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

NCT02566044 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: CQBW276X22012014-004915-35
• Study Type: interventional
• Target: 16
• Locations: 2 countries
• Sites: 4

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.

Conditions

Pulmonary Cystic Fibrosis

Keywords

Cystic Fibrosis

Outcome Measures

Primary Outcomes (5)

• 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

• 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

• 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

• 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

• 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 Outcomes (2)

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

  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.

  Baseline to EOS

Study Arms (2)

CQBW276

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

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

Interventions

Placebo OTHER

Placebo

Placebo

QBW276 DRUG

0.3 mg and 1.5 mg strengths

CQBW276

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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%

You may not qualify if:

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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (4)

Novartis Investigative Site

New York, New York, 10032, United States

Location

Novartis Investigative Site

Dallas, Texas, 75390-9034, United States

Location

Novartis Investigative Site

Cologne, 50924, Germany

Location

Novartis Investigative Site

Essen, 45147, Germany

Location

Related Links

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

MeSH Terms

Conditions

Cystic Fibrosis

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceutical

novartis.email@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 18, 2015
• First Posted: October 1, 2015
• Study Start: September 27, 2017
• Primary Completion: April 24, 2018
• Study Completion: April 24, 2018
• Last Updated: December 30, 2020
• Results First Posted: July 17, 2019

Record last verified: 2019-06

Locations

US (2); DE (2)