Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

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: NCT01972776
Recruitment Status : Terminated (Part 1 was completed. Part 2 was terminated for safety reasons.)
First Posted : October 30, 2013
Results First Posted : March 24, 2016
Last Update Posted : March 24, 2016
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

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.

Condition or disease Intervention/treatment Phase
COPD Drug: QBM076 Drug: Placebo Phase 2

Detailed 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.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 48 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: A Two Part, Double Blind, Placebo Controlled, Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamic Effects of Multiple Doses of QBM076 in Patients With COPD
Study Start Date : November 2013
Actual Primary Completion Date : May 2015
Actual Study Completion Date : May 2015

Arm Intervention/treatment
Experimental: QBM076 Part 1 Cohort 1
Participants received QBM076 25 mg twice daily (bid) for 14 days.
Drug: QBM076
Supplied in 25 mg and 75 mg capsules

Experimental: QBM076 Part 1 Cohort 2
Participants received QBM076 75 mg bid for 14 days.
Drug: QBM076
Supplied in 25 mg and 75 mg capsules

Experimental: QBM076 Part 1 Cohort 3
Participants received QBM076 150 mg bid for 14 days.
Drug: QBM076
Supplied in 25 mg and 75 mg capsules

Placebo Comparator: Placebo Part 1
Participants in each cohort received matching placebo for 14 days.
Drug: Placebo
Matching placebo capsules
Other Name: Matching placebo capsules

Experimental: QBM076 Part 2
Participants received QBM076 150 mg bid for 8 weeks.
Drug: QBM076
Supplied in 25 mg and 75 mg capsules

Placebo Comparator: Placebo Part 2
Participants received matching placebo for 8 weeks.
Drug: Placebo
Matching placebo capsules
Other Name: Matching placebo capsules




Primary Outcome Measures :
  1. Percentage of Participants With Adverse Events (Part 1) [ Time Frame: 14 days ]
    Adverse events were counted and corresponding percentages were tabulated.

  2. Change From Baseline in Lung Clearance Index (LCI) (Part 2) [ Time Frame: Baseline, 8 weeks ]
  3. Change From Baseline in Absolute Number of Sputum Neutrophils (Part 2) [ Time Frame: Baseline, 8 weeks ]
  4. Change From Baseline in Transition Dyspnea Index (TDI) (Part 2) [ Time Frame: Baseline, 8 weeks ]
  5. Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) (Part 2) [ Time Frame: Baseline, 8 weeks ]

Secondary Outcome Measures :
  1. Area Under the Plasma Concentration-time Curve From Time Zero to the End of the Dosing Interval, Tau (AUCtau) (Part 1) [ Time Frame: day 1 (from pre-dose to 12 hours post dose) ]
    Venous blood samples were collected for concentration-time profiles.

  2. AUCtau, Steady State (AUCtau,ss) (Part 1) [ Time Frame: day 14 (from pre-dose to 72 hours post dose) ]
    Venous blood samples were collected for concentration-time profiles.

  3. Observed Maximum Plasma Concentration Following Drug Administration (Cmax) (Part 1) [ Time Frame: day 1 (from pre-dose to 12 hours post dose) ]
    Venous blood samples were collected for concentration-time profiles.

  4. Cmax,ss (Part 1) [ Time Frame: day 14 (from pre-dose to 72 hours post dose) ]
    Venous blood samples were collected for concentration-time profiles.

  5. Time to Reach the Maximum Concentration After Drug Administration (Tmax) (Part 1) [ Time Frame: day 1 (from pre-dose to 12 hours post dose) ]
    Venous blood samples were collected for concentration-time profiles.

  6. Tmax,ss (Part 1) [ Time Frame: day 14 (from pre-dose to 72 hours post dose) ]
    Venous blood samples were collected for concentration-time profiles.

  7. Change From Baseline in Cluster of Differentiation 11b (CD11b) (Part 1) [ Time Frame: baseline, day 14 ]
    Whole blood samples were taken by either direct venipuncture or an indwelling cannula inserted in a forearm vein in order to measure CD11b expression on neutrophils. A negative change from baseline indicates improvement.

  8. Change From Baseline in Chemokine (C-X-C Motif) Receptor 2 (CXCR2) Receptor Occupancy (Part 1) [ Time Frame: baseline, day 14 ]
    Whole blood samples were taken by either direct venipuncture or an indwelling cannula inserted in a forearm vein in order to measure CXCR2 receptor occupancy on neutrophils. A positive change from baseline indicates improvement.

  9. Change From Baseline in Forced Expiratory Volume in One Second (FEV1) (Part 1) [ Time Frame: baseline, day 14 pre-dose ]
    FEV1 is the amount of air that can be exhaled in one second. FEV1 will be measured by spirometry and performed at approximately the same time of day on each visit to avoid diurnal variation. All spirometry calibrations and evaluations followed the recommendations of the American Thoracic Society / European Respiratory Society guidelines for acceptability. A positive change from baseline in FEV1 indicates improvement in lung function.

  10. Change From Baseline in Lung Clearance Index 2.5 (LCI2.5) (Part 1) [ Time Frame: baseline, day 14 pre-dose ]
    Lung clearance index (LCI) is a measure of abnormal ventilation distribution derived from the multiple breath inert gas washout (MBW) technique. LCI is equal to the cumulative expired volume/functional residual capacity. LCI was measured at baseline and day 14. LCI was analyzed using a Bayesian model for repeated measurements. The model may investigate effects for pre-dose baseline, treatment, time, age, COPD class, treatment by time interaction, and baseline by time interaction. A positive change from baseline indicates improvement.

  11. Change From Baseline in Forced Expirtory Flow 25-75 (FEF25-75), Forced Expiratory Volume 3 (FEV3)/Forced Vital Capacity (FVC), 1-(FEV3/FVC), FEV6, FEV1/FEV6 and Post-bronchodilator Forced Expiratory Volume in 1 Second (FEV1) (Part 2) [ Time Frame: baseline, day 56 ]
  12. AUC0-24 (Part 2) [ Time Frame: day 1, day 56 ]
  13. Cmax Between 0h and 24h (Part 2) [ Time Frame: day 1, day 56 ]
  14. Tmax Between 0h and 24h (Part 2) [ Time Frame: day 1, day 56 ]
  15. Change From Baseline in Percentage Sputum Neutrophils (Part 2) [ Time Frame: baseline, day 56 ]
  16. Change From Baseline in Diffusing Capacity of the Lung for Carbon Monoxide (DLco) (Part 2) [ Time Frame: baseline, day 56 ]
  17. Change From Baseline in Scond/Sacin as Measured by Multiple Breath Nitrogen Washout (MBNW) (Part 2) [ Time Frame: baseline, day 56 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   35 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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)

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): NCT01972776


Locations
Layout table for location information
United States, Virginia
Novartis Investigative Site
Richmond, Virginia, United States, 23225
Germany
Novartis Investigative Site
Berlin, Germany, 10117
Novartis Investigative Site
Frankfurt, Germany, 60596
Novartis Investigative Site
Grosshansdorf, Germany, 22947
Novartis Investigative Site
Hannover, Germany, 30625
Romania
Novartis Investigative Site
Bucharest, Romania, Sector 5
United Kingdom
Novartis Investigative Site
Manchester, United Kingdom, M23 9QZ
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Layout table for investigator information
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals

Layout table for additonal information
Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01972776     History of Changes
Other Study ID Numbers: CQBM076X2203
2012-005615-92 ( EudraCT Number )
First Posted: October 30, 2013    Key Record Dates
Results First Posted: March 24, 2016
Last Update Posted: March 24, 2016
Last Verified: February 2016

Keywords provided by Novartis ( Novartis Pharmaceuticals ):
COPD, inflammation, small airways, LCI, PFTs, lung heterogeneity

Additional relevant MeSH terms:
Layout table for MeSH terms
Pulmonary Disease, Chronic Obstructive
Lung Diseases, Obstructive
Lung Diseases
Respiratory Tract Diseases