Pulmonary Cystic Fibrosis
Conditions
Keywords
Cystic Fibrosis
Brief summary
This is a study of multiple doses of inhaled QBW276 in patients with cystic fibrosis on top of standard of care. The study was divided into 3 Cohorts. Cohorts 1 and 2 are designed to be a randomized, double-blind, placebo-controlled, parallel arm, multiple dose study to assess the safety, tolerability, pharmacokinetics, and preliminary efficacy of inhaled QBW276 over 1 week (cohort 1) or 2 weeks (cohort 2) in patients with cystic fibrosis regardless of their genotype. The study was terminated after Cohort 2 due to the resource issues.
Interventions
OTHERPlacebo
Placebo
DRUGQBW276
0.3 mg and 1.5 mg strengths
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NA
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Cohorts 1 and 2 = any genotype on any standard of care treatment * Cohort 3 = F508del homozygotes on standard of care at that time * FEV₁between 40 and 100% * LCI2.5 ≥ 8 if FEV₁is more than 80%
Exclusion criteria
* Adrenal or electrolyte abnormalities * Lung transplant * Autonomic dysfunction (e.g. recurrent episodes of fainting, palpitations, etc.)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cohorts 1 and 2: Pharmacokinetics (Cmax) of QBW276, QBP545, and QBV697 in Plasma | Cohort 1: day 1, 7; Cohort 2: day 1, 14 | 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 |
| Cohorts 1 and 2: Pharmacokinetics (AUCtau) of QBW276, QBP545, and QBV697 in Plasma | Day 1, 7 and 14 | 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 |
| Cohorts 1 and 2: Pharmacokinetics Accumulation Ratio (Racc) of QBW276, QBP545, and QBV697 in Plasma | Cohort 1: 7 days; Cohort 2: 14 days | 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. |
| Cohorts 1 and 2: Safety Assessments, Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]). | Cohort 1: day 1-7; Cohort 2: day 1-14 | Adverse events were summarized by the number of patients having any adverse event overall and presented in the safety section. Study was prematurely terminated |
| Cohorts 1 and 2: Pharmacokinetics (Tmax) of QBW276, QBP545, and QBV697 in Plasma | Day 1, 7 and 14 | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cohorts 1 and 2: Change From Baseline in Percent Predicted Forced Expiratory Volume in the First Second by Spirometry (% Predicted FEV1) | Baseline to End of study (EOS) | 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. |
| Cohorts 1, 2: Change From Baseline in Lung Clearance Index (LCI) From Baseline to Day 7 for Cohort 1, Day 14 for Cohort 2. | Baseline to EOS | Change in Lung Clearance Index (LCI) will be conducted by multiple breath nitrogen washout according to international standards |
Countries
Germany, United States
Participant flow
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.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 QBW276 QBW276 3mg bid | 6 |
| Cohort 2 QBW276 QBW276 6mg bid | 6 |
| Placebo Placebo to QBW276 dose 3mg bid Cohort 1, and Placebo to QBW276 dose 6mg bid Cohort 2. | 4 |
| Total | 16 |
Baseline characteristics
| Characteristic | Cohort 1 QBW276 | Cohort 2 QBW276 | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 36.5 Years STANDARD_DEVIATION 7.66 | 34.8 Years STANDARD_DEVIATION 8.06 | 28.8 Years STANDARD_DEVIATION 11.53 | 33.9 Years STANDARD_DEVIATION 8.83 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 6 Participants | 4 Participants | 16 Participants |
| Sex: Female, Male Female | 0 Participants | 3 Participants | 0 Participants | 3 Participants |
| Sex: Female, Male Male | 6 Participants | 3 Participants | 4 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 | 0 / 4 |
| other Total, other adverse events | 2 / 6 | 6 / 6 | 0 / 4 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 4 |
Outcome results
Primary
Cohorts 1 and 2: Pharmacokinetics Accumulation Ratio (Racc) of QBW276, QBP545, and QBV697 in Plasma
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 QBW276 | Cohorts 1 and 2: Pharmacokinetics Accumulation Ratio (Racc) of QBW276, QBP545, and QBV697 in Plasma | 1.20 Ratio | Standard Error 0.047 |
| Cohort 2 QBW276 | Cohorts 1 and 2: Pharmacokinetics Accumulation Ratio (Racc) of QBW276, QBP545, and QBV697 in Plasma | 1.28 Ratio | Standard Error 0.122 |
| Placebo | Cohorts 1 and 2: Pharmacokinetics Accumulation Ratio (Racc) of QBW276, QBP545, and QBV697 in Plasma | 1.84 Ratio | Standard Error 0.384 |
| Cohort 2 QBW276 | Cohorts 1 and 2: Pharmacokinetics Accumulation Ratio (Racc) of QBW276, QBP545, and QBV697 in Plasma | 1.59 Ratio | Standard Error 0.126 |
| Cohort 2 QBP545 | Cohorts 1 and 2: Pharmacokinetics Accumulation Ratio (Racc) of QBW276, QBP545, and QBV697 in Plasma | 1.01 Ratio | Standard Error 0.714 |
| Cohort 2 QBV697 | Cohorts 1 and 2: Pharmacokinetics Accumulation Ratio (Racc) of QBW276, QBP545, and QBV697 in Plasma | 1.74 Ratio | Standard Error 0.765 |
Primary
Cohorts 1 and 2: Pharmacokinetics (AUCtau) of QBW276, QBP545, and QBV697 in Plasma
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 QBW276 | Cohorts 1 and 2: Pharmacokinetics (AUCtau) of QBW276, QBP545, and QBV697 in Plasma | Day 1 | 0.0332 hr*ng/mL | — |
| Cohort 1 QBW276 | Cohorts 1 and 2: Pharmacokinetics (AUCtau) of QBW276, QBP545, and QBV697 in Plasma | Day 7 | 0.0278 hr*ng/mL | Standard Deviation 0.0362 |
| Cohort 2 QBW276 | Cohorts 1 and 2: Pharmacokinetics (AUCtau) of QBW276, QBP545, and QBV697 in Plasma | Day 1 | 14.3 hr*ng/mL | Standard Deviation 4.09 |
| Cohort 2 QBW276 | Cohorts 1 and 2: Pharmacokinetics (AUCtau) of QBW276, QBP545, and QBV697 in Plasma | Day 7 | 18 hr*ng/mL | Standard Deviation 4.21 |
| Placebo | Cohorts 1 and 2: Pharmacokinetics (AUCtau) of QBW276, QBP545, and QBV697 in Plasma | Day 1 | 1.35 hr*ng/mL | Standard Deviation 0.827 |
| Placebo | Cohorts 1 and 2: Pharmacokinetics (AUCtau) of QBW276, QBP545, and QBV697 in Plasma | Day 7 | 1.80 hr*ng/mL | Standard Deviation 0.797 |
| Cohort 2 QBW276 | Cohorts 1 and 2: Pharmacokinetics (AUCtau) of QBW276, QBP545, and QBV697 in Plasma | Day 1 | 0.0634 hr*ng/mL | Standard Deviation 0.0473 |
| Cohort 2 QBW276 | Cohorts 1 and 2: Pharmacokinetics (AUCtau) of QBW276, QBP545, and QBV697 in Plasma | Day 14 | 0.0918 hr*ng/mL | Standard Deviation 0.0689 |
| Cohort 2 QBP545 | Cohorts 1 and 2: Pharmacokinetics (AUCtau) of QBW276, QBP545, and QBV697 in Plasma | Day 1 | 13.9 hr*ng/mL | Standard Deviation 6.57 |
| Cohort 2 QBP545 | Cohorts 1 and 2: Pharmacokinetics (AUCtau) of QBW276, QBP545, and QBV697 in Plasma | Day 14 | 30.6 hr*ng/mL | Standard Deviation 6.59 |
| Cohort 2 QBV697 | Cohorts 1 and 2: Pharmacokinetics (AUCtau) of QBW276, QBP545, and QBV697 in Plasma | Day 1 | 1.79 hr*ng/mL | Standard Deviation 1.54 |
| Cohort 2 QBV697 | Cohorts 1 and 2: Pharmacokinetics (AUCtau) of QBW276, QBP545, and QBV697 in Plasma | Day 14 | 2.94 hr*ng/mL | Standard Deviation 1.59 |
Primary
Cohorts 1 and 2: Pharmacokinetics (Cmax) of QBW276, QBP545, and QBV697 in Plasma
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 QBW276 | Cohorts 1 and 2: Pharmacokinetics (Cmax) of QBW276, QBP545, and QBV697 in Plasma | Day 1 | 0.159 ng/mL | — |
| Cohort 1 QBW276 | Cohorts 1 and 2: Pharmacokinetics (Cmax) of QBW276, QBP545, and QBV697 in Plasma | Day 7 | 0.145 ng/mL | Standard Deviation 0.114 |
| Cohort 2 QBW276 | Cohorts 1 and 2: Pharmacokinetics (Cmax) of QBW276, QBP545, and QBV697 in Plasma | Day 1 | 3.88 ng/mL | Standard Deviation 1.38 |
| Cohort 2 QBW276 | Cohorts 1 and 2: Pharmacokinetics (Cmax) of QBW276, QBP545, and QBV697 in Plasma | Day 7 | 5.46 ng/mL | Standard Deviation 1.26 |
| Placebo | Cohorts 1 and 2: Pharmacokinetics (Cmax) of QBW276, QBP545, and QBV697 in Plasma | Day 1 | 1.21 ng/mL | Standard Deviation 0.415 |
| Placebo | Cohorts 1 and 2: Pharmacokinetics (Cmax) of QBW276, QBP545, and QBV697 in Plasma | Day 7 | 1.45 ng/mL | Standard Deviation 0.504 |
| Cohort 2 QBW276 | Cohorts 1 and 2: Pharmacokinetics (Cmax) of QBW276, QBP545, and QBV697 in Plasma | Day 1 | 0.174 ng/mL | Standard Deviation 0.0716 |
| Cohort 2 QBW276 | Cohorts 1 and 2: Pharmacokinetics (Cmax) of QBW276, QBP545, and QBV697 in Plasma | Day 14 | 0.267 ng/mL | Standard Deviation 0.109 |
| Cohort 2 QBP545 | Cohorts 1 and 2: Pharmacokinetics (Cmax) of QBW276, QBP545, and QBV697 in Plasma | Day 1 | 5.98 ng/mL | Standard Deviation 3.72 |
| Cohort 2 QBP545 | Cohorts 1 and 2: Pharmacokinetics (Cmax) of QBW276, QBP545, and QBV697 in Plasma | Day 14 | 7.80 ng/mL | Standard Deviation 4.34 |
| Cohort 2 QBV697 | Cohorts 1 and 2: Pharmacokinetics (Cmax) of QBW276, QBP545, and QBV697 in Plasma | Day 1 | 1.63 ng/mL | Standard Deviation 0.931 |
| Cohort 2 QBV697 | Cohorts 1 and 2: Pharmacokinetics (Cmax) of QBW276, QBP545, and QBV697 in Plasma | Day 14 | 3.07 ng/mL | Standard Deviation 1.72 |
Primary
Cohorts 1 and 2: Pharmacokinetics (Tmax) of QBW276, QBP545, and QBV697 in Plasma
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
Population: 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 | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1 QBW276 | Cohorts 1 and 2: Pharmacokinetics (Tmax) of QBW276, QBP545, and QBV697 in Plasma | Day 1 | 0.183 hr |
| Cohort 1 QBW276 | Cohorts 1 and 2: Pharmacokinetics (Tmax) of QBW276, QBP545, and QBV697 in Plasma | Day 7 | 0.183 hr |
| Cohort 2 QBW276 | Cohorts 1 and 2: Pharmacokinetics (Tmax) of QBW276, QBP545, and QBV697 in Plasma | Day 1 | 0.375 hr |
| Cohort 2 QBW276 | Cohorts 1 and 2: Pharmacokinetics (Tmax) of QBW276, QBP545, and QBV697 in Plasma | Day 7 | 0.500 hr |
| Placebo | Cohorts 1 and 2: Pharmacokinetics (Tmax) of QBW276, QBP545, and QBV697 in Plasma | Day 1 | 0.433 hr |
| Placebo | Cohorts 1 and 2: Pharmacokinetics (Tmax) of QBW276, QBP545, and QBV697 in Plasma | Day 7 | 0.375 hr |
| Cohort 2 QBW276 | Cohorts 1 and 2: Pharmacokinetics (Tmax) of QBW276, QBP545, and QBV697 in Plasma | Day 1 | 0.250 hr |
| Cohort 2 QBW276 | Cohorts 1 and 2: Pharmacokinetics (Tmax) of QBW276, QBP545, and QBV697 in Plasma | Day 14 | 0.258 hr |
| Cohort 2 QBP545 | Cohorts 1 and 2: Pharmacokinetics (Tmax) of QBW276, QBP545, and QBV697 in Plasma | Day 1 | 0.250 hr |
| Cohort 2 QBP545 | Cohorts 1 and 2: Pharmacokinetics (Tmax) of QBW276, QBP545, and QBV697 in Plasma | Day 14 | 0.500 hr |
| Cohort 2 QBV697 | Cohorts 1 and 2: Pharmacokinetics (Tmax) of QBW276, QBP545, and QBV697 in Plasma | Day 1 | 0.250 hr |
| Cohort 2 QBV697 | Cohorts 1 and 2: Pharmacokinetics (Tmax) of QBW276, QBP545, and QBV697 in Plasma | Day 14 | 0.500 hr |
Primary
Cohorts 1 and 2: Safety Assessments, Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]).
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
Population: Safety set: The safety analysis set included all patients that received any study drug
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1 QBW276 | Cohorts 1 and 2: Safety Assessments, Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]). | Serious AE | 0 Participants |
| Cohort 1 QBW276 | Cohorts 1 and 2: Safety Assessments, Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]). | Death | 0 Participants |
| Cohort 1 QBW276 | Cohorts 1 and 2: Safety Assessments, Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]). | Subjects with at least one AE | 2 Participants |
| Cohort 2 QBW276 | Cohorts 1 and 2: Safety Assessments, Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]). | Serious AE | 0 Participants |
| Cohort 2 QBW276 | Cohorts 1 and 2: Safety Assessments, Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]). | Death | 0 Participants |
| Cohort 2 QBW276 | Cohorts 1 and 2: Safety Assessments, Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]). | Subjects with at least one AE | 6 Participants |
| Placebo | Cohorts 1 and 2: Safety Assessments, Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]). | Death | 0 Participants |
| Placebo | Cohorts 1 and 2: Safety Assessments, Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]). | Subjects with at least one AE | 0 Participants |
| Placebo | Cohorts 1 and 2: Safety Assessments, Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]). | Serious AE | 0 Participants |
Secondary
Cohorts 1, 2: Change From Baseline in Lung Clearance Index (LCI) From Baseline to Day 7 for Cohort 1, Day 14 for Cohort 2.
Change in Lung Clearance Index (LCI) will be conducted by multiple breath nitrogen washout according to international standards
Time frame: Baseline to 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 QBW276 | 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 |
| Cohort 2 QBW276 | Cohorts 1, 2: Change From Baseline in Lung Clearance Index (LCI) From Baseline to Day 7 for Cohort 1, Day 14 for Cohort 2. | 2.478 Ratio | Standard Deviation 3.1397 |
| Placebo | Cohorts 1, 2: Change From Baseline in Lung Clearance Index (LCI) From Baseline to Day 7 for Cohort 1, Day 14 for Cohort 2. | 0.470 Ratio | Standard Deviation 0.4101 |
Secondary
Cohorts 1 and 2: Change From Baseline in Percent Predicted Forced Expiratory Volume in the First Second by Spirometry (% Predicted FEV1)
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)
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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 QBW276 | 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 2.3 |
| Cohort 2 QBW276 | 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 1.32 |
| Placebo | Cohorts 1 and 2: Change From Baseline in Percent Predicted Forced Expiratory Volume in the First Second by Spirometry (% Predicted FEV1) | -2.7 Percent predicted FEV1 | Standard Deviation 3.71 |