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

Novartis

Status and phase: Terminated; Phase 2

Conditions: COPD

Treatments: Drug: QBM076; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT01972776

CQBM076X2203

2012-005615-92 (EudraCT Number)

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 48 patients

Sex: All

Ages: 35 to 75 years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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48 participants in 6 patient groups, including a placebo group

QBM076 Part 1 Cohort 1

Experimental group

Description:

Participants received QBM076 25 mg twice daily (bid) for 14 days.

Treatment:

Drug: QBM076

QBM076 Part 1 Cohort 2

Experimental group

Description:

Participants received QBM076 75 mg bid for 14 days.

Treatment:

Drug: QBM076

QBM076 Part 1 Cohort 3

Experimental group

Description:

Participants received QBM076 150 mg bid for 14 days.

Treatment:

Drug: QBM076

Placebo Part 1

Placebo Comparator group

Description:

Participants in each cohort received matching placebo for 14 days.

Treatment:

Drug: Placebo

QBM076 Part 2

Experimental group

Description:

Participants received QBM076 150 mg bid for 8 weeks.

Treatment:

Drug: QBM076

Placebo Part 2

Placebo Comparator group

Description:

Participants received matching placebo for 8 weeks.

Treatment:

Drug: Placebo