A Study To Examine The Safety, Pharmacokinetics And Pharmacodynamics Of PF-03635659 In Patients With Chronic Obstructive Pulmonary Disease

Study Overview
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Brief Summary
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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).

Official Title
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A Phase 2A, Double Blind, Placebo-Controlled, Single Dose, 5-Way Crossover Study Assessing The Pharmacodynamic, Pharmacokinetic And Safety Profiles Of Oral Inhaled PF-03635659 In Patients With Moderate Chronic Obstructive Pulmonary Disease.

Conditions
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Pulmonary Disease, Chronic Obstructive, Lung Diseases, Respiratory Tract Diseases, Chronic Obstructive Airway Disease, COPD

Intervention / Treatment
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* Drug: placebo
* Drug: active comparator
* Drug: Low Dose PF-03635659
* Drug: Mid Dose PF-03635659
* Drug: High Dose PF-03635659


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: 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.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br> | Drug: placebo<br>* oral inhaled formulation, single dose<br>|
| Active Comparator: active comparator<br> | Drug: active comparator<br>* oral inhaled formulation, single dose<br>|
| Experimental: PF-03635659<br> | Drug: Low Dose PF-03635659<br>* oral inhaled formulation, single dose, low dose<br>Drug: Mid Dose PF-03635659<br>* oral inhaled formulation, single dose, mid dose<br>Drug: High Dose PF-03635659<br>* oral inhaled formulation, single dose, high dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) | 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. | Baseline, 24, 24.5 hrs post-dose | 
| 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 | 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). | 1 hr pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 36, 48 hrs post-dose | 
| 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) | Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast). | 1 hr pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 36, 48 hrs post-dose | 
| Dose Normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration | 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). | 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 Extrapolated Infinite Time [AUC(0-∞)] | 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-∞). | 1 hr pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 36, 48 hrs post-dose | 
| Dose Normalized Area Under the Curve From Time Zero Extrapolated to Infinite Time | 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). | 1 hr pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 36, 48 hrs post-dose | 
| Plasma Decay Half-Life (t1/2) | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. | 1 hr pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 36, 48 hrs post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak Forced Expiratory Volume in 1 Second (FEV1) | 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. | Baseline up to 48 hrs post-dose | 
| Weighted Average Forced Expiratory Volume in 1 Second (FEV1) Response | 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. | Baseline up to 24.5 hrs post-dose | 
| Change From Baseline in Force Vital Capacity (FVC) | 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. | Baseline, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24, 24.5, 36, 48 hrs post-dose | 
| Change From Baseline in Inspiratory Capacity (IC) | 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. | Baseline, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24, 24.5, 36, 48 hrs pot-dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Safety, Pharmacokinetics, Pharmacodynamics, PF-03635659, COPD