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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02566044
Recruitment Status : Completed
First Posted : October 1, 2015
Results First Posted : July 17, 2019
Last Update Posted : July 17, 2019
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief 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.


Condition or disease Intervention/treatment Phase
Pulmonary Cystic Fibrosis Other: Placebo Drug: QBW276 Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 16 participants
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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
Actual Study Start Date : September 27, 2017
Actual Primary Completion Date : April 24, 2018
Actual Study Completion Date : April 24, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Cystic Fibrosis

Arm Intervention/treatment
Experimental: CQBW276

Cohorts 1 and 2 will enroll 8 patients each (6:2 QBW276 and placebo, respectively).

Cohort 1: dose is 3 mg bid (6 mg daily) QBW276 or placebo for 7 days. Cohort 2: dose and frequency will be confirmed after cohort 1 is complete. The duration is 14 days.

Cohort 3: dose and frequency will be confirmed after cohort 2 is complete. The duration is approximately 4 months. Patients will be randomized to one of two treatment sequences: QBW276 in Period 1 and Placebo in Period 2 or Placebo in Period 1 and QBW276 in Period 2. Twenty four patients are required to complete cohort 3.

Drug: QBW276
0.3 mg and 1.5 mg strengths

Placebo Comparator: Placebo

Cohorts 1 and 2 will enroll 8 patients each (6:2 QBW276 and placebo, respectively).

Cohort 1: dose is 3 mg bid (6 mg daily) QBW276 or placebo for 7 days. Cohort 2: dose and frequency will be confirmed after cohort 1 is complete. The duration is 14 days.

Cohort 3: dose and frequency will be confirmed after cohort 2 is complete. The duration is approximately 4 months. Patients will be randomized to one of two treatment sequences: QBW276 in Period 1 and Placebo in Period 2 or Placebo in Period 1 and QBW276 in Period 2. Twenty four patients are required to complete cohort 3.

Other: Placebo
Placebo




Primary Outcome Measures :
  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 Outcome Measures :
  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



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02566044


Locations
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United States, New York
Novartis Investigative Site
New York, New York, United States, 10032
United States, Texas
Novartis Investigative Site
Dallas, Texas, United States, 75390-9034
Germany
Novartis Investigative Site
Essen, Germany, 45147
Novartis Investigative Site
Koeln, Germany, 50924
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  Study Documents (Full-Text)

Documents provided by Novartis ( Novartis Pharmaceuticals ):
Statistical Analysis Plan  [PDF] September 20, 2017
Study Protocol  [PDF] June 28, 2018


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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02566044     History of Changes
Other Study ID Numbers: CQBW276X2201
2014-004915-35 ( EudraCT Number )
First Posted: October 1, 2015    Key Record Dates
Results First Posted: July 17, 2019
Last Update Posted: July 17, 2019
Last Verified: June 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Cystic Fibrosis
Additional relevant MeSH terms:
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Cystic Fibrosis
Fibrosis
Pathologic Processes
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases