Trial Outcomes & Findings for Safety, Tolerability, Pharmacokinetics, and Preliminary Pharmacodynamics of QBW251 in Healthy Subjects and Cystic Fibrosis Patients (NCT NCT02190604)

NCT ID: NCT02190604

Last Updated: 2020-12-30

Results Overview

All adverse events (in healthy volunteers) reported.

• Recruitment status: TERMINATED
• Study phase: PHASE1/PHASE2
• Target enrollment: 153 participants
• Primary outcome timeframe: Day 1 to Day 36
• Results posted on: 2020-12-30

Participant Flow

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.

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.

Participant milestones

Measure	Part 1 Cohort 1: QBW251 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).	Part 1 Cohort 2: QBW251 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).	Part 1 Cohort 3: QBW251 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).	Part 1 Cohort 4: QBW251 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).	Part 1 Cohort 5: QBW251 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).	Part 1 Cohort 6: QBW251 (Fasting/Fed), Same Subjects 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).	Part 1 Cohort 7: QBW251 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).	Part 1 Cohort 8: QBW251 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).	Part 1 Placebo 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).	Part 2 Cohort 1: QBW251 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).	Part 2 Cohort 2: QBW251 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).	Part 2 Cohort 3: QBW251 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).	Part 2 Cohort 4: QBW251 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).	Part 2 Cohort 5: QBW251 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).	Part 2 Placebo 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).	Part 3 Cohort 1: QBW251 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.	Part 3 Cohort 2: QBW251 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.	Part 3 Cohort 3: QBW251 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.	Part 3 Placebo 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.
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
Part 1 and 2 (Healthy Volunteers) COMPLETED	6	6	6	6	6	6	6	6	16	6	6	6	6	5	8	0	0	0	0
Part 1 and 2 (Healthy Volunteers) NOT COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	0	1	2	0	0	0	0
Part 3 (Patients) STARTED	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	6	12	19	12
Part 3 (Patients) COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	6	12	19	12
Part 3 (Patients) NOT COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0

Reasons for withdrawal

Measure	Part 1 Cohort 1: QBW251 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).	Part 1 Cohort 2: QBW251 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).	Part 1 Cohort 3: QBW251 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).	Part 1 Cohort 4: QBW251 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).	Part 1 Cohort 5: QBW251 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).	Part 1 Cohort 6: QBW251 (Fasting/Fed), Same Subjects 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).	Part 1 Cohort 7: QBW251 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).	Part 1 Cohort 8: QBW251 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).	Part 1 Placebo 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).	Part 2 Cohort 1: QBW251 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).	Part 2 Cohort 2: QBW251 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).	Part 2 Cohort 3: QBW251 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).	Part 2 Cohort 4: QBW251 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).	Part 2 Cohort 5: QBW251 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).	Part 2 Placebo 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).	Part 3 Cohort 1: QBW251 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.	Part 3 Cohort 2: QBW251 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.	Part 3 Cohort 3: QBW251 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.	Part 3 Placebo 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.
Part 1 and 2 (Healthy Volunteers) Adverse Event	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0	0
Part 1 and 2 (Healthy Volunteers) Lost to Follow-up	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Part 3 Cohort 2: QBW251 n=12 Participants 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.	Part 3 Cohort 3: QBW251 n=19 Participants 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.	Part 3 Placebo n=12 Participants 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 n=153 Participants Total of all reporting groups	Part 3 Cohort 1: QBW251 n=6 Participants 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.	Part 1 Cohort 1: QBW251 n=6 Participants 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).	Part 1 Cohort 2: QBW251 n=6 Participants 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).	Part 1 Cohort 3: QBW251 n=6 Participants 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).	Part 1 Cohort 4: QBW251 n=6 Participants 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).	Part 1 Cohort 6: QBW251 n=6 Participants 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).	Part 1 Cohort 6: QBW251 (Fastin / Fed), Same Subjects n=6 Participants 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).	Part 1 Cohort 7: QBW251 n=6 Participants 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).	Part 1 Cohort 8: QBW251 n=6 Participants 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).	Part 1 Placebo n=16 Participants 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).	Part 2 Cohort 1: QBW251 n=6 Participants 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).	Part 2 Cohort 2: QBW251 n=6 Participants 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).	Part 2 Cohort 3: QBW251 n=6 Participants 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).	Part 2 Cohort 4: QBW251 n=6 Participants 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).	Part 2 Cohort 5: QBW251 n=6 Participants 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).	Part 2 Placebo n=10 Participants 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).
Age, Continuous Part 1, HV (n= 64)	NA Years STANDARD_DEVIATION NA • n=136 Participants	NA Years STANDARD_DEVIATION NA • n=44 Participants	NA Years STANDARD_DEVIATION NA • n=667 Participants	34.4 Years STANDARD_DEVIATION 9.92 • n=7 Participants	NA Years STANDARD_DEVIATION NA • n=135 Participants	36.3 Years STANDARD_DEVIATION 8.69 • n=5 Participants	35 Years STANDARD_DEVIATION 14.25 • n=7 Participants	43.5 Years STANDARD_DEVIATION 3.39 • n=5 Participants	33.3 Years STANDARD_DEVIATION 9.61 • n=4 Participants	44.2 Years STANDARD_DEVIATION 8.23 • n=21 Participants	43.6 Years STANDARD_DEVIATION 9.07 • n=10 Participants	28.2 Years STANDARD_DEVIATION 9.28 • n=115 Participants	33.2 Years STANDARD_DEVIATION 9.47 • n=6 Participants	30.3 Years STANDARD_DEVIATION 9.18 • n=6 Participants	NA Years STANDARD_DEVIATION NA • n=64 Participants	NA Years STANDARD_DEVIATION NA • n=17 Participants	NA Years STANDARD_DEVIATION NA • n=21 Participants	NA Years STANDARD_DEVIATION NA • n=22 Participants	NA Years STANDARD_DEVIATION NA • n=8 Participants	NA Years STANDARD_DEVIATION NA • n=16 Participants
Age, Continuous Part 2, HV (n=40)	NA Years STANDARD_DEVIATION NA • n=136 Participants	NA Years STANDARD_DEVIATION NA • n=44 Participants	NA Years STANDARD_DEVIATION NA • n=667 Participants	29.7 Years STANDARD_DEVIATION 7.82 • n=7 Participants	NA Years STANDARD_DEVIATION NA • n=135 Participants	NA Years STANDARD_DEVIATION NA • n=5 Participants	NA Years STANDARD_DEVIATION NA • n=7 Participants	NA Years STANDARD_DEVIATION NA • n=5 Participants	NA Years STANDARD_DEVIATION NA • n=4 Participants	NA Years STANDARD_DEVIATION NA • n=21 Participants	NA Years STANDARD_DEVIATION NA • n=10 Participants	NA Years STANDARD_DEVIATION NA • n=115 Participants	NA Years STANDARD_DEVIATION NA • n=6 Participants	NA Years STANDARD_DEVIATION NA • n=6 Participants	30.3 Years STANDARD_DEVIATION 5.13 • n=64 Participants	30.5 Years STANDARD_DEVIATION 5.89 • n=17 Participants	29.2 Years STANDARD_DEVIATION 11.62 • n=21 Participants	31.7 Years STANDARD_DEVIATION 13.22 • n=22 Participants	27.8 Years STANDARD_DEVIATION 5 • n=8 Participants	29 Years STANDARD_DEVIATION 6.22 • n=16 Participants
Age, Continuous Part 3, CF patients (n=49)	32.7 Years STANDARD_DEVIATION 13.77 • n=136 Participants	27 Years STANDARD_DEVIATION 5.44 • n=44 Participants	27.9 Years STANDARD_DEVIATION 6.37 • n=667 Participants	30.1 Years STANDARD_DEVIATION 9.18 • n=7 Participants	39.3 Years STANDARD_DEVIATION 5.47 • n=135 Participants	NA Years STANDARD_DEVIATION NA • n=5 Participants	NA Years STANDARD_DEVIATION NA • n=7 Participants	NA Years STANDARD_DEVIATION NA • n=5 Participants	NA Years STANDARD_DEVIATION NA • n=4 Participants	NA Years STANDARD_DEVIATION NA • n=21 Participants	NA Years STANDARD_DEVIATION NA • n=10 Participants	NA Years STANDARD_DEVIATION NA • n=115 Participants	NA Years STANDARD_DEVIATION NA • n=6 Participants	NA Years STANDARD_DEVIATION NA • n=6 Participants	NA Years STANDARD_DEVIATION NA • n=64 Participants	NA Years STANDARD_DEVIATION NA • n=17 Participants	NA Years STANDARD_DEVIATION NA • n=21 Participants	NA Years STANDARD_DEVIATION NA • n=22 Participants	NA Years STANDARD_DEVIATION NA • n=8 Participants	NA Years STANDARD_DEVIATION NA • n=16 Participants
Sex: Female, Male Female	5 Participants n=136 Participants	9 Participants n=44 Participants	4 Participants n=667 Participants	19 Participants n=7 Participants	1 Participants n=135 Participants	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=6 Participants	0 Participants n=6 Participants	0 Participants n=64 Participants	0 Participants n=17 Participants	0 Participants n=21 Participants	0 Participants n=22 Participants	0 Participants n=8 Participants	0 Participants n=16 Participants
Sex: Female, Male Male	7 Participants n=136 Participants	10 Participants n=44 Participants	8 Participants n=667 Participants	134 Participants n=7 Participants	5 Participants n=135 Participants	6 Participants n=5 Participants	6 Participants n=7 Participants	6 Participants n=5 Participants	6 Participants n=4 Participants	6 Participants n=21 Participants	6 Participants n=10 Participants	6 Participants n=115 Participants	6 Participants n=6 Participants	16 Participants n=6 Participants	6 Participants n=64 Participants	6 Participants n=17 Participants	6 Participants n=21 Participants	6 Participants n=22 Participants	6 Participants n=8 Participants	10 Participants n=16 Participants

PRIMARY outcome

Timeframe: Day 1 to Day 36

Population: All treated subjects were included in the data analysis. Subjects were analyzed according to the study treatment(s) received.

All adverse events (in healthy volunteers) reported.

Outcome measures

Measure	Part 1 Cohort 4: QBW251 n=6 Participants 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).	Part 1 Cohort 5: QBW251 n=6 Participants 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).	Part 1 Cohort 6: QBW251 n=6 Participants 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).	Part 1 Cohort 6: QBW251(Fed) n=5 Participants 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).	Part 1 Cohort 7: QBW251 n=6 Participants 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).	Part 1 Cohort 8: QBW251 n=6 Participants 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).	Part 1 Placebo n=16 Participants 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).	Part 2 Cohort 1: QBW251 n=6 Participants 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).	Part 2 Cohort 2: QBW251 n=6 Participants 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).	Part 2 Cohort 3: QBW251 n=6 Participants 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).	Part 2 Cohort 4: QBW251 n=6 Participants 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).	Part 2 Cohort 5: QBW251 n=6 Participants 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).	Part 2 Placebo n=10 Participants 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).	Part 1 Cohort 1: QBW251 n=6 Participants 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	Part 1 Cohort 2: QBW251 n=6 Participants 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).	Part 1 Cohort 3: QBW251 n=6 Participants 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).
Part 1 and 2:Number of Participants (Healthy Volunteers) With Reported Adverse Events Receiving QBW251 Adverse events	1 Participants	2 Participants	2 Participants	1 Participants	1 Participants	4 Participants	8 Participants	3 Participants	6 Participants	3 Participants	6 Participants	4 Participants	7 Participants	3 Participants	2 Participants	0 Participants
Part 1 and 2:Number of Participants (Healthy Volunteers) With Reported Adverse Events Receiving QBW251 Serious adverse events	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Part 1 and 2:Number of Participants (Healthy Volunteers) With Reported Adverse Events Receiving QBW251 Death	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Baseline and Day 15

Population: Pharmacodynamics (PD) analysis set: All randomized patients were included in the PD analysis

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.

Outcome measures

Measure	Part 1 Cohort 4: QBW251 n=5 Participants 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).	Part 1 Cohort 5: QBW251 n=11 Participants 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).	Part 1 Cohort 6: QBW251 n=17 Participants 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).	Part 1 Cohort 6: QBW251(Fed) n=11 Participants 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).	Part 1 Cohort 7: QBW251 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).	Part 1 Cohort 8: QBW251 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).	Part 1 Placebo 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).	Part 2 Cohort 1: QBW251 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).	Part 2 Cohort 2: QBW251 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).	Part 2 Cohort 3: QBW251 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).	Part 2 Cohort 4: QBW251 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).	Part 2 Cohort 5: QBW251 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).	Part 2 Placebo 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).	Part 1 Cohort 1: QBW251 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	Part 1 Cohort 2: QBW251 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).	Part 1 Cohort 3: QBW251 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).
Part 3: Change in Lung Clearance Index (LCI) From Baseline to Day 15	0.27 Ratio Standard Deviation 0.769	-0.85 Ratio Standard Deviation 1.798	-0.13 Ratio Standard Deviation 2.276	0.28 Ratio Standard Deviation 1.959	—	—	—	—	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Day 1 to Day 56

Population: Safety analysis set: All randomized patients were included in the safety analysis

All adverse events and serious adverse events (in patients) reported.

Outcome measures

Measure	Part 1 Cohort 4: QBW251 n=6 Participants 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).	Part 1 Cohort 5: QBW251 n=12 Participants 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).	Part 1 Cohort 6: QBW251 n=19 Participants 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).	Part 1 Cohort 6: QBW251(Fed) n=12 Participants 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).	Part 1 Cohort 7: QBW251 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).	Part 1 Cohort 8: QBW251 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).	Part 1 Placebo 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).	Part 2 Cohort 1: QBW251 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).	Part 2 Cohort 2: QBW251 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).	Part 2 Cohort 3: QBW251 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).	Part 2 Cohort 4: QBW251 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).	Part 2 Cohort 5: QBW251 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).	Part 2 Placebo 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).	Part 1 Cohort 1: QBW251 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	Part 1 Cohort 2: QBW251 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).	Part 1 Cohort 3: QBW251 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).
Part 3: Number of Participants (Patients) With Reported Adverse Events Receiving QBW251 Adverse Events (AE)	6 Participants	8 Participants	18 Participants	8 Participants	—	—	—	—	—	—	—	—	—	—	—	—
Part 3: Number of Participants (Patients) With Reported Adverse Events Receiving QBW251 Serious Adverse Events (SAE)	1 Participants	1 Participants	1 Participants	0 Participants	—	—	—	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Baseline and Day 15

Population: Pharmacodynamics (PD) analysis set: All randomized patients were included in the PD analysis

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

Outcome measures

Measure	Part 1 Cohort 4: QBW251 n=5 Participants 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).	Part 1 Cohort 5: QBW251 n=11 Participants 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).	Part 1 Cohort 6: QBW251 n=16 Participants 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).	Part 1 Cohort 6: QBW251(Fed) n=12 Participants 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).	Part 1 Cohort 7: QBW251 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).	Part 1 Cohort 8: QBW251 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).	Part 1 Placebo 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).	Part 2 Cohort 1: QBW251 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).	Part 2 Cohort 2: QBW251 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).	Part 2 Cohort 3: QBW251 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).	Part 2 Cohort 4: QBW251 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).	Part 2 Cohort 5: QBW251 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).	Part 2 Placebo 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).	Part 1 Cohort 1: QBW251 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	Part 1 Cohort 2: QBW251 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).	Part 1 Cohort 3: QBW251 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).
Part 3:Change in Forced Expiratory Volume in 1 Second (FEV1) at Day 15	0.58 Liters Standard Error 2.476	5.99 Liters Standard Error 1.648	-1.16 Liters Standard Error 1.059	-1.46 Liters Standard Error 1.229	—	—	—	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Baseline and Day 14

Population: Pharmacodynamics (PD) analysis set: All randomized patients were included in the PD analysis

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

Outcome measures

Measure	Part 1 Cohort 4: QBW251 n=5 Participants 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).	Part 1 Cohort 5: QBW251 n=11 Participants 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).	Part 1 Cohort 6: QBW251 n=19 Participants 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).	Part 1 Cohort 6: QBW251(Fed) n=12 Participants 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).	Part 1 Cohort 7: QBW251 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).	Part 1 Cohort 8: QBW251 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).	Part 1 Placebo 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).	Part 2 Cohort 1: QBW251 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).	Part 2 Cohort 2: QBW251 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).	Part 2 Cohort 3: QBW251 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).	Part 2 Cohort 4: QBW251 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).	Part 2 Cohort 5: QBW251 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).	Part 2 Placebo 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).	Part 1 Cohort 1: QBW251 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	Part 1 Cohort 2: QBW251 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).	Part 1 Cohort 3: QBW251 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).
Part 3: Change in Cystic Fibrosis Questionnaire-Revised Reported Outcomes	16.06 Units on a scale Standard Error 6.872	5.04 Units on a scale Standard Error 4.617	-2.62 Units on a scale Standard Error 2.853	-2.06 Units on a scale Standard Error 4.415	—	—	—	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: 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)

Population: 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.

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)

Outcome measures

Measure	Part 1 Cohort 4: QBW251 n=6 Participants 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).	Part 1 Cohort 5: QBW251 n=6 Participants 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).	Part 1 Cohort 6: QBW251 n=6 Participants 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).	Part 1 Cohort 6: QBW251(Fed) n=6 Participants 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).	Part 1 Cohort 7: QBW251 n=6 Participants 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).	Part 1 Cohort 8: QBW251 n=6 Participants 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).	Part 1 Placebo n=5 Participants 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).	Part 2 Cohort 1: QBW251 n=6 Participants 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).	Part 2 Cohort 2: QBW251 n=6 Participants 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).	Part 2 Cohort 3: QBW251 n=16 Participants 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).	Part 2 Cohort 4: QBW251 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).	Part 2 Cohort 5: QBW251 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).	Part 2 Placebo 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).	Part 1 Cohort 1: QBW251 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	Part 1 Cohort 2: QBW251 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).	Part 1 Cohort 3: QBW251 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).
Part 1: AUC0-t in Healthy Volunteers	52.5 hr*ng/mL Standard Deviation 28.1	73.7 hr*ng/mL Standard Deviation 51.8	692 hr*ng/mL Standard Deviation 389	1650 hr*ng/mL Standard Deviation 907	5470 hr*ng/mL Standard Deviation 1070	9450 hr*ng/mL Standard Deviation 1740	7470 hr*ng/mL Standard Deviation 2190	20200 hr*ng/mL Standard Deviation 11500	35900 hr*ng/mL Standard Deviation 9100	NA hr*ng/mL Standard Deviation NA Not calculated	—	—	—	—	—	—

SECONDARY outcome

Timeframe: 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)

Population: 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

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

Outcome measures

Measure	Part 1 Cohort 4: QBW251 n=6 Participants 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).	Part 1 Cohort 5: QBW251 n=6 Participants 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).	Part 1 Cohort 6: QBW251 n=6 Participants 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).	Part 1 Cohort 6: QBW251(Fed) n=6 Participants 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).	Part 1 Cohort 7: QBW251 n=6 Participants 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).	Part 1 Cohort 8: QBW251 n=6 Participants 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).	Part 1 Placebo n=5 Participants 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).	Part 2 Cohort 1: QBW251 n=6 Participants 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).	Part 2 Cohort 2: QBW251 n=6 Participants 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).	Part 2 Cohort 3: QBW251 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).	Part 2 Cohort 4: QBW251 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).	Part 2 Cohort 5: QBW251 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).	Part 2 Placebo 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).	Part 1 Cohort 1: QBW251 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	Part 1 Cohort 2: QBW251 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).	Part 1 Cohort 3: QBW251 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).
Part 1: Maximum Concentration (Cmax) in Healthy Volunteers	21.1 ug/L Standard Deviation 11.9	24.7 ug/L Standard Deviation 15.9	186 ug/L Standard Deviation 82.3	459 ug/L Standard Deviation 267	1110 ug/L Standard Deviation 330	1910 ug/L Standard Deviation 413	1090 ug/L Standard Deviation 449	2680 ug/L Standard Deviation 1000	4540 ug/L Standard Deviation 930	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: 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)

Population: 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

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).

Outcome measures

Measure	Part 1 Cohort 4: QBW251 n=6 Participants 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).	Part 1 Cohort 5: QBW251 n=6 Participants 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).	Part 1 Cohort 6: QBW251 n=6 Participants 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).	Part 1 Cohort 6: QBW251(Fed) n=6 Participants 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).	Part 1 Cohort 7: QBW251 n=6 Participants 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).	Part 1 Cohort 8: QBW251 n=6 Participants 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).	Part 1 Placebo n=5 Participants 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).	Part 2 Cohort 1: QBW251 n=6 Participants 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).	Part 2 Cohort 2: QBW251 n=6 Participants 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).	Part 2 Cohort 3: QBW251 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).	Part 2 Cohort 4: QBW251 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).	Part 2 Cohort 5: QBW251 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).	Part 2 Placebo 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).	Part 1 Cohort 1: QBW251 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	Part 1 Cohort 2: QBW251 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).	Part 1 Cohort 3: QBW251 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).
Part 1: Time to Maximum Concentration (Tmax) in Healthy Volunteers	0.756 hr Standard Deviation 0.268	1.25 hr Standard Deviation 0.612	1.33 hr Standard Deviation 0.516	1.50 hr Standard Deviation 0.548	1.50 hr Standard Deviation 0.837	2.17 hr Standard Deviation 1.17	3.40 hr Standard Deviation 0.894	2.52 hr Standard Deviation 0.850	1.83 hr Standard Deviation 0.753	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: 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)

Population: 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

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).

Outcome measures

Measure	Part 1 Cohort 4: QBW251 n=6 Participants 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).	Part 1 Cohort 5: QBW251 n=6 Participants 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).	Part 1 Cohort 6: QBW251 n=6 Participants 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).	Part 1 Cohort 6: QBW251(Fed) n=6 Participants 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).	Part 1 Cohort 7: QBW251 n=6 Participants 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).	Part 1 Cohort 8: QBW251 n=6 Participants 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).	Part 1 Placebo n=5 Participants 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).	Part 2 Cohort 1: QBW251 n=6 Participants 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).	Part 2 Cohort 2: QBW251 n=6 Participants 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).	Part 2 Cohort 3: QBW251 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).	Part 2 Cohort 4: QBW251 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).	Part 2 Cohort 5: QBW251 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).	Part 2 Placebo 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).	Part 1 Cohort 1: QBW251 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	Part 1 Cohort 2: QBW251 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).	Part 1 Cohort 3: QBW251 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).
Part 1: T1/2 in Healthy Volunteers	NA hr Standard Deviation NA There were not enough time points to calculated the T1/2	NA hr Standard Deviation NA There were not enough time points to calculated the T1/2	10.3 hr Standard Deviation 4.24	10.1 hr Standard Deviation 3.35	12.0 hr Standard Deviation 2.26	12.7 hr Standard Deviation 1.99	15.6 hr Standard Deviation 5.03	12.8 hr Standard Deviation 3.85	10.7 hr Standard Deviation 2.19	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: 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)

Population: 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

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)

Outcome measures

Measure	Part 1 Cohort 4: QBW251 n=6 Participants 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).	Part 1 Cohort 5: QBW251 n=6 Participants 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).	Part 1 Cohort 6: QBW251 n=6 Participants 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).	Part 1 Cohort 6: QBW251(Fed) n=6 Participants 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).	Part 1 Cohort 7: QBW251 n=6 Participants 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).	Part 1 Cohort 8: QBW251 n=6 Participants 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).	Part 1 Placebo n=5 Participants 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).	Part 2 Cohort 1: QBW251 n=6 Participants 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).	Part 2 Cohort 2: QBW251 n=6 Participants 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).	Part 2 Cohort 3: QBW251 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).	Part 2 Cohort 4: QBW251 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).	Part 2 Cohort 5: QBW251 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).	Part 2 Placebo 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).	Part 1 Cohort 1: QBW251 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	Part 1 Cohort 2: QBW251 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).	Part 1 Cohort 3: QBW251 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).
Part 1: AUCinf in Healthy Volunteers	NA hr*ng/mL Standard Deviation NA Not calculated due to insufficient data	NA hr*ng/mL Standard Deviation NA Not calculated due to insufficient data	731 hr*ng/mL Standard Deviation 387	1680 hr*ng/mL Standard Deviation 903	5510 hr*ng/mL Standard Deviation 1080	9480 hr*ng/mL Standard Deviation 1740	7540 hr*ng/mL Standard Deviation 2220	20300 hr*ng/mL Standard Deviation 11500	36000 hr*ng/mL Standard Deviation 9120	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: 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)

Population: 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

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)

Outcome measures

Measure	Part 1 Cohort 4: QBW251 n=6 Participants 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).	Part 1 Cohort 5: QBW251 n=6 Participants 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).	Part 1 Cohort 6: QBW251 n=6 Participants 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).	Part 1 Cohort 6: QBW251(Fed) n=6 Participants 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).	Part 1 Cohort 7: QBW251 n=6 Participants 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).	Part 1 Cohort 8: QBW251 n=6 Participants 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).	Part 1 Placebo n=5 Participants 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).	Part 2 Cohort 1: QBW251 n=6 Participants 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).	Part 2 Cohort 2: QBW251 n=6 Participants 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).	Part 2 Cohort 3: QBW251 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).	Part 2 Cohort 4: QBW251 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).	Part 2 Cohort 5: QBW251 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).	Part 2 Placebo 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).	Part 1 Cohort 1: QBW251 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	Part 1 Cohort 2: QBW251 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).	Part 1 Cohort 3: QBW251 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).
Part 1: CL/F in Healthy Volunteers	NA L/hr Standard Deviation NA Not calculated due to insufficient data	NA L/hr Standard Deviation NA Not calculated due to insufficient data	123 L/hr Standard Deviation 49.0	114 L/hr Standard Deviation 63.9	56.2 L/hr Standard Deviation 11.0	54.5 L/hr Standard Deviation 11.9	71.6 L/hr Standard Deviation 22.6	45.9 L/hr Standard Deviation 19.9	29.7 L/hr Standard Deviation 9.00	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: 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)

Population: 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

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.

Outcome measures

Measure	Part 1 Cohort 4: QBW251 n=6 Participants 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).	Part 1 Cohort 5: QBW251 n=6 Participants 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).	Part 1 Cohort 6: QBW251 n=6 Participants 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).	Part 1 Cohort 6: QBW251(Fed) n=6 Participants 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).	Part 1 Cohort 7: QBW251 n=6 Participants 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).	Part 1 Cohort 8: QBW251 n=6 Participants 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).	Part 1 Placebo n=5 Participants 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).	Part 2 Cohort 1: QBW251 n=6 Participants 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).	Part 2 Cohort 2: QBW251 n=6 Participants 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).	Part 2 Cohort 3: QBW251 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).	Part 2 Cohort 4: QBW251 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).	Part 2 Cohort 5: QBW251 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).	Part 2 Placebo 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).	Part 1 Cohort 1: QBW251 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	Part 1 Cohort 2: QBW251 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).	Part 1 Cohort 3: QBW251 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).
Part 1: Vz/F in Healthy Volunteers	NA Liters Standard Deviation NA Not calculated due to insufficient data	NA Liters Standard Deviation NA Not calculated due to insufficient data	1700 Liters Standard Deviation 772	1490 Liters Standard Deviation 622	957 Liters Standard Deviation 151	995 Liters Standard Deviation 235	1580 Liters Standard Deviation 587	827 Liters Standard Deviation 375	447 Liters Standard Deviation 112	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: 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)

Population: 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

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

Outcome measures

Measure	Part 1 Cohort 4: QBW251 n=6 Participants 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).	Part 1 Cohort 5: QBW251 n=6 Participants 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).	Part 1 Cohort 6: QBW251 n=6 Participants 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).	Part 1 Cohort 6: QBW251(Fed) n=6 Participants 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).	Part 1 Cohort 7: QBW251 n=6 Participants 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).	Part 1 Cohort 8: QBW251 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).	Part 1 Placebo 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).	Part 2 Cohort 1: QBW251 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).	Part 2 Cohort 2: QBW251 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).	Part 2 Cohort 3: QBW251 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).	Part 2 Cohort 4: QBW251 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).	Part 2 Cohort 5: QBW251 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).	Part 2 Placebo 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).	Part 1 Cohort 1: QBW251 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	Part 1 Cohort 2: QBW251 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).	Part 1 Cohort 3: QBW251 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).
Part 2: AUCtau in Healthy Volunteers Day1	1800 hr*ng/mL Standard Deviation 794	6170 hr*ng/mL Standard Deviation 1250	16100 hr*ng/mL Standard Deviation 8170	7160 hr*ng/mL Standard Deviation 1960	18800 hr*ng/mL Standard Deviation 6360	—	—	—	—	—	—	—	—	—	—	—
Part 2: AUCtau in Healthy Volunteers Day 14	2060 hr*ng/mL Standard Deviation 708	7620 hr*ng/mL Standard Deviation 1470	28300 hr*ng/mL Standard Deviation 5570	12100 hr*ng/mL Standard Deviation 4930	80300 hr*ng/mL Standard Deviation 56300	—	—	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: 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)

Population: 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

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.

Outcome measures

Measure	Part 1 Cohort 4: QBW251 n=6 Participants 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).	Part 1 Cohort 5: QBW251 n=6 Participants 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).	Part 1 Cohort 6: QBW251 n=6 Participants 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).	Part 1 Cohort 6: QBW251(Fed) n=6 Participants 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).	Part 1 Cohort 7: QBW251 n=6 Participants 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).	Part 1 Cohort 8: QBW251 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).	Part 1 Placebo 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).	Part 2 Cohort 1: QBW251 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).	Part 2 Cohort 2: QBW251 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).	Part 2 Cohort 3: QBW251 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).	Part 2 Cohort 4: QBW251 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).	Part 2 Cohort 5: QBW251 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).	Part 2 Placebo 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).	Part 1 Cohort 1: QBW251 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	Part 1 Cohort 2: QBW251 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).	Part 1 Cohort 3: QBW251 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).
Part 2: Maximum Concentration (Cmax) in Healthy Volunteers Day 1	541 ug/L Standard Deviation 338	1650 ug/L Standard Deviation 343	2790 ug/L Standard Deviation 1040	1650 ug/L Standard Deviation 188	3720 ug/L Standard Deviation 1530	—	—	—	—	—	—	—	—	—	—	—
Part 2: Maximum Concentration (Cmax) in Healthy Volunteers Day 14	430 ug/L Standard Deviation 145	1500 ug/L Standard Deviation 442	3840 ug/L Standard Deviation 868	2190 ug/L Standard Deviation 769	9420 ug/L Standard Deviation 4330	—	—	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: 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)

Population: 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

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.

Outcome measures

Measure	Part 1 Cohort 4: QBW251 n=6 Participants 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).	Part 1 Cohort 5: QBW251 n=6 Participants 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).	Part 1 Cohort 6: QBW251 n=6 Participants 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).	Part 1 Cohort 6: QBW251(Fed) n=6 Participants 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).	Part 1 Cohort 7: QBW251 n=6 Participants 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).	Part 1 Cohort 8: QBW251 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).	Part 1 Placebo 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).	Part 2 Cohort 1: QBW251 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).	Part 2 Cohort 2: QBW251 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).	Part 2 Cohort 3: QBW251 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).	Part 2 Cohort 4: QBW251 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).	Part 2 Cohort 5: QBW251 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).	Part 2 Placebo 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).	Part 1 Cohort 1: QBW251 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	Part 1 Cohort 2: QBW251 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).	Part 1 Cohort 3: QBW251 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).
Part 2: Time to Maximum Concentration (Tmax) in Healthy Volunteers Day 1	1.67 hr Standard Deviation 0.816	1.17 hr Standard Deviation 0.408	2.33 hr Standard Deviation 1.21	2.68 hr Standard Deviation 0.813	3.67 hr Standard Deviation 0.516	—	—	—	—	—	—	—	—	—	—	—
Part 2: Time to Maximum Concentration (Tmax) in Healthy Volunteers Day 2	2.17 hr Standard Deviation 1.17	2.17 hr Standard Deviation 0.408	2.33 hr Standard Deviation 1.03	3.25 hr Standard Deviation 1.41	3.80 hr Standard Deviation 0.447	—	—	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: 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)

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.

Outcome measures

Measure	Part 1 Cohort 4: QBW251 n=6 Participants 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).	Part 1 Cohort 5: QBW251 n=6 Participants 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).	Part 1 Cohort 6: QBW251 n=6 Participants 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).	Part 1 Cohort 6: QBW251(Fed) n=6 Participants 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).	Part 1 Cohort 7: QBW251 n=5 Participants 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).	Part 1 Cohort 8: QBW251 n=14 Participants 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).	Part 1 Placebo 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).	Part 2 Cohort 1: QBW251 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).	Part 2 Cohort 2: QBW251 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).	Part 2 Cohort 3: QBW251 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).	Part 2 Cohort 4: QBW251 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).	Part 2 Cohort 5: QBW251 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).	Part 2 Placebo 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).	Part 1 Cohort 1: QBW251 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	Part 1 Cohort 2: QBW251 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).	Part 1 Cohort 3: QBW251 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).
Part 2: AUC0-t	2060 hr*ng/mL Standard Deviation 708	7620 hr*ng/mL Standard Deviation 1470	28300 hr*ng/mL Standard Deviation 5570	12100 hr*ng/mL Standard Deviation 4930	80300 hr*ng/mL Standard Deviation 56300	NA hr*ng/mL Standard Deviation NA Not calculated	—	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: 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)

Population: 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

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.

Outcome measures

Measure	Part 1 Cohort 4: QBW251 n=6 Participants 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).	Part 1 Cohort 5: QBW251 n=6 Participants 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).	Part 1 Cohort 6: QBW251 n=6 Participants 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).	Part 1 Cohort 6: QBW251(Fed) n=6 Participants 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).	Part 1 Cohort 7: QBW251 n=6 Participants 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).	Part 1 Cohort 8: QBW251 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).	Part 1 Placebo 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).	Part 2 Cohort 1: QBW251 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).	Part 2 Cohort 2: QBW251 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).	Part 2 Cohort 3: QBW251 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).	Part 2 Cohort 4: QBW251 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).	Part 2 Cohort 5: QBW251 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).	Part 2 Placebo 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).	Part 1 Cohort 1: QBW251 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	Part 1 Cohort 2: QBW251 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).	Part 1 Cohort 3: QBW251 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).
Part 2: Cav in Healthy Volunteers	85.8 ug/L Standard Deviation 29.5	318 ug/L Standard Deviation 61.1	1180 ug/L Standard Deviation 232	NA ug/L Standard Deviation NA Not calculated due to insufficient data	NA ug/L Standard Deviation NA Not calculated due to insufficient data	—	—	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: 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)

Population: 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

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.

Outcome measures

Measure	Part 1 Cohort 4: QBW251 n=6 Participants 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).	Part 1 Cohort 5: QBW251 n=6 Participants 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).	Part 1 Cohort 6: QBW251 n=6 Participants 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).	Part 1 Cohort 6: QBW251(Fed) n=6 Participants 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).	Part 1 Cohort 7: QBW251 n=6 Participants 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).	Part 1 Cohort 8: QBW251 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).	Part 1 Placebo 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).	Part 2 Cohort 1: QBW251 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).	Part 2 Cohort 2: QBW251 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).	Part 2 Cohort 3: QBW251 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).	Part 2 Cohort 4: QBW251 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).	Part 2 Cohort 5: QBW251 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).	Part 2 Placebo 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).	Part 1 Cohort 1: QBW251 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	Part 1 Cohort 2: QBW251 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).	Part 1 Cohort 3: QBW251 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).
Part 2: CL/F in Healthy Volunteers	80.8 L/hr Standard Deviation 29.7	54.0 L/hr Standard Deviation 9.40	27.5 L/hr Standard Deviation 5.98	NA L/hr Standard Deviation NA Not calculated due to insufficient data	NA L/hr Standard Deviation NA Not calculated due to insufficient data	—	—	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: 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)

Population: 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

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.

Outcome measures

Measure	Part 1 Cohort 4: QBW251 n=6 Participants 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).	Part 1 Cohort 5: QBW251 n=6 Participants 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).	Part 1 Cohort 6: QBW251 n=6 Participants 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).	Part 1 Cohort 6: QBW251(Fed) n=6 Participants 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).	Part 1 Cohort 7: QBW251 n=6 Participants 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).	Part 1 Cohort 8: QBW251 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).	Part 1 Placebo 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).	Part 2 Cohort 1: QBW251 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).	Part 2 Cohort 2: QBW251 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).	Part 2 Cohort 3: QBW251 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).	Part 2 Cohort 4: QBW251 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).	Part 2 Cohort 5: QBW251 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).	Part 2 Placebo 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).	Part 1 Cohort 1: QBW251 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	Part 1 Cohort 2: QBW251 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).	Part 1 Cohort 3: QBW251 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).
Part 2: Vz/F in Healthy Volunteers	1330 Liters Standard Deviation 550	1120 Liters Standard Deviation 395	608 Liters Standard Deviation 255	NA Liters Standard Deviation NA Not calculated due to insufficient data	NA Liters Standard Deviation NA Not calculated due to insufficient data	—	—	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: 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)

Population: 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

Accumulation ratio (Racc). In this analysis Racc will be reported using blood samples taken on Days 1 - 14 from healthy volunteers.

Outcome measures

Measure	Part 1 Cohort 4: QBW251 n=6 Participants 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).	Part 1 Cohort 5: QBW251 n=6 Participants 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).	Part 1 Cohort 6: QBW251 n=6 Participants 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).	Part 1 Cohort 6: QBW251(Fed) n=6 Participants 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).	Part 1 Cohort 7: QBW251 n=6 Participants 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).	Part 1 Cohort 8: QBW251 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).	Part 1 Placebo 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).	Part 2 Cohort 1: QBW251 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).	Part 2 Cohort 2: QBW251 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).	Part 2 Cohort 3: QBW251 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).	Part 2 Cohort 4: QBW251 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).	Part 2 Cohort 5: QBW251 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).	Part 2 Placebo 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).	Part 1 Cohort 1: QBW251 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	Part 1 Cohort 2: QBW251 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).	Part 1 Cohort 3: QBW251 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).
Part 2: Racc in Healthy Volunteers	1.27 Ratio Standard Deviation 0.425	1.25 Ratio Standard Deviation 0.199	2.08 Ratio Standard Deviation 0.913	1.66 Ratio Standard Deviation 0.386	3.88 Ratio Standard Deviation 2.07	—	—	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: 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)

Population: 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

terminal elimination half-life (T1/2). In this analysis T1/2 will be reported using blood samples taken on Day 14 from healthy volunteers.

Outcome measures

Measure	Part 1 Cohort 4: QBW251 n=6 Participants 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).	Part 1 Cohort 5: QBW251 n=6 Participants 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).	Part 1 Cohort 6: QBW251 n=6 Participants 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).	Part 1 Cohort 6: QBW251(Fed) n=6 Participants 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).	Part 1 Cohort 7: QBW251 n=6 Participants 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).	Part 1 Cohort 8: QBW251 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).	Part 1 Placebo 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).	Part 2 Cohort 1: QBW251 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).	Part 2 Cohort 2: QBW251 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).	Part 2 Cohort 3: QBW251 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).	Part 2 Cohort 4: QBW251 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).	Part 2 Cohort 5: QBW251 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).	Part 2 Placebo 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).	Part 1 Cohort 1: QBW251 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	Part 1 Cohort 2: QBW251 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).	Part 1 Cohort 3: QBW251 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).
Part 2: T1/2 in Healthy Volunteers	11.3 hr Standard Deviation 1.44	14.1 hr Standard Deviation 3.80	15.1 hr Standard Deviation 4.40	NA hr Standard Deviation NA Not calculated due to insufficient data	NA hr Standard Deviation NA Not calculated due to insufficient data	—	—	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4, 8 hr post-dose in Day 1, Day 14

Population: 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

Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)

Outcome measures

Measure	Part 1 Cohort 4: QBW251 n=6 Participants 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).	Part 1 Cohort 5: QBW251 n=12 Participants 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).	Part 1 Cohort 6: QBW251 n=19 Participants 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).	Part 1 Cohort 6: QBW251(Fed) 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).	Part 1 Cohort 7: QBW251 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).	Part 1 Cohort 8: QBW251 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).	Part 1 Placebo 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).	Part 2 Cohort 1: QBW251 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).	Part 2 Cohort 2: QBW251 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).	Part 2 Cohort 3: QBW251 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).	Part 2 Cohort 4: QBW251 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).	Part 2 Cohort 5: QBW251 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).	Part 2 Placebo 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).	Part 1 Cohort 1: QBW251 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	Part 1 Cohort 2: QBW251 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).	Part 1 Cohort 3: QBW251 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).
Part 3: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of QBW251 in CF Patients Day 1	1110 ng × hr /mL Standard Deviation 709	7530 ng × hr /mL Standard Deviation 2480	6020 ng × hr /mL Standard Deviation 2960	—	—	—	—	—	—	—	—	—	—	—	—	—
Part 3: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of QBW251 in CF Patients Day 14	1760 ng × hr /mL Standard Deviation 943	18900 ng × hr /mL Standard Deviation 6850	NA ng × hr /mL Standard Deviation NA PK parameters were not calculated for Day 14 as blood samples were collected up to 2 hours post-dose.	—	—	—	—	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4, 8 hr post-dose in Day 1, Day2

Population: 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

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

Outcome measures

Measure	Part 1 Cohort 4: QBW251 n=6 Participants 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).	Part 1 Cohort 5: QBW251 n=12 Participants 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).	Part 1 Cohort 6: QBW251 n=19 Participants 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).	Part 1 Cohort 6: QBW251(Fed) 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).	Part 1 Cohort 7: QBW251 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).	Part 1 Cohort 8: QBW251 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).	Part 1 Placebo 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).	Part 2 Cohort 1: QBW251 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).	Part 2 Cohort 2: QBW251 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).	Part 2 Cohort 3: QBW251 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).	Part 2 Cohort 4: QBW251 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).	Part 2 Cohort 5: QBW251 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).	Part 2 Placebo 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).	Part 1 Cohort 1: QBW251 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	Part 1 Cohort 2: QBW251 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).	Part 1 Cohort 3: QBW251 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).
Part 3: Plasma Concentration at the Last Quantifiable Time Point (Clast) of QBW251 in CF Patients Day 1	42.3 ng/mL Standard Deviation 14.1	423 ng/mL Standard Deviation 275	653 ng/mL Standard Deviation 318	—	—	—	—	—	—	—	—	—	—	—	—	—
Part 3: Plasma Concentration at the Last Quantifiable Time Point (Clast) of QBW251 in CF Patients Day 14	86.4 ng/mL Standard Deviation 16.3	1570 ng/mL Standard Deviation 813	NA ng/mL Standard Deviation NA PK parameters were not calculated for Day 14 as blood samples were collected up to 2 hours post-dose	—	—	—	—	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4, 8 hr post-dose in Day 1, Day 14

Population: 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

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

Outcome measures

Measure	Part 1 Cohort 4: QBW251 n=6 Participants 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).	Part 1 Cohort 5: QBW251 n=12 Participants 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).	Part 1 Cohort 6: QBW251 n=19 Participants 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).	Part 1 Cohort 6: QBW251(Fed) 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).	Part 1 Cohort 7: QBW251 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).	Part 1 Cohort 8: QBW251 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).	Part 1 Placebo 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).	Part 2 Cohort 1: QBW251 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).	Part 2 Cohort 2: QBW251 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).	Part 2 Cohort 3: QBW251 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).	Part 2 Cohort 4: QBW251 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).	Part 2 Cohort 5: QBW251 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).	Part 2 Placebo 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).	Part 1 Cohort 1: QBW251 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	Part 1 Cohort 2: QBW251 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).	Part 1 Cohort 3: QBW251 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).
Part 3: Maximum Concentration (Cmax) in CF Patients Day 1	419 ng/mL Standard Deviation 316	1950 ng/mL Standard Deviation 715	2380 ng/mL Standard Deviation 1240	—	—	—	—	—	—	—	—	—	—	—	—	—
Part 3: Maximum Concentration (Cmax) in CF Patients Day 14	632 ng/mL Standard Deviation 438	4080 ng/mL Standard Deviation 1780	NA ng/mL Standard Deviation NA PK parameters were not calculated for Day 14 as blood samples were collected up to 2 hours post-dose	—	—	—	—	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4, 8 hr post-dose in Day 1, Day 14

Population: 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

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

Outcome measures

Measure	Part 1 Cohort 4: QBW251 n=6 Participants 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).	Part 1 Cohort 5: QBW251 n=12 Participants 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).	Part 1 Cohort 6: QBW251 n=19 Participants 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).	Part 1 Cohort 6: QBW251(Fed) 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).	Part 1 Cohort 7: QBW251 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).	Part 1 Cohort 8: QBW251 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).	Part 1 Placebo 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).	Part 2 Cohort 1: QBW251 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).	Part 2 Cohort 2: QBW251 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).	Part 2 Cohort 3: QBW251 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).	Part 2 Cohort 4: QBW251 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).	Part 2 Cohort 5: QBW251 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).	Part 2 Placebo 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).	Part 1 Cohort 1: QBW251 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	Part 1 Cohort 2: QBW251 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).	Part 1 Cohort 3: QBW251 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).
Part 3: Tlast in CF Patients Day 1	7.99 hr Standard Deviation 0.0136	7.95 hr Standard Deviation 0.149	5.80 hr Standard Deviation 0.639	—	—	—	—	—	—	—	—	—	—	—	—	—
Part 3: Tlast in CF Patients Day 14	7.97 hr Standard Deviation 0.0667	7.96 hr Standard Deviation 0.0554	NA hr Standard Deviation NA PK parameters were not calculated for Day 14 as blood samples were collected up to 2 hours post-dose	—	—	—	—	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Pre-dose (0 hr), 0.25, 0.5, 1, 2, 3, 4, 8 hr post-dose in Day 1, Day 14

Population: 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

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

Outcome measures

Measure	Part 1 Cohort 4: QBW251 n=6 Participants 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).	Part 1 Cohort 5: QBW251 n=12 Participants 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).	Part 1 Cohort 6: QBW251 n=19 Participants 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).	Part 1 Cohort 6: QBW251(Fed) 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).	Part 1 Cohort 7: QBW251 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).	Part 1 Cohort 8: QBW251 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).	Part 1 Placebo 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).	Part 2 Cohort 1: QBW251 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).	Part 2 Cohort 2: QBW251 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).	Part 2 Cohort 3: QBW251 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).	Part 2 Cohort 4: QBW251 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).	Part 2 Cohort 5: QBW251 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).	Part 2 Placebo 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).	Part 1 Cohort 1: QBW251 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	Part 1 Cohort 2: QBW251 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).	Part 1 Cohort 3: QBW251 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).
Part 3: Time to Maximum Concentration (Tmax) Day 1	3.17 hr Standard Deviation 2.47	3.08 hr Standard Deviation 1.68	3.18 hr Standard Deviation 0.838	—	—	—	—	—	—	—	—	—	—	—	—	—
Part 3: Time to Maximum Concentration (Tmax) Day 14	1.82 hr Standard Deviation 0.750	2.39 hr Standard Deviation 0.973	NA hr Standard Deviation NA PK parameters were not calculated for Day 14 as blood samples were collected up to 2 hours post-dose	—	—	—	—	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: 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

Population: 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

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.

Outcome measures

Measure	Part 1 Cohort 4: QBW251 n=6 Participants 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).	Part 1 Cohort 5: QBW251 n=6 Participants 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).	Part 1 Cohort 6: QBW251 n=6 Participants 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).	Part 1 Cohort 6: QBW251(Fed) n=5 Participants 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).	Part 1 Cohort 7: QBW251 n=5 Participants 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).	Part 1 Cohort 8: QBW251 n=14 Participants 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).	Part 1 Placebo 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).	Part 2 Cohort 1: QBW251 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).	Part 2 Cohort 2: QBW251 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).	Part 2 Cohort 3: QBW251 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).	Part 2 Cohort 4: QBW251 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).	Part 2 Cohort 5: QBW251 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).	Part 2 Placebo 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).	Part 1 Cohort 1: QBW251 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	Part 1 Cohort 2: QBW251 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).	Part 1 Cohort 3: QBW251 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).
Part 2: Ae0-t in Healthy Volunteers	2.36 L/hr Standard Deviation 1.84	2.20 L/hr Standard Deviation 1.26	1.21 L/hr Standard Deviation 0.697	0.419 L/hr Standard Deviation 0.271	0.140 L/hr Standard Deviation 0.0936	NA L/hr Standard Deviation NA Not calculated	—	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: 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.

Population: 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

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.

Outcome measures

Measure	Part 1 Cohort 4: QBW251 n=6 Participants 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).	Part 1 Cohort 5: QBW251 n=6 Participants 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).	Part 1 Cohort 6: QBW251 n=6 Participants 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).	Part 1 Cohort 6: QBW251(Fed) n=6 Participants 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).	Part 1 Cohort 7: QBW251 n=6 Participants 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).	Part 1 Cohort 8: QBW251 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).	Part 1 Placebo 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).	Part 2 Cohort 1: QBW251 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).	Part 2 Cohort 2: QBW251 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).	Part 2 Cohort 3: QBW251 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).	Part 2 Cohort 4: QBW251 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).	Part 2 Cohort 5: QBW251 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).	Part 2 Placebo 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).	Part 1 Cohort 1: QBW251 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	Part 1 Cohort 2: QBW251 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).	Part 1 Cohort 3: QBW251 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).
Part 2: CLr in Healthy Volunteers	2.36 L/hr Standard Deviation 1.84	2.20 L/hr Standard Deviation 1.26	1.21 L/hr Standard Deviation 0.697	0.419 L/hr Standard Deviation 0.271	0.140 L/hr Standard Deviation 0.0936	—	—	—	—	—	—	—	—	—	—	—

Adverse Events

Part 1 Placebo

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Part 1 QBW251 10mg

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Part 1 QBW251 25mg

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Part 1 QBW251 150mg

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Part 1 QBW251 300mg

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Part 1 QBW251 500mg

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Part 1 QBW251 500mg (Fed)

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Part 1 QBW251 750mg

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Part 1 QBW251 1000mg

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Part 2 Placebo

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Part 2 QBW251 150mg

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Part 2 QBW251 400mg

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Part 2 QBW251 750mg

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Part 2 QBW251 450mg BID

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Part 2 QBW251 750mg BID

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Part 3 Placebo C1/C2/C3

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Part 3 QBW251 150mg BID C1

Serious events: 1 serious events

Other events: 5 other events

Deaths: 0 deaths

Part 3 QBW251 450mg BID C2

Serious events: 1 serious events

Other events: 8 other events

Deaths: 0 deaths

Part 3 QBW251 450mg BID C3

Serious events: 1 serious events

Other events: 18 other events

Deaths: 0 deaths

Serious adverse events

Measure	Part 1 Placebo n=16 participants at risk Part 1 Placebo	Part 1 QBW251 10mg n=6 participants at risk Part 1 QBW251 10mg	Part 1 QBW251 25mg n=6 participants at risk Part 1 QBW251 25mg	Part 1 QBW251 150mg n=6 participants at risk Part 1 QBW251 150mg	Part 1 QBW251 300mg n=6 participants at risk Part 1 QBW251 300mg	Part 1 QBW251 500mg n=6 participants at risk Part 1 QBW251 500mg	Part 1 QBW251 500mg (Fed) n=5 participants at risk Part 1 QBW251 500mg (fed)	Part 1 QBW251 750mg n=6 participants at risk Part 1 QBW251 750mg	Part 1 QBW251 1000mg n=6 participants at risk Part 1 QBW251 1000mg	Part 2 Placebo n=10 participants at risk Part 2 Placebo	Part 2 QBW251 150mg n=6 participants at risk Part 2 QBW251 150mg	Part 2 QBW251 400mg n=6 participants at risk Part 2 QBW251 400mg	Part 2 QBW251 750mg n=6 participants at risk Part 2 QBW251 750mg	Part 2 QBW251 450mg BID n=6 participants at risk Part 2 QBW251 450mg BID	Part 2 QBW251 750mg BID n=6 participants at risk Part 2 QBW251 750mg BID	Part 3 Placebo C1/C2/C3 n=12 participants at risk Part 3 Placebo C1/C2/C3	Part 3 QBW251 150mg BID C1 n=6 participants at risk Part 3 QBW251 150mg BID C1	Part 3 QBW251 450mg BID C2 n=12 participants at risk Part 3 QBW251 450mg BID C2	Part 3 QBW251 450mg BID C3 n=19 participants at risk Part 3 QBW251 450mg BID C3
Infections and infestations INFECTIVE PULMONARY EXACERBATION OF CYSTIC FIBROSIS	0.00% 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	8.3% 1/12	5.3% 1/19
Infections and infestations SINUSITIS	0.00% 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	16.7% 1/6	0.00% 0/12	0.00% 0/19

Other adverse events

Measure	Part 1 Placebo n=16 participants at risk Part 1 Placebo	Part 1 QBW251 10mg n=6 participants at risk Part 1 QBW251 10mg	Part 1 QBW251 25mg n=6 participants at risk Part 1 QBW251 25mg	Part 1 QBW251 150mg n=6 participants at risk Part 1 QBW251 150mg	Part 1 QBW251 300mg n=6 participants at risk Part 1 QBW251 300mg	Part 1 QBW251 500mg n=6 participants at risk Part 1 QBW251 500mg	Part 1 QBW251 500mg (Fed) n=5 participants at risk Part 1 QBW251 500mg (fed)	Part 1 QBW251 750mg n=6 participants at risk Part 1 QBW251 750mg	Part 1 QBW251 1000mg n=6 participants at risk Part 1 QBW251 1000mg	Part 2 Placebo n=10 participants at risk Part 2 Placebo	Part 2 QBW251 150mg n=6 participants at risk Part 2 QBW251 150mg	Part 2 QBW251 400mg n=6 participants at risk Part 2 QBW251 400mg	Part 2 QBW251 750mg n=6 participants at risk Part 2 QBW251 750mg	Part 2 QBW251 450mg BID n=6 participants at risk Part 2 QBW251 450mg BID	Part 2 QBW251 750mg BID n=6 participants at risk Part 2 QBW251 750mg BID	Part 3 Placebo C1/C2/C3 n=12 participants at risk Part 3 Placebo C1/C2/C3	Part 3 QBW251 150mg BID C1 n=6 participants at risk Part 3 QBW251 150mg BID C1	Part 3 QBW251 450mg BID C2 n=12 participants at risk Part 3 QBW251 450mg BID C2	Part 3 QBW251 450mg BID C3 n=19 participants at risk Part 3 QBW251 450mg BID C3
Ear and labyrinth disorders EAR DISCOMFORT	0.00% 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	10.0% 1/10	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
Ear and labyrinth disorders EAR PAIN	0.00% 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	16.7% 1/6	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
Ear and labyrinth disorders TINNITUS	0.00% 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	16.7% 1/6	0.00% 0/12	0.00% 0/19
Gastrointestinal disorders ABDOMINAL DISCOMFORT	0.00% 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	8.3% 1/12	5.3% 1/19
Cardiac disorders PALPITATIONS	0.00% 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	8.3% 1/12	16.7% 1/6	0.00% 0/12	0.00% 0/19
Congenital, familial and genetic disorders ICHTHYOSIS	0.00% 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	8.3% 1/12	0.00% 0/6	0.00% 0/12	0.00% 0/19
Gastrointestinal disorders ABDOMINAL DISTENSION	0.00% 0/16	0.00% 0/6	16.7% 1/6	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
Gastrointestinal disorders ABDOMINAL PAIN	0.00% 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	10.0% 1/10	0.00% 0/6	0.00% 0/6	16.7% 1/6	0.00% 0/6	0.00% 0/6	0.00% 0/12	0.00% 0/6	0.00% 0/12	5.3% 1/19
Gastrointestinal disorders ABDOMINAL PAIN LOWER	0.00% 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	16.7% 1/6	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
Gastrointestinal disorders APHTHOUS STOMATITIS	0.00% 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	16.7% 1/6	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
Gastrointestinal disorders DIARRHOEA	6.2% 1/16	0.00% 0/6	0.00% 0/6	0.00% 0/6	16.7% 1/6	0.00% 0/6	0.00% 0/5	0.00% 0/6	0.00% 0/6	10.0% 1/10	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	10.5% 2/19
Gastrointestinal disorders FAECES DISCOLOURED	0.00% 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	8.3% 1/12	0.00% 0/19
Gastrointestinal disorders FLATULENCE	0.00% 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	20.0% 2/10	0.00% 0/6	0.00% 0/6	0.00% 0/6	66.7% 4/6	0.00% 0/6	0.00% 0/12	0.00% 0/6	8.3% 1/12	0.00% 0/19
Gastrointestinal disorders GASTROOESOPHAGEAL REFLUX DISEASE	0.00% 0/16	0.00% 0/6	16.7% 1/6	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	8.3% 1/12	0.00% 0/19
Gastrointestinal disorders GINGIVAL DISORDER	0.00% 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	16.7% 1/6	0.00% 0/12	0.00% 0/19
Gastrointestinal disorders NAUSEA	0.00% 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	16.7% 1/6	0.00% 0/6	0.00% 0/6	0.00% 0/6	0.00% 0/12	16.7% 1/6	33.3% 4/12	10.5% 2/19
Gastrointestinal disorders SALIVA ALTERED	0.00% 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	16.7% 1/6	0.00% 0/12	0.00% 0/6	0.00% 0/12	0.00% 0/19
Gastrointestinal disorders SALIVARY GLAND PAIN	0.00% 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	16.7% 1/6	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
Gastrointestinal disorders VOMITING	0.00% 0/16	0.00% 0/6	0.00% 0/6	0.00% 0/6	16.7% 1/6	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	10.5% 2/19
General disorders ASTHENIA	0.00% 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	8.3% 1/12	5.3% 1/19
General disorders CHEST DISCOMFORT	0.00% 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	16.7% 2/12	0.00% 0/6	0.00% 0/12	5.3% 1/19
General disorders CHEST PAIN	0.00% 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	16.7% 1/6	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
General disorders FATIGUE	0.00% 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	25.0% 3/12	10.5% 2/19
General disorders INFLUENZA LIKE ILLNESS	0.00% 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	16.7% 1/6	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
General disorders PAIN	0.00% 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	8.3% 1/12	5.3% 1/19
General disorders PERIPHERAL SWELLING	0.00% 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	8.3% 1/12	0.00% 0/19
General disorders PYREXIA	0.00% 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	8.3% 1/12	5.3% 1/19
General disorders SENSATION OF FOREIGN BODY	0.00% 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	8.3% 1/12	0.00% 0/6	0.00% 0/12	0.00% 0/19
General disorders THIRST	0.00% 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	16.7% 1/6	0.00% 0/6	0.00% 0/12	0.00% 0/6	0.00% 0/12	0.00% 0/19
General disorders VESSEL PUNCTURE SITE BRUISE	0.00% 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	5.3% 1/19
Infections and infestations BRONCHITIS	0.00% 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	5.3% 1/19
Infections and infestations BRONCHOPULMONARY ASPERGILLOSIS ALLERGIC	0.00% 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	8.3% 1/12	5.3% 1/19
Infections and infestations FOLLICULITIS	0.00% 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	16.7% 1/6	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
Infections and infestations FUNGAL INFECTION	0.00% 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	5.3% 1/19
Infections and infestations GASTROENTERITIS	0.00% 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	10.0% 1/10	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
Infections and infestations INFECTIVE PULMONARY EXACERBATION OF CYSTIC FIBROSIS	0.00% 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	25.0% 3/12	16.7% 1/6	0.00% 0/12	10.5% 2/19
Infections and infestations NASOPHARYNGITIS	6.2% 1/16	0.00% 0/6	0.00% 0/6	0.00% 0/6	0.00% 0/6	0.00% 0/6	20.0% 1/5	0.00% 0/6	16.7% 1/6	10.0% 1/10	0.00% 0/6	16.7% 1/6	0.00% 0/6	0.00% 0/6	0.00% 0/6	8.3% 1/12	0.00% 0/6	0.00% 0/12	0.00% 0/19
Infections and infestations ORAL HERPES	0.00% 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	16.7% 1/6	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
Infections and infestations PHARYNGITIS	0.00% 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	10.0% 1/10	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
Infections and infestations SINUSITIS	0.00% 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	16.7% 1/6	0.00% 0/12	0.00% 0/19
Infections and infestations UPPER RESPIRATORY TRACT INFECTION	0.00% 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	5.3% 1/19
Infections and infestations VIRAL UPPER RESPIRATORY TRACT INFECTION	0.00% 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	5.3% 1/19
Injury, poisoning and procedural complications ARTHROPOD BITE	0.00% 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	5.3% 1/19
Injury, poisoning and procedural complications LIGAMENT SPRAIN	0.00% 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	8.3% 1/12	0.00% 0/6	0.00% 0/12	0.00% 0/19
Injury, poisoning and procedural complications SKIN WOUND	0.00% 0/16	0.00% 0/6	0.00% 0/6	16.7% 1/6	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
Investigations ADENOVIRUS TEST POSITIVE	0.00% 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	5.3% 1/19
Investigations BLOOD ALKALINE PHOSPHATASE INCREASED	0.00% 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	5.3% 1/19
Investigations BLOOD POTASSIUM DECREASED	0.00% 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	5.3% 1/19
Investigations BREATH SOUNDS ABNORMAL	0.00% 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	5.3% 1/19
Investigations CORONAVIRUS TEST POSITIVE	0.00% 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	5.3% 1/19
Metabolism and nutrition disorders DECREASED APPETITE	0.00% 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	5.3% 1/19
Metabolism and nutrition disorders HYPOGLYCAEMIA	0.00% 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	5.3% 1/19
Metabolism and nutrition disorders VITAMIN D DEFICIENCY	0.00% 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	8.3% 1/12	0.00% 0/6	0.00% 0/12	0.00% 0/19
Musculoskeletal and connective tissue disorders BACK PAIN	0.00% 0/16	0.00% 0/6	16.7% 1/6	0.00% 0/6	0.00% 0/6	0.00% 0/6	0.00% 0/5	16.7% 1/6	0.00% 0/6	0.00% 0/10	0.00% 0/6	16.7% 1/6	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
Musculoskeletal and connective tissue disorders JOINT SWELLING	0.00% 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	8.3% 1/12	0.00% 0/19
Musculoskeletal and connective tissue disorders MUSCLE SPASMS	0.00% 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	5.3% 1/19
Musculoskeletal and connective tissue disorders MUSCULOSKELETAL CHEST PAIN	0.00% 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	8.3% 1/12	0.00% 0/6	0.00% 0/12	0.00% 0/19
Musculoskeletal and connective tissue disorders MUSCULOSKELETAL PAIN	0.00% 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	10.0% 1/10	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
Musculoskeletal and connective tissue disorders MUSCULOSKELETAL STIFFNESS	0.00% 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	16.7% 1/6	0.00% 0/10	0.00% 0/6	16.7% 1/6	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
Musculoskeletal and connective tissue disorders NECK PAIN	0.00% 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	5.3% 1/19
Musculoskeletal and connective tissue disorders PAIN IN EXTREMITY	6.2% 1/16	0.00% 0/6	16.7% 1/6	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	8.3% 1/12	0.00% 0/6	0.00% 0/12	0.00% 0/19
Nervous system disorders BALANCE DISORDER	0.00% 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	10.0% 1/10	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
Nervous system disorders DIZZINESS	18.8% 3/16	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	33.3% 2/6	20.0% 2/10	0.00% 0/6	0.00% 0/6	0.00% 0/6	16.7% 1/6	0.00% 0/6	0.00% 0/12	0.00% 0/6	16.7% 2/12	5.3% 1/19
Nervous system disorders HEADACHE	12.5% 2/16	33.3% 2/6	0.00% 0/6	0.00% 0/6	16.7% 1/6	33.3% 2/6	0.00% 0/5	0.00% 0/6	33.3% 2/6	40.0% 4/10	0.00% 0/6	16.7% 1/6	0.00% 0/6	16.7% 1/6	33.3% 2/6	0.00% 0/12	16.7% 1/6	25.0% 3/12	21.1% 4/19
Nervous system disorders HYPERAESTHESIA	6.2% 1/16	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% 0/19
Nervous system disorders PRESYNCOPE	0.00% 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	16.7% 1/6	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
Nervous system disorders SCIATICA	0.00% 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	8.3% 1/12	0.00% 0/19
Nervous system disorders SYNCOPE	0.00% 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	16.7% 1/6	0.00% 0/6	0.00% 0/12	16.7% 1/6	0.00% 0/12	5.3% 1/19
Nervous system disorders TREMOR	0.00% 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	5.3% 1/19
Psychiatric disorders AGITATION	0.00% 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	5.3% 1/19
Psychiatric disorders DEPRESSION	0.00% 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	5.3% 1/19
Psychiatric disorders INSOMNIA	0.00% 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	8.3% 1/12	16.7% 1/6	0.00% 0/12	0.00% 0/19
Psychiatric disorders STRESS	0.00% 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	5.3% 1/19
Renal and urinary disorders CHROMATURIA	0.00% 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	5.3% 1/19
Renal and urinary disorders GLYCOSURIA	0.00% 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	5.3% 1/19
Renal and urinary disorders PROTEINURIA	0.00% 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	5.3% 1/19
Respiratory, thoracic and mediastinal disorders BRONCHIAL OBSTRUCTION	0.00% 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	8.3% 1/12	0.00% 0/6	0.00% 0/12	0.00% 0/19
Respiratory, thoracic and mediastinal disorders COUGH	0.00% 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	16.7% 1/6	0.00% 0/6	66.7% 4/6	0.00% 0/6	16.7% 2/12	16.7% 1/6	8.3% 1/12	21.1% 4/19
Respiratory, thoracic and mediastinal disorders DYSPNOEA	0.00% 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	16.7% 1/6	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
Respiratory, thoracic and mediastinal disorders EPISTAXIS	0.00% 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	10.0% 1/10	0.00% 0/6	0.00% 0/6	16.7% 1/6	0.00% 0/6	0.00% 0/6	0.00% 0/12	0.00% 0/6	0.00% 0/12	0.00% 0/19
Respiratory, thoracic and mediastinal disorders HAEMOPTYSIS	0.00% 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	8.3% 1/12	0.00% 0/6	0.00% 0/12	10.5% 2/19
Respiratory, thoracic and mediastinal disorders NASAL CONGESTION	6.2% 1/16	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	16.7% 1/6	0.00% 0/6	0.00% 0/6	0.00% 0/6	0.00% 0/12	0.00% 0/6	0.00% 0/12	10.5% 2/19
Respiratory, thoracic and mediastinal disorders NASAL DISCOMFORT	0.00% 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	16.7% 1/6	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
Respiratory, thoracic and mediastinal disorders OROPHARYNGEAL PAIN	0.00% 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	16.7% 1/6	0.00% 0/6	0.00% 0/6	16.7% 1/6	0.00% 0/6	0.00% 0/12	0.00% 0/6	8.3% 1/12	0.00% 0/19
Respiratory, thoracic and mediastinal disorders PAINFUL RESPIRATION	0.00% 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	5.3% 1/19
Respiratory, thoracic and mediastinal disorders PRODUCTIVE COUGH	0.00% 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	8.3% 1/12	0.00% 0/6	0.00% 0/12	0.00% 0/19
Respiratory, thoracic and mediastinal disorders PULMONARY CONGESTION	0.00% 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	16.7% 2/12	5.3% 1/19
Respiratory, thoracic and mediastinal disorders RHINORRHOEA	0.00% 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	16.7% 1/6	0.00% 0/6	0.00% 0/12	0.00% 0/6	8.3% 1/12	10.5% 2/19
Respiratory, thoracic and mediastinal disorders SINUS CONGESTION	0.00% 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	16.7% 1/6	0.00% 0/12	5.3% 1/19
Respiratory, thoracic and mediastinal disorders SNEEZING	0.00% 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	5.3% 1/19
Respiratory, thoracic and mediastinal disorders SPUTUM INCREASED	0.00% 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	16.7% 2/12	50.0% 3/6	0.00% 0/12	26.3% 5/19
Respiratory, thoracic and mediastinal disorders THROAT IRRITATION	0.00% 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	16.7% 1/6	0.00% 0/6	0.00% 0/6	0.00% 0/12	16.7% 1/6	0.00% 0/12	0.00% 0/19
Respiratory, thoracic and mediastinal disorders TONSILLAR DISORDER	0.00% 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	8.3% 1/12	0.00% 0/6	0.00% 0/12	0.00% 0/19
Skin and subcutaneous tissue disorders ERYTHEMA	0.00% 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	5.3% 1/19
Skin and subcutaneous tissue disorders HEAT RASH	0.00% 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	16.7% 1/6	0.00% 0/12	0.00% 0/6	0.00% 0/12	0.00% 0/19
Skin and subcutaneous tissue disorders NIGHT SWEATS	0.00% 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	8.3% 1/12	0.00% 0/19
Skin and subcutaneous tissue disorders PHOTOSENSITIVITY REACTION	0.00% 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	5.3% 1/19
Skin and subcutaneous tissue disorders PRURITUS	0.00% 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	10.5% 2/19
Skin and subcutaneous tissue disorders PRURITUS GENERALISED	6.2% 1/16	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% 0/19
Skin and subcutaneous tissue disorders RASH	0.00% 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	5.3% 1/19
Skin and subcutaneous tissue disorders RASH ERYTHEMATOUS	0.00% 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	16.7% 1/6	0.00% 0/12	0.00% 0/19
Skin and subcutaneous tissue disorders RASH PRURITIC	0.00% 0/16	16.7% 1/6	0.00% 0/6	0.00% 0/6	0.00% 0/6	0.00% 0/6	0.00% 0/5	0.00% 0/6	16.7% 1/6	0.00% 0/10	0.00% 0/6	16.7% 1/6	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
Skin and subcutaneous tissue disorders URTICARIA	0.00% 0/16	16.7% 1/6	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
Vascular disorders HOT FLUSH	0.00% 0/16	16.7% 1/6	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

Additional Information

Study Director

Novartis

Phone: 862-778-8300

Results disclosure agreements

• Principal investigator is a sponsor employee 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.
• Publication restrictions are in place

Restriction type: OTHER