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Trial record 3 of 212 for:    Suspended, Terminated, Withdrawn Studies | Interventional Studies | COPD

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

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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 )

Tracking Information
First Submitted Date  ICMJE October 24, 2013
First Posted Date  ICMJE October 30, 2013
Results First Submitted Date  ICMJE January 22, 2016
Results First Posted Date  ICMJE March 24, 2016
Last Update Posted Date March 24, 2016
Study Start Date  ICMJE November 2013
Actual Primary Completion Date May 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 24, 2016)
  • Percentage of Participants With Adverse Events (Part 1) [ Time Frame: 14 days ]
    Adverse events were counted and corresponding percentages were tabulated.
  • 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 ]
Original Primary Outcome Measures  ICMJE
 (submitted: October 24, 2013)
  • Occurrence of an adverse event in multiple doses of QBM076 for 14 days of treatment [ Time Frame: 14 days ]
    Adverse events will be counted within each treatment for each part of the study and corresponding percentages will be tabulated.
  • Change in Lung clearance Index (LCI) [ Time Frame: Baseline (day -1) and 56 days ]
    LCI as measured by multiple breath nitrogen washout is the time taken to wash out nitrogen whilst breathing 100% oxygen. LCI will be measured at baseline and day 14. LCI will be 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.
  • Change in absolute number of sputum neutrophils [ Time Frame: Baseline (day -1) and day 56 ]
    Log sputum neutrophils will be 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.
  • Change in ventilation/perfusion homogeneity [ Time Frame: Baseline (day -1) and 56 days ]
    Ventilation defect volume will be 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.
  • Questionnaire TDI [ Time Frame: Baseline (day -1) and 56 days ]
    Transition Dyspnea Index (TDI) captures changes from baseline. The TDI score is based on three domains with each domain scored from -3 (major deterioration) to +3 (major improvement), to give an overall score of -9 to +9, a negative score indicating a deterioration from baseline. A TDI focal score of 1 is considered to be a clinically significant improvement from baseline. Mixed model uses baseline TDI, baseline inhaled corticosteroid (ICS) use, FEV1 prior to inhalation of short acting beta-agonist (SABA), and FEV1 45 minutes post-inhalation of SABA as covariates.
  • Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) [ Time Frame: Baseline (day -1) and 56 days ]
    Forced expiratory volume in 1 second (FEV1) is the amount of air that can be exhaled in one second. FEV1 will be measured by spirometry performed at approximately the same time of day on each visit to avoid diurnal variation. All spirometry calibrations and evaluations will follow the recommendations of the American Thoracic Society / European Respiratory Society guidelines for acceptability. A positive change from baseline in FEV1 will indicate improvement in lung function.
Change History Complete list of historical versions of study NCT01972776 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: February 24, 2016)
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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 ]
  • AUC0-24 (Part 2) [ Time Frame: day 1, day 56 ]
  • Cmax Between 0h and 24h (Part 2) [ Time Frame: day 1, day 56 ]
  • Tmax Between 0h and 24h (Part 2) [ Time Frame: day 1, day 56 ]
  • Change From Baseline in Percentage Sputum Neutrophils (Part 2) [ Time Frame: baseline, day 56 ]
  • Change From Baseline in Diffusing Capacity of the Lung for Carbon Monoxide (DLco) (Part 2) [ Time Frame: baseline, day 56 ]
  • Change From Baseline in Scond/Sacin as Measured by Multiple Breath Nitrogen Washout (MBNW) (Part 2) [ Time Frame: baseline, day 56 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: October 24, 2013)
  • AUC0-t Plasma concentration of QBM076 between 0h and 72h on Days 1 and 14 [ Time Frame: 14 days ]
    Blood samples will be taken from each subject participating in the study (placebo group and active treatment group). AUC0-t will be listed by treatment and subject. Descriptive summary statistics will include mean (arithmetic and geometric), SD, and CV (arithmetic and geometric), median, minimum and maximum.
  • Cmax Plasma concentration of QBM076 between 0h and 72h on Days 1 and 14 [ Time Frame: 14 days ]
    Blood samples will be taken from each subject participating in the study (placebo group and active treatment group). Cmax will be listed by treatment and subject. Descriptive summary statistics will include mean (arithmetic and geometric), SD, and CV (arithmetic and geometric), median, minimum and maximum.
  • Tmax Plasma concentration of QBM076 between 0h and 72h on Days 1 and 14 [ Time Frame: 14 days ]
    Blood samples will be taken from each subject participating in the study (placebo group and active treatment group). Tmax will be listed by treatment and subject. Tmax is generally evaluated by a nonparametric method, median values and ranges will be given for this parameter
  • Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) [ Time Frame: 14 days ]
    Forced expiratory volume in 1 second (FEV1) is the amount of air that can be exhaled in one second. FEV1 will be measured by spirometry performed at approximately the same time of day on each visit to avoid diurnal variation. All spirometry calibrations and evaluations will follow 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.
  • Change in CD11b expression from baseline [ Time Frame: 14 days ]
    The change in CD11b expression will be presented as a percentage change from baseline on days 1 and 14
  • AUC0-t Plasma concentration of QBM076 between 0h and 24h on Days 1 and 56 [ Time Frame: 56 days ]
    Blood samples will be taken from each subject participating in the study (placebo group and active treatment group). AUC0-t will be listed by treatment and subject. Descriptive summary statistics will include mean (arithmetic and geometric), SD, and CV (arithmetic and geometric), median, minimum and maximum.
  • Cmax Plasma concentration of QBM076 between 0h and 24h on Days 1 and 56 [ Time Frame: 56 days ]
    Blood samples will be taken from each subject participating in the study (placebo group and active treatment group). Cmax will be listed by treatment and subject. Descriptive summary statistics will include mean (arithmetic and geometric), SD, and CV (arithmetic and geometric), median, minimum and maximum.
  • Tmax Plasma concentration of QBM076 between 0h and 24h on Days 1 and 56 [ Time Frame: 56 days ]
    Blood samples will be taken from each subject participating in the study (placebo group and active treatment group). Tmax will be listed by treatment and subject. Tmax is generally evaluated by a nonparametric method, median values and ranges will be given for this parameter
  • Change in percentage sputum neutrophils [ Time Frame: 56 days ]
    Log sputum neutrophils will be 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.
  • Change in diffusing capacity of the lung for carbon monoxide (DLco) [ Time Frame: 56 days ]
    DLco involves measuring the partial pressure difference between inspired and expired carbon monoxide. Descriptive statistics will be provided by treatment for measurements performed at baseline, days 14, 28 and 56.
  • Change in Scond/Sacin as measured by multiple breath nitrogen washout (MBNW) [ Time Frame: 56 days ]
    Multiple breath nitrogen washout involves administration of 100% oxygen, and measures the time taken to washout nitrogen. Parameters Scond and Sacin are measures taken from the curve of nitrogen concentration whilst being washed out from the lung during oxygen administration. Descriptive statistics will be provided by treatment at baseline and on days 14, 28, and 56.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Safety, Tolerability and Efficacy Study in Chronic Obstructive Pulmonary Disease (COPD) Patients With QBM076.
Official Title  ICMJE 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
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.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Condition  ICMJE COPD
Intervention  ICMJE
  • Drug: QBM076
    Supplied in 25 mg and 75 mg capsules
  • Drug: Placebo
    Matching placebo capsules
    Other Name: Matching placebo capsules
Study Arms  ICMJE
  • Experimental: QBM076 Part 1 Cohort 1
    Participants received QBM076 25 mg twice daily (bid) for 14 days.
    Intervention: Drug: QBM076
  • Experimental: QBM076 Part 1 Cohort 2
    Participants received QBM076 75 mg bid for 14 days.
    Intervention: Drug: QBM076
  • Experimental: QBM076 Part 1 Cohort 3
    Participants received QBM076 150 mg bid for 14 days.
    Intervention: Drug: QBM076
  • Placebo Comparator: Placebo Part 1
    Participants in each cohort received matching placebo for 14 days.
    Intervention: Drug: Placebo
  • Experimental: QBM076 Part 2
    Participants received QBM076 150 mg bid for 8 weeks.
    Intervention: Drug: QBM076
  • Placebo Comparator: Placebo Part 2
    Participants received matching placebo for 8 weeks.
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: September 29, 2015)
48
Original Estimated Enrollment  ICMJE
 (submitted: October 24, 2013)
122
Actual Study Completion Date  ICMJE May 2015
Actual Primary Completion Date May 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 35 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Germany,   Romania,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01972776
Other Study ID Numbers  ICMJE CQBM076X2203
2012-005615-92 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Novartis ( Novartis Pharmaceuticals )
Study Sponsor  ICMJE Novartis Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
PRS Account Novartis
Verification Date February 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP