Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Safety, Pharmacokinetics and Pharmacodynamics Study of Inhaled QBW276 in Patients With Cystic Fibrosis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02566044
Recruitment Status : Completed
First Posted : October 1, 2015
Results First Posted : July 17, 2019
Last Update Posted : July 17, 2019
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type Interventional
Study Design Intervention Model: Crossover Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Pulmonary Cystic Fibrosis
Interventions Other: Placebo
Drug: QBW276
Enrollment 16
Recruitment Details  
Pre-assignment Details The study was terminated after completion of all randomized patients in Cohort 2 due to strategic issues. All patients completed the study prior to termination.
Arm/Group Title Cohort 1 QBW276 Cohort 2 QBW276 Placebo
Hide Arm/Group Description QBW276 3mg bid QBW276 6mg bid Placebo to QBW276 dose 3mg bid Cohort 1, and Placebo to QBW276 dose 6mg bid Cohort 2.
Period Title: Overall Study
Started 6 6 4
Completed 6 6 4
Not Completed 0 0 0
Arm/Group Title Cohort 1 QBW276 Cohort 2 QBW276 Placebo Total
Hide Arm/Group Description QBW276 3mg bid QBW276 6mg bid Placebo to QBW276 dose 3mg bid Cohort 1, and Placebo to QBW276 dose 6mg bid Cohort 2. Total of all reporting groups
Overall Number of Baseline Participants 6 6 4 16
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 6 participants 6 participants 4 participants 16 participants
36.5  (7.66) 34.8  (8.06) 28.8  (11.53) 33.9  (8.83)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 6 participants 4 participants 16 participants
Female
0
   0.0%
3
  50.0%
0
   0.0%
3
  18.8%
Male
6
 100.0%
3
  50.0%
4
 100.0%
13
  81.3%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 6 participants 4 participants 16 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
White
6
 100.0%
6
 100.0%
4
 100.0%
16
 100.0%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1.Primary Outcome
Title Cohorts 1 and 2: Safety Assessments, Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]).
Hide Description Adverse events were summarized by the number of patients having any adverse event overall and presented in the safety section. Study was prematurely terminated
Time Frame Cohort 1: day 1-7; Cohort 2: day 1-14
Hide Outcome Measure Data
Hide Analysis Population Description
Safety set: The safety analysis set included all patients that received any study drug
Arm/Group Title Cohort 1 QBW276 Cohort 2 QBW276 Placebo
Hide Arm/Group Description:
QBW276 3mg bid
QBW276 6mg bid
Placebo to QBW276 dose 3mg bid Cohort 1, and Placebo to QBW276 dose 6mg bid Cohort 2.
Overall Number of Participants Analyzed 6 6 4
Measure Type: Number
Unit of Measure: Participants
Death 0 0 0
Serious AE 0 0 0
Subjects with at least one AE 2 6 0
2.Primary Outcome
Title Cohorts 1 and 2: Pharmacokinetics (Cmax) of QBW276, QBP545, and QBV697 in Plasma
Hide Description Blood collection will be used to observe the maximum plasma concentration (Cmax) following administration of QBW276. Pharmacokinetic blood samples were collected at the time points. In Cohorts 1 and 2 this consisted of multiple samples through 6 hours after inhalation on Days 1 and 7 in Cohort 1 and Days 1 and 14 in Cohort 2 with predose samples on selected days. The Cmax, was determined using the actual recorded sampling times and noncompartmental methods. Since steady state was likely reached by Day 7, Cmax on Days 7 or 14 correspond to Cmax,ss
Time Frame Cohort 1: day 1, 7; Cohort 2: day 1, 14
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic set: The PK analysis set included all patients with at least one available valid (i.e., not flagged for exclusion) PK concentration measurement, who received study drug, and experienced no protocol deviations with relevant impact on PK data.
Arm/Group Title Cohort 1 QBW276 Cohort 1 QBP545 Cohort 1 QBV697 Cohort 2 QBW276 Cohort 2 QBP545 Cohort 2 QBV697
Hide Arm/Group Description:
QBW276 3mg bid
formation of metabolites QBP545
formation of metabolites QBV697
QBW276 6mg bid
formation of metabolites QBP545
formation of metabolites QBV697
Overall Number of Participants Analyzed 6 6 6 6 6 6
Mean (Standard Deviation)
Unit of Measure: ng/mL
Day 1 Number Analyzed 2 participants 6 participants 6 participants 4 participants 6 participants 6 participants
0.159  (NA) 3.88  (1.38) 1.21  (0.415) 0.174  (0.0716) 5.98  (3.72) 1.63  (0.931)
Day 7 Number Analyzed 3 participants 6 participants 6 participants 0 participants 0 participants 0 participants
0.145  (0.114) 5.46  (1.26) 1.45  (0.504)
Day 14 Number Analyzed 0 participants 0 participants 0 participants 6 participants 6 participants 5 participants
0.267  (0.109) 7.80  (4.34) 3.07  (1.72)
3.Primary Outcome
Title Cohorts 1 and 2: Pharmacokinetics (Tmax) of QBW276, QBP545, and QBV697 in Plasma
Hide Description Blood collection will be used to observe the maximum plasma concentration (Tmax) following administration of QBW276. Pharmacokinetic blood samples were collected at the time points. In Cohorts 1 and 2 this consisted of multiple samples through 6 hours after inhalation on Days 1 and 7 in Cohort 1 and Days 1 and 14 in Cohort 2 with predose samples on selected days. The Tmax, was determined using the actual recorded sampling times and noncompartmental methods. Since steady state was likely reached by Day 7, Tmax on Days 7 or 14 correspond to Tmax,ss
Time Frame Day 1, 7 and 14
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic set: The PK analysis set included all patients with at least one available valid (i.e., not flagged for exclusion) PK concentration measurement, who received study drug, and experienced no protocol deviations with relevant impact on PK data.
Arm/Group Title Cohort 1 QBW276 Cohort 1 QBP545 Cohort 1 QBV697 Cohort 2 QBW276 Cohort 2 QBP545 Cohort 2 QBV697
Hide Arm/Group Description:
QBW276 3mg bid
formation of metabolites QBP545
formation of metabolites QBV697
QBW276 6mg bid
formation of metabolites QBP545
formation of metabolites QBV697
Overall Number of Participants Analyzed 6 6 6 6 6 6
Median (Full Range)
Unit of Measure: hr
Day 1 Number Analyzed 2 participants 6 participants 6 participants 4 participants 6 participants 6 participants
0.183
(0.167 to 0.200)
0.375
(0.233 to 0.933)
0.433
(0.233 to 0.500)
0.250
(0.167 to 0.250)
0.250
(0.167 to 2.03)
0.250
(0.167 to 1.03)
Day 7 Number Analyzed 3 participants 6 participants 6 participants 0 participants 0 participants 0 participants
0.183
(0.167 to 0.183)
0.500
(0.250 to 0.967)
0.375
(0.167 to 2.0)
Day 14 Number Analyzed 0 participants 0 participants 0 participants 6 participants 6 participants 6 participants
0.258
(0.233 to 0.533)
0.500
(0.267 to 0.533)
0.500
(0.233 to 0.533)
4.Primary Outcome
Title Cohorts 1 and 2: Pharmacokinetics (AUCtau) of QBW276, QBP545, and QBV697 in Plasma
Hide Description Blood collection will be used to observe the maximum plasma concentration (AUCtau) following administration of QBW276. Pharmacokinetic blood samples were collected at the time points. In Cohorts 1 and 2 this consisted of multiple samples through 6 hours after inhalation on Days 1 and 7 in Cohort 1 and Days 1 and 14 in Cohort 2 with predose samples on selected days. The AUCtau, was determined using the actual recorded sampling times and noncompartmental methods. Since steady state was likely reached by Day 7, AUCtau on Days 7 or 14 correspond to AUClast,ss
Time Frame Day 1, 7 and 14
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic set: The PK analysis set included all patients with at least one available valid (i.e., not flagged for exclusion) PK concentration measurement, who received study drug, and experienced no protocol deviations with relevant impact on PK data.
Arm/Group Title Cohort 1 QBW276 Cohort 1 QBP545 Cohort 1 QBV697 Cohort 2 QBW276 Cohort 2 QBP545 Cohort 2 QBV697
Hide Arm/Group Description:
QBW276 3mg bid
formation of metabolites QBP545
formation of metabolites QBV697
QBW276 6mg bid
formation of metabolites QBP545
formation of metabolites QBV697
Overall Number of Participants Analyzed 6 6 6 6 6 6
Mean (Standard Deviation)
Unit of Measure: hr*ng/mL
Day 1 Number Analyzed 2 participants 6 participants 6 participants 4 participants 5 participants 6 participants
0.0332 [1]   (NA) 14.3  (4.09) 1.35  (0.827) 0.0634  (0.0473) 13.9  (6.57) 1.79  (1.54)
Day 7 Number Analyzed 3 participants 6 participants 6 participants 0 participants 0 participants 0 participants
0.0278  (0.0362) 18  (4.21) 1.80  (0.797)
Day 14 Number Analyzed 0 participants 0 participants 0 participants 6 participants 5 participants 5 participants
0.0918  (0.0689) 30.6  (6.59) 2.94  (1.59)
[1]
NA- Not achievable
5.Primary Outcome
Title Cohorts 1 and 2: Pharmacokinetics Accumulation Ratio (Racc) of QBW276, QBP545, and QBV697 in Plasma
Hide Description The accumulation ratio (Racc) will be reported using blood samples taken on days 1 -7 in cohort 1 and days 1-14 in cohort 2. Accumulation ratio (Racc) for QBW276 and metabolites was not calculated by PK software for patients where BLOQ values were observed for all blood samples in their PK profile.
Time Frame Cohort 1: 7 days; Cohort 2: 14 days
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic set: The PK analysis set included all patients with at least one available valid (i.e., not flagged for exclusion) PK concentration measurement, who received study drug, and experienced no protocol deviations with relevant impact on PK data.
Arm/Group Title Cohort 1 QBW276 Cohort 1 QBP545 Cohort 1 QBV697 Cohort 2 QBW276 Cohort 2 QBP545 Cohort 2 QBV697
Hide Arm/Group Description:
QBW276 3mg bid
formation of metabolites QBP545
formation of metabolites QBV697
QBW276 6mg bid
formation of metabolites QBP545
formation of metabolites QBV697
Overall Number of Participants Analyzed 6 6 6 6 6 6
Mean (Standard Error)
Unit of Measure: Ratio
1.20  (0.047) 1.28  (0.122) 1.84  (0.384) 1.59  (0.126) 1.01  (0.714) 1.74  (0.765)
6.Secondary Outcome
Title Cohorts 1 and 2: Change From Baseline in Percent Predicted Forced Expiratory Volume in the First Second by Spirometry (% Predicted FEV1)
Hide Description To evaluate the response to multiple doses of inhaled QBW276 in percent predicted forced expiratory volume in the first second by spirometry according to international standards over 1 or 2 weeks of treatment compared with placebo in patients with cystic fibrosis.
Time Frame Baseline to End of study (EOS)
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacodynamics analysis set: The PD analysis set included all patients with available PD data and no major protocol deviations with relevant impact on PD data.
Arm/Group Title Cohort 1 QBW276 Cohort 2 QBW276 Placebo
Hide Arm/Group Description:
QBW276 3mg bid
QBW276 6mg bid
Placebo to QBW276 dose 3mg bid Cohort 1, and Placebo to QBW276 dose 6mg bid Cohort 2.
Overall Number of Participants Analyzed 6 6 4
Mean (Standard Deviation)
Unit of Measure: Percent predicted FEV1
-0.1  (2.30) -0.1  (1.32) -2.7  (3.71)
7.Secondary Outcome
Title Cohorts 1, 2: Change From Baseline in Lung Clearance Index (LCI) From Baseline to Day 7 for Cohort 1, Day 14 for Cohort 2.
Hide Description Change in Lung Clearance Index (LCI) will be conducted by multiple breath nitrogen washout according to international standards
Time Frame Baseline to EOS
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacodynamics analysis set: The PD analysis set included all patients with available PD data and no major protocol deviations with relevant impact on PD data.
Arm/Group Title Cohort 1 QBW276 Cohort 2 QBW276 Placebo
Hide Arm/Group Description:
QBW276 3mg bid
QBW276 6mg bid
Placebo to QBW276 dose 3mg bid Cohort 1, and Placebo to QBW276 dose 6mg bid Cohort 2.
Overall Number of Participants Analyzed 6 6 4
Mean (Standard Deviation)
Unit of Measure: Ratio
1.530  (2.0167) 2.478  (3.1397) 0.470  (0.4101)
Time Frame Up to 18 days
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Cohort 1 QBW276 Cohort 2 QBW276 Placebo
Hide Arm/Group Description QBW276 3 mg bid QBW276 6 mg bid Placebo to QBW276 dose 3mg bid Cohort 1, and Placebo to QBW276 dose 6mg bid Cohort 2.
All-Cause Mortality
Cohort 1 QBW276 Cohort 2 QBW276 Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/6 (0.00%)   0/6 (0.00%)   0/4 (0.00%) 
Show Serious Adverse Events Hide Serious Adverse Events
Cohort 1 QBW276 Cohort 2 QBW276 Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/6 (0.00%)   0/6 (0.00%)   0/4 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 2%
Cohort 1 QBW276 Cohort 2 QBW276 Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   2/6 (33.33%)   6/6 (100.00%)   0/4 (0.00%) 
Ear and labyrinth disorders       
Vertigo  1  0/6 (0.00%)  1/6 (16.67%)  0/4 (0.00%) 
Gastrointestinal disorders       
Abdominal distension  1  0/6 (0.00%)  1/6 (16.67%)  0/4 (0.00%) 
Abdominal pain upper  1  0/6 (0.00%)  1/6 (16.67%)  0/4 (0.00%) 
General disorders       
Feeling cold  1  0/6 (0.00%)  1/6 (16.67%)  0/4 (0.00%) 
Mucosal dryness  1  0/6 (0.00%)  1/6 (16.67%)  0/4 (0.00%) 
Pyrexia  1  0/6 (0.00%)  1/6 (16.67%)  0/4 (0.00%) 
Immune system disorders       
Seasonal allergy  1  0/6 (0.00%)  1/6 (16.67%)  0/4 (0.00%) 
Investigations       
Alanine aminotransferase increased  1  0/6 (0.00%)  1/6 (16.67%)  0/4 (0.00%) 
Aspartate aminotransferase increased  1  0/6 (0.00%)  1/6 (16.67%)  0/4 (0.00%) 
Blood creatine phosphokinase increased  1  0/6 (0.00%)  1/6 (16.67%)  0/4 (0.00%) 
Blood uric acid increased  1  0/6 (0.00%)  1/6 (16.67%)  0/4 (0.00%) 
Metabolism and nutrition disorders       
Hypoglycaemia  1  0/6 (0.00%)  1/6 (16.67%)  0/4 (0.00%) 
Musculoskeletal and connective tissue disorders       
Joint swelling  1  0/6 (0.00%)  1/6 (16.67%)  0/4 (0.00%) 
Musculoskeletal chest pain  1  0/6 (0.00%)  1/6 (16.67%)  0/4 (0.00%) 
Nervous system disorders       
Headache  1  0/6 (0.00%)  3/6 (50.00%)  0/4 (0.00%) 
Renal and urinary disorders       
Haematuria  1  1/6 (16.67%)  0/6 (0.00%)  0/4 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Cough  1  0/6 (0.00%)  4/6 (66.67%)  0/4 (0.00%) 
Dyspnoea  1  1/6 (16.67%)  2/6 (33.33%)  0/4 (0.00%) 
Haemoptysis  1  0/6 (0.00%)  1/6 (16.67%)  0/4 (0.00%) 
Oropharyngeal pain  1  0/6 (0.00%)  1/6 (16.67%)  0/4 (0.00%) 
Pulmonary congestion  1  0/6 (0.00%)  1/6 (16.67%)  0/4 (0.00%) 
Sinus congestion  1  0/6 (0.00%)  1/6 (16.67%)  0/4 (0.00%) 
Sputum increased  1  0/6 (0.00%)  1/6 (16.67%)  0/4 (0.00%) 
Wheezing  1  0/6 (0.00%)  1/6 (16.67%)  0/4 (0.00%) 
Skin and subcutaneous tissue disorders       
Hyperhidrosis  1  0/6 (0.00%)  1/6 (16.67%)  0/4 (0.00%) 
Rash papular  1  0/6 (0.00%)  1/6 (16.67%)  0/4 (0.00%) 
1
Term from vocabulary, MedDRA (21.0)
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 Pharmaceutical
Phone: 862-778-8300
EMail: novartis.email@novartis.com
Layout table for additonal information
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT02566044     History of Changes
Other Study ID Numbers: CQBW276X2201
2014-004915-35 ( EudraCT Number )
First Submitted: September 18, 2015
First Posted: October 1, 2015
Results First Submitted: April 15, 2019
Results First Posted: July 17, 2019
Last Update Posted: July 17, 2019