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

NCT01972776 | Terminated Phase 2 Results DMC

• 2 other identifiers: CQBM076X22032012-005615-92
• Study Type: interventional
• Target: 48
• Locations: 4 countries
• Sites: 7

Brief Summary

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.

Conditions

COPD

Keywords

COPD, inflammation, small airways, LCI, PFTs, lung heterogeneity

Outcome Measures

Primary Outcomes (5)

• Percentage of Participants With Adverse Events (Part 1)

  Adverse events were counted and corresponding percentages were tabulated.

  14 days

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

  Baseline, 8 weeks

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

  Baseline, 8 weeks

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

  Baseline, 8 weeks

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

  Baseline, 8 weeks

Secondary Outcomes (17)

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

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

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

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

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

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

• Cmax,ss (Part 1)

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

• Time to Reach the Maximum Concentration After Drug Administration (Tmax) (Part 1)

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

Study Arms (6)

QBM076 Part 1 Cohort 1

EXPERIMENTAL

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

Drug: QBM076

QBM076 Part 1 Cohort 2

EXPERIMENTAL

Participants received QBM076 75 mg bid for 14 days.

Drug: QBM076

QBM076 Part 1 Cohort 3

EXPERIMENTAL

Participants received QBM076 150 mg bid for 14 days.

Drug: QBM076

Placebo Part 1

PLACEBO COMPARATOR

Participants in each cohort received matching placebo for 14 days.

Drug: Placebo

QBM076 Part 2

EXPERIMENTAL

Participants received QBM076 150 mg bid for 8 weeks.

Drug: QBM076

Placebo Part 2

PLACEBO COMPARATOR

Participants received matching placebo for 8 weeks.

Drug: Placebo

Interventions

QBM076 DRUG

Supplied in 25 mg and 75 mg capsules

QBM076 Part 1 Cohort 1; QBM076 Part 1 Cohort 2; QBM076 Part 1 Cohort 3; QBM076 Part 2

Placebo DRUG

Matching placebo capsules

Also known as: Matching placebo capsules

Placebo Part 1; Placebo Part 2

Eligibility Criteria

• Age: 35 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (7)

Novartis Investigative Site

Richmond, Virginia, 23225, United States

Location

Novartis Investigative Site

Berlin, 10117, Germany

Location

Novartis Investigative Site

Frankfurt, 60596, Germany

Location

Novartis Investigative Site

Großhansdorf, 22947, Germany

Location

Novartis Investigative Site

Hanover, 30625, Germany

Location

Novartis Investigative Site

Bucharest, Sector 5, Romania

Location

Novartis Investigative Site

Manchester, M23 9QZ, United Kingdom

Location

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive; Inflammation

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

Part 2 was terminated after 21 patients were enrolled. Three of the 21 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 bid.

Results Point of Contact

• Title: Study Director
• Organization: Novartis

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 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 24, 2013
• First Posted: October 30, 2013
• Study Start: November 1, 2013
• Primary Completion: May 1, 2015
• Study Completion: May 1, 2015
• Last Updated: March 24, 2016
• Results First Posted: March 24, 2016

Record last verified: 2016-02

Locations

RO (1); US (1); DE (4); GB (1)