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

• Register: EUCTR
• Last refreshed on: 4 August 2015
• Main ID: EUCTR2012-005615-92-GB
• Date of registration: 20/09/2013
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public 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
• Scientific 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
• Date of first enrolment: 14/11/2013
• Target sample size: 122
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-005615-92
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2

Countries of recruitment

Germany, Hungary, Netherlands, United Kingdom, United States

Contacts

• Name: Medical Information Services
• Affiliation: Novartis Pharmaceuticals UK Ltd

• Name: Medical Information Services
• Affiliation: Novartis Pharmaceuticals UK Ltd

Key inclusion & exclusion criteria

Inclusion criteria:
• Part 1:
- Patients, smokers or ex-smokers with stable GOLD spirometry grades I-III COPD according to the current GOLD strategy (GOLD 2013)
- FEV1 =40% of predicted and FEV1:FVC ratio =0.7 post bronchodilator
- DLCO =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 with stable GOLD spirometry grades I-III COPD according to the current GOLD strategy (GOLD 2013)
- a stable medical regimen for at least 4 weeks prior to screening
- hsCRP=1.5 mg/L; FEV1 =30% of predicted and FEV1:FVC ratio =0.7 post bronchodilator, respectively with LCI=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 on HRCT of airway thickening by visual inspection
- women of child bearing potential can be enrolled as long as they agree to use effective contraception (except hormonal contraceptives, due to the risk of drug-drug interaction with QBM076) as described in the protocol.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 40
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 82

Exclusion criteria:
• Part 1:
- Gold Grade IV COPD, moderate to significant emphysema, or evidence of active malignancy
- medication considered potential for DDI
- CrCl <40ml/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 Class IV COPD
- medication considered a potential for DDI
- serum creatinine =1.9 mg/dL
- more than 1 exacerbation requiring antibiotics or oral steroids and/or hospitalization within 3 months of screening
- current smokers
- any malignancy
- HRCT chest screen failure based on preset criteria for bronchial thickening, emphysematous changes and extent of bronchiectasis
- use of daily oral steroids, theophylline, PDE4 inhibitors or oral antibiotic use (eg.macrolides)



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Chronic Obstructive Pulmonary Disease (COPD)
MedDRA version: 17.1 Level: LLT Classification code 10010952 Term: COPD System Organ Class: 100000004855

Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

Intervention(s)

Product Name: QBM076 25mg
Product Code: QBM076
Pharmaceutical Form: Capsule, hard
Current Sponsor code: QBM076
Other descriptive name: QBM076
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 25-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Product Name: QBM076 75mg
Product Code: QBM076
Pharmaceutical Form: Capsule, hard
Current Sponsor code: QBM076
Other descriptive name: QBM076
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 75-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: Throughout the entirety of Part 1 and Part 2, for details please refer to protocol.

Main Objective: Part 1: To evaluate the safety and tolerability of multiple ascending doses of QBM076 in current or ex-smoking patients with stable COPD with spirometry grades I-III (according to the current GOLD strategy (GOLD 2013)) for 14 consecutive days of treatment.
Part 2: To evaluate the preliminary efficacy of 8 consecutive weeks of QBM076 in current or ex-smoking patients with stable COPD with spirometry grades I-III (according to the current GOLD strategy (GOLD 2013)).
1. LCI;
2. absolute neutrophil count in sputum;
3. spirometry FEV1;
4. TDI.

Secondary Objective: Part 1
• To evaluate the pharmacokinetics of multiple doses of QBM076 for 14 consecutive days.
• To evaluate the effects of multiple doses of QBM076 for 14 consecutive days on CD11b inhibition, CXCR2 receptor occupancy, LCI and PFTs

Part 2
• safety and tolerability of multiple doses of QBM076 in current or ex-smoking COPD patients for 8 consecutive weeks
• pharmacokinetics of multiple doses of QBM076 for 8 consecutive weeks
• preliminary efficacy at 8 weeks of multiple doses of QBM076 in COPD patients as reflected in changes in:
- Measurements associated with MBNW
- Change in % neutrophils in sputum
- FEF25-75, FEV3/FVC, 1-(FEV3/FVC), FEV6, FEV1/FEV6 and postbronchodilator FEV11 measured by spirometry
- Additional PFT measurements performed in a body plethysmography box including DLCO, IC, FRCTLC, RV and RV/TLC ratio
- Assessment of air trapping as assessed by the exhalation phase of the HRCT

Primary end point(s): Part 1:
The primary variable for the safety objective is occurrence of an adverse event in multiple doses of QBM076 for 14 days of treatment.

Part 2:
The primary variables for the efficacy objective are LCI, absolute number of sputum neutrophils, FEV1 and TDI.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Throughout the entirety of Part 1 and Part 2, for details please refer to protocol.

Secondary end point(s): Efficacy / Pharmacodynamics
Part 1
To evaluate the pharmacodynamic response to multiple doses of QMB076 in COPD patients as reflected by changes in LCI, sputum neutrophils, and lung function to Day 14.

Part 2
Secondary and exploratory pharmacodynamic variables include respiratory resistance as measured by FOT, PFT measurements performed in a body plethysmography box including, DLCO, FVC, and FVC/FEV1 ratio. The descriptive statistics for each variable will be provided by treatment for each part of the study.

Safety

Vital signs
All vital signs data will be listed by treatment, subject, and visit/time and if ranges are available abnormalities (and relevant orthostatic changes) will be flagged. Summary statistics will be provided by treatment and visit/time.

ECG evaluations
All ECG data will be listed by treatment, subject and visit/time, abnormalities will be flagged. Summary statistics will be provided by treatment and visit/time.

Clinical laboratory evaluations
All laboratory data will be listed by treatment, subject, and visit/time and if normal ranges are available abnormalities will be flagged. Summary statistics will be provided by treatment and visit/time.

Adverse events
All information obtained on adverse events will be displayed by treatment and subject. The number and percentage of subjects with adverse events will be tabulated by body system and preferred term with a breakdown by treatment. A subject with multiple adverse events within a body system is only counted once towards the total of this body system.

Pharmacokinetics (including exploratory assessment of dose proportionality)

Pharmacokinetic / pharmacodynamic interactions
An exploratory analysis of the relationship between pharmacokinetic and pharmacodynamic measures will be explored using a model based approach, if the data permits.

Secondary ID(s)

2012-005615-92-DE

CQBM076X2203

Source(s) of Monetary Support

Novartis Pharma Services AG