Trial Outcomes & Findings for Safety, Pharmacokinetics and Pharmacodynamics Study of Inhaled QBW276 in Patients With Cystic Fibrosis (NCT NCT02566044)
NCT ID: NCT02566044
Last Updated: 2020-12-30
Results Overview
Adverse events were summarized by the number of patients having any adverse event overall and presented in the safety section. Study was prematurely terminated
COMPLETED
PHASE1/PHASE2
16 participants
Cohort 1: day 1-7; Cohort 2: day 1-14
2020-12-30
Participant Flow
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.
Participant milestones
| Measure |
Cohort 1 QBW276
QBW276 3mg bid
|
Cohort 2 QBW276
QBW276 6mg bid
|
Placebo
Placebo to QBW276 dose 3mg bid Cohort 1, and Placebo to QBW276 dose 6mg bid Cohort 2.
|
|---|---|---|---|
|
Overall Study
STARTED
|
6
|
6
|
4
|
|
Overall Study
COMPLETED
|
6
|
6
|
4
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Safety, Pharmacokinetics and Pharmacodynamics Study of Inhaled QBW276 in Patients With Cystic Fibrosis
Baseline characteristics by cohort
| Measure |
Cohort 1 QBW276
n=6 Participants
QBW276 3mg bid
|
Cohort 2 QBW276
n=6 Participants
QBW276 6mg bid
|
Placebo
n=4 Participants
Placebo to QBW276 dose 3mg bid Cohort 1, and Placebo to QBW276 dose 6mg bid Cohort 2.
|
Total
n=16 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
36.5 Years
STANDARD_DEVIATION 7.66 • n=5 Participants
|
34.8 Years
STANDARD_DEVIATION 8.06 • n=7 Participants
|
28.8 Years
STANDARD_DEVIATION 11.53 • n=5 Participants
|
33.9 Years
STANDARD_DEVIATION 8.83 • n=4 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
6 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
13 Participants
n=4 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
White
|
6 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
16 Participants
n=4 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: Cohort 1: day 1-7; Cohort 2: day 1-14Population: Safety set: The safety analysis set included all patients that received any study drug
Adverse events were summarized by the number of patients having any adverse event overall and presented in the safety section. Study was prematurely terminated
Outcome measures
| Measure |
Cohort 1 QBW276
n=6 Participants
QBW276 3mg bid
|
Cohort 2 QBW276
n=6 Participants
QBW276 6mg bid
|
Placebo
n=4 Participants
Placebo to QBW276 dose 3mg bid Cohort 1, and Placebo to QBW276 dose 6mg bid Cohort 2.
|
Cohort 2 QBW276
QBW276 6mg bid
|
Cohort 2 QBP545
formation of metabolites QBP545
|
Cohort 2 QBV697
formation of metabolites QBV697
|
|---|---|---|---|---|---|---|
|
Cohorts 1 and 2: Safety Assessments, Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]).
Death
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
|
Cohorts 1 and 2: Safety Assessments, Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]).
Serious AE
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
|
Cohorts 1 and 2: Safety Assessments, Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]).
Subjects with at least one AE
|
2 Participants
|
6 Participants
|
0 Participants
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Cohort 1: day 1, 7; Cohort 2: day 1, 14Population: 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.
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
Outcome measures
| Measure |
Cohort 1 QBW276
n=6 Participants
QBW276 3mg bid
|
Cohort 2 QBW276
n=6 Participants
QBW276 6mg bid
|
Placebo
n=6 Participants
Placebo to QBW276 dose 3mg bid Cohort 1, and Placebo to QBW276 dose 6mg bid Cohort 2.
|
Cohort 2 QBW276
n=6 Participants
QBW276 6mg bid
|
Cohort 2 QBP545
n=6 Participants
formation of metabolites QBP545
|
Cohort 2 QBV697
n=6 Participants
formation of metabolites QBV697
|
|---|---|---|---|---|---|---|
|
Cohorts 1 and 2: Pharmacokinetics (Cmax) of QBW276, QBP545, and QBV697 in Plasma
Day 1
|
0.159 ng/mL
Standard Deviation NA
|
3.88 ng/mL
Standard Deviation 1.38
|
1.21 ng/mL
Standard Deviation 0.415
|
0.174 ng/mL
Standard Deviation 0.0716
|
5.98 ng/mL
Standard Deviation 3.72
|
1.63 ng/mL
Standard Deviation 0.931
|
|
Cohorts 1 and 2: Pharmacokinetics (Cmax) of QBW276, QBP545, and QBV697 in Plasma
Day 7
|
0.145 ng/mL
Standard Deviation 0.114
|
5.46 ng/mL
Standard Deviation 1.26
|
1.45 ng/mL
Standard Deviation 0.504
|
—
|
—
|
—
|
|
Cohorts 1 and 2: Pharmacokinetics (Cmax) of QBW276, QBP545, and QBV697 in Plasma
Day 14
|
—
|
—
|
—
|
0.267 ng/mL
Standard Deviation 0.109
|
7.80 ng/mL
Standard Deviation 4.34
|
3.07 ng/mL
Standard Deviation 1.72
|
PRIMARY outcome
Timeframe: Day 1, 7 and 14Population: 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.
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
Outcome measures
| Measure |
Cohort 1 QBW276
n=6 Participants
QBW276 3mg bid
|
Cohort 2 QBW276
n=6 Participants
QBW276 6mg bid
|
Placebo
n=6 Participants
Placebo to QBW276 dose 3mg bid Cohort 1, and Placebo to QBW276 dose 6mg bid Cohort 2.
|
Cohort 2 QBW276
n=6 Participants
QBW276 6mg bid
|
Cohort 2 QBP545
n=6 Participants
formation of metabolites QBP545
|
Cohort 2 QBV697
n=6 Participants
formation of metabolites QBV697
|
|---|---|---|---|---|---|---|
|
Cohorts 1 and 2: Pharmacokinetics (Tmax) of QBW276, QBP545, and QBV697 in Plasma
Day 1
|
0.183 hr
Interval 0.167 to 0.2
|
0.375 hr
Interval 0.233 to 0.933
|
0.433 hr
Interval 0.233 to 0.5
|
0.250 hr
Interval 0.167 to 0.25
|
0.250 hr
Interval 0.167 to 2.03
|
0.250 hr
Interval 0.167 to 1.03
|
|
Cohorts 1 and 2: Pharmacokinetics (Tmax) of QBW276, QBP545, and QBV697 in Plasma
Day 7
|
0.183 hr
Interval 0.167 to 0.183
|
0.500 hr
Interval 0.25 to 0.967
|
0.375 hr
Interval 0.167 to 2.0
|
—
|
—
|
—
|
|
Cohorts 1 and 2: Pharmacokinetics (Tmax) of QBW276, QBP545, and QBV697 in Plasma
Day 14
|
—
|
—
|
—
|
0.258 hr
Interval 0.233 to 0.533
|
0.500 hr
Interval 0.267 to 0.533
|
0.500 hr
Interval 0.233 to 0.533
|
PRIMARY outcome
Timeframe: Day 1, 7 and 14Population: 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.
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
Outcome measures
| Measure |
Cohort 1 QBW276
n=6 Participants
QBW276 3mg bid
|
Cohort 2 QBW276
n=6 Participants
QBW276 6mg bid
|
Placebo
n=6 Participants
Placebo to QBW276 dose 3mg bid Cohort 1, and Placebo to QBW276 dose 6mg bid Cohort 2.
|
Cohort 2 QBW276
n=6 Participants
QBW276 6mg bid
|
Cohort 2 QBP545
n=6 Participants
formation of metabolites QBP545
|
Cohort 2 QBV697
n=6 Participants
formation of metabolites QBV697
|
|---|---|---|---|---|---|---|
|
Cohorts 1 and 2: Pharmacokinetics (AUCtau) of QBW276, QBP545, and QBV697 in Plasma
Day 1
|
0.0332 hr*ng/mL
Standard Deviation NA
NA- Not achievable
|
14.3 hr*ng/mL
Standard Deviation 4.09
|
1.35 hr*ng/mL
Standard Deviation 0.827
|
0.0634 hr*ng/mL
Standard Deviation 0.0473
|
13.9 hr*ng/mL
Standard Deviation 6.57
|
1.79 hr*ng/mL
Standard Deviation 1.54
|
|
Cohorts 1 and 2: Pharmacokinetics (AUCtau) of QBW276, QBP545, and QBV697 in Plasma
Day 7
|
0.0278 hr*ng/mL
Standard Deviation 0.0362
|
18 hr*ng/mL
Standard Deviation 4.21
|
1.80 hr*ng/mL
Standard Deviation 0.797
|
—
|
—
|
—
|
|
Cohorts 1 and 2: Pharmacokinetics (AUCtau) of QBW276, QBP545, and QBV697 in Plasma
Day 14
|
—
|
—
|
—
|
0.0918 hr*ng/mL
Standard Deviation 0.0689
|
30.6 hr*ng/mL
Standard Deviation 6.59
|
2.94 hr*ng/mL
Standard Deviation 1.59
|
PRIMARY outcome
Timeframe: Cohort 1: 7 days; Cohort 2: 14 daysPopulation: 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.
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.
Outcome measures
| Measure |
Cohort 1 QBW276
n=6 Participants
QBW276 3mg bid
|
Cohort 2 QBW276
n=6 Participants
QBW276 6mg bid
|
Placebo
n=6 Participants
Placebo to QBW276 dose 3mg bid Cohort 1, and Placebo to QBW276 dose 6mg bid Cohort 2.
|
Cohort 2 QBW276
n=6 Participants
QBW276 6mg bid
|
Cohort 2 QBP545
n=6 Participants
formation of metabolites QBP545
|
Cohort 2 QBV697
n=6 Participants
formation of metabolites QBV697
|
|---|---|---|---|---|---|---|
|
Cohorts 1 and 2: Pharmacokinetics Accumulation Ratio (Racc) of QBW276, QBP545, and QBV697 in Plasma
|
1.20 Ratio
Standard Error 0.047
|
1.28 Ratio
Standard Error 0.122
|
1.84 Ratio
Standard Error 0.384
|
1.59 Ratio
Standard Error 0.126
|
1.01 Ratio
Standard Error 0.714
|
1.74 Ratio
Standard Error 0.765
|
SECONDARY outcome
Timeframe: Baseline to End of study (EOS)Population: 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.
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.
Outcome measures
| Measure |
Cohort 1 QBW276
n=6 Participants
QBW276 3mg bid
|
Cohort 2 QBW276
n=6 Participants
QBW276 6mg bid
|
Placebo
n=4 Participants
Placebo to QBW276 dose 3mg bid Cohort 1, and Placebo to QBW276 dose 6mg bid Cohort 2.
|
Cohort 2 QBW276
QBW276 6mg bid
|
Cohort 2 QBP545
formation of metabolites QBP545
|
Cohort 2 QBV697
formation of metabolites QBV697
|
|---|---|---|---|---|---|---|
|
Cohorts 1 and 2: Change From Baseline in Percent Predicted Forced Expiratory Volume in the First Second by Spirometry (% Predicted FEV1)
|
-0.1 Percent predicted FEV1
Standard Deviation 2.30
|
-0.1 Percent predicted FEV1
Standard Deviation 1.32
|
-2.7 Percent predicted FEV1
Standard Deviation 3.71
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline to EOSPopulation: 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.
Change in Lung Clearance Index (LCI) will be conducted by multiple breath nitrogen washout according to international standards
Outcome measures
| Measure |
Cohort 1 QBW276
n=6 Participants
QBW276 3mg bid
|
Cohort 2 QBW276
n=6 Participants
QBW276 6mg bid
|
Placebo
n=4 Participants
Placebo to QBW276 dose 3mg bid Cohort 1, and Placebo to QBW276 dose 6mg bid Cohort 2.
|
Cohort 2 QBW276
QBW276 6mg bid
|
Cohort 2 QBP545
formation of metabolites QBP545
|
Cohort 2 QBV697
formation of metabolites QBV697
|
|---|---|---|---|---|---|---|
|
Cohorts 1, 2: Change From Baseline in Lung Clearance Index (LCI) From Baseline to Day 7 for Cohort 1, Day 14 for Cohort 2.
|
1.530 Ratio
Standard Deviation 2.0167
|
2.478 Ratio
Standard Deviation 3.1397
|
0.470 Ratio
Standard Deviation 0.4101
|
—
|
—
|
—
|
Adverse Events
Cohort 1 QBW276
Cohort 2 QBW276
Placebo
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Cohort 1 QBW276
n=6 participants at risk
QBW276 3 mg bid
|
Cohort 2 QBW276
n=6 participants at risk
QBW276 6 mg bid
|
Placebo
n=4 participants at risk
Placebo to QBW276 dose 3mg bid Cohort 1, and Placebo to QBW276 dose 6mg bid Cohort 2.
|
|---|---|---|---|
|
Ear and labyrinth disorders
Vertigo
|
0.00%
0/6 • Up to 18 days
|
16.7%
1/6 • Up to 18 days
|
0.00%
0/4 • Up to 18 days
|
|
Gastrointestinal disorders
Abdominal distension
|
0.00%
0/6 • Up to 18 days
|
16.7%
1/6 • Up to 18 days
|
0.00%
0/4 • Up to 18 days
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.00%
0/6 • Up to 18 days
|
16.7%
1/6 • Up to 18 days
|
0.00%
0/4 • Up to 18 days
|
|
General disorders
Feeling cold
|
0.00%
0/6 • Up to 18 days
|
16.7%
1/6 • Up to 18 days
|
0.00%
0/4 • Up to 18 days
|
|
General disorders
Mucosal dryness
|
0.00%
0/6 • Up to 18 days
|
16.7%
1/6 • Up to 18 days
|
0.00%
0/4 • Up to 18 days
|
|
General disorders
Pyrexia
|
0.00%
0/6 • Up to 18 days
|
16.7%
1/6 • Up to 18 days
|
0.00%
0/4 • Up to 18 days
|
|
Immune system disorders
Seasonal allergy
|
0.00%
0/6 • Up to 18 days
|
16.7%
1/6 • Up to 18 days
|
0.00%
0/4 • Up to 18 days
|
|
Investigations
Alanine aminotransferase increased
|
0.00%
0/6 • Up to 18 days
|
16.7%
1/6 • Up to 18 days
|
0.00%
0/4 • Up to 18 days
|
|
Investigations
Aspartate aminotransferase increased
|
0.00%
0/6 • Up to 18 days
|
16.7%
1/6 • Up to 18 days
|
0.00%
0/4 • Up to 18 days
|
|
Investigations
Blood creatine phosphokinase increased
|
0.00%
0/6 • Up to 18 days
|
16.7%
1/6 • Up to 18 days
|
0.00%
0/4 • Up to 18 days
|
|
Investigations
Blood uric acid increased
|
0.00%
0/6 • Up to 18 days
|
16.7%
1/6 • Up to 18 days
|
0.00%
0/4 • Up to 18 days
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
0.00%
0/6 • Up to 18 days
|
16.7%
1/6 • Up to 18 days
|
0.00%
0/4 • Up to 18 days
|
|
Musculoskeletal and connective tissue disorders
Joint swelling
|
0.00%
0/6 • Up to 18 days
|
16.7%
1/6 • Up to 18 days
|
0.00%
0/4 • Up to 18 days
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
0.00%
0/6 • Up to 18 days
|
16.7%
1/6 • Up to 18 days
|
0.00%
0/4 • Up to 18 days
|
|
Nervous system disorders
Headache
|
0.00%
0/6 • Up to 18 days
|
50.0%
3/6 • Up to 18 days
|
0.00%
0/4 • Up to 18 days
|
|
Renal and urinary disorders
Haematuria
|
16.7%
1/6 • Up to 18 days
|
0.00%
0/6 • Up to 18 days
|
0.00%
0/4 • Up to 18 days
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/6 • Up to 18 days
|
66.7%
4/6 • Up to 18 days
|
0.00%
0/4 • Up to 18 days
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
16.7%
1/6 • Up to 18 days
|
33.3%
2/6 • Up to 18 days
|
0.00%
0/4 • Up to 18 days
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
0.00%
0/6 • Up to 18 days
|
16.7%
1/6 • Up to 18 days
|
0.00%
0/4 • Up to 18 days
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
0.00%
0/6 • Up to 18 days
|
16.7%
1/6 • Up to 18 days
|
0.00%
0/4 • Up to 18 days
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary congestion
|
0.00%
0/6 • Up to 18 days
|
16.7%
1/6 • Up to 18 days
|
0.00%
0/4 • Up to 18 days
|
|
Respiratory, thoracic and mediastinal disorders
Sinus congestion
|
0.00%
0/6 • Up to 18 days
|
16.7%
1/6 • Up to 18 days
|
0.00%
0/4 • Up to 18 days
|
|
Respiratory, thoracic and mediastinal disorders
Sputum increased
|
0.00%
0/6 • Up to 18 days
|
16.7%
1/6 • Up to 18 days
|
0.00%
0/4 • Up to 18 days
|
|
Respiratory, thoracic and mediastinal disorders
Wheezing
|
0.00%
0/6 • Up to 18 days
|
16.7%
1/6 • Up to 18 days
|
0.00%
0/4 • Up to 18 days
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
0.00%
0/6 • Up to 18 days
|
16.7%
1/6 • Up to 18 days
|
0.00%
0/4 • Up to 18 days
|
|
Skin and subcutaneous tissue disorders
Rash papular
|
0.00%
0/6 • Up to 18 days
|
16.7%
1/6 • Up to 18 days
|
0.00%
0/4 • Up to 18 days
|
Additional Information
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