A Study To Examine The Safety, Pharmacokinetics And Pharmacodynamics Of PF-03635659 In Patients With Chronic Obstructive Pulmonary Disease
- Conditions
- Chronic Obstructive Airway DiseaseCOPDLung DiseasesPulmonary Disease, Chronic ObstructiveRespiratory Tract Diseases
- Interventions
- Drug: placeboDrug: active comparator
- Registration Number
- NCT01033487
- Lead Sponsor
- Pfizer
- Brief Summary
PF-03635659 is being developed for the treatment of chronic obstructive pulmonary disease. This is a study to examine the safety, pharmacokinetics and pharmacodynamics of PF-03635659 in patients with Chronic Obstructive Pulmonary Disease (COPD).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 22
- Male or female (women of non-childbearing potential) subjects between the ages of 40 and 80 years, inclusive with a diagnosis of moderate COPD (GOLD, 2007 update) and who meet the following criteria for GOLD stage II disease
- Body Mass Index (BMI) of less than 35.5 kg/m2; and a total body weight >40 kg (88 lbs).
- Current smokers, or ex-smokers who have abstained from smoking for at least 6 months
- Subjects having more than 2 exacerbations requiring treatment with oral steroids or hospitalization for the treatment of COPD in the previous year.
- History of lower respiratory tract infection or significant disease instability during the month preceding screening or during the period between screening and randomization.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description PF-03635659 Mid Dose PF-03635659 - Placebo placebo - active comparator active comparator - PF-03635659 Low Dose PF-03635659 - PF-03635659 High Dose PF-03635659 -
- Primary Outcome Measures
Name Time Method Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) Baseline, 24, 24.5 hrs post-dose FEV1 was the mean volume of air that can be forced out in 1 second after taking a deep breath. Trough FEV1 was calculated as the average of the largest FEV1 value from 3 readings recorded at 24 hours (hrs) and 24.5 hrs post-dose. Baseline FEV1 value was calculated as average of 2 largest pre-dose readings on Day 1 for each period. Change from baseline in trough FEV1 was the difference between trough FEV1 and baseline FEV1.
Maximum Observed Plasma Concentration (Cmax) 1 hr pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 36, 48 hrs post-dose Dose Normalized Maximum Observed Plasma Concentration 1 hr pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 36, 48 hrs post-dose Cmax was normalized to a 1 mcg fine particle dose (40, 128 and 320 mcg for the nominal doses of 180, 580 and 1450 mcg respectively).
Time to Reach Maximum Observed Plasma Concentration (Tmax) 1 hr pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 36, 48 hrs post-dose Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) 1 hr pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 36, 48 hrs post-dose Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast).
Dose Normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration 1 hr pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 36, 48 hrs post-dose Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast). AUClast was normalized to a 1 mcg fine particle dose (40, 128 and 320 mcg for the nominal doses of 180, 580 and 1450 mcg respectively).
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC(0-∞)] 1 hr pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 36, 48 hrs post-dose AUC (0-∞) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-∞). It was obtained from AUC (0 - t) plus AUC (t-∞).
Dose Normalized Area Under the Curve From Time Zero Extrapolated to Infinite Time 1 hr pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 36, 48 hrs post-dose AUC (0-∞) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-∞). It was obtained from AUC (0 - t) plus AUC (t-∞). AUC (0-∞) was dose normalized to a 1 mcg fine particle dose (40, 128 and 320 mcg for the nominal doses of 180, 580 and 1450 mcg respectively).
Plasma Decay Half-Life (t1/2) 1 hr pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 36, 48 hrs post-dose Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
- Secondary Outcome Measures
Name Time Method Peak Forced Expiratory Volume in 1 Second (FEV1) Baseline up to 48 hrs post-dose FEV1 was the mean volume of air that can be forced out in 1 second after taking a deep breath. Peak FEV1 was defined as change from baseline in maximum FEV1. Maximum FEV1 = maximum forced expiratory volume in 1 second, recorded between 0.5 hrs to 48 hrs post-dose. Baseline FEV1 value was calculated as average of two largest pre-dose readings on Day 1 for each period.
Weighted Average Forced Expiratory Volume in 1 Second (FEV1) Response Baseline up to 24.5 hrs post-dose FEV1 was the mean volume of air that can be forced out in 1 second after taking a deep breath. Weighted average FEV1 was defined as the average area under the effect curve (AUEC) change from baseline FEV1 (the area under the FEV1 effect curve over 24.5 hrs post-dose for each study period corrected for the pre-dose baseline value) divided by 24.5. Baseline FEV1 value was calculated as the average of two largest pre-dose readings on Day 1 for each period.
Change From Baseline in Force Vital Capacity (FVC) Baseline, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24, 24.5, 36, 48 hrs post-dose FVC was the maximum amount of air exhaled from the lungs after taking the deepest breath possible. Baseline FVC value was calculated as average of two largest pre-dose readings on Day 1 for each period. Change from baseline in FVC was the difference between FVC and baseline FVC.
Change From Baseline in Inspiratory Capacity (IC) Baseline, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24, 24.5, 36, 48 hrs pot-dose IC was the maximum volume of air that can be inhaled in to the lungs after breathing out normally. Baseline IC value was calculated as average of two largest pre-dose readings on Day 1 for each period. Change from baseline in IC was the difference between IC and baseline IC.
Trial Locations
- Locations (1)
Pfizer Investigational Site
🇩🇪Berlin, Germany