Safety, Pharmacokinetics and Pharmacodynamics Study of Inhaled QBW276 in Patients With Cystic Fibrosis

Pulmonary Cystic Fibrosis Clinical Trial

Official title:

A Randomized, Double-blind, Placebo-controlled Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Multiple Doses of Inhaled QBW276 in Patients With Cystic Fibrosis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02566044
• Other study ID #: CQBW276X2201
• Secondary ID: 2014-004915-35
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: September 27, 2017
• Est. completion date: April 24, 2018

Study information

• Verified date: June 2019
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: April 24, 2018
• Est. primary completion date: April 24, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Cohorts 1 and 2 = any genotype on any standard of care treatment
• Cohort 3 = F508del homozygotes on standard of care at that time
• FEV1between 40 and 100%
• LCI2.5 = 8 if FEV1is more than 80%

Exclusion Criteria:

• Adrenal or electrolyte abnormalities
• Lung transplant
• Autonomic dysfunction (e.g. recurrent episodes of fainting, palpitations, etc.)

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis
• Pulmonary Cystic Fibrosis

Intervention

Other:
• Placebo
Placebo

Drug:
• QBW276
0.3 mg and 1.5 mg strengths

Locations

Country	Name	City	State
Germany	Novartis Investigative Site	Essen
Germany	Novartis Investigative Site	Koeln
United States	Novartis Investigative Site	Dallas	Texas
United States	Novartis Investigative Site	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Cohort 1: day 1-7; Cohort 2: day 1-14
Primary	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	Cohort 1: day 1, 7; Cohort 2: day 1, 14
Primary	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	Day 1, 7 and 14
Primary	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	Day 1, 7 and 14
Primary	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.	Cohort 1: 7 days; Cohort 2: 14 days
Secondary	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.	Baseline to End of study (EOS)
Secondary	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	Baseline to EOS

External Links

•   A Plain Language Trial Summary is available on novartisclinicatrials.com