COPD
Conditions
Keywords
COPD, inflammation, small airways, LCI, PFTs, lung heterogeneity
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.
Interventions
DRUGQBM076
Supplied in 25 mg and 75 mg capsules
DRUGPlacebo
Matching placebo capsules
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
35 Years to 75 Years
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Adverse Events (Part 1) | 14 days | Adverse events were counted and corresponding percentages were tabulated. |
| 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 | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Tmax,ss (Part 1) | 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) | 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) | 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) | 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) | 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) | baseline, day 56 | — |
| Area Under the Plasma Concentration-time Curve From Time Zero to the End of the Dosing Interval, Tau (AUCtau) (Part 1) | day 1 (from pre-dose to 12 hours post dose) | Venous blood samples were collected for concentration-time profiles. |
| 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 | — |
| AUC0-24 (Part 2) | day 1, day 56 | — |
| AUCtau, Steady State (AUCtau,ss) (Part 1) | 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) | day 1 (from pre-dose to 12 hours post dose) | Venous blood samples were collected for concentration-time profiles. |
| Cmax,ss (Part 1) | 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) | day 1 (from pre-dose to 12 hours post dose) | Venous blood samples were collected for concentration-time profiles. |
Countries
Germany, Romania, United Kingdom, United States
Participant flow
Recruitment details
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.
Participants by arm
| Arm | Count |
|---|---|
| QBM076 Part 1 Cohort 1 Participants received QBM076 25 mg bid for 14 days. | 6 |
| QBM076 Part 1 Cohort 2 Participants received QBM076 75 mg bid for 14 days. | 6 |
| QBM076 Part 1 Cohort 3 Participants received QBM076 150 mg bid for 14 days. | 8 |
| Placebo Part 1 Participants in each cohort received matching placebo bid for 14 days. | 7 |
| QBM076 Part 2 Participants received QBM076 150 mg bid for 8 weeks. | 14 |
| Placebo Part 2 Participants received matching placebo bid for 8 weeks. | 7 |
| Total | 48 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Part 1 | Adverse Event | 0 | 0 | 1 | 1 | 0 | 0 |
| Part 1 | Withdrawal by Subject | 0 | 0 | 1 | 0 | 0 | 0 |
| Part 2 | Administrative problems | 0 | 0 | 0 | 0 | 10 | 7 |
| Part 2 | Adverse Event | 0 | 0 | 0 | 0 | 3 | 0 |
Baseline characteristics
| Characteristic | QBM076 Part 1 Cohort 1 | QBM076 Part 1 Cohort 2 | QBM076 Part 1 Cohort 3 | Placebo Part 1 | QBM076 Part 2 | Placebo Part 2 | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 63 Years STANDARD_DEVIATION 5.6 | 64 Years STANDARD_DEVIATION 7.5 | 65 Years STANDARD_DEVIATION 4.5 | 61 Years STANDARD_DEVIATION 2.9 | 64 Years STANDARD_DEVIATION 5.5 | 66 Years STANDARD_DEVIATION 5.6 | 64 Years STANDARD_DEVIATION 5.3 |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 4 Participants | 4 Participants | 7 Participants | 5 Participants | 24 Participants |
| Sex: Female, Male Male | 4 Participants | 4 Participants | 4 Participants | 3 Participants | 7 Participants | 2 Participants | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 2 / 6 | 3 / 6 | 5 / 8 | 4 / 7 | 8 / 14 | 3 / 7 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 8 | 1 / 7 | 2 / 14 | 0 / 7 |
Outcome results
Primary
Change From Baseline in Absolute Number of Sputum Neutrophils (Part 2)
Time frame: Baseline, 8 weeks
Population: Part 2 was terminated early. Therefore, primary and secondary outcomes for part 2 were not assessed.
Primary
Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) (Part 2)
Time frame: Baseline, 8 weeks
Population: Part 2 was terminated early. Therefore, primary and secondary outcomes for part 2 were not assessed.
Primary
Change From Baseline in Lung Clearance Index (LCI) (Part 2)
Time frame: Baseline, 8 weeks
Population: Part 2 was terminated early. Therefore, primary and secondary outcomes for part 2 were not assessed.
Primary
Change From Baseline in Transition Dyspnea Index (TDI) (Part 2)
Time frame: Baseline, 8 weeks
Population: Part 2 was terminated early. Therefore, primary and secondary outcomes for part 2 were not assessed.
Primary
Percentage of Participants With Adverse Events (Part 1)
Adverse events were counted and corresponding percentages were tabulated.
Time frame: 14 days
Population: All randomized part 1 participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| QBM076 Part 1 Cohort 1 | Percentage of Participants With Adverse Events (Part 1) | 33 percentage of participants |
| QBM076 Part 1 Cohort 2 | Percentage of Participants With Adverse Events (Part 1) | 50 percentage of participants |
| QBM076 Part 1 Cohort 3 | Percentage of Participants With Adverse Events (Part 1) | 63 percentage of participants |
| Placebo Part 1 | Percentage of Participants With Adverse Events (Part 1) | 71 percentage of participants |
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.
Time frame: day 1 (from pre-dose to 12 hours post dose)
Population: All Part 1 participants who received active treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| QBM076 Part 1 Cohort 1 | Area Under the Plasma Concentration-time Curve From Time Zero to the End of the Dosing Interval, Tau (AUCtau) (Part 1) | 431 ng*h/mL | Standard Deviation 158 |
| QBM076 Part 1 Cohort 2 | Area Under the Plasma Concentration-time Curve From Time Zero to the End of the Dosing Interval, Tau (AUCtau) (Part 1) | 2060 ng*h/mL | Standard Deviation 829 |
| QBM076 Part 1 Cohort 3 | Area Under the Plasma Concentration-time Curve From Time Zero to the End of the Dosing Interval, Tau (AUCtau) (Part 1) | 7640 ng*h/mL | Standard Deviation 6770 |
Secondary
AUC0-24 (Part 2)
Time frame: day 1, day 56
Population: Part 2 was terminated early. Therefore, primary and secondary outcomes for part 2 were not assessed.
Secondary
AUCtau, Steady State (AUCtau,ss) (Part 1)
Venous blood samples were collected for concentration-time profiles.
Time frame: day 14 (from pre-dose to 72 hours post dose)
Population: All Part 1 participants who received active treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| QBM076 Part 1 Cohort 1 | AUCtau, Steady State (AUCtau,ss) (Part 1) | 601 ng*h/mL | Standard Deviation 112 |
| QBM076 Part 1 Cohort 2 | AUCtau, Steady State (AUCtau,ss) (Part 1) | 2220 ng*h/mL | Standard Deviation 787 |
| QBM076 Part 1 Cohort 3 | AUCtau, Steady State (AUCtau,ss) (Part 1) | 6660 ng*h/mL | Standard Deviation 4320 |
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.
Time frame: baseline, day 14
Population: All Randomized Part 1 participants were considered for the analysis but participants with both baseline and day 14 values were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| QBM076 Part 1 Cohort 1 | Change From Baseline in Chemokine (C-X-C Motif) Receptor 2 (CXCR2) Receptor Occupancy (Part 1) | 98 percent change |
| QBM076 Part 1 Cohort 2 | Change From Baseline in Chemokine (C-X-C Motif) Receptor 2 (CXCR2) Receptor Occupancy (Part 1) | 104 percent change |
| QBM076 Part 1 Cohort 3 | Change From Baseline in Chemokine (C-X-C Motif) Receptor 2 (CXCR2) Receptor Occupancy (Part 1) | 129 percent change |
| Placebo Part 1 | Change From Baseline in Chemokine (C-X-C Motif) Receptor 2 (CXCR2) Receptor Occupancy (Part 1) | 37 percent change |
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.
Time frame: baseline, day 14
Population: All Randomized Part 1 participants were considered for the analysis but participants with both baseline and day 14 values were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| QBM076 Part 1 Cohort 1 | Change From Baseline in Cluster of Differentiation 11b (CD11b) (Part 1) | -69 percentage change |
| QBM076 Part 1 Cohort 2 | Change From Baseline in Cluster of Differentiation 11b (CD11b) (Part 1) | -89 percentage change |
| QBM076 Part 1 Cohort 3 | Change From Baseline in Cluster of Differentiation 11b (CD11b) (Part 1) | -75 percentage change |
| Placebo Part 1 | Change From Baseline in Cluster of Differentiation 11b (CD11b) (Part 1) | -37 percentage change |
Secondary
Change From Baseline in Diffusing Capacity of the Lung for Carbon Monoxide (DLco) (Part 2)
Time frame: baseline, day 56
Population: Part 2 was terminated early. Therefore, primary and secondary outcomes for part 2 were not assessed.
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.
Time frame: baseline, day 14 pre-dose
Population: All Randomized Part 1 participants were considered for the analysis but participants with both baseline and day 14 values were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| QBM076 Part 1 Cohort 1 | Change From Baseline in Forced Expiratory Volume in One Second (FEV1) (Part 1) | -0.116 mL | Standard Error 0.05 |
| QBM076 Part 1 Cohort 2 | Change From Baseline in Forced Expiratory Volume in One Second (FEV1) (Part 1) | -0.008 mL | Standard Error 0.05 |
| QBM076 Part 1 Cohort 3 | Change From Baseline in Forced Expiratory Volume in One Second (FEV1) (Part 1) | 0.117 mL | Standard Error 0.05 |
| Placebo Part 1 | Change From Baseline in Forced Expiratory Volume in One Second (FEV1) (Part 1) | 0.039 mL | Standard Error 0.05 |
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)
Time frame: baseline, day 56
Population: Part 2 was terminated early. Therefore, primary and secondary outcomes for part 2 were not assessed.
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.
Time frame: baseline, day 14 pre-dose
Population: All Randomized Part 1 participants were considered for the analysis but participants with both baseline and day 14 values were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| QBM076 Part 1 Cohort 1 | Change From Baseline in Lung Clearance Index 2.5 (LCI2.5) (Part 1) | 1.145 index score | Standard Error 0.42 |
| QBM076 Part 1 Cohort 2 | Change From Baseline in Lung Clearance Index 2.5 (LCI2.5) (Part 1) | 0.136 index score | Standard Error 0.42 |
| QBM076 Part 1 Cohort 3 | Change From Baseline in Lung Clearance Index 2.5 (LCI2.5) (Part 1) | 0.660 index score | Standard Error 0.42 |
| Placebo Part 1 | Change From Baseline in Lung Clearance Index 2.5 (LCI2.5) (Part 1) | 0.063 index score | Standard Error 0.42 |
Secondary
Change From Baseline in Percentage Sputum Neutrophils (Part 2)
Time frame: baseline, day 56
Population: Part 2 was terminated early. Therefore, primary and secondary outcomes for part 2 were not assessed.
Secondary
Change From Baseline in Scond/Sacin as Measured by Multiple Breath Nitrogen Washout (MBNW) (Part 2)
Time frame: baseline, day 56
Population: Part 2 was terminated early. Therefore, primary and secondary outcomes for part 2 were not assessed.
Secondary
Cmax Between 0h and 24h (Part 2)
Time frame: day 1, day 56
Population: Part 2 was terminated early. Therefore, primary and secondary outcomes for part 2 were not assessed.
Secondary
Cmax,ss (Part 1)
Venous blood samples were collected for concentration-time profiles.
Time frame: day 14 (from pre-dose to 72 hours post dose)
Population: All Part 1 participants who received active treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| QBM076 Part 1 Cohort 1 | Cmax,ss (Part 1) | 91.0 ng/mL | Standard Deviation 13.9 |
| QBM076 Part 1 Cohort 2 | Cmax,ss (Part 1) | 338 ng/mL | Standard Deviation 123 |
| QBM076 Part 1 Cohort 3 | Cmax,ss (Part 1) | 2380 ng/mL | Standard Deviation 2680 |
Secondary
Observed Maximum Plasma Concentration Following Drug Administration (Cmax) (Part 1)
Venous blood samples were collected for concentration-time profiles.
Time frame: day 1 (from pre-dose to 12 hours post dose)
Population: All Part 1 participants who received active treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| QBM076 Part 1 Cohort 1 | Observed Maximum Plasma Concentration Following Drug Administration (Cmax) (Part 1) | 69.5 ng/mL | Standard Deviation 28.8 |
| QBM076 Part 1 Cohort 2 | Observed Maximum Plasma Concentration Following Drug Administration (Cmax) (Part 1) | 366 ng/mL | Standard Deviation 192 |
| QBM076 Part 1 Cohort 3 | Observed Maximum Plasma Concentration Following Drug Administration (Cmax) (Part 1) | 1810 ng/mL | Standard Deviation 1790 |
Secondary
Time to Reach the Maximum Concentration After Drug Administration (Tmax) (Part 1)
Venous blood samples were collected for concentration-time profiles.
Time frame: day 1 (from pre-dose to 12 hours post dose)
Population: All Part 1 participants who received active treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| QBM076 Part 1 Cohort 1 | Time to Reach the Maximum Concentration After Drug Administration (Tmax) (Part 1) | 3.05 hours |
| QBM076 Part 1 Cohort 2 | Time to Reach the Maximum Concentration After Drug Administration (Tmax) (Part 1) | 3.01 hours |
| QBM076 Part 1 Cohort 3 | Time to Reach the Maximum Concentration After Drug Administration (Tmax) (Part 1) | 3.04 hours |
Secondary
Tmax Between 0h and 24h (Part 2)
Time frame: day 1, day 56
Population: Part 2 was terminated early. Therefore, primary and secondary outcomes for part 2 were not assessed.
Secondary
Tmax,ss (Part 1)
Venous blood samples were collected for concentration-time profiles.
Time frame: day 14 (from pre-dose to 72 hours post dose)
Population: All Part 1 participants who received active treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| QBM076 Part 1 Cohort 1 | Tmax,ss (Part 1) | 2.00 hours |
| QBM076 Part 1 Cohort 2 | Tmax,ss (Part 1) | 2.00 hours |
| QBM076 Part 1 Cohort 3 | Tmax,ss (Part 1) | 2.05 hours |