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Completed

NCT Number: NCT02566044

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

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.

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Key information

Conditions

Pulmonary Cystic Fibrosis Congenital, Hereditary, and Neonatal Diseases and Abnormalities Cystic Fibrosis Digestive System Diseases Genetic Diseases, Inborn Infant, Newborn, Diseases Lung Diseases Pancreatic Diseases Respiratory Tract Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Novartis Investigative Site, Cologne, Germany

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.)

Treatment and study plan

Placebo

Other

Placebo

QBW276

Drug

0.3 mg and 1.5 mg strengths

Primary outcomes

  1. Cohorts 1 and 2: Safety Assessments, Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]).

    Time frame: Cohort 1: day 1-7; Cohort 2: day 1-14

    Adverse events were summarized by the number of patients having any adverse event overall and presented in the safety section. Study was prematurely terminated

  2. Cohorts 1 and 2: Pharmacokinetics (Cmax) of QBW276, QBP545, and QBV697 in Plasma

    Time frame: Cohort 1: day 1, 7; Cohort 2: day 1, 14

    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

  3. Cohorts 1 and 2: Pharmacokinetics (Tmax) of QBW276, QBP545, and QBV697 in Plasma

    Time frame: Day 1, 7 and 14

    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

  4. Cohorts 1 and 2: Pharmacokinetics (AUCtau) of QBW276, QBP545, and QBV697 in Plasma

    Time frame: Day 1, 7 and 14

    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

  5. Cohorts 1 and 2: Pharmacokinetics Accumulation Ratio (Racc) of QBW276, QBP545, and QBV697 in Plasma

    Time frame: Cohort 1: 7 days; Cohort 2: 14 days

    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.

Secondary outcomes

  1. Cohorts 1 and 2: Change From Baseline in Percent Predicted Forced Expiratory Volume in the First Second by Spirometry (% Predicted FEV1)

    Time frame: Baseline to End of study (EOS)

    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.

  2. Cohorts 1, 2: Change From Baseline in Lung Clearance Index (LCI) From Baseline to Day 7 for Cohort 1, Day 14 for Cohort 2.

    Time frame: Baseline to EOS

    Change in Lung Clearance Index (LCI) will be conducted by multiple breath nitrogen washout according to international standards

Sponsors and collaborators

Lead sponsor

Novartis Pharmaceuticals

Industry

Registry information

Official study 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

Important dates

Study start
2017
Primary completion
2018
Study completion
2018
First posted
Oct 1, 2015
Registry last updated
Dec 30, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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