Clinical trial NCT02190604
Conditions: Cystic Fibrosis
Keywords: FEV1- Forced Expiratory volume LCI - Lung Clearance Index CFTR - cystic fibrosis transmembrane conductance regulator cystic fibrosis allergic bronchopulmonary aspergillosis
Sponsor: Novartis Pharmaceuticals
Start date: 2012-07-31; Completion date: 2015-11-30
Enrollment: 153 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This study is designed to assess the safety, tolerability, pharmacokinetics and preliminary pharmacodynamics (proof of concept) of QBW251 in healthy subjects and cystic fibrosis patients following single and multiple doses. This first-in-human and proof of concept study will consist of 4 parts, with Parts 1 and 2 in healthy volunteers and Parts 3 and 4 in cystic fibrosis patients.

Detailed description:

Arms: arm 1: 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). arm 2: 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). arm 3: 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). arm 4: 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). arm 5: 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). arm 6: 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). arm 7: 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). arm 8: 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). arm 9: 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). arm 10: 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). arm 11: 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). arm 12: 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). arm 13: 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). arm 14: 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). arm 15: 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). arm 16: 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). arm 17: 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. arm 18: 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. arm 19: 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. arm 20: 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.
Interventions: intervention 1: Placebo intervention 2: QBW251
Intervention descriptions: intervention 1: Capsule- oral dose intervention 2: Capsule - oral dose

Protocol documents: