Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 2012-005615-92 | EudraCT Number |
Not provided
Not provided
Not provided
Part 1 was completed. Part 2 was terminated for safety reasons.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| QBM076 Part 1 Cohort 1 | Experimental | Participants received QBM076 25 mg twice daily (bid) for 14 days. |
|
| QBM076 Part 1 Cohort 2 | Experimental | Participants received QBM076 75 mg bid for 14 days. |
|
| QBM076 Part 1 Cohort 3 | Experimental | Participants received QBM076 150 mg bid for 14 days. |
|
| Placebo Part 1 | Placebo Comparator | Participants in each cohort received matching placebo for 14 days. |
|
| QBM076 Part 2 | Experimental | Participants received QBM076 150 mg bid for 8 weeks. |
|
| Placebo Part 2 | Placebo Comparator | Participants received matching placebo for 8 weeks. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| QBM076 | Drug | Supplied in 25 mg and 75 mg capsules |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | day 1 (from pre-dose to 12 hours post dose) |
| AUCtau, Steady State (AUCtau,ss) (Part 1) |
Not provided
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.
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Novartis Pharmaceuticals | Novartis Pharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Novartis Investigative Site | Richmond | Virginia | 23225 | United States | ||
| Novartis Investigative Site |
Not provided
In part 1, participants were randomly assigned to one of two treatment arms in a ratio of 3:1 for each cohort. In part 2, participants were stratified by smoking status (current versus ex-smoker) and randomized in a ratio of 2:1 into one of two treatments.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | QBM076 Part 1 Cohort 1 | Participants received QBM076 25 mg bid for 14 days. |
| FG001 | QBM076 Part 1 Cohort 2 | Participants received QBM076 75 mg bid for 14 days. |
| FG002 | QBM076 Part 1 Cohort 3 | Participants received QBM076 150 mg bid for 14 days. |
| FG003 | Placebo Part 1 | Participants in each cohort received matching placebo bid for 14 days. |
| FG004 | QBM076 Part 2 | Participants received QBM076 150 mg bid for 8 weeks. |
| FG005 | Placebo Part 2 | Participants received matching placebo bid for 8 weeks. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Part 1 |
|
| ||||||||||||||||||
| Part 2 |
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | QBM076 Part 1 Cohort 1 | Participants received QBM076 25 mg bid for 14 days. |
| BG001 | QBM076 Part 1 Cohort 2 | Participants received QBM076 75 mg bid for 14 days. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Percentage of Participants With Adverse Events (Part 1) | Adverse events were counted and corresponding percentages were tabulated. | All randomized part 1 participants | Posted | Number | percentage of participants | 14 days |
|
Not provided
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Part 1: QBM076 B.I.D 25 mg | Part 1: QBM076 B.I.D 25 mg |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Radius fracture | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal distension | Gastrointestinal disorders | MedDRA | Systematic Assessment |
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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Novartis | 862-778-8300 |
Not provided
| ID | Term |
|---|---|
| D029424 | Pulmonary Disease, Chronic Obstructive |
| D007249 | Inflammation |
| ID | Term |
|---|---|
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D002908 | Chronic Disease |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Placebo | Drug | Matching placebo capsules |
|
|
Venous blood samples were collected for concentration-time profiles. |
| 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. | day 1 (from pre-dose to 12 hours post dose) |
| Cmax,ss (Part 1) | Venous blood samples were collected for concentration-time profiles. | day 14 (from pre-dose to 72 hours post dose) |
| Time to Reach the Maximum Concentration After Drug Administration (Tmax) (Part 1) | Venous blood samples were collected for concentration-time profiles. | day 1 (from pre-dose to 12 hours post dose) |
| Tmax,ss (Part 1) | Venous blood samples were collected for concentration-time profiles. | day 14 (from pre-dose to 72 hours post dose) |
| Change From Baseline in Cluster of Differentiation 11b (CD11b) (Part 1) | 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. | baseline, day 14 |
| Change From Baseline in Chemokine (C-X-C Motif) Receptor 2 (CXCR2) Receptor Occupancy (Part 1) | 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. | baseline, day 14 |
| Change From Baseline in Forced Expiratory Volume in One Second (FEV1) (Part 1) | 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. | baseline, day 14 pre-dose |
| Change From Baseline in Lung Clearance Index 2.5 (LCI2.5) (Part 1) | 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. | baseline, day 14 pre-dose |
| 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) | baseline, day 56 |
| AUC0-24 (Part 2) | day 1, day 56 |
| Cmax Between 0h and 24h (Part 2) | day 1, day 56 |
| Tmax Between 0h and 24h (Part 2) | day 1, day 56 |
| Change From Baseline in Percentage Sputum Neutrophils (Part 2) | baseline, day 56 |
| Change From Baseline in Diffusing Capacity of the Lung for Carbon Monoxide (DLco) (Part 2) | baseline, day 56 |
| Change From Baseline in Scond/Sacin as Measured by Multiple Breath Nitrogen Washout (MBNW) (Part 2) | baseline, day 56 |
| Berlin |
| 10117 |
| Germany |
| Novartis Investigative Site | Frankfurt | 60596 | Germany |
| Novartis Investigative Site | Großhansdorf | 22947 | Germany |
| Novartis Investigative Site | Hanover | 30625 | Germany |
| Novartis Investigative Site | Bucharest | Sector 5 | Romania |
| Novartis Investigative Site | Manchester | M23 9QZ | United Kingdom |
| Adverse Event |
|
| COMPLETED |
|
| NOT COMPLETED |
|
|
| BG002 | QBM076 Part 1 Cohort 3 | Participants received QBM076 150 mg bid for 14 days. |
| BG003 | Placebo Part 1 | Participants in each cohort received matching placebo bid for 14 days. |
| BG004 | QBM076 Part 2 | Participants received QBM076 150 mg bid for 8 weeks. |
| BG005 | Placebo Part 2 | Participants received matching placebo bid for 8 weeks. |
| BG006 | Total | Total of all reporting groups |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
Participants received QBM076 150 mg bid for 14 days.
| OG003 | Placebo Part 1 | Participants in each cohort received matching placebo bid for 14 days. |
|
|
| Primary | Change From Baseline in Lung Clearance Index (LCI) (Part 2) | Part 2 was terminated early. Therefore, primary and secondary outcomes for part 2 were not assessed. | Posted | Baseline, 8 weeks |
|
|
| Primary | Change From Baseline in Absolute Number of Sputum Neutrophils (Part 2) | Part 2 was terminated early. Therefore, primary and secondary outcomes for part 2 were not assessed. | Posted | Baseline, 8 weeks |
|
|
| Primary | Change From Baseline in Transition Dyspnea Index (TDI) (Part 2) | Part 2 was terminated early. Therefore, primary and secondary outcomes for part 2 were not assessed. | Posted | Baseline, 8 weeks |
|
|
| Primary | Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) (Part 2) | Part 2 was terminated early. Therefore, primary and secondary outcomes for part 2 were not assessed. | Posted | Baseline, 8 weeks |
|
|
| Secondary | 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. | All Part 1 participants who received active treatment. | Posted | Mean | Standard Deviation | ng*h/mL | day 1 (from pre-dose to 12 hours post dose) |
|
|
|
| Secondary | AUCtau, Steady State (AUCtau,ss) (Part 1) | Venous blood samples were collected for concentration-time profiles. | All Part 1 participants who received active treatment. | Posted | Mean | Standard Deviation | ng*h/mL | day 14 (from pre-dose to 72 hours post dose) |
|
|
|
| Secondary | Observed Maximum Plasma Concentration Following Drug Administration (Cmax) (Part 1) | Venous blood samples were collected for concentration-time profiles. | All Part 1 participants who received active treatment. | Posted | Mean | Standard Deviation | ng/mL | day 1 (from pre-dose to 12 hours post dose) |
|
|
|
| Secondary | Cmax,ss (Part 1) | Venous blood samples were collected for concentration-time profiles. | All Part 1 participants who received active treatment. | Posted | Mean | Standard Deviation | ng/mL | day 14 (from pre-dose to 72 hours post dose) |
|
|
|
| Secondary | Time to Reach the Maximum Concentration After Drug Administration (Tmax) (Part 1) | Venous blood samples were collected for concentration-time profiles. | All Part 1 participants who received active treatment. | Posted | Median | Full Range | hours | day 1 (from pre-dose to 12 hours post dose) |
|
|
|
| Secondary | Tmax,ss (Part 1) | Venous blood samples were collected for concentration-time profiles. | All Part 1 participants who received active treatment. | Posted | Median | Full Range | hours | day 14 (from pre-dose to 72 hours post dose) |
|
|
|
| Secondary | Change From Baseline in Cluster of Differentiation 11b (CD11b) (Part 1) | 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. | All Randomized Part 1 participants were considered for the analysis but participants with both baseline and day 14 values were analyzed. | Posted | Number | percentage change | baseline, day 14 |
|
|
|
| Secondary | Change From Baseline in Chemokine (C-X-C Motif) Receptor 2 (CXCR2) Receptor Occupancy (Part 1) | 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. | All Randomized Part 1 participants were considered for the analysis but participants with both baseline and day 14 values were analyzed. | Posted | Number | percent change | baseline, day 14 |
|
|
|
| Secondary | Change From Baseline in Forced Expiratory Volume in One Second (FEV1) (Part 1) | 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. | All Randomized Part 1 participants were considered for the analysis but participants with both baseline and day 14 values were analyzed. | Posted | Mean | Standard Error | mL | baseline, day 14 pre-dose |
|
|
|
| Secondary | Change From Baseline in Lung Clearance Index 2.5 (LCI2.5) (Part 1) | 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. | All Randomized Part 1 participants were considered for the analysis but participants with both baseline and day 14 values were analyzed. | Posted | Mean | Standard Error | index score | baseline, day 14 pre-dose |
|
|
|
| Secondary | 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) | Part 2 was terminated early. Therefore, primary and secondary outcomes for part 2 were not assessed. | Posted | baseline, day 56 |
|
|
| Secondary | AUC0-24 (Part 2) | Part 2 was terminated early. Therefore, primary and secondary outcomes for part 2 were not assessed. | Posted | day 1, day 56 |
|
|
| Secondary | Cmax Between 0h and 24h (Part 2) | Part 2 was terminated early. Therefore, primary and secondary outcomes for part 2 were not assessed. | Posted | day 1, day 56 |
|
|
| Secondary | Tmax Between 0h and 24h (Part 2) | Part 2 was terminated early. Therefore, primary and secondary outcomes for part 2 were not assessed. | Posted | day 1, day 56 |
|
|
| Secondary | Change From Baseline in Percentage Sputum Neutrophils (Part 2) | Part 2 was terminated early. Therefore, primary and secondary outcomes for part 2 were not assessed. | Posted | baseline, day 56 |
|
|
| Secondary | Change From Baseline in Diffusing Capacity of the Lung for Carbon Monoxide (DLco) (Part 2) | Part 2 was terminated early. Therefore, primary and secondary outcomes for part 2 were not assessed. | Posted | baseline, day 56 |
|
|
| Secondary | Change From Baseline in Scond/Sacin as Measured by Multiple Breath Nitrogen Washout (MBNW) (Part 2) | Part 2 was terminated early. Therefore, primary and secondary outcomes for part 2 were not assessed. | Posted | baseline, day 56 |
|
|
| 0 |
| 6 |
| 2 |
| 6 |
| EG001 | Part 1: QBM076 B.I.D 75 mg | Part 1: QBM076 B.I.D 75 mg | 0 | 6 | 3 | 6 |
| EG002 | Part 1: QBM076 B.I.D 150 mg | Part 1: QBM076 B.I.D 150 mg | 0 | 8 | 5 | 8 |
| EG003 | Part 1: Placebo | Part 1: Placebo | 1 | 7 | 4 | 7 |
| EG004 | Part 2: QBM076 B.I.D 150 mg | Part 2: QBM076 B.I.D 150 mg | 2 | 14 | 8 | 14 |
| EG005 | Part 2:QBM076 B.I.D Placebo | Part 2:QBM076 B.I.D Placebo | 0 | 7 | 3 | 7 |
| Hepatic enzyme increased | Investigations | MedDRA | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Abdominal tenderness | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Dry mouth | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Flatulence | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Toothache | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Catheter site eczema | General disorders | MedDRA | Systematic Assessment |
|
| Catheter site erythema | General disorders | MedDRA | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA | Systematic Assessment |
|
| Therapeutic response unexpected | General disorders | MedDRA | Systematic Assessment |
|
| Vessel puncture site bruise | General disorders | MedDRA | Systematic Assessment |
|
| Vessel puncture site haematoma | General disorders | MedDRA | Systematic Assessment |
|
| Hepatotoxicity | Hepatobiliary disorders | MedDRA | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA | Systematic Assessment |
|
| Rhinitis | Infections and infestations | MedDRA | Systematic Assessment |
|
| Contusion | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
|
| Eyelid injury | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
|
| Procedural complication | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
|
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Lethargy | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
|
| Increased upper airway secretion | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
|
| Skin exfoliation | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
|
| Hot flush | Vascular disorders | MedDRA | Systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA | Systematic Assessment |
|
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.
| D020969 |
| Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |