Trial Outcomes & Findings for A Safety, Tolerability and Efficacy Study With QBW251 in COPD Patients With QBW251 (NCT NCT02449018)

NCT ID: NCT02449018

Last Updated: 2021-01-05

Results Overview

Change from baseline to Day 29 in LCI as measured by multiple breath nitrogen washout (MBNW) technique. MBNW is the time taken to wash out nitrogen while breathing 100% oxygen.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 92 participants
• Primary outcome timeframe: Baseline and Day 29
• Results posted on: 2021-01-05

Participant Flow

Participant milestones

Measure	QBW251 QBW251(28 day treatment period) and placebo (42 days, run-in and wash-out periods)	Placebo Placebo (70 days, run-in, treatment and wash-out periods)
Overall Study STARTED	64	28
Overall Study COMPLETED	52	26
Overall Study NOT COMPLETED	12	2

Reasons for withdrawal

Measure	QBW251 QBW251(28 day treatment period) and placebo (42 days, run-in and wash-out periods)	Placebo Placebo (70 days, run-in, treatment and wash-out periods)
Overall Study Abnormal laboratory value	0	1
Overall Study Administrative problems	1	0
Overall Study Adverse Event	5	1
Overall Study Protocol deviation	4	0
Overall Study Patient decision	2	0

Baseline Characteristics

A Safety, Tolerability and Efficacy Study With QBW251 in COPD Patients With QBW251

Baseline characteristics by cohort

Measure	QBW251 n=64 Participants QBW251(28 day treatment period) and placebo (42 days, run-in and wash-out periods)	Placebo n=28 Participants Placebo (70 days, run-in, treatment and wash-out periods)	Total n=92 Participants Total of all reporting groups
Age, Continuous	63.6 Years STANDARD_DEVIATION 6.61 • n=5 Participants	64.9 Years STANDARD_DEVIATION 7.55 • n=7 Participants	64.0 Years STANDARD_DEVIATION 6.89 • n=5 Participants
Sex: Female, Male Female	31 Participants n=5 Participants	9 Participants n=7 Participants	40 Participants n=5 Participants
Sex: Female, Male Male	33 Participants n=5 Participants	19 Participants n=7 Participants	52 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Day 29

Population: Pharmacodynamics (PD): analysis set included all patients with available PD data and no major protocol deviations with relevant impact on PD data.

Change from baseline to Day 29 in LCI as measured by multiple breath nitrogen washout (MBNW) technique. MBNW is the time taken to wash out nitrogen while breathing 100% oxygen.

Outcome measures

Measure	QBW251 n=50 Participants QBW251(28 day treatment period) and placebo (42 days, run-in and wash-out periods)	Placebo n=24 Participants Placebo (70 days, run-in, treatment and wash-out periods)
Change From Baseline in Lung Clearance Index (LCI)	-0.03 Days Standard Deviation 1.28	-0.16 Days Standard Deviation 1.15

SECONDARY outcome

Timeframe: Day 29

Population: Pharmacodynamics (PD): analysis set included all patients with available PD data and no major protocol deviations with relevant impact on PD data.

Change From Baseline to Day 29 in FEV1 will be measured by spirometer before bronchodilator administration. Forced Expiratory Volume in 1 Second (FEV1) is the amount of air that can be exhaled in 1 second. All spirometry calibrations and evaluations will follow the recommendations of the American Thoracic Society / European Respiratory Society guidelines for acceptability.

Outcome measures

Measure	QBW251 n=51 Participants QBW251(28 day treatment period) and placebo (42 days, run-in and wash-out periods)	Placebo n=23 Participants Placebo (70 days, run-in, treatment and wash-out periods)
Change From Baseline in FEV1 Pre-bronchodilator	0.04 Liters Standard Deviation 0.24	-0.02 Liters Standard Deviation 0.23

SECONDARY outcome

Timeframe: Day 29

Population: Pharmacodynamics (PD): analysis set included all patients with available PD data and no major protocol deviations with relevant impact on PD data.

Change From Baseline to Day 29 in FEV1 will be measured by spirometer after bronchodilator administration. Forced Expiratory Volume in 1 Second (FEV1) is the amount of air that can be exhaled in 1 second. All spirometry calibrations and evaluations will follow the recommendations of the American Thoracic Society / European Respiratory Society guidelines for acceptability.

Outcome measures

Measure	QBW251 n=51 Participants QBW251(28 day treatment period) and placebo (42 days, run-in and wash-out periods)	Placebo n=24 Participants Placebo (70 days, run-in, treatment and wash-out periods)
Change From Baseline in FEV1 Post-bronchodilator	0.05 Liters Standard Deviation 0.21	-0.02 Liters Standard Deviation 0.16

SECONDARY outcome

Timeframe: Day 29

Population: Pharmacodynamics (PD): analysis set included all patients with available PD data and no major protocol deviations with relevant impact on PD data.

Change From Baseline to Day 29 in FVC will be measured by spirometer before bronchodilator administration. Forced Vital Capacity (FVC) is the maximum amount of air a person can expel from the lungs after a maximum inhalation. All spirometry calibrations and evaluations will follow the recommendations of the American Thoracic Society / European Respiratory Society guidelines for acceptability. Forced vital capacity (FVC) as a measure of lung function, measured before bronchodilator

Outcome measures

Measure	QBW251 n=51 Participants QBW251(28 day treatment period) and placebo (42 days, run-in and wash-out periods)	Placebo n=23 Participants Placebo (70 days, run-in, treatment and wash-out periods)
Change From Baseline in FVC Pre Bronchodilator	0.07 Liters Standard Deviation 0.05	0.01 Liters Standard Deviation 0.07

SECONDARY outcome

Timeframe: Day 29

Population: Pharmacodynamics (PD): analysis set included all patients with available PD data and no major protocol deviations with relevant impact on PD data.

Change From Baseline to Day 29 in FVC will be measured by spirometer after bronchodilator administration. Forced Vital Capacity (FVC) is the maximum amount of air a person can expel from the lungs after a maximum inhalation. All spirometry calibrations and evaluations will follow the recommendations of the American Thoracic Society / European Respiratory Society guidelines for acceptability. Forced vital capacity (FVC) as a measure of lung function, measured after bronchodilator

Outcome measures

Measure	QBW251 n=51 Participants QBW251(28 day treatment period) and placebo (42 days, run-in and wash-out periods)	Placebo n=24 Participants Placebo (70 days, run-in, treatment and wash-out periods)
Change From Baseline in FVC Post- Bronchodilator	0.03 Liters Standard Deviation 0.04	0.01 Liters Standard Deviation 0.05

SECONDARY outcome

Timeframe: Day 29

Population: Pharmacodynamics (PD): analysis set included all patients with available PD data and no major protocol deviations with relevant impact on PD data.

Change From Baseline to Day 29 in TLC will be measured by spirometry. Total lung capacity (TLC) is the volume in the lungs at maximal inflation. All spirometry calibrations and evaluations will follow the recommendations of the American Thoracic Society / European Respiratory Society guidelines for acceptability.

Outcome measures

Measure	QBW251 n=50 Participants QBW251(28 day treatment period) and placebo (42 days, run-in and wash-out periods)	Placebo n=24 Participants Placebo (70 days, run-in, treatment and wash-out periods)
Change From Baseline in TLC	0.01 Liters Standard Deviation 0.07	-0.07 Liters Standard Deviation 0.10

SECONDARY outcome

Timeframe: Day 29

Population: Pharmacodynamics (PD): analysis set included all patients with available PD data and no major protocol deviations with relevant impact on PD data

Change From Baseline to Day 29 in RV will be measured by spirometry. Residual volume (RV) is the volume of air remaining in the lungs after a maximal exhalation. All spirometry calibrations and evaluations will follow the recommendations of the American Thoracic Society / European Respiratory Society guidelines for acceptability.

Outcome measures

Measure	QBW251 n=48 Participants QBW251(28 day treatment period) and placebo (42 days, run-in and wash-out periods)	Placebo n=24 Participants Placebo (70 days, run-in, treatment and wash-out periods)
Change From Baseline in RV	0.03 Liters Standard Deviation 0.07	-0.02 Liters Standard Deviation 0.10

SECONDARY outcome

Timeframe: Day 29

Population: Pharmacodynamics (PD): analysis set included all patients with available PD data and no major protocol deviations with relevant impact on PD data

Change From Baseline to Day 29 in FRC will be measured by spirometry. Functional residual capacity (FRC) is the volume in the lungs at the end-expiratory position. All spirometry calibrations and evaluations will follow the recommendations of the American Thoracic Society / European Respiratory Society guidelines for acceptability.

Outcome measures

Measure	QBW251 n=50 Participants QBW251(28 day treatment period) and placebo (42 days, run-in and wash-out periods)	Placebo n=24 Participants Placebo (70 days, run-in, treatment and wash-out periods)
Change From Baseline in FRC	0.01 Liters Standard Deviation 0.07	-0.02 Liters Standard Deviation 0.09

SECONDARY outcome

Timeframe: Day 29

Population: Pharmacodynamics (PD): analysis set included all patients with available PD data and no major protocol deviations with relevant impact on PD data

Diffusing capacity of the lung for carbon monoxide (DLCO) is the extent to which oxygen passes from the lung to the blood.

Outcome measures

Measure	QBW251 n=42 Participants QBW251(28 day treatment period) and placebo (42 days, run-in and wash-out periods)	Placebo n=22 Participants Placebo (70 days, run-in, treatment and wash-out periods)
Change From Baseline in DLCO	-0.91 ml/min/mmHg Standard Error 0.24	-0.25 ml/min/mmHg Standard Error 0.34

SECONDARY outcome

Timeframe: Day 1, Day 28

Population: Pharmacokinetics (PK): all patients with at least one available valid PK concentration measurement, who received study drug, and no protocol deviations with relevant impact on PK data. 3 patients had no sufficient concentration data on Day 1 and 2 patients had no concentration data on Days 1 and 28. 7 patients had no concentration data on Day 28

Tmax is the time to reach the maximum concentration after drug administration.

Outcome measures

Measure	QBW251 n=62 Participants QBW251(28 day treatment period) and placebo (42 days, run-in and wash-out periods)	Placebo Placebo (70 days, run-in, treatment and wash-out periods)
Plasma Concentration of QBW251 by TMax (0-8hours) Day 1	1.27 hr Interval 0.983 to 8.03	—
Plasma Concentration of QBW251 by TMax (0-8hours) Day 28	1.98 hr Interval 0.933 to 7.97	—

SECONDARY outcome

Timeframe: Day 1, Day 28

Population: Pharmacokinetics (PK): all patients with at least one available valid PK concentration measurement, who received study drug, and no protocol deviations with relevant impact on PK data. 3 patients had no sufficient concentration data on Day 1 and 2 patients had no concentration data on Days 1 and 28. 7 patients had no concentration data on Day 28

Cmax is the observed maximum plasma concentration following drug administration.

Outcome measures

Measure	QBW251 n=62 Participants QBW251(28 day treatment period) and placebo (42 days, run-in and wash-out periods)	Placebo Placebo (70 days, run-in, treatment and wash-out periods)
Plasma Concentration of QBW251 by CMax (0-8hours) Day 1	1250 ng/mL Standard Deviation 840	—
Plasma Concentration of QBW251 by CMax (0-8hours) Day 28	1640 ng/mL Standard Deviation 916	—

SECONDARY outcome

Timeframe: Day 1, Day 28

Population: Pharmacokinetics (PK): all patients with at least one available valid PK concentration measurement, who received study drug, and no protocol deviations with relevant impact on PK data. 3 patients had no sufficient concentration data on Day 1 and 2 patients had no concentration data on Days 1 and 28. 7 patients had no concentration data on Day 28

AUClast is the area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration.

Outcome measures

Measure	QBW251 n=62 Participants QBW251(28 day treatment period) and placebo (42 days, run-in and wash-out periods)	Placebo Placebo (70 days, run-in, treatment and wash-out periods)
Plasma Concentration of QBW251 by AUClast (0-8hours) Day 1	3830 hr×ng/mL Standard Deviation 3280	—
Plasma Concentration of QBW251 by AUClast (0-8hours) Day 28	6840 hr×ng/mL Standard Deviation 4490	—

SECONDARY outcome

Timeframe: Day 1, Day 28

Population: PK analysis set: included all patients with at least one available valid PK concentration measurement. Due to practicalities of study conduct PK samples were collected only up to 8 hours. As a result, from noncompartmental analysis AUClast was not calculated up to 12 hours after dosing So this data is not available.

AUC 0-12h is the area under the plasma concentration-time curve from time zero to 12 hours.

Outcome measures

Outcome data not reported

Adverse Events

QBW251 300 mg Bid

Serious events: 4 serious events

Other events: 6 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Measure	QBW251 300 mg Bid n=64 participants at risk QBW251 (28 day treatment period) and placebo (42 days, run-in and wash-out periods)	Placebo n=28 participants at risk Placebo (70 days, run-in, treatment and wash-out periods)
Gastrointestinal disorders Vomiting	1.6% 1/64 • Treatment-emergent adverse events	0.00% 0/28 • Treatment-emergent adverse events
Infections and infestations Pneumonia	1.6% 1/64 • Treatment-emergent adverse events	0.00% 0/28 • Treatment-emergent adverse events
Metabolism and nutrition disorders Hypokalaemia	1.6% 1/64 • Treatment-emergent adverse events	0.00% 0/28 • Treatment-emergent adverse events
Nervous system disorders Cerebrovascular accident	1.6% 1/64 • Treatment-emergent adverse events	0.00% 0/28 • Treatment-emergent adverse events
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	1.6% 1/64 • Treatment-emergent adverse events	0.00% 0/28 • Treatment-emergent adverse events
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	1.6% 1/64 • Treatment-emergent adverse events	0.00% 0/28 • Treatment-emergent adverse events

Other adverse events

Measure	QBW251 300 mg Bid n=64 participants at risk QBW251 (28 day treatment period) and placebo (42 days, run-in and wash-out periods)	Placebo n=28 participants at risk Placebo (70 days, run-in, treatment and wash-out periods)
Gastrointestinal disorders Diarrhoea	3.1% 2/64 • Treatment-emergent adverse events	7.1% 2/28 • Treatment-emergent adverse events
Gastrointestinal disorders Nausea	1.6% 1/64 • Treatment-emergent adverse events	7.1% 2/28 • Treatment-emergent adverse events
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	4.7% 3/64 • Treatment-emergent adverse events	7.1% 2/28 • Treatment-emergent adverse events

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 8627781873

Results disclosure agreements

• Principal investigator is a sponsor employee 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
• Publication restrictions are in place

Restriction type: OTHER