of QBW25 150 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
Multiple doses of QBW251 400 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
Multiple doses of QBW251 750 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
Multiple doses of QBW251 450 mg bid in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
Multiple doses of QBW251 750 mg bid in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
Overall Number of Participants Analyzed 6 6 6 6 6
Mean (Standard Deviation)
Unit of Measure: ug/L
Day 1 541  (338) 1650  (343) 2790  (1040) 1650  (188) 3720  (1530)
Day 14 430  (145) 1500  (442) 3840  (868) 2190  (769) 9420  (4330)
15.Secondary Outcome
Title Part 2: Time to Maximum Concentration (Tmax) in Healthy Volunteers
Hide Description Pharmacokinetics of QBW251 in plasma after multiple doses: time to reach the maximum concentration after administration of QBW251. In this analysis Tmax will be reported using blood samples taken on Days 1 and 14 from healthy volunteers.
Time Frame Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose Day 1 and 14; ( If B ID dosing, 12 hours samples will be pre-dosed)
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Hide Analysis Population Description
Pharmacokinetics analysis: All subjects with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received study drug, and experienced no protocol deviations with relevant impact on PK data were included in the PK data analysis
Arm/Group Title Part 2 Cohort 1: QBW251 Part 2 Cohort 2: QBW251 Part 2 Cohort 3: QBW251 Part 2 Cohort 4: QBW251 Part 2 Cohort 5: QBW251
Hide Arm/Group Description:
Multiple doses of QBW25 150 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
Multiple doses of QBW251 400 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
Multiple doses of QBW251 750 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
Multiple doses of QBW251 450 mg bid in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
Multiple doses of QBW251 750 mg bid in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
Overall Number of Participants Analyzed 6 6 6 6 6
Mean (Standard Deviation)
Unit of Measure: hr
Day 1 1.67  (0.816) 1.17  (0.408) 2.33  (1.21) 2.68  (0.813) 3.67  (0.516)
Day 2 2.17  (1.17) 2.17  (0.408) 2.33  (1.03) 3.25  (1.41) 3.80  (0.447)
16.Secondary Outcome
Title Part 2: AUC0-t
Hide Description Pharmacokinetics of QBW251 in plasma: area under the plasma concentration versus time curve from time zero to time of last measurable concentration. In this analysis AUC0-t will be reported using blood samples taken on Day 14 are from healthy volunteers.
Time Frame Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose Day 14; ( If B ID dosing, 12 hours samples will be pre-dosed)
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Hide Analysis Population Description
[Not Specified]
Arm/Group Title Part 2 Cohort 1: QBW251 Part 2 Cohort 2: QBW251 Part 2 Cohort 3: QBW251 Part 2 Cohort 4: QBW251 Part 2 Cohort 5: QBW251 Part 2 Placebo
Hide Arm/Group Description:
Multiple doses of QBW25 150 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
Multiple doses of QBW251 400 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
Multiple doses of QBW251 750 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
Multiple doses of QBW251 450 mg bid in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
Multiple doses of QBW251 750 mg bid in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
Placebo to QBW251 in all cohorts of part 2 in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
Overall Number of Participants Analyzed 6 6 6 6 5 14
Mean (Standard Deviation)
Unit of Measure: hr*ng/mL
2060  (708) 7620  (1470) 28300  (5570) 12100  (4930) 80300  (56300) NA [1]   (NA)
[1]
Not calculated
17.Secondary Outcome
Title Part 2: Cav in Healthy Volunteers
Hide Description The average drug concentration in plasma during multiple dosing. In this analysis Cav will be reported using blood samples taken on Days 1 and 14 are from healthy volunteers.
Time Frame Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose Day 1 and 14; ( If B ID dosing, 12 hours samples will be pre-dosed)
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Hide Analysis Population Description
Pharmacokinetics analysis: All subjects with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received study drug, and experienced no protocol deviations with relevant impact on PK data were included in the PK data analysis
Arm/Group Title Part 2 Cohort 1: QBW251 Part 2 Cohort 2: QBW251 Part 2 Cohort 3: QBW251 Part 2 Cohort 4: QBW251 Part 2 Cohort 5: QBW251
Hide Arm/Group Description:
Multiple doses of QBW25 150 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
Multiple doses of QBW251 400 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
Multiple doses of QBW251 750 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
Multiple doses of QBW251 450 mg bid in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
Multiple doses of QBW251 750 mg bid in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
Overall Number of Participants Analyzed 6 6 6 6 6
Mean (Standard Deviation)
Unit of Measure: ug/L
85.8  (29.5) 318  (61.1) 1180  (232) NA [1]   (NA) NA [1]   (NA)
[1]
Not calculated due to insufficient data
18.Secondary Outcome
Title Part 2: CL/F in Healthy Volunteers
Hide Description apparent systemic clearance from plasma following extravascular administration. In this analysis CL/F will be reported using blood samples taken on Day 14 from healthy volunteers.
Time Frame Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose Day 14; ( If B ID dosing, 12 hours samples will be pre-dosed)
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Hide Analysis Population Description
Pharmacokinetics analysis: All subjects with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received study drug, and experienced no protocol deviations with relevant impact on PK data were included in the PK data analysis
Arm/Group Title Part 2 Cohort 1: QBW251 Part 2 Cohort 2: QBW251 Part 2 Cohort 3: QBW251 Part 2 Cohort 4: QBW251 Part 2 Cohort 5: QBW251
Hide Arm/Group Description:
Multiple doses of QBW25 150 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
Multiple doses of QBW251 400 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
Multiple doses of QBW251 750 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
Multiple doses of QBW251 450 mg bid in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
Multiple doses of QBW251 750 mg bid in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
Overall Number of Participants Analyzed 6 6 6 6 6
Mean (Standard Deviation)
Unit of Measure: L/hr
80.8  (29.7) 54.0  (9.40) 27.5  (5.98) NA [1]   (NA) NA [1]   (NA)
[1]
Not calculated due to insufficient data
19.Secondary Outcome
Title Part 2: Vz/F in Healthy Volunteers
Hide Description Apparent volume of distribution during the terminal elimination phase following extravascular administration. In this analysis Vz/F will be reported using blood samples taken on Day 14 from healthy volunteers.
Time Frame Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose Day 14; ( If B ID dosing, 12 hours samples will be pre-dosed)
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Hide Analysis Population Description
Pharmacokinetics analysis: All subjects with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received study drug, and experienced no protocol deviations with relevant impact on PK data were included in the PK data analysis
Arm/Group Title Part 2 Cohort 1: QBW251 Part 2 Cohort 2: QBW251 Part 2 Cohort 3: QBW251 Part 2 Cohort 4: QBW251 Part 2 Cohort 5: QBW251
Hide Arm/Group Description:
Multiple doses of QBW25 150 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
Multiple doses of QBW251 400 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
Multiple doses of QBW251 750 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
Multiple doses of QBW251 450 mg bid in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
Multiple doses of QBW251 750 mg bid in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
Overall Number of Participants Analyzed 6 6 6 6 6
Mean (Standard Deviation)
Unit of Measure: Liters
1330  (550) 1120  (395) 608  (255) NA [1]   (NA) NA [1]   (NA)
[1]
Not calculated due to insufficient data
20.Secondary Outcome
Title Part 2: Racc in Healthy Volunteers
Hide Description Accumulation ratio (Racc). In this analysis Racc will be reported using blood samples taken on Days 1 - 14 from healthy volunteers.
Time Frame Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose Day 1 - 14; ( If B ID dosing, 12 hours samples will be pre-dosed)
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Hide Analysis Population Description
Pharmacokinetics analysis: All subjects with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received study drug, and experienced no protocol deviations with relevant impact on PK data were included in the PK data analysis
Arm/Group Title Part 2 Cohort 1: QBW251 Part 2 Cohort 2: QBW251 Part 2 Cohort 3: QBW251 Part 2 Cohort 4: QBW251 Part 2 Cohort 5: QBW251
Hide Arm/Group Description:
Multiple doses of QBW25 150 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
Multiple doses of QBW251 400 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
Multiple doses of QBW251 750 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
Multiple doses of QBW251 450 mg bid in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
Multiple doses of QBW251 750 mg bid in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
Overall Number of Participants Analyzed 6 6 6 6 6
Mean (Standard Deviation)
Unit of Measure: Ratio
1.27  (0.425) 1.25  (0.199) 2.08  (0.913) 1.66  (0.386) 3.88  (2.07)
21.Secondary Outcome
Title Part 2: T1/2 in Healthy Volunteers
Hide Description terminal elimination half-life (T1/2). In this analysis T1/2 will be reported using blood samples taken on Day 14 from healthy volunteers.
Time Frame Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose Day 14; ( If B ID dosing, 12 hours samples will be pre-dosed)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetics analysis: All subjects with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received study drug, and experienced no protocol deviations with relevant impact on PK data were included in the PK data analysis
Arm/Group Title Part 2 Cohort 1: QBW251 Part 2 Cohort 2: QBW251 Part 2 Cohort 3: QBW251 Part 2 Cohort 4: QBW251 Part 2 Cohort 5: QBW251
Hide Arm/Group Description:
Multiple doses of QBW25 150 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
Multiple doses of QBW251 400 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
Multiple doses of QBW251 750 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
Multiple doses of QBW251 450 mg bid in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
Multiple doses of QBW251 750 mg bid in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
Overall Number of Participants Analyzed 6 6 6 6 6
Mean (Standard Deviation)
Unit of Measure: hr
11.3  (1.44) 14.1  (3.80) 15.1  (4.40) NA [1]   (NA) NA [1]   (NA)
[1]
Not calculated due to insufficient data
22.Secondary Outcome
Title Part 3: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of QBW251 in CF Patients
Hide Description Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)
Time Frame Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4, 8 hr post-dose in Day 1, Day 14
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Hide Analysis Population Description
Pharmacokinetics analysis: All subjects with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received study drug, and experienced no protocol deviations with relevant impact on PK data were included in the PK data analysis
Arm/Group Title Part 3 Cohort 1: QBW251 Part 3 Cohort 2: QBW251 Part 3 Cohort 3: QBW251
Hide Arm/Group Description:
150 mg b.i.d. Multiple doses. Patients having a class III, IV, V, or VI mutation on one allele and any other CFTR mutation on the other allele in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.
450 mg b.i.d. Multiple doses. Patients having a class III, IV, V, or VI mutation on one allele and any other CFTR mutation on the other allele in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.
450 mg b.i.d. Multiple doses. Patients who are homozygous for the F508del mutation in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.
Overall Number of Participants Analyzed 6 12 19
Mean (Standard Deviation)
Unit of Measure: ng × hr /mL
Day 1 1110  (709) 7530  (2480) 6020  (2960)
Day 14 1760  (943) 18900  (6850) NA [1]   (NA)
[1]
PK parameters were not calculated for Day 14 as blood samples were collected up to 2 hours post-dose.
23.Secondary Outcome
Title Part 3: Plasma Concentration at the Last Quantifiable Time Point (Clast) of QBW251 in CF Patients
Hide Description Blood samples were collected at timepoints prespecified in the study protocol. Tlast of QBW251 was the last time point when blood sample collected was quantifiable
Time Frame Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4, 8 hr post-dose in Day 1, Day2
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetics analysis: All subjects with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received study drug, and experienced no protocol deviations with relevant impact on PK data were included in the PK data analysis
Arm/Group Title Part 3 Cohort 1: QBW251 Part 3 Cohort 2: QBW251 Part 3 Cohort 3: QBW251
Hide Arm/Group Description:
150 mg b.i.d. Multiple doses. Patients having a class III, IV, V, or VI mutation on one allele and any other CFTR mutation on the other allele in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.
450 mg b.i.d. Multiple doses. Patients having a class III, IV, V, or VI mutation on one allele and any other CFTR mutation on the other allele in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.
450 mg b.i.d. Multiple doses. Patients who are homozygous for the F508del mutation in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.
Overall Number of Participants Analyzed 6 12 19
Mean (Standard Deviation)
Unit of Measure: ng/mL
Day 1 42.3  (14.1) 423  (275) 653  (318)
Day 14 86.4  (16.3) 1570  (813) NA [1]   (NA)
[1]
PK parameters were not calculated for Day 14 as blood samples were collected up to 2 hours post-dose
24.Secondary Outcome
Title Part 3: Maximum Concentration (Cmax) in CF Patients
Hide Description Observed maximum plasma concentration following administration of QBW251. In this analysis Cmax will be reported using blood samples taken on Day 1and day 14 from patients
Time Frame Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4, 8 hr post-dose in Day 1, Day 14
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetics analysis: All subjects with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received study drug, and experienced no protocol deviations with relevant impact on PK data were included in the PK data analysis
Arm/Group Title Part 3 Cohort 1: QBW251 Part 3 Cohort 2: QBW251 Part 3 Cohort 3: QBW251
Hide Arm/Group Description:
150 mg b.i.d. Multiple doses. Patients having a class III, IV, V, or VI mutation on one allele and any other CFTR mutation on the other allele in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.
450 mg b.i.d. Multiple doses. Patients having a class III, IV, V, or VI mutation on one allele and any other CFTR mutation on the other allele in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.
450 mg b.i.d. Multiple doses. Patients who are homozygous for the F508del mutation in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.
Overall Number of Participants Analyzed 6 12 19
Mean (Standard Deviation)
Unit of Measure: ng/mL
Day 1 419  (316) 1950  (715) 2380  (1240)
Day 14 632  (438) 4080  (1780) NA [1]   (NA)
[1]
PK parameters were not calculated for Day 14 as blood samples were collected up to 2 hours post-dose
25.Secondary Outcome
Title Part 3: Tlast in CF Patients
Hide Description Blood samples were collected at timepoints prespecified in the study protocol. Tlast of QBW251 was the last time point when blood sample collected was quantifiable day 1 and day 14
Time Frame Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4, 8 hr post-dose in Day 1, Day 14
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetics analysis: All subjects with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received study drug, and experienced no protocol deviations with relevant impact on PK data were included in the PK data analysis
Arm/Group Title Part 3 Cohort 1: QBW251 Part 3 Cohort 2: QBW251 Part 3 Cohort 3: QBW251
Hide Arm/Group Description:
150 mg b.i.d. Multiple doses. Patients having a class III, IV, V, or VI mutation on one allele and any other CFTR mutation on the other allele in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.
450 mg b.i.d. Multiple doses. Patients having a class III, IV, V, or VI mutation on one allele and any other CFTR mutation on the other allele in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.
450 mg b.i.d. Multiple doses. Patients who are homozygous for the F508del mutation in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.
Overall Number of Participants Analyzed 6 12 19
Mean (Standard Deviation)
Unit of Measure: hr
Day 1 7.99  (0.0136) 7.95  (0.149) 5.80  (0.639)
Day 14 7.97  (0.0667) 7.96  (0.0554) NA [1]   (NA)
[1]
PK parameters were not calculated for Day 14 as blood samples were collected up to 2 hours post-dose
26.Secondary Outcome
Title Part 3: Time to Maximum Concentration (Tmax)
Hide Description Pharmacokinetics of QBW251 in plasma after multiple doses: time to reach the maximum concentration after administration of QBW251. In this analysis Tmax will be reported using blood samples taken on Days 1 and 14 in patients
Time Frame Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4, 8 hr post-dose in Day 1, Day 14
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Pharmacokinetics analysis: All subjects with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received study drug, and experienced no protocol deviations with relevant impact on PK data were included in the PK data analysis
Arm/Group Title Part 3 Cohort 1: QBW251 Part 3 Cohort 2: QBW251 Part 3 Cohort 3: QBW251
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150 mg b.i.d. Multiple doses. Patients having a class III, IV, V, or VI mutation on one allele and any other CFTR mutation on the other allele in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.
450 mg b.i.d. Multiple doses. Patients having a class III, IV, V, or VI mutation on one allele and any other CFTR mutation on the other allele in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.
450 mg b.i.d. Multiple doses. Patients who are homozygous for the F508del mutation in patients. treatment period (Day 1 to Day 14) with study visits on Days 1, 4, 7 and 14 with follow-up visits on Days 15, 28 and 42.
Overall Number of Participants Analyzed 6 12 19
Mean (Standard Deviation)
Unit of Measure: hr
Day 1 3.17  (2.47) 3.08  (1.68) 3.18  (0.838)
Day 14 1.82  (0.750) 2.39  (0.973) NA [1]   (NA)
[1]
PK parameters were not calculated for Day 14 as blood samples were collected up to 2 hours post-dose
27.Secondary Outcome
Title Part 2: Ae0-t in Healthy Volunteers
Hide Description Pharmacokinetics of QBW251 in urine: amount of drug excreted in urine from time zero until last measurable concentration. In this analysis Ae0-t will be reported using urine samples taken on Day 1 from healthy volunteers.
Time Frame Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose Day 1
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Hide Analysis Population Description
All subjects with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received study drug, and experienced no protocol deviations with relevant impact on PK data were included in the PK data analysis
Arm/Group Title Part 2 Cohort 1: QBW251 Part 2 Cohort 2: QBW251 Part 2 Cohort 3: QBW251 Part 2 Cohort 4: QBW251 Part 2 Cohort 5: QBW251 Part 2 Placebo
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Multiple doses of QBW25 150 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
Multiple doses of QBW251 400 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
Multiple doses of QBW251 750 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
Multiple doses of QBW251 450 mg bid in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
Multiple doses of QBW251 750 mg bid in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
Placebo to QBW251 in all cohorts of part 2 in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
Overall Number of Participants Analyzed 6 6 6 5 5 14
Mean (Standard Deviation)
Unit of Measure: L/hr
2.36  (1.84) 2.20  (1.26) 1.21  (0.697) 0.419  (0.271) 0.140  (0.0936) NA [1]   (NA)
[1]
Not calculated
28.Secondary Outcome
Title Part 2: CLr in Healthy Volunteers
Hide Description Pharmacokinetics of QBW251 in urine: renal clearance following drug administration. In this analysis CLr will be reported using urine samples taken on Day 1 from healthy volunteers.
Time Frame Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4 , 8 hr post-dose at Day 1; 24, 48, 72 and 96 hr post dose Day 1; Day 14 was calculated as urine was only collected up to 12 hours on Day 1 thus CLr cannot be calculated.
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Hide Analysis Population Description
Pharmacokinetics analysis: All subjects with at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, who received study drug, and experienced no protocol deviations with relevant impact on PK data were included in the PK data analysis
Arm/Group Title Part 2 Cohort 1: QBW251 Part 2 Cohort 2: QBW251 Part 2 Cohort 3: QBW251 Part 2 Cohort 4: QBW251 Part 2 Cohort 5: QBW251
Hide Arm/Group Description:
Multiple doses of QBW25 150 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
Multiple doses of QBW251 400 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
Multiple doses of QBW251 750 mg qd in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
Multiple doses of QBW251 450 mg bid in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
Multiple doses of QBW251 750 mg bid in Healthy Volunteers. 14-day treatment period, follow-up study visits (Days 18, 22 and 29) and one End-of-Study evaluation (Day 36).
Overall Number of Participants Analyzed 6 6 6 6 6
Mean (Standard Deviation)
Unit of Measure: L/hr
2.36  (1.84) 2.20  (1.26) 1.21  (0.697) 0.419  (0.271) 0.140  (0.0936)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Part 1 Placebo Part 1 QBW251 10mg Part 1 QBW251 25mg Part 1 QBW251 150mg Part 1 QBW251 300mg Part 1 QBW251 500mg Part 1 QBW251 500mg (Fed) Part 1 QBW251 750mg Part 1 QBW251 1000mg Part 2 Placebo Part 2 QBW251 150mg Part 2 QBW251 400mg Part 2 QBW251 750mg Part 2 QBW251 450mg BID Part 2 QBW251 750mg BID Part 3 Placebo C1/C2/C3 Part 3 QBW251 150mg BID C1 Part 3 QBW251 450mg BID C2 Part 3 QBW251 450mg BID C3
Hide Arm/Group Description Part 1 Placebo Part 1 QBW251 10mg Part 1 QBW251 25mg Part 1 QBW251 150mg Part 1 QBW251 300mg Part 1 QBW251 500mg Part 1 QBW251 500mg (fed) Part 1 QBW251 750mg Part 1 QBW251 1000mg Part 2 Placebo Part 2 QBW251 150mg Part 2 QBW251 400mg Part 2 QBW251 750mg Part 2 QBW251 450mg BID Part 2 QBW251 750mg BID Part 3 Placebo C1/C2/C3 Part 3 QBW251 150mg BID C1 Part 3 QBW251 450mg BID C2 Part 3 QBW251 450mg BID C3
All-Cause Mortality
Part 1 Placebo Part 1 QBW251 10mg Part 1 QBW251 25mg Part 1 QBW251 150mg Part 1 QBW251 300mg Part 1 QBW251 500mg Part 1 QBW251 500mg (Fed) Part 1 QBW251 750mg Part 1 QBW251 1000mg Part 2 Placebo Part 2 QBW251 150mg Part 2 QBW251 400mg Part 2 QBW251 750mg Part 2 QBW251 450mg BID Part 2 QBW251 750mg BID Part 3 Placebo C1/C2/C3 Part 3 QBW251 150mg BID C1 Part 3 QBW251 450mg BID C2 Part 3 QBW251 450mg BID C3
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/--   --/--   --/--   --/--   --/--   --/--   --/--   --/--   --/--   --/--   --/--   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Part 1 Placebo Part 1 QBW251 10mg Part 1 QBW251 25mg Part 1 QBW251 150mg Part 1 QBW251 300mg Part 1 QBW251 500mg Part 1 QBW251 500mg (Fed) Part 1 QBW251 750mg Part 1 QBW251 1000mg Part 2 Placebo Part 2 QBW251 150mg Part 2 QBW251 400mg Part 2 QBW251 750mg Part 2 QBW251 450mg BID Part 2 QBW251 750mg BID Part 3 Placebo C1/C2/C3 Part 3 QBW251 150mg BID C1 Part 3 QBW251 450mg BID C2 Part 3 QBW251 450mg BID C3
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/16 (0.00%)   0/6 (0.00%)   0/6 (0.00%)   0/6 (0.00%)   0/6 (0.00%)   0/6 (0.00%)   0/5 (0.00%)   0/6 (0.00%)   0/6 (0.00%)   0/10 (0.00%)   0/6 (0.00%)   0/6 (0.00%)   0/6 (0.00%)   0/6 (0.00%)   0/6 (0.00%)   0/12 (0.00%)   1/6 (16.67%)   1/12 (8.33%)   1/19 (5.26%) 
Infections and infestations                                       
INFECTIVE PULMONARY EXACERBATION OF CYSTIC FIBROSIS  1  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  1/12 (8.33%)  1/19 (5.26%) 
SINUSITIS  1  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/6 (16.67%)  0/12 (0.00%)  0/19 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Part 1 Placebo Part 1 QBW251 10mg Part 1 QBW251 25mg Part 1 QBW251 150mg Part 1 QBW251 300mg Part 1 QBW251 500mg Part 1 QBW251 500mg (Fed) Part 1 QBW251 750mg Part 1 QBW251 1000mg Part 2 Placebo Part 2 QBW251 150mg Part 2 QBW251 400mg Part 2 QBW251 750mg Part 2 QBW251 450mg BID Part 2 QBW251 750mg BID Part 3 Placebo C1/C2/C3 Part 3 QBW251 150mg BID C1 Part 3 QBW251 450mg BID C2 Part 3 QBW251 450mg BID C3
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   8/16 (50.00%)   3/6 (50.00%)   2/6 (33.33%)   1/6 (16.67%)   2/6 (33.33%)   2/6 (33.33%)   1/5 (20.00%)   1/6 (16.67%)   4/6 (66.67%)   7/10 (70.00%)   3/6 (50.00%)   6/6 (100.00%)   3/6 (50.00%)   6/6 (100.00%)   4/6 (66.67%)   8/12 (66.67%)   5/6 (83.33%)   8/12 (66.67%)   18/19 (94.74%) 
Cardiac disorders                                       
PALPITATIONS  1  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/12 (8.33%)  1/6 (16.67%)  0/12 (0.00%)  0/19 (0.00%) 
Congenital, familial and genetic disorders                                       
ICHTHYOSIS  1  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/12 (8.33%)  0/6 (0.00%)  0/12 (0.00%)  0/19 (0.00%) 
Ear and labyrinth disorders                                       
EAR DISCOMFORT  1  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/10 (10.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/19 (0.00%) 
EAR PAIN  1  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/19 (0.00%) 
TINNITUS  1  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/6 (16.67%)  0/12 (0.00%)  0/19 (0.00%) 
Gastrointestinal disorders                                       
ABDOMINAL DISCOMFORT  1  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  1/12 (8.33%)  1/19 (5.26%) 
ABDOMINAL DISTENSION  1  0/16 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/19 (0.00%) 
ABDOMINAL PAIN  1  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/10 (10.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/19 (5.26%) 
ABDOMINAL PAIN LOWER  1  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/19 (0.00%) 
APHTHOUS STOMATITIS  1  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/19 (0.00%) 
DIARRHOEA  1  1/16 (6.25%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/10 (10.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  2/19 (10.53%) 
FAECES DISCOLOURED  1  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  1/12 (8.33%)  0/19 (0.00%) 
FLATULENCE  1  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  2/10 (20.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  4/6 (66.67%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  1/12 (8.33%)  0/19 (0.00%) 
GASTROOESOPHAGEAL REFLUX DISEASE  1  0/16 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  1/12 (8.33%)  0/19 (0.00%) 
GINGIVAL DISORDER  1  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/6 (16.67%)  0/12 (0.00%)  0/19 (0.00%) 
NAUSEA  1  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/6 (16.67%)  4/12 (33.33%)  2/19 (10.53%) 
SALIVA ALTERED  1  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/12 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/19 (0.00%) 
SALIVARY GLAND PAIN  1  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/19 (0.00%) 
VOMITING  1  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  2/19 (10.53%) 
General disorders                                       
ASTHENIA  1  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  1/12 (8.33%)  1/19 (5.26%) 
CHEST DISCOMFORT  1  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  2/12 (16.67%)  0/6 (0.00%)  0/12 (0.00%)  1/19 (5.26%) 
CHEST PAIN  1  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/19 (0.00%) 
FATIGUE  1  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  3/12 (25.00%)  2/19 (10.53%) 
INFLUENZA LIKE ILLNESS  1  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/19 (0.00%) 
PAIN  1  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  1/12 (8.33%)  1/19 (5.26%) 
PERIPHERAL SWELLING  1  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  1/12 (8.33%)  0/19 (0.00%) 
PYREXIA  1  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  1/12 (8.33%)  1/19 (5.26%) 
SENSATION OF FOREIGN BODY  1  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/12 (8.33%)  0/6 (0.00%)  0/12 (0.00%)  0/19 (0.00%) 
THIRST  1  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/19 (0.00%) 
VESSEL PUNCTURE SITE BRUISE  1  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/19 (5.26%) 
Infections and infestations                                       
BRONCHITIS  1  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/19 (5.26%) 
BRONCHOPULMONARY ASPERGILLOSIS ALLERGIC  1  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  1/12 (8.33%)  1/19 (5.26%) 
FOLLICULITIS  1  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/19 (0.00%) 
FUNGAL INFECTION  1  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/19 (5.26%) 
GASTROENTERITIS  1  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/10 (10.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/19 (0.00%) 
INFECTIVE PULMONARY EXACERBATION OF CYSTIC FIBROSIS  1  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  3/12 (25.00%)  1/6 (16.67%)  0/12 (0.00%)  2/19 (10.53%) 
NASOPHARYNGITIS  1  1/16 (6.25%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/5 (20.00%)  0/6 (0.00%)  1/6 (16.67%)  1/10 (10.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/12 (8.33%)  0/6 (0.00%)  0/12 (0.00%)  0/19 (0.00%) 
ORAL HERPES  1  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/19 (0.00%) 
PHARYNGITIS  1  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/10 (10.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/19 (0.00%) 
SINUSITIS  1  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/6 (16.67%)  0/12 (0.00%)  0/19 (0.00%) 
UPPER RESPIRATORY TRACT INFECTION  1  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/19 (5.26%) 
VIRAL UPPER RESPIRATORY TRACT INFECTION  1  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/19 (5.26%) 
Injury, poisoning and procedural complications                                       
ARTHROPOD BITE  1  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/19 (5.26%) 
LIGAMENT SPRAIN  1  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/12 (8.33%)  0/6 (0.00%)  0/12 (0.00%)  0/19 (0.00%) 
SKIN WOUND  1  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/19 (0.00%) 
Investigations                                       
ADENOVIRUS TEST POSITIVE  1  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/19 (5.26%) 
BLOOD ALKALINE PHOSPHATASE INCREASED  1  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/19 (5.26%) 
BLOOD POTASSIUM DECREASED  1  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/19 (5.26%) 
BREATH SOUNDS ABNORMAL  1  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/19 (5.26%) 
CORONAVIRUS TEST POSITIVE  1  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/19 (5.26%) 
Metabolism and nutrition disorders                                       
DECREASED APPETITE  1  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/19 (5.26%) 
HYPOGLYCAEMIA  1  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/19 (5.26%) 
VITAMIN D DEFICIENCY  1  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/12 (8.33%)  0/6 (0.00%)  0/12 (0.00%)  0/19 (0.00%) 
Musculoskeletal and connective tissue disorders                                       
BACK PAIN  1  0/16 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/19 (0.00%) 
JOINT SWELLING  1  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  1/12 (8.33%)  0/19 (0.00%) 
MUSCLE SPASMS  1  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/19 (5.26%) 
MUSCULOSKELETAL CHEST PAIN  1  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/12 (8.33%)  0/6 (0.00%)  0/12 (0.00%)  0/19 (0.00%) 
MUSCULOSKELETAL PAIN  1  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/10 (10.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/19 (0.00%) 
MUSCULOSKELETAL STIFFNESS  1  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/10 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/19 (0.00%) 
NECK PAIN  1  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/19 (5.26%) 
PAIN IN EXTREMITY  1  1/16 (6.25%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/12 (8.33%)  0/6 (0.00%)  0/12 (0.00%)  0/19 (0.00%) 
Nervous system disorders                                       
BALANCE DISORDER  1  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/10 (10.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/19 (0.00%) 
DIZZINESS  1  3/16 (18.75%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  2/6 (33.33%)  2/10 (20.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  2/12 (16.67%)  1/19 (5.26%) 
HEADACHE  1  2/16 (12.50%)  2/6 (33.33%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  2/6 (33.33%)  0/5 (0.00%)  0/6 (0.00%)  2/6 (33.33%)  4/10 (40.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  1/6 (16.67%)  2/6 (33.33%)  0/12 (0.00%)  1/6 (16.67%)  3/12 (25.00%)  4/19 (21.05%) 
HYPERAESTHESIA  1  1/16 (6.25%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/19 (0.00%) 
PRESYNCOPE  1  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/19 (0.00%) 
SCIATICA  1  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  1/12 (8.33%)  0/19 (0.00%) 
SYNCOPE  1  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/12 (0.00%)  1/6 (16.67%)  0/12 (0.00%)  1/19 (5.26%) 
TREMOR  1  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/19 (5.26%) 
Psychiatric disorders                                       
AGITATION  1  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/19 (5.26%) 
DEPRESSION  1  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/19 (5.26%) 
INSOMNIA  1  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/12 (8.33%)  1/6 (16.67%)  0/12 (0.00%)  0/19 (0.00%) 
STRESS  1  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/19 (5.26%) 
Renal and urinary disorders                                       
CHROMATURIA  1  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/19 (5.26%) 
GLYCOSURIA  1  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/19 (5.26%) 
PROTEINURIA  1  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/19 (5.26%) 
Respiratory, thoracic and mediastinal disorders                                       
BRONCHIAL OBSTRUCTION  1  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/12 (8.33%)  0/6 (0.00%)  0/12 (0.00%)  0/19 (0.00%) 
COUGH  1  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  4/6 (66.67%)  0/6 (0.00%)  2/12 (16.67%)  1/6 (16.67%)  1/12 (8.33%)  4/19 (21.05%) 
DYSPNOEA  1  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/19 (0.00%) 
EPISTAXIS  1  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/10 (10.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/19 (0.00%) 
HAEMOPTYSIS  1  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/12 (8.33%)  0/6 (0.00%)  0/12 (0.00%)  2/19 (10.53%) 
NASAL CONGESTION  1  1/16 (6.25%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  2/19 (10.53%) 
NASAL DISCOMFORT  1  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/19 (0.00%) 
OROPHARYNGEAL PAIN  1  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  1/12 (8.33%)  0/19 (0.00%) 
PAINFUL RESPIRATION  1  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/19 (5.26%) 
PRODUCTIVE COUGH  1  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/12 (8.33%)  0/6 (0.00%)  0/12 (0.00%)  0/19 (0.00%) 
PULMONARY CONGESTION  1  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  2/12 (16.67%)  1/19 (5.26%) 
RHINORRHOEA  1  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  1/12 (8.33%)  2/19 (10.53%) 
SINUS CONGESTION  1  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/6 (16.67%)  0/12 (0.00%)  1/19 (5.26%) 
SNEEZING  1  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/19 (5.26%) 
SPUTUM INCREASED  1  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  2/12 (16.67%)  3/6 (50.00%)  0/12 (0.00%)  5/19 (26.32%) 
THROAT IRRITATION  1  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/6 (16.67%)  0/12 (0.00%)  0/19 (0.00%) 
TONSILLAR DISORDER  1  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/12 (8.33%)  0/6 (0.00%)  0/12 (0.00%)  0/19 (0.00%) 
Skin and subcutaneous tissue disorders                                       
ERYTHEMA  1  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/19 (5.26%) 
HEAT RASH  1  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/12 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/19 (0.00%) 
NIGHT SWEATS  1  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  1/12 (8.33%)  0/19 (0.00%) 
PHOTOSENSITIVITY REACTION  1  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/19 (5.26%) 
PRURITUS  1  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  2/19 (10.53%) 
PRURITUS GENERALISED  1  1/16 (6.25%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/19 (0.00%) 
RASH  1  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/19 (5.26%) 
RASH ERYTHEMATOUS  1  0/16 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/6 (16.67%)  0/12 (0.00%)  0/19 (0.00%) 
RASH PRURITIC  1  0/16 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/10 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/19 (0.00%) 
URTICARIA  1  0/16 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/19 (0.00%) 
Vascular disorders                                       
HOT FLUSH  1  0/16 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/10 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/19 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
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 terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.
Results Point of Contact
Name/Title: Study Director
Organization: Novartis
Phone: 862-778-8300
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT02190604     History of Changes
Other Study ID Numbers: CQBW251X2101
2011-005085-37 ( EudraCT Number )
First Submitted: July 11, 2014
First Posted: July 15, 2014
Results First Submitted: November 23, 2016
Results First Posted: July 19, 2017
Last Update Posted: July 19, 2017