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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT01033487
First received: December 15, 2009
Last updated: January 22, 2016
Last verified: January 2016
  Purpose
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).

Condition Intervention Phase
Pulmonary Disease, Chronic Obstructive
Lung Diseases
Respiratory Tract Diseases
Chronic Obstructive Airway Disease
COPD
Drug: placebo
Drug: active comparator
Drug: Low Dose PF-03635659
Drug: Mid Dose PF-03635659
Drug: High Dose PF-03635659
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: 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.

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) [ Time Frame: Baseline, 24, 24.5 hrs post-dose ] [ Designated as safety issue: No ]
    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) [ Time Frame: 1 hr pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 36, 48 hrs post-dose ] [ Designated as safety issue: No ]
  • Dose Normalized Maximum Observed Plasma Concentration [ Time Frame: 1 hr pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 36, 48 hrs post-dose ] [ Designated as safety issue: No ]
    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) [ Time Frame: 1 hr pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 36, 48 hrs post-dose ] [ Designated as safety issue: No ]
  • Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) [ Time Frame: 1 hr pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 36, 48 hrs post-dose ] [ Designated as safety issue: No ]
    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 [ Time Frame: 1 hr pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 36, 48 hrs post-dose ] [ Designated as safety issue: No ]
    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-∞)] [ Time Frame: 1 hr pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 36, 48 hrs post-dose ] [ Designated as safety issue: No ]
    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 [ Time Frame: 1 hr pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 36, 48 hrs post-dose ] [ Designated as safety issue: No ]
    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) [ Time Frame: 1 hr pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 36, 48 hrs post-dose ] [ Designated as safety issue: No ]
    Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.


Secondary Outcome Measures:
  • Peak Forced Expiratory Volume in 1 Second (FEV1) [ Time Frame: Baseline up to 48 hrs post-dose ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline up to 24.5 hrs post-dose ] [ Designated as safety issue: No ]
    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) [ Time Frame: Baseline, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24, 24.5, 36, 48 hrs post-dose ] [ Designated as safety issue: No ]
    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) [ Time Frame: Baseline, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24, 24.5, 36, 48 hrs pot-dose ] [ Designated as safety issue: No ]
    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.


Enrollment: 22
Study Start Date: January 2010
Study Completion Date: June 2010
Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   40 Years to 80 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01033487

Locations
Germany
Pfizer Investigational Site
Berlin, Germany, 10117
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01033487     History of Changes
Other Study ID Numbers: B0431010 
Study First Received: December 15, 2009
Results First Received: August 9, 2012
Last Updated: January 22, 2016
Health Authority: Germany: BfArM

Keywords provided by Pfizer:
Safety
Pharmacokinetics
Pharmacodynamics
PF-03635659
COPD

Additional relevant MeSH terms:
Lung Diseases
Lung Diseases, Obstructive
Pulmonary Disease, Chronic Obstructive
Chronic Disease
Respiratory Tract Diseases
Disease Attributes
Pathologic Processes

ClinicalTrials.gov processed this record on July 27, 2016