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

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.

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).

Study Overview

• Status: Completed
• Conditions: Respiratory Tract Diseases; Lung Diseases; Pulmonary Disease, Chronic Obstructive; COPD; Chronic Obstructive Airway Disease
• Intervention / Treatment: Drug: placebo; Drug: active comparator; Drug: Low Dose PF-03635659; Drug: Mid Dose PF-03635659; Drug: High Dose PF-03635659

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 10117
    • Pfizer Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: January 1, 2010
• Primary Completion (Actual): June 1, 2010
• Study Completion (Actual): June 1, 2010

Study Registration Dates

• First Submitted: December 15, 2009
• First Submitted That Met QC Criteria: December 15, 2009
• First Posted (Estimate): December 16, 2009

Study Record Updates

• Last Update Posted (Estimate): February 19, 2016
• Last Update Submitted That Met QC Criteria: January 22, 2016
• Last Verified: January 1, 2016

More Information

Terms related to this study

• Keywords: Safety; COPD; Pharmacokinetics; Pharmacodynamics; PF-03635659
• Additional Relevant MeSH Terms: Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Respiratory Tract Diseases
• Other Study ID Numbers: B0431010