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

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ClinicalTrials.gov Identifier: NCT02449018
Recruitment Status : Completed
First Posted : May 20, 2015
Results First Posted : April 2, 2018
Last Update Posted : January 5, 2021
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Chronic Obstructive Pulmonary Disease, COPD
Interventions Drug: QBW251
Drug: Placebo
Enrollment 92
Recruitment Details  
Pre-assignment Details  
Arm/Group Title QBW251 Placebo
Hide Arm/Group Description QBW251(28 day treatment period) and placebo (42 days, run-in and wash-out periods) Placebo (70 days, run-in, treatment and wash-out periods)
Period Title: Overall Study
Started 64 28
Completed 52 26
Not Completed 12 2
Reason Not Completed
Abnormal laboratory value             0             1
Administrative problems             1             0
Adverse Event             5             1
Protocol deviation             4             0
Patient decision             2             0
Arm/Group Title QBW251 Placebo Total
Hide Arm/Group Description QBW251(28 day treatment period) and placebo (42 days, run-in and wash-out periods) Placebo (70 days, run-in, treatment and wash-out periods) Total of all reporting groups
Overall Number of Baseline Participants 64 28 92
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 64 participants 28 participants 92 participants
63.6  (6.61) 64.9  (7.55) 64.0  (6.89)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 64 participants 28 participants 92 participants
Female
31
  48.4%
9
  32.1%
40
  43.5%
Male
33
  51.6%
19
  67.9%
52
  56.5%
1.Primary Outcome
Title Change From Baseline in Lung Clearance Index (LCI)
Hide Description 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.
Time Frame Baseline and Day 29
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacodynamics (PD): analysis set included all patients with available PD data and no major protocol deviations with relevant impact on PD data.
Arm/Group Title QBW251 Placebo
Hide Arm/Group Description:
QBW251(28 day treatment period) and placebo (42 days, run-in and wash-out periods)
Placebo (70 days, run-in, treatment and wash-out periods)
Overall Number of Participants Analyzed 50 24
Mean (Standard Deviation)
Unit of Measure: Days
-0.03  (1.28) -0.16  (1.15)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection QBW251, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.130
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.28
Confidence Interval (2-Sided) 90%
-0.24 to 0.79
Parameter Dispersion
Type: Standard Deviation
Value: 0.31
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change From Baseline in FEV1 Pre-bronchodilator
Hide Description 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.
Time Frame Day 29
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacodynamics (PD): analysis set included all patients with available PD data and no major protocol deviations with relevant impact on PD data.
Arm/Group Title QBW251 Placebo
Hide Arm/Group Description:
QBW251(28 day treatment period) and placebo (42 days, run-in and wash-out periods)
Placebo (70 days, run-in, treatment and wash-out periods)
Overall Number of Participants Analyzed 51 23
Mean (Standard Deviation)
Unit of Measure: Liters
0.04  (0.24) -0.02  (0.23)
3.Secondary Outcome
Title Change From Baseline in FEV1 Post-bronchodilator
Hide Description 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.
Time Frame Day 29
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacodynamics (PD): analysis set included all patients with available PD data and no major protocol deviations with relevant impact on PD data.
Arm/Group Title QBW251 Placebo
Hide Arm/Group Description:
QBW251(28 day treatment period) and placebo (42 days, run-in and wash-out periods)
Placebo (70 days, run-in, treatment and wash-out periods)
Overall Number of Participants Analyzed 51 24
Mean (Standard Deviation)
Unit of Measure: Liters
0.05  (0.21) -0.02  (0.16)
4.Secondary Outcome
Title Change From Baseline in FVC Pre Bronchodilator
Hide Description 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
Time Frame Day 29
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacodynamics (PD): analysis set included all patients with available PD data and no major protocol deviations with relevant impact on PD data.
Arm/Group Title QBW251 Placebo
Hide Arm/Group Description:
QBW251(28 day treatment period) and placebo (42 days, run-in and wash-out periods)
Placebo (70 days, run-in, treatment and wash-out periods)
Overall Number of Participants Analyzed 51 23
Least Squares Mean (Standard Deviation)
Unit of Measure: Liters
0.07  (0.05) 0.01  (0.07)
5.Secondary Outcome
Title Change From Baseline in FVC Post- Bronchodilator
Hide Description 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
Time Frame Day 29
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacodynamics (PD): analysis set included all patients with available PD data and no major protocol deviations with relevant impact on PD data.
Arm/Group Title QBW251 Placebo
Hide Arm/Group Description:
QBW251(28 day treatment period) and placebo (42 days, run-in and wash-out periods)
Placebo (70 days, run-in, treatment and wash-out periods)
Overall Number of Participants Analyzed 51 24
Least Squares Mean (Standard Deviation)
Unit of Measure: Liters
0.03  (0.04) 0.01  (0.05)
6.Secondary Outcome
Title Change From Baseline in TLC
Hide Description 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.
Time Frame Day 29
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacodynamics (PD): analysis set included all patients with available PD data and no major protocol deviations with relevant impact on PD data.
Arm/Group Title QBW251 Placebo
Hide Arm/Group Description:
QBW251(28 day treatment period) and placebo (42 days, run-in and wash-out periods)
Placebo (70 days, run-in, treatment and wash-out periods)
Overall Number of Participants Analyzed 50 24
Least Squares Mean (Standard Deviation)
Unit of Measure: Liters
0.01  (0.07) -0.07  (0.10)
7.Secondary Outcome
Title Change From Baseline in RV
Hide Description 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.
Time Frame Day 29
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacodynamics (PD): analysis set included all patients with available PD data and no major protocol deviations with relevant impact on PD data
Arm/Group Title QBW251 Placebo
Hide Arm/Group Description:
QBW251(28 day treatment period) and placebo (42 days, run-in and wash-out periods)
Placebo (70 days, run-in, treatment and wash-out periods)
Overall Number of Participants Analyzed 48 24
Least Squares Mean (Standard Deviation)
Unit of Measure: Liters
0.03  (0.07) -0.02  (0.10)
8.Secondary Outcome
Title Change From Baseline in FRC
Hide Description 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.
Time Frame Day 29
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacodynamics (PD): analysis set included all patients with available PD data and no major protocol deviations with relevant impact on PD data
Arm/Group Title QBW251 Placebo
Hide Arm/Group Description:
QBW251(28 day treatment period) and placebo (42 days, run-in and wash-out periods)
Placebo (70 days, run-in, treatment and wash-out periods)
Overall Number of Participants Analyzed 50 24
Least Squares Mean (Standard Deviation)
Unit of Measure: Liters
0.01  (0.07) -0.02  (0.09)
9.Secondary Outcome
Title Change From Baseline in DLCO
Hide Description Diffusing capacity of the lung for carbon monoxide (DLCO) is the extent to which oxygen passes from the lung to the blood.
Time Frame Day 29
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacodynamics (PD): analysis set included all patients with available PD data and no major protocol deviations with relevant impact on PD data
Arm/Group Title QBW251 Placebo
Hide Arm/Group Description:
QBW251(28 day treatment period) and placebo (42 days, run-in and wash-out periods)
Placebo (70 days, run-in, treatment and wash-out periods)
Overall Number of Participants Analyzed 42 22
Least Squares Mean (Standard Error)
Unit of Measure: ml/min/mmHg
-0.91  (0.24) -0.25  (0.34)
10.Secondary Outcome
Title Plasma Concentration of QBW251 by TMax (0-8hours)
Hide Description Tmax is the time to reach the maximum concentration after drug administration.
Time Frame Day 1, Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
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
Arm/Group Title QBW251
Hide Arm/Group Description:
QBW251(28 day treatment period) and placebo (42 days, run-in and wash-out periods)
Overall Number of Participants Analyzed 62
Median (Full Range)
Unit of Measure: hr
Day 1 Number Analyzed 57 participants
1.27
(0.983 to 8.03)
Day 28 Number Analyzed 53 participants
1.98
(0.933 to 7.97)
11.Secondary Outcome
Title Plasma Concentration of QBW251 by CMax (0-8hours)
Hide Description Cmax is the observed maximum plasma concentration following drug administration.
Time Frame Day 1, Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
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
Arm/Group Title QBW251
Hide Arm/Group Description:
QBW251(28 day treatment period) and placebo (42 days, run-in and wash-out periods)
Overall Number of Participants Analyzed 62
Mean (Standard Deviation)
Unit of Measure: ng/mL
Day 1 Number Analyzed 57 participants
1250  (840)
Day 28 Number Analyzed 53 participants
1640  (916)
12.Secondary Outcome
Title Plasma Concentration of QBW251 by AUClast (0-8hours)
Hide Description AUClast is the area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration.
Time Frame Day 1, Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
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
Arm/Group Title QBW251
Hide Arm/Group Description:
QBW251(28 day treatment period) and placebo (42 days, run-in and wash-out periods)
Overall Number of Participants Analyzed 62
Mean (Standard Deviation)
Unit of Measure: hr×ng/mL
Day 1 Number Analyzed 57 participants
3830  (3280)
Day 28 Number Analyzed 53 participants
6840  (4490)
13.Secondary Outcome
Title Plasma Concentration of QBW251 by AUC0-12h
Hide Description AUC 0-12h is the area under the plasma concentration-time curve from time zero to 12 hours.
Time Frame Day 1, Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title QBW251 Placebo
Hide Arm/Group Description:
QBW251(28 day treatment period) and placebo (42 days, run-in and wash-out periods)
Placebo (70 days, run-in, treatment and wash-out periods)
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame Treatment-emergent adverse events
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Placebo QBW251 300 mg Bid
Hide Arm/Group Description Placebo (70 days, run-in, treatment and wash-out periods) QBW251 (28 day treatment period) and placebo (42 days, run-in and wash-out periods)
All-Cause Mortality
Placebo QBW251 300 mg Bid
Affected / at Risk (%) Affected / at Risk (%)
Total   0/28 (0.00%)   0/64 (0.00%) 
Hide Serious Adverse Events
Placebo QBW251 300 mg Bid
Affected / at Risk (%) Affected / at Risk (%)
Total   0/28 (0.00%)   4/64 (6.25%) 
Gastrointestinal disorders     
Vomiting  1  0/28 (0.00%)  1/64 (1.56%) 
Infections and infestations     
Pneumonia  1  0/28 (0.00%)  1/64 (1.56%) 
Metabolism and nutrition disorders     
Hypokalaemia  1  0/28 (0.00%)  1/64 (1.56%) 
Nervous system disorders     
Cerebrovascular accident  1  0/28 (0.00%)  1/64 (1.56%) 
Respiratory, thoracic and mediastinal disorders     
Acute respiratory failure  1  0/28 (0.00%)  1/64 (1.56%) 
Chronic obstructive pulmonary disease  1  0/28 (0.00%)  1/64 (1.56%) 
1
Term from vocabulary, MedDRA (19.1)
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo QBW251 300 mg Bid
Affected / at Risk (%) Affected / at Risk (%)
Total   5/28 (17.86%)   6/64 (9.38%) 
Gastrointestinal disorders     
Diarrhoea  1  2/28 (7.14%)  2/64 (3.13%) 
Nausea  1  2/28 (7.14%)  1/64 (1.56%) 
Respiratory, thoracic and mediastinal disorders     
Chronic obstructive pulmonary disease  1  2/28 (7.14%)  3/64 (4.69%) 
1
Term from vocabulary, MedDRA (19.1)
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
Phone: 8627781873
Layout table for additonal information
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT02449018    
Other Study ID Numbers: CQBW251X2201
First Submitted: March 30, 2015
First Posted: May 20, 2015
Results First Submitted: January 18, 2018
Results First Posted: April 2, 2018
Last Update Posted: January 5, 2021