A Safety, Tolerability and Efficacy Study in Chronic Obstructive Pulmonary Disease (COPD) Patients With QBM076.

Phase 2TerminatedNCT01972776

Novartis Pharmaceuticals48 enrolled

Overview

This was a 2 Part study. Part 1 was a safety and tolerability study in GOLD I-III COPD patients. Part 2 was an efficacy study in GOLD I-III COPD patients.

Part 1 was a double-blind, randomized, placebo-controlled, non-confirmatory study in chronic bronchitis COPD patients. Part 1 consisted of up to 27-days of screening period, one baseline period of 1 day, 13 days of bid dosing with study treatment, morning only treatment on Day 14, follow up visits on Days 15 - 17, followed by a Study Completion evaluation. Twenty-seven patients were randomized in a 3:1 ratio to 3 cohorts.. Part 2 was a double-blind, randomized, placebo-controlled, non-confirmatory study in Gold spirometry grades I-III COPD patients. Part 2 consisted of up to 20 days of screening period, a 9 day run in period, one baseline period of 1 day, 55 days of bid dosing, morning only dosing on Day 56, followed by Study Completion evaluation. It was planned to randomize 90 patients in a 2:1 ratio, but part 2 was terminated after 21 patients were enrolled. Three of the 21 part 2 patients experienced moderate to severe (up to 17-fold) asymptomatic and reversible elevation of liver transaminase levels after 3 weeks of treatment with QBM076 150 mg twice daily. Two of these patients had liver transaminase levels high enough to be reported as serious adverse events suspected to be related to the study drug.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

TRIPLE

Enrollment

Conditions

COPD

Interventions

QBM076DRUG

Supplied in 25 mg and 75 mg capsules

PlaceboDRUG

Matching placebo capsules

Eligibility

Sex: ALLMin age: 35 YearsMax age: 75 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Part 1: Patients, smokers or ex-smokers with stable chronic bronchitis GOLD class I-III chronic obstructive pulmonary disease (COPD); forced expiratory volume in 1 second ≥40% of predicted and forced expiratory volume in 1 second:forced vital capacity ratio ≤0.7 post bronchodilator, respectively; diffusing capacity of the lung for carbon monoxide ≥40%; a stable medical regimen for at least 4 weeks prior to screening. Current smokers can be enrolled if they currently smoke ≤1ppd for last 3 months. * Part 2: Patients, smokers or ex-smokers with GOLD spirometry class I-III COPD; a stable medical regimen for at least 4 weeks prior to screening; high sensitivity C reactive protein≥1.5 mg/L; forced expiratory volume in 1 second ≥30% of predicted and forced expiratory volume in 1 second:forced vital capacity ratio ≤0.7 post bronchodilator, respectively; with mean lung clearance index 2.5% ≥8; Ex-smokers with at least 10 pack year smoking history; or current smokers with at least 10 pack year smoking history who smoke ≤ 1ppd on average for last 3 months.; evidence of air trapping based on radiologic criteria; women of child bearing potential using effective methods of contraception Exclusion Criteria: * Part 1:Gold Class IV COPD, of moderate to significant emphysema, or evidence of malignancy; medication considered potential for drug drug interaction; creatinine clearance \<30ml/min; more than 1 exacerbation requiring antibiotics or oral steroids and/or hospitalization within 3 months of screening; women of child bearing potential • Part 2: Gold spirometry grade IV COPD; medication considered a potential for drug drug interaction; serum creatinine ≥1.9 mg/dL; more than 1 exacerbation requiring antibiotics or oral steroids within 2 months and/or hospitalization within 3 months of screening; any malignancy; evidence of severe emphysema as determined by HRCT; use of oral steroids, theophylline, phosphodiesterase-4 inhibitors or oral antibiotic use (eg.macrolides)

Locations (7)

Novartis Investigative Site

Richmond, Virginia, United States

Novartis Investigative Site

Berlin, Germany

Novartis Investigative Site

Frankfurt, Germany

Novartis Investigative Site

Großhansdorf, Germany

Outcomes

Primary Outcomes

Percentage of Participants With Adverse Events (Part 1)

Adverse events were counted and corresponding percentages were tabulated.

Time frame: 14 days

Change From Baseline in Lung Clearance Index (LCI) (Part 2)

Time frame: Baseline, 8 weeks

Change From Baseline in Absolute Number of Sputum Neutrophils (Part 2)

Time frame: Baseline, 8 weeks

Change From Baseline in Transition Dyspnea Index (TDI) (Part 2)

Time frame: Baseline, 8 weeks

Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) (Part 2)

Time frame: Baseline, 8 weeks

Secondary Outcomes

Area Under the Plasma Concentration-time Curve From Time Zero to the End of the Dosing Interval, Tau (AUCtau) (Part 1)

Venous blood samples were collected for concentration-time profiles.

Time frame: day 1 (from pre-dose to 12 hours post dose)

AUCtau, Steady State (AUCtau,ss) (Part 1)

Venous blood samples were collected for concentration-time profiles.

Time frame: day 14 (from pre-dose to 72 hours post dose)

Observed Maximum Plasma Concentration Following Drug Administration (Cmax) (Part 1)

Venous blood samples were collected for concentration-time profiles.

Time frame: day 1 (from pre-dose to 12 hours post dose)

Cmax,ss (Part 1)

Data from ClinicalTrials.gov

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