This is a study of multiple doses of inhaled QBW276 in patients with cystic fibrosis on top of standard of care. The study was divided into 3 Cohorts. Cohorts 1 and 2 are designed to be a randomized, double-blind, placebo-controlled, parallel arm, multiple dose study to assess the safety, tolerability, pharmacokinetics, and preliminary efficacy of inhaled QBW276 over 1 week (cohort 1) or 2 weeks (cohort 2) in patients with cystic fibrosis regardless of their genotype. The study was terminated after Cohort 2 due to the resource issues.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
16
Novartis Investigative Site
New York, New York, United States
Novartis Investigative Site
Dallas, Texas, United States
Novartis Investigative Site
Cologne, Germany
Novartis Investigative Site
Essen, Germany
Cohorts 1 and 2: Safety Assessments, Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]).
Adverse events were summarized by the number of patients having any adverse event overall and presented in the safety section. Study was prematurely terminated
Time frame: Cohort 1: day 1-7; Cohort 2: day 1-14
Cohorts 1 and 2: Pharmacokinetics (Cmax) of QBW276, QBP545, and QBV697 in Plasma
Blood collection will be used to observe the maximum plasma concentration (Cmax) following administration of QBW276. Pharmacokinetic blood samples were collected at the time points. In Cohorts 1 and 2 this consisted of multiple samples through 6 hours after inhalation on Days 1 and 7 in Cohort 1 and Days 1 and 14 in Cohort 2 with predose samples on selected days. The Cmax, was determined using the actual recorded sampling times and noncompartmental methods. Since steady state was likely reached by Day 7, Cmax on Days 7 or 14 correspond to Cmax,ss
Time frame: Cohort 1: day 1, 7; Cohort 2: day 1, 14
Cohorts 1 and 2: Pharmacokinetics (Tmax) of QBW276, QBP545, and QBV697 in Plasma
Blood collection will be used to observe the maximum plasma concentration (Tmax) following administration of QBW276. Pharmacokinetic blood samples were collected at the time points. In Cohorts 1 and 2 this consisted of multiple samples through 6 hours after inhalation on Days 1 and 7 in Cohort 1 and Days 1 and 14 in Cohort 2 with predose samples on selected days. The Tmax, was determined using the actual recorded sampling times and noncompartmental methods. Since steady state was likely reached by Day 7, Tmax on Days 7 or 14 correspond to Tmax,ss
Time frame: Day 1, 7 and 14
Cohorts 1 and 2: Pharmacokinetics (AUCtau) of QBW276, QBP545, and QBV697 in Plasma
Blood collection will be used to observe the maximum plasma concentration (AUCtau) following administration of QBW276. Pharmacokinetic blood samples were collected at the time points. In Cohorts 1 and 2 this consisted of multiple samples through 6 hours after inhalation on Days 1 and 7 in Cohort 1 and Days 1 and 14 in Cohort 2 with predose samples on selected days. The AUCtau, was determined using the actual recorded sampling times and noncompartmental methods. Since steady state was likely reached by Day 7, AUCtau on Days 7 or 14 correspond to AUClast,ss
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Time frame: Day 1, 7 and 14
Cohorts 1 and 2: Pharmacokinetics Accumulation Ratio (Racc) of QBW276, QBP545, and QBV697 in Plasma
The accumulation ratio (Racc) will be reported using blood samples taken on days 1 -7 in cohort 1 and days 1-14 in cohort 2. Accumulation ratio (Racc) for QBW276 and metabolites was not calculated by PK software for patients where BLOQ values were observed for all blood samples in their PK profile.
Time frame: Cohort 1: 7 days; Cohort 2: 14 days
Cohorts 1 and 2: Change From Baseline in Percent Predicted Forced Expiratory Volume in the First Second by Spirometry (% Predicted FEV1)
To evaluate the response to multiple doses of inhaled QBW276 in percent predicted forced expiratory volume in the first second by spirometry according to international standards over 1 or 2 weeks of treatment compared with placebo in patients with cystic fibrosis.
Time frame: Baseline to End of study (EOS)
Cohorts 1, 2: Change From Baseline in Lung Clearance Index (LCI) From Baseline to Day 7 for Cohort 1, Day 14 for Cohort 2.
Change in Lung Clearance Index (LCI) will be conducted by multiple breath nitrogen washout according to international standards
Time frame: Baseline to EOS