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.

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01033487

Enrollment

Registered

2009-12-16

Start date

2010-01-31

Completion date

2010-06-30

Last updated

2016-02-19

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

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

Keywords

Safety, Pharmacokinetics, Pharmacodynamics, PF-03635659, COPD

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).

Interventions

DRUGplacebo

oral inhaled formulation, single dose

DRUGactive comparator

oral inhaled formulation, single dose

DRUGLow Dose PF-03635659

oral inhaled formulation, single dose, low dose

DRUGMid Dose PF-03635659

oral inhaled formulation, single dose, mid dose

DRUGHigh Dose PF-03635659

oral inhaled formulation, single dose, high dose

Study design

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

TREATMENT

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

40 Years to 80 Years

Healthy volunteers

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.

Design outcomes

Primary

Measure	Time frame	Description
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.
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).
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	—

Secondary

Measure	Time frame	Description
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.
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.

Countries

Germany

Participant flow

Participants by arm

Arm	Count
Entire Study Population Includes all participants randomized to receive PBO Spiriva (tiotropium) 18 mcg capsule along with PBO PF-03635659 dry powder first, PBO Spiriva (tiotropium) 18 mcg capsule along with PF-03635659 180 mcg dry powder first, PBO Spiriva (tiotropium) 18 mcg capsule along with PF-03635659 580 mcg dry powder first, PBO Spiriva (tiotropium) 18 mcg capsule along with PF-03635659 1450 mcg dry powder first, Spiriva (tiotropium) 18 mcg capsule along with PBO PF-03635659 dry powder first.	22
Total	22

Arm

Count

Entire Study Population

Includes all participants randomized to receive PBO Spiriva (tiotropium) 18 mcg capsule along with PBO PF-03635659 dry powder first, PBO Spiriva (tiotropium) 18 mcg capsule along with PF-03635659 180 mcg dry powder first, PBO Spiriva (tiotropium) 18 mcg capsule along with PF-03635659 580 mcg dry powder first, PBO Spiriva (tiotropium) 18 mcg capsule along with PF-03635659 1450 mcg dry powder first, Spiriva (tiotropium) 18 mcg capsule along with PBO PF-03635659 dry powder first.

Total

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003	FG004	FG005	FG006	FG007	FG008	FG009
Fourth Intervention Period	Adverse Event	0	0	0	0	0	0	0	0	1	0

Baseline characteristics

Characteristic	Entire Study Population
Age, Continuous	58.7 Years STANDARD_DEVIATION 9.3
Sex: Female, Male Female	6 Participants
Sex: Female, Male Male	16 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —	— / —	— / —
other Total, other adverse events	2 / 22	3 / 22	1 / 21	6 / 22	4 / 22
serious Total, serious adverse events	0 / 22	0 / 22	0 / 21	1 / 22	0 / 22

Outcome results

Primary

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-∞).

Time frame: 1 hr pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 36, 48 hrs post-dose

Population: Data was not analyzed because a well characterized terminal phase was not observed for the parameter.

Primary

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).

Time frame: 1 hr pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 36, 48 hrs post-dose

Population: PK parameter analysis population included all randomized and treated participants who had at least 1 of the PK parameters of interest in at least 1 treatment period.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
PF-03635659 180 mcg	Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)	598.40 pg*hr/mL	Standard Deviation 329.21
PF-03635659 580 mcg	Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)	2513.00 pg*hr/mL	Standard Deviation 1408.5

Primary

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.

Time frame: Baseline, 24, 24.5 hrs post-dose

Population: Full Analysis Set (FAS) population included all randomized participants and who had received at least one dose of randomized treatment.

Arm	Measure	Group	Value (MEAN)	Dispersion
PF-03635659 180 mcg	Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1)	Baseline	1.61 Liter	Standard Deviation 0.409
PF-03635659 180 mcg	Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1)	Change in Trough FEV1	0.147 Liter	Standard Deviation 0.1802
PF-03635659 580 mcg	Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1)	Baseline	1.58 Liter	Standard Deviation 0.407
PF-03635659 580 mcg	Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1)	Change in Trough FEV1	0.167 Liter	Standard Deviation 0.1456
PF-03635659 1450 mcg	Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1)	Baseline	1.62 Liter	Standard Deviation 0.393
PF-03635659 1450 mcg	Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1)	Change in Trough FEV1	0.188 Liter	Standard Deviation 0.1794
Spiriva (Tiotropium) 18 mcg	Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1)	Change in Trough FEV1	0.115 Liter	Standard Deviation 0.1734
Spiriva (Tiotropium) 18 mcg	Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1)	Baseline	1.62 Liter	Standard Deviation 0.426
Placebo	Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1)	Baseline	1.67 Liter	Standard Deviation 0.427
Placebo	Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1)	Change in Trough FEV1	0.038 Liter	Standard Deviation 0.1486

Comparison: Emax model was used with sequence, period and baseline covariate as fixed effects. Lower (1-sided) 90 percent (%) confidence interval (CI) was reported.Emax Model

Comparison: Emax model was used with sequence, period and baseline covariate as fixed effects. Lower (1-sided) 90% CI was reported.Emax Model

Comparison: Emax model was used with sequence, period and baseline covariate as fixed effects. Lower (1-sided) 80% CI was reported.Emax Model

Primary

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).

Time frame: 1 hr pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 36, 48 hrs post-dose

Population: Data was not analyzed because a well characterized terminal phase was not observed for the parameter.

Primary

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).

Time frame: 1 hr pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 36, 48 hrs post-dose

Population: PK parameter analysis population included all randomized and treated participants who had at least 1 of the PK parameters of interest in at least 1 treatment period.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
PF-03635659 180 mcg	Dose Normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration	4.676 (pg*hr/mL)/mcg	Standard Deviation 2.5755
PF-03635659 580 mcg	Dose Normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration	7.856 (pg*hr/mL)/mcg	Standard Deviation 4.4075

Primary

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).

Time frame: 1 hr pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 36, 48 hrs post-dose

Population: PK parameter analysis population included all randomized and treated participants who had at least 1 of the PK parameters of interest in at least 1 treatment period.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
PF-03635659 180 mcg	Dose Normalized Maximum Observed Plasma Concentration	1.331 (pg/mL)/mcg	Standard Deviation 1.0046
PF-03635659 580 mcg	Dose Normalized Maximum Observed Plasma Concentration	1.323 (pg/mL)/mcg	Standard Deviation 0.4766
PF-03635659 1450 mcg	Dose Normalized Maximum Observed Plasma Concentration	1.474 (pg/mL)/mcg	Standard Deviation 0.6327

Primary

Maximum Observed Plasma Concentration (Cmax)

Time frame: 1 hr pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 36, 48 hrs post-dose

Population: Pharmacokinetic (PK) parameter analysis population included all randomized and treated participants who had at least 1 of the PK parameters of interest in at least 1 treatment period.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
PF-03635659 180 mcg	Maximum Observed Plasma Concentration (Cmax)	53.21 Picogram/milliliter (pg/mL)	Standard Deviation 40.163
PF-03635659 580 mcg	Maximum Observed Plasma Concentration (Cmax)	169.4 Picogram/milliliter (pg/mL)	Standard Deviation 61.112
PF-03635659 1450 mcg	Maximum Observed Plasma Concentration (Cmax)	471.2 Picogram/milliliter (pg/mL)	Standard Deviation 202.73

Primary

Plasma Decay Half-Life (t1/2)

Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.

Time frame: 1 hr pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 36, 48 hrs post-dose

Population: Data was not analyzed because a well characterized terminal phase was not observed for the parameter.

Primary

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

Population: PK parameter analysis population included all randomized and treated participants who had at least 1 of the PK parameters of interest in at least 1 treatment period. Here, 'N' (number of participants analyzed) is signifying those participants who were evaluable for this measure for each group respectively.

Arm	Measure	Value (MEDIAN)
PF-03635659 180 mcg	Time to Reach Maximum Observed Plasma Concentration (Tmax)	0.533 hr
PF-03635659 580 mcg	Time to Reach Maximum Observed Plasma Concentration (Tmax)	0.950 hr
PF-03635659 1450 mcg	Time to Reach Maximum Observed Plasma Concentration (Tmax)	0.467 hr

Secondary

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.

Time frame: Baseline, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24, 24.5, 36, 48 hrs post-dose

Population: FAS population included all randomized participants and who had received at least one dose of randomized treatment.

Arm	Measure	Group	Value (MEAN)	Dispersion
PF-03635659 180 mcg	Change From Baseline in Force Vital Capacity (FVC)	Change at 24.5 hr	0.217 Liter	Standard Deviation 0.2811
PF-03635659 180 mcg	Change From Baseline in Force Vital Capacity (FVC)	Change at 2 hr	0.203 Liter	Standard Deviation 0.2662
PF-03635659 180 mcg	Change From Baseline in Force Vital Capacity (FVC)	Change at 0.5 hr	0.212 Liter	Standard Deviation 0.2389
PF-03635659 180 mcg	Change From Baseline in Force Vital Capacity (FVC)	Change at 1 hr	0.173 Liter	Standard Deviation 0.1972
PF-03635659 180 mcg	Change From Baseline in Force Vital Capacity (FVC)	Change at 48 hr	0.193 Liter	Standard Deviation 0.2732
PF-03635659 180 mcg	Change From Baseline in Force Vital Capacity (FVC)	Change at 24 hr	0.174 Liter	Standard Deviation 0.3031
PF-03635659 180 mcg	Change From Baseline in Force Vital Capacity (FVC)	Change at 4 hr	0.144 Liter	Standard Deviation 0.3344
PF-03635659 180 mcg	Change From Baseline in Force Vital Capacity (FVC)	Change at 36 hr	0.002 Liter	Standard Deviation 0.2666
PF-03635659 180 mcg	Change From Baseline in Force Vital Capacity (FVC)	Baseline	3.461 Liter	Standard Deviation 0.8987
PF-03635659 180 mcg	Change From Baseline in Force Vital Capacity (FVC)	Change at 8 hr	0.152 Liter	Standard Deviation 0.2832
PF-03635659 180 mcg	Change From Baseline in Force Vital Capacity (FVC)	Change at 16 hr	0.000 Liter	Standard Deviation 0.3428
PF-03635659 180 mcg	Change From Baseline in Force Vital Capacity (FVC)	Change at 6 hr	0.123 Liter	Standard Deviation 0.3018
PF-03635659 180 mcg	Change From Baseline in Force Vital Capacity (FVC)	Change at 10 hr	0.172 Liter	Standard Deviation 0.4062
PF-03635659 180 mcg	Change From Baseline in Force Vital Capacity (FVC)	Change at 12 hr	0.094 Liter	Standard Deviation 0.2972
PF-03635659 580 mcg	Change From Baseline in Force Vital Capacity (FVC)	Baseline	3.421 Liter	Standard Deviation 0.9194
PF-03635659 580 mcg	Change From Baseline in Force Vital Capacity (FVC)	Change at 8 hr	0.276 Liter	Standard Deviation 0.2509
PF-03635659 580 mcg	Change From Baseline in Force Vital Capacity (FVC)	Change at 10 hr	0.257 Liter	Standard Deviation 0.2846
PF-03635659 580 mcg	Change From Baseline in Force Vital Capacity (FVC)	Change at 36 hr	0.005 Liter	Standard Deviation 0.2217
PF-03635659 580 mcg	Change From Baseline in Force Vital Capacity (FVC)	Change at 0.5 hr	0.245 Liter	Standard Deviation 0.2541
PF-03635659 580 mcg	Change From Baseline in Force Vital Capacity (FVC)	Change at 1 hr	0.214 Liter	Standard Deviation 0.2699
PF-03635659 580 mcg	Change From Baseline in Force Vital Capacity (FVC)	Change at 48 hr	0.156 Liter	Standard Deviation 0.2877
PF-03635659 580 mcg	Change From Baseline in Force Vital Capacity (FVC)	Change at 24.5 hr	0.249 Liter	Standard Deviation 0.2171
PF-03635659 580 mcg	Change From Baseline in Force Vital Capacity (FVC)	Change at 2 hr	0.264 Liter	Standard Deviation 0.2825
PF-03635659 580 mcg	Change From Baseline in Force Vital Capacity (FVC)	Change at 24 hr	0.200 Liter	Standard Deviation 0.2528
PF-03635659 580 mcg	Change From Baseline in Force Vital Capacity (FVC)	Change at 4 hr	0.280 Liter	Standard Deviation 0.2987
PF-03635659 580 mcg	Change From Baseline in Force Vital Capacity (FVC)	Change at 16 hr	0.053 Liter	Standard Deviation 0.2912
PF-03635659 580 mcg	Change From Baseline in Force Vital Capacity (FVC)	Change at 6 hr	0.259 Liter	Standard Deviation 0.268
PF-03635659 580 mcg	Change From Baseline in Force Vital Capacity (FVC)	Change at 12 hr	0.221 Liter	Standard Deviation 0.3151
PF-03635659 1450 mcg	Change From Baseline in Force Vital Capacity (FVC)	Change at 6 hr	0.233 Liter	Standard Deviation 0.2524
PF-03635659 1450 mcg	Change From Baseline in Force Vital Capacity (FVC)	Baseline	3.474 Liter	Standard Deviation 0.8385
PF-03635659 1450 mcg	Change From Baseline in Force Vital Capacity (FVC)	Change at 0.5 hr	0.243 Liter	Standard Deviation 0.2337
PF-03635659 1450 mcg	Change From Baseline in Force Vital Capacity (FVC)	Change at 1 hr	0.237 Liter	Standard Deviation 0.2887
PF-03635659 1450 mcg	Change From Baseline in Force Vital Capacity (FVC)	Change at 2 hr	0.284 Liter	Standard Deviation 0.2661
PF-03635659 1450 mcg	Change From Baseline in Force Vital Capacity (FVC)	Change at 4 hr	0.254 Liter	Standard Deviation 0.271
PF-03635659 1450 mcg	Change From Baseline in Force Vital Capacity (FVC)	Change at 8 hr	0.253 Liter	Standard Deviation 0.312
PF-03635659 1450 mcg	Change From Baseline in Force Vital Capacity (FVC)	Change at 10 hr	0.260 Liter	Standard Deviation 0.2968
PF-03635659 1450 mcg	Change From Baseline in Force Vital Capacity (FVC)	Change at 12 hr	0.163 Liter	Standard Deviation 0.318
PF-03635659 1450 mcg	Change From Baseline in Force Vital Capacity (FVC)	Change at 16 hr	0.120 Liter	Standard Deviation 0.2885
PF-03635659 1450 mcg	Change From Baseline in Force Vital Capacity (FVC)	Change at 24 hr	0.178 Liter	Standard Deviation 0.3551
PF-03635659 1450 mcg	Change From Baseline in Force Vital Capacity (FVC)	Change at 24.5 hr	0.217 Liter	Standard Deviation 0.3388
PF-03635659 1450 mcg	Change From Baseline in Force Vital Capacity (FVC)	Change at 36 hr	0.043 Liter	Standard Deviation 0.2585
PF-03635659 1450 mcg	Change From Baseline in Force Vital Capacity (FVC)	Change at 48 hr	0.130 Liter	Standard Deviation 0.2736
Spiriva (Tiotropium) 18 mcg	Change From Baseline in Force Vital Capacity (FVC)	Change at 6 hr	0.304 Liter	Standard Deviation 0.439
Spiriva (Tiotropium) 18 mcg	Change From Baseline in Force Vital Capacity (FVC)	Change at 12 hr	0.174 Liter	Standard Deviation 0.4518
Spiriva (Tiotropium) 18 mcg	Change From Baseline in Force Vital Capacity (FVC)	Change at 4 hr	0.268 Liter	Standard Deviation 0.4412
Spiriva (Tiotropium) 18 mcg	Change From Baseline in Force Vital Capacity (FVC)	Baseline	3.457 Liter	Standard Deviation 0.9118
Spiriva (Tiotropium) 18 mcg	Change From Baseline in Force Vital Capacity (FVC)	Change at 16 hr	0.174 Liter	Standard Deviation 0.3825
Spiriva (Tiotropium) 18 mcg	Change From Baseline in Force Vital Capacity (FVC)	Change at 2 hr	0.279 Liter	Standard Deviation 0.3763
Spiriva (Tiotropium) 18 mcg	Change From Baseline in Force Vital Capacity (FVC)	Change at 0.5 hr	0.247 Liter	Standard Deviation 0.2505
Spiriva (Tiotropium) 18 mcg	Change From Baseline in Force Vital Capacity (FVC)	Change at 24 hr	0.166 Liter	Standard Deviation 0.378
Spiriva (Tiotropium) 18 mcg	Change From Baseline in Force Vital Capacity (FVC)	Change at 1 hr	0.223 Liter	Standard Deviation 0.3361
Spiriva (Tiotropium) 18 mcg	Change From Baseline in Force Vital Capacity (FVC)	Change at 24.5 hr	0.146 Liter	Standard Deviation 0.3961
Spiriva (Tiotropium) 18 mcg	Change From Baseline in Force Vital Capacity (FVC)	Change at 48 hr	0.135 Liter	Standard Deviation 0.3675
Spiriva (Tiotropium) 18 mcg	Change From Baseline in Force Vital Capacity (FVC)	Change at 8 hr	0.263 Liter	Standard Deviation 0.447
Spiriva (Tiotropium) 18 mcg	Change From Baseline in Force Vital Capacity (FVC)	Change at 36 hr	0.043 Liter	Standard Deviation 0.417
Spiriva (Tiotropium) 18 mcg	Change From Baseline in Force Vital Capacity (FVC)	Change at 10 hr	0.298 Liter	Standard Deviation 0.434
Placebo	Change From Baseline in Force Vital Capacity (FVC)	Change at 10 hr	-0.063 Liter	Standard Deviation 0.2729
Placebo	Change From Baseline in Force Vital Capacity (FVC)	Change at 48 hr	0.019 Liter	Standard Deviation 0.2364
Placebo	Change From Baseline in Force Vital Capacity (FVC)	Change at 12 hr	-0.033 Liter	Standard Deviation 0.2762
Placebo	Change From Baseline in Force Vital Capacity (FVC)	Change at 4 hr	-0.038 Liter	Standard Deviation 0.2675
Placebo	Change From Baseline in Force Vital Capacity (FVC)	Change at 6 hr	0.004 Liter	Standard Deviation 0.2527
Placebo	Change From Baseline in Force Vital Capacity (FVC)	Change at 24.5 hr	0.022 Liter	Standard Deviation 0.2694
Placebo	Change From Baseline in Force Vital Capacity (FVC)	Change at 0.5 hr	0.027 Liter	Standard Deviation 0.2081
Placebo	Change From Baseline in Force Vital Capacity (FVC)	Change at 16 hr	-0.195 Liter	Standard Deviation 0.3567
Placebo	Change From Baseline in Force Vital Capacity (FVC)	Change at 2 hr	0.050 Liter	Standard Deviation 0.2421
Placebo	Change From Baseline in Force Vital Capacity (FVC)	Baseline	3.522 Liter	Standard Deviation 0.8929
Placebo	Change From Baseline in Force Vital Capacity (FVC)	Change at 36 hr	-0.131 Liter	Standard Deviation 0.3108
Placebo	Change From Baseline in Force Vital Capacity (FVC)	Change at 8 hr	0.025 Liter	Standard Deviation 0.2583
Placebo	Change From Baseline in Force Vital Capacity (FVC)	Change at 24 hr	0.006 Liter	Standard Deviation 0.3141
Placebo	Change From Baseline in Force Vital Capacity (FVC)	Change at 1 hr	0.050 Liter	Standard Deviation 0.2146

Secondary

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.

Time frame: Baseline, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24, 24.5, 36, 48 hrs pot-dose

Population: FAS population included all randomized participants and who had received at least one dose of randomized treatment.

Arm	Measure	Group	Value (MEAN)	Dispersion
PF-03635659 180 mcg	Change From Baseline in Inspiratory Capacity (IC)	Baseline	2.517 Liter	Standard Deviation 0.6577
PF-03635659 180 mcg	Change From Baseline in Inspiratory Capacity (IC)	Change at 12 hr	0.022 Liter	Standard Deviation 0.2961
PF-03635659 180 mcg	Change From Baseline in Inspiratory Capacity (IC)	Change at 8 hr	0.128 Liter	Standard Deviation 0.3734
PF-03635659 180 mcg	Change From Baseline in Inspiratory Capacity (IC)	Change at 10 hr	0.077 Liter	Standard Deviation 0.3658
PF-03635659 180 mcg	Change From Baseline in Inspiratory Capacity (IC)	Change at 36 hr	-0.055 Liter	Standard Deviation 0.2639
PF-03635659 180 mcg	Change From Baseline in Inspiratory Capacity (IC)	Change at 1 hr	0.159 Liter	Standard Deviation 0.195
PF-03635659 180 mcg	Change From Baseline in Inspiratory Capacity (IC)	Change at 24.5 hr	0.057 Liter	Standard Deviation 0.2349
PF-03635659 180 mcg	Change From Baseline in Inspiratory Capacity (IC)	Change at 2 hr	0.180 Liter	Standard Deviation 0.2514
PF-03635659 180 mcg	Change From Baseline in Inspiratory Capacity (IC)	Change at 48 hr	0.020 Liter	Standard Deviation 0.2151
PF-03635659 180 mcg	Change From Baseline in Inspiratory Capacity (IC)	Change at 24 hr	0.060 Liter	Standard Deviation 0.2636
PF-03635659 180 mcg	Change From Baseline in Inspiratory Capacity (IC)	Change at 4 hr	0.190 Liter	Standard Deviation 0.2517
PF-03635659 180 mcg	Change From Baseline in Inspiratory Capacity (IC)	Change at 0.5 hr	0.090 Liter	Standard Deviation 0.144
PF-03635659 180 mcg	Change From Baseline in Inspiratory Capacity (IC)	Change at 16 hr	-0.076 Liter	Standard Deviation 0.3463
PF-03635659 180 mcg	Change From Baseline in Inspiratory Capacity (IC)	Change at 6 hr	0.185 Liter	Standard Deviation 0.402
PF-03635659 580 mcg	Change From Baseline in Inspiratory Capacity (IC)	Change at 6 hr	0.090 Liter	Standard Deviation 0.3085
PF-03635659 580 mcg	Change From Baseline in Inspiratory Capacity (IC)	Change at 4 hr	0.158 Liter	Standard Deviation 0.2293
PF-03635659 580 mcg	Change From Baseline in Inspiratory Capacity (IC)	Change at 2 hr	0.168 Liter	Standard Deviation 0.2523
PF-03635659 580 mcg	Change From Baseline in Inspiratory Capacity (IC)	Change at 8 hr	0.102 Liter	Standard Deviation 0.2056
PF-03635659 580 mcg	Change From Baseline in Inspiratory Capacity (IC)	Change at 0.5 hr	0.123 Liter	Standard Deviation 0.1519
PF-03635659 580 mcg	Change From Baseline in Inspiratory Capacity (IC)	Change at 10 hr	0.146 Liter	Standard Deviation 0.2449
PF-03635659 580 mcg	Change From Baseline in Inspiratory Capacity (IC)	Change at 12 hr	0.058 Liter	Standard Deviation 0.2411
PF-03635659 580 mcg	Change From Baseline in Inspiratory Capacity (IC)	Baseline	2.559 Liter	Standard Deviation 0.5708
PF-03635659 580 mcg	Change From Baseline in Inspiratory Capacity (IC)	Change at 36 hr	-0.124 Liter	Standard Deviation 0.2845
PF-03635659 580 mcg	Change From Baseline in Inspiratory Capacity (IC)	Change at 24 hr	-0.051 Liter	Standard Deviation 0.3049
PF-03635659 580 mcg	Change From Baseline in Inspiratory Capacity (IC)	Change at 16 hr	-0.064 Liter	Standard Deviation 0.2537
PF-03635659 580 mcg	Change From Baseline in Inspiratory Capacity (IC)	Change at 1 hr	0.212 Liter	Standard Deviation 0.2255
PF-03635659 580 mcg	Change From Baseline in Inspiratory Capacity (IC)	Change at 48 hr	-0.034 Liter	Standard Deviation 0.3568
PF-03635659 580 mcg	Change From Baseline in Inspiratory Capacity (IC)	Change at 24.5 hr	0.023 Liter	Standard Deviation 0.2545
PF-03635659 1450 mcg	Change From Baseline in Inspiratory Capacity (IC)	Change at 6 hr	0.201 Liter	Standard Deviation 0.2554
PF-03635659 1450 mcg	Change From Baseline in Inspiratory Capacity (IC)	Baseline	2.488 Liter	Standard Deviation 0.5639
PF-03635659 1450 mcg	Change From Baseline in Inspiratory Capacity (IC)	Change at 0.5 hr	0.150 Liter	Standard Deviation 0.2091
PF-03635659 1450 mcg	Change From Baseline in Inspiratory Capacity (IC)	Change at 1 hr	0.208 Liter	Standard Deviation 0.259
PF-03635659 1450 mcg	Change From Baseline in Inspiratory Capacity (IC)	Change at 2 hr	0.218 Liter	Standard Deviation 0.2285
PF-03635659 1450 mcg	Change From Baseline in Inspiratory Capacity (IC)	Change at 4 hr	0.193 Liter	Standard Deviation 0.2507
PF-03635659 1450 mcg	Change From Baseline in Inspiratory Capacity (IC)	Change at 8 hr	0.111 Liter	Standard Deviation 0.2981
PF-03635659 1450 mcg	Change From Baseline in Inspiratory Capacity (IC)	Change at 10 hr	0.094 Liter	Standard Deviation 0.2645
PF-03635659 1450 mcg	Change From Baseline in Inspiratory Capacity (IC)	Change at 12 hr	0.018 Liter	Standard Deviation 0.2537
PF-03635659 1450 mcg	Change From Baseline in Inspiratory Capacity (IC)	Change at 16 hr	-0.096 Liter	Standard Deviation 0.2867
PF-03635659 1450 mcg	Change From Baseline in Inspiratory Capacity (IC)	Change at 24 hr	-0.001 Liter	Standard Deviation 0.2207
PF-03635659 1450 mcg	Change From Baseline in Inspiratory Capacity (IC)	Change at 24.5 hr	0.018 Liter	Standard Deviation 0.3165
PF-03635659 1450 mcg	Change From Baseline in Inspiratory Capacity (IC)	Change at 36 hr	-0.036 Liter	Standard Deviation 0.2365
PF-03635659 1450 mcg	Change From Baseline in Inspiratory Capacity (IC)	Change at 48 hr	0.080 Liter	Standard Deviation 0.2519
Spiriva (Tiotropium) 18 mcg	Change From Baseline in Inspiratory Capacity (IC)	Change at 6 hr	0.163 Liter	Standard Deviation 0.2454
Spiriva (Tiotropium) 18 mcg	Change From Baseline in Inspiratory Capacity (IC)	Change at 12 hr	0.158 Liter	Standard Deviation 0.1789
Spiriva (Tiotropium) 18 mcg	Change From Baseline in Inspiratory Capacity (IC)	Change at 4 hr	0.201 Liter	Standard Deviation 0.193
Spiriva (Tiotropium) 18 mcg	Change From Baseline in Inspiratory Capacity (IC)	Change at 16 hr	-0.005 Liter	Standard Deviation 0.2723
Spiriva (Tiotropium) 18 mcg	Change From Baseline in Inspiratory Capacity (IC)	Change at 2 hr	0.200 Liter	Standard Deviation 0.2283
Spiriva (Tiotropium) 18 mcg	Change From Baseline in Inspiratory Capacity (IC)	Baseline	2.473 Liter	Standard Deviation 0.6199
Spiriva (Tiotropium) 18 mcg	Change From Baseline in Inspiratory Capacity (IC)	Change at 24 hr	0.107 Liter	Standard Deviation 0.2276
Spiriva (Tiotropium) 18 mcg	Change From Baseline in Inspiratory Capacity (IC)	Change at 1 hr	0.207 Liter	Standard Deviation 0.1834
Spiriva (Tiotropium) 18 mcg	Change From Baseline in Inspiratory Capacity (IC)	Change at 24.5 hr	0.095 Liter	Standard Deviation 0.2353
Spiriva (Tiotropium) 18 mcg	Change From Baseline in Inspiratory Capacity (IC)	Change at 0.5 hr	0.119 Liter	Standard Deviation 0.1795
Spiriva (Tiotropium) 18 mcg	Change From Baseline in Inspiratory Capacity (IC)	Change at 48 hr	0.046 Liter	Standard Deviation 0.2643
Spiriva (Tiotropium) 18 mcg	Change From Baseline in Inspiratory Capacity (IC)	Change at 8 hr	0.181 Liter	Standard Deviation 0.2096
Spiriva (Tiotropium) 18 mcg	Change From Baseline in Inspiratory Capacity (IC)	Change at 36 hr	-0.008 Liter	Standard Deviation 0.3173
Spiriva (Tiotropium) 18 mcg	Change From Baseline in Inspiratory Capacity (IC)	Change at 10 hr	0.214 Liter	Standard Deviation 0.2487
Placebo	Change From Baseline in Inspiratory Capacity (IC)	Change at 8 hr	-0.051 Liter	Standard Deviation 0.2379
Placebo	Change From Baseline in Inspiratory Capacity (IC)	Change at 48 hr	-0.067 Liter	Standard Deviation 0.2326
Placebo	Change From Baseline in Inspiratory Capacity (IC)	Change at 12 hr	-0.094 Liter	Standard Deviation 0.3679
Placebo	Change From Baseline in Inspiratory Capacity (IC)	Change at 4 hr	-0.014 Liter	Standard Deviation 0.1781
Placebo	Change From Baseline in Inspiratory Capacity (IC)	Change at 10 hr	-0.009 Liter	Standard Deviation 0.2343
Placebo	Change From Baseline in Inspiratory Capacity (IC)	Baseline	2.543 Liter	Standard Deviation 0.6576
Placebo	Change From Baseline in Inspiratory Capacity (IC)	Change at 24.5 hr	0.012 Liter	Standard Deviation 0.1977
Placebo	Change From Baseline in Inspiratory Capacity (IC)	Change at 16 hr	-0.199 Liter	Standard Deviation 0.2622
Placebo	Change From Baseline in Inspiratory Capacity (IC)	Change at 2 hr	0.066 Liter	Standard Deviation 0.2064
Placebo	Change From Baseline in Inspiratory Capacity (IC)	Change at 0.5 hr	0.031 Liter	Standard Deviation 0.1278
Placebo	Change From Baseline in Inspiratory Capacity (IC)	Change at 6 hr	-0.036 Liter	Standard Deviation 0.2228
Placebo	Change From Baseline in Inspiratory Capacity (IC)	Change at 36 hr	-0.146 Liter	Standard Deviation 0.1888
Placebo	Change From Baseline in Inspiratory Capacity (IC)	Change at 24 hr	-0.045 Liter	Standard Deviation 0.1723
Placebo	Change From Baseline in Inspiratory Capacity (IC)	Change at 1 hr	0.035 Liter	Standard Deviation 0.1358

Secondary

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.

Time frame: Baseline up to 48 hrs post-dose

Population: FAS population included all randomized participants and who had received at least one dose of randomized treatment.

Arm	Measure	Value (MEAN)	Dispersion
PF-03635659 180 mcg	Peak Forced Expiratory Volume in 1 Second (FEV1)	0.270 Liter	Standard Deviation 0.1561
PF-03635659 580 mcg	Peak Forced Expiratory Volume in 1 Second (FEV1)	0.380 Liter	Standard Deviation 0.1563
PF-03635659 1450 mcg	Peak Forced Expiratory Volume in 1 Second (FEV1)	0.383 Liter	Standard Deviation 0.1621
Spiriva (Tiotropium) 18 mcg	Peak Forced Expiratory Volume in 1 Second (FEV1)	0.325 Liter	Standard Deviation 0.1508
Placebo	Peak Forced Expiratory Volume in 1 Second (FEV1)	0.139 Liter	Standard Deviation 0.1448

Comparison: Mixed effects analysis of variance (ANOVA) was used with sequence, period and baseline covariate as fixed effects, and participant within sequence as a random effect. Lower (1-sided) 90% CI was reported.ANOVA

Comparison: Mixed effects ANOVA was used with sequence, period and baseline covariate as fixed effects, and participant within sequence as a random effect. Lower (1-sided) 90% CI was reported.ANOVA

Secondary

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.

Time frame: Baseline up to 24.5 hrs post-dose

Population: FAS population included all randomized participants and who had received at least one dose of randomized treatment.

Arm	Measure	Value (MEAN)	Dispersion
PF-03635659 180 mcg	Weighted Average Forced Expiratory Volume in 1 Second (FEV1) Response	0.091 Liter	Standard Deviation 0.1593
PF-03635659 580 mcg	Weighted Average Forced Expiratory Volume in 1 Second (FEV1) Response	0.167 Liter	Standard Deviation 0.1489
PF-03635659 1450 mcg	Weighted Average Forced Expiratory Volume in 1 Second (FEV1) Response	0.172 Liter	Standard Deviation 0.1553
Spiriva (Tiotropium) 18 mcg	Weighted Average Forced Expiratory Volume in 1 Second (FEV1) Response	0.149 Liter	Standard Deviation 0.1679
Placebo	Weighted Average Forced Expiratory Volume in 1 Second (FEV1) Response	-0.033 Liter	Standard Deviation 0.1321

Comparison: Mixed effects ANOVA was used with sequence, period and baseline covariate as fixed effects, and participant within sequence as a random effect. Lower (1-sided) 90% CI was reported.ANOVA

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026

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

Conditions

Keywords

Brief summary

Related papers

Interventions

Sponsors

Study design

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Countries

Participant flow

Participants by arm

Withdrawals & dropouts

Baseline characteristics

Adverse events

Outcome results

Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC(0-∞)]

Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)

Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1)

Dose Normalized Area Under the Curve From Time Zero Extrapolated to Infinite Time

Dose Normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration

Dose Normalized Maximum Observed Plasma Concentration

Maximum Observed Plasma Concentration (Cmax)

Plasma Decay Half-Life (t1/2)

Time to Reach Maximum Observed Plasma Concentration (Tmax)

Change From Baseline in Force Vital Capacity (FVC)

Change From Baseline in Inspiratory Capacity (IC)

Peak Forced Expiratory Volume in 1 Second (FEV1)

Weighted Average Forced Expiratory Volume in 1 Second (FEV1) Response