A Safety, Tolerability and Efficacy Study in COPD Patients With QBM076.

COPD Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01972776
• Other study ID #: CQBM076X2203
• Secondary ID: 2012-005615-92
• Status: Terminated
• Phase: Phase 2
• First received: October 24, 2013
• Last updated: September 29, 2015
• Start date: November 2013
• Est. completion date: December 2015

Study information

• Verified date: September 2015
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationGermany: Federal Institute for Drugs and Medical DevicesUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyUnited Kingdom: Research Ethics CommitteeGermany: Ethics Commission
• Study type: Interventional

Clinical Trial Summary

This is a 2 Part study. Part 1 is a safety and tolerability study in GOLD I-III COPD patients. Part 2 is an efficacy study in GOLD I-III COPD patients.

Description:

Part 1 is a double-blind, randomized, placebo-controlled, non-confirmatory study in chronic bronchitis COPD patients. 32 patients will be enrolled in up to 4 cohorts. Patients will be randomized in a 3:1 ratio. Part 1 will consist 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.

Part 2 is a double-blind, randomized, placebo-controlled, non-confirmatory study in Gold spirometry grades I-III COPD patients. 90 patients will be randomized in a 2:1 ratio. The study will consist 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 48
• Est. completion date: December 2015
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 35 Years to 75 Years

Eligibility

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 interation; 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)

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• COPD

Intervention

Drug:
• QBM076
QBM076 taken orally twice per day during 14 days for Part 1 - QBM076 taken orally twice per day during 8 weeks for Part 2
• placebo
Placebo taken orally twice per day during 14 days for Part 1 - Placebo taken orally twice per day during 8 weeks for Part 2

Locations

Country	Name	City	State
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Frankfurt
Germany	Novartis Investigative Site	Grosshansdorf
Germany	Novartis Investigative Site	Hannover
Romania	Novartis Investigative Site	Bucharest
United Kingdom	Novartis Investigative Site	Manchester
United States	Novartis Investigative Site	Richmond	Virginia

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Germany,  Romania,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Occurrence of an adverse event in multiple doses of QBM076 for 14 days of treatment in Part 1	Adverse events will be counted within each treatment for each part of the study and corresponding percentages will be tabulated.	14 days	Yes
Primary	Change in Lung clearance Index (LCI)	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.	Baseline (day -1) and 8 weeks	No
Primary	Change in absolute number of sputum neutrophils	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.	Baseline (day -1) and 8 weeks	No
Primary	Questionnaire TDI	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.	Baseline (day -1) and 8 weeks	No
Primary	Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1)	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.	Baseline (day -1) and 8 weeks	No
Secondary	AUC0-t Plasma concentration of QBM076 between 0h and 72h on Days 1 and 14	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.	14 days	No
Secondary	Cmax Plasma concentration of QBM076 between 0h and 72h on Days 1 and 14	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.	14 days	No
Secondary	Tmax Plasma concentration of QBM076 between 0h and 72h on Days 1 and 14	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	14 days	No
Secondary	Change From Baseline in FEF25-75, FEV3/FVC, 1-(FEV3/FVC), FEV6, FEV1/FEV6 and post-bronchodilator Forced Expiratory Volume in 1 Second (FEV1)	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.	8 weeks	No
Secondary	Change in CD11b expression from baseline	The change in CD11b expression will be presented as a percentage change from baseline on days 1 and 14	14 days	No
Secondary	AUC0-t Plasma concentration of QBM076 between 0h and 24h on Days 1 and 56	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.	8 weeks	No
Secondary	Cmax Plasma concentration of QBM076 between 0h and 24h on Days 1 and 56	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.	8 weeks	No
Secondary	Tmax Plasma concentration of QBM076 between 0h and 24h on Days 1 and 56	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	8 weeks	No
Secondary	Change in percentage sputum neutrophils	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.	8 weeks	No
Secondary	Change in diffusing capacity of the lung for carbon monoxide (DLco)	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.	8 weeks	No
Secondary	Change in Scond/Sacin as measured by multiple breath nitrogen washout (MBNW)	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.	8 weeks	No
Secondary	Change in CXCR2 receptor occupancy from baseline	The change in CXCR2 receptor occupancy will be presented as a percentage change from baseline on days 1 and 14	14 days	No