COPDPhase 2NCT01972776
A Safety, Tolerability and Efficacy Study in Chronic Obstructive Pulmonary Disease (COPD) Patients With QBM076.
A Phase 2 study testing QBM076 in people with COPD, run by Novartis Pharmaceuticals at 7 sites in 4 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 35 to 75 years
- Conditions the study is for
- COPD
- What is being tested?
- QBM076
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 48 participants
- Where
- 7 sitesin 4 countries
- Study dates
- Nov 2013to May 2015
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 35 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
Trial locations and contacts
7 sites in 4 countries.
7 sites in 4 countries
Germany4 sites
Novartis Investigative Site
Berlin, 10117
Novartis Investigative Site
Frankfurt, 60596
Novartis Investigative Site
Großhansdorf, 22947
Novartis Investigative Site
Hanover, 30625
United States1 site
Novartis Investigative Site
Richmond, Virginia, 23225
About this study
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
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.
Read the 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.
- Conditions
- COPD
- Being tested
- QBM076, Placebo
- Keywords
- COPD, inflammation, small airways, LCI, PFTs, lung heterogeneity
- Medical subject headings
- Pulmonary Disease, Chronic Obstructive, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
QBM076Drug
Supplied in 25 mg and 75 mg capsules
PlaceboDrug
Also called Matching placebo capsules
Matching placebo capsules
| Study group | Role | What they receive |
|---|---|---|
| QBM076 Part 1 Cohort 1 | Experimental | Participants received QBM076 25 mg twice daily (bid) for 14 days. Receives: Drug: QBM076 |
| QBM076 Part 1 Cohort 2 | Experimental | Participants received QBM076 75 mg bid for 14 days. Receives: Drug: QBM076 |
| QBM076 Part 1 Cohort 3 | Experimental | Participants received QBM076 150 mg bid for 14 days. Receives: Drug: QBM076 |
| Placebo Part 1 | Placebo comparator | Participants in each cohort received matching placebo for 14 days. Receives: Drug: Placebo |
| QBM076 Part 2 | Experimental | Participants received QBM076 150 mg bid for 8 weeks. Receives: Drug: QBM076 |
| Placebo Part 2 | Placebo comparator | Participants received matching placebo for 8 weeks. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Adverse Events (Part 1)
Adverse events were counted and corresponding percentages were tabulated.
Measured: 14 days
Change From Baseline in Lung Clearance Index (LCI) (Part 2)
Measured: Baseline, 8 weeks
Change From Baseline in Absolute Number of Sputum Neutrophils (Part 2)
Measured: Baseline, 8 weeks
Change From Baseline in Transition Dyspnea Index (TDI) (Part 2)
Measured: Baseline, 8 weeks
Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) (Part 2)
Measured: Baseline, 8 weeks
Secondary outcomes (17)
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.
Measured: day 1 (from pre-dose to 12 hours post dose)
AUCtau, Steady State (AUCtau,ss) (Part 1)
Venous blood samples were collected for concentration-time profiles.
Measured: 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.
Measured: day 1 (from pre-dose to 12 hours post dose)
Cmax,ss (Part 1)
Venous blood samples were collected for concentration-time profiles.
Measured: 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.
Measured: day 1 (from pre-dose to 12 hours post dose)
Tmax,ss (Part 1)
Venous blood samples were collected for concentration-time profiles.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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)
Measured: baseline, day 56
AUC0-24 (Part 2)
Measured: day 1, day 56
Cmax Between 0h and 24h (Part 2)
Measured: day 1, day 56
Tmax Between 0h and 24h (Part 2)
Measured: day 1, day 56
Change From Baseline in Percentage Sputum Neutrophils (Part 2)
Measured: baseline, day 56
Change From Baseline in Diffusing Capacity of the Lung for Carbon Monoxide (DLco) (Part 2)
Measured: baseline, day 56
Change From Baseline in Scond/Sacin as Measured by Multiple Breath Nitrogen Washout (MBNW) (Part 2)
Measured: baseline, day 56
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Oct 2013 (estimated)
- Study startNov 2013
- Primary completionMay 2015
- Study completionMay 2015
Why it stopped: Part 1 was completed. Part 2 was terminated for safety reasons.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for COPDStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 48 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01972776
- Sponsor's protocol ID
- CQBM076X2203
- Other IDs
- 2012-005615-92
- Status last verified
- Feb 2016
- First submitted
- 24 Oct 2013
- Last updated
- 24 Mar 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 24 Mar 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01972776
- Acronym / sponsor ID
- CQBM076X2203
- Conditions
- COPD
- Keywords
- COPD, inflammation, small airways, LCI, PFTs, lung heterogeneity
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Part 1 was completed. Part 2 was terminated for safety reasons.
- Enrolment
- 48 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Nov 2013
- Primary completion
- May 2015 (actual)
- Study completion
- May 2015 (actual)
- First posted
- 30 Oct 2013 (estimated)
- Results
- Posted 24 Mar 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| QBM076 Part 1 Cohort 1 | Experimental | Drug: QBM076Participants received QBM076 25 mg twice daily (bid) for 14 days. |
| QBM076 Part 1 Cohort 2 | Experimental | Drug: QBM076Participants received QBM076 75 mg bid for 14 days. |
| QBM076 Part 1 Cohort 3 | Experimental | Drug: QBM076Participants received QBM076 150 mg bid for 14 days. |
| Placebo Part 1 | Placebo comparator | Drug: PlaceboParticipants in each cohort received matching placebo for 14 days. |
| QBM076 Part 2 | Experimental | Drug: QBM076Participants received QBM076 150 mg bid for 8 weeks. |
| Placebo Part 2 | Placebo comparator | Drug: PlaceboParticipants received matching placebo for 8 weeks. |
Who may qualify
- Ages
- 35 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- 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.
Key exclusion criteria (1 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| QBM076Supplied in 25 mg and 75 mg capsules | Drug | QBM076 Part 1 Cohort 1, QBM076 Part 1 Cohort 2, QBM076 Part 1 Cohort 3, QBM076 Part 2 |
| PlaceboAlso: Matching placebo capsulesMatching placebo capsules | Drug | Placebo Part 1, Placebo Part 2 |
Primary outcome
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
17 secondary outcomes
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)
AUCtau, Steady State (AUCtau,ss) (Part 1)
Time frame: day 14 (from pre-dose to 72 hours post dose)
Observed Maximum Plasma Concentration Following Drug Administration (Cmax) (Part 1)
Time frame: day 1 (from pre-dose to 12 hours post dose)
Cmax,ss (Part 1)
Time frame: day 14 (from pre-dose to 72 hours post dose)
Time to Reach the Maximum Concentration After Drug Administration (Tmax) (Part 1)
Time frame: day 1 (from pre-dose to 12 hours post dose)
Tmax,ss (Part 1)
Time frame: day 14 (from pre-dose to 72 hours post dose)
Change From Baseline in Cluster of Differentiation 11b (CD11b) (Part 1)
Time frame: baseline, day 14
Change From Baseline in Chemokine (C-X-C Motif) Receptor 2 (CXCR2) Receptor Occupancy (Part 1)
Time frame: baseline, day 14
Change From Baseline in Forced Expiratory Volume in One Second (FEV1) (Part 1)
Time frame: baseline, day 14 pre-dose
Change From Baseline in Lung Clearance Index 2.5 (LCI2.5) (Part 1)
Time frame: 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)
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Mar 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
7 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing QBM076 in people with COPD, run by Novartis Pharmaceuticals at 7 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 24 Mar 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in Germany, United States, Romania, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Mar 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants With Adverse Events (Part 1) (time frame: 14 days). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Mar 2016.