Trial Outcomes & Findings for An Evaluation Of PF-03715455 In Moderate To Severe Chronic Obstructive Pulmonary Disease (NCT NCT02366637)

NCT ID: NCT02366637

Last Updated: 2016-07-06

Results Overview

FEV1 is the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration. Trough FEV1 was obtained from spirometry, performed before study treatment administration.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

13 participants

Primary outcome timeframe

Baseline (Day 1), Day 29 (Week 4)

Results posted on

2016-07-06

Participant Flow

Participants were randomly assigned in a 1:1 ratio to receive either PF-03715455 680 micrograms (mcg) twice daily for 4 weeks or matching placebo in Period 1. Participants who were randomized to PF-03715455 during Period 1 then received placebo for 4 weeks during Period 2 after a 28 to 49-day washout period, and vice versa.

Participant milestones

Participant milestones
Measure
PF-03715455 680 mcg Twice Daily
PF-03715455 680 mcg dry powder capsule was administered by oral inhalation twice daily via a Miat mondose inhaler device for 4 weeks in each treatment period. Dosing in each treatment period was separated by a washout period of 28 to 49 days.
Placebo
Matching placebo was administered by oral inhalation twice daily via a Miat mondose inhaler device for 4 weeks in each treatment period. Dosing in each treatment period was separated by a washout period of 28 to 49 days.
First Intervention Period
STARTED
7
6
First Intervention Period
COMPLETED
1
1
First Intervention Period
NOT COMPLETED
6
5
Washout Period 28 to 49 Days
STARTED
1
1
Washout Period 28 to 49 Days
COMPLETED
1
1
Washout Period 28 to 49 Days
NOT COMPLETED
0
0
Second Intervention Period
STARTED
1
1
Second Intervention Period
COMPLETED
0
0
Second Intervention Period
NOT COMPLETED
1
1

Reasons for withdrawal

Reasons for withdrawal
Measure
PF-03715455 680 mcg Twice Daily
PF-03715455 680 mcg dry powder capsule was administered by oral inhalation twice daily via a Miat mondose inhaler device for 4 weeks in each treatment period. Dosing in each treatment period was separated by a washout period of 28 to 49 days.
Placebo
Matching placebo was administered by oral inhalation twice daily via a Miat mondose inhaler device for 4 weeks in each treatment period. Dosing in each treatment period was separated by a washout period of 28 to 49 days.
First Intervention Period
Adverse Event
0
1
First Intervention Period
Study Terminated by Sponsor
6
4
Second Intervention Period
Study Terminated by Sponsor
1
1

Baseline Characteristics

An Evaluation Of PF-03715455 In Moderate To Severe Chronic Obstructive Pulmonary Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
All Participants
n=13 Participants
All participants who received at least 1 dose of study drug (PF-03715455 or placebo).
Age, Continuous
62.0 years
STANDARD_DEVIATION 6.5 • n=5 Participants
Sex: Female, Male
Female
8 Participants
n=5 Participants
Sex: Female, Male
Male
5 Participants
n=5 Participants

PRIMARY outcome

Timeframe: Baseline (Day 1), Day 29 (Week 4)

Population: The modified intent-to-treat (mITT) analysis set included all randomized participants who received at least 1 dose of study drug; n=number of participants analyzed in respective arms for category.

FEV1 is the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration. Trough FEV1 was obtained from spirometry, performed before study treatment administration.

Outcome measures

Outcome measures
Measure
PF-03715455 680 mcg Twice Daily
n=8 Participants
PF-03715455 680 mcg dry powder capsule was administered by oral inhalation twice daily via a Miat mondose inhaler device for 4 weeks in each treatment period. Dosing in each treatment period was separated by a washout period of 28 to 49 days.
Placebo
n=7 Participants
Matching placebo was administered by oral inhalation twice daily via a Miat mondose inhaler device for 4 weeks in each treatment period. Dosing in each treatment period was separated by a washout period of 28 to 49 days.
Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) at Week 4
Baseline (n=8,7)
1.368 liters
Standard Deviation 0.3534
1.456 liters
Standard Deviation 0.5209
Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) at Week 4
Change at Week 4 (n=6,6)
-0.047 liters
Standard Deviation 0.0983
0.080 liters
Standard Deviation 0.2310

SECONDARY outcome

Timeframe: Baseline, Week 1 to Week 4

Population: It was not meaningful to summarize sputum cell counts as there were too few participants in the sputum sub-study and, of those, too few adequate sputum specimens to be meaningfully summarized.

Sputum cell counts included total neutrophils counts and differential (percent \[%\]), total cell count, total macrophage count and differential (%). Change over 4 weeks was to be presented.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, Day 7 (Week 1), Day 21 (Week 3), Day 29 (Week 4)

Population: The mITT analysis set included all randomized participants who received at least 1 dose of study drug; n=number of participants analyzed in respective arms for category.

FEV1 is the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration. FVC is the volume of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. FEV1 Baseline and Change at Week 4 are already reported under Primary Outcome Measure 1.

Outcome measures

Outcome measures
Measure
PF-03715455 680 mcg Twice Daily
n=8 Participants
PF-03715455 680 mcg dry powder capsule was administered by oral inhalation twice daily via a Miat mondose inhaler device for 4 weeks in each treatment period. Dosing in each treatment period was separated by a washout period of 28 to 49 days.
Placebo
n=7 Participants
Matching placebo was administered by oral inhalation twice daily via a Miat mondose inhaler device for 4 weeks in each treatment period. Dosing in each treatment period was separated by a washout period of 28 to 49 days.
Change From Baseline in Trough FEV1 and Forced Vital Capacity (FVC) at Weeks 1, 3, and 4
FEV1: Change at Week 1 (n=8,7)
-0.065 liters
Standard Deviation 0.1231
-0.001 liters
Standard Deviation 0.2559
Change From Baseline in Trough FEV1 and Forced Vital Capacity (FVC) at Weeks 1, 3, and 4
FEV1: Change at Week 3 (n=8,7)
-0.039 liters
Standard Deviation 0.2194
-0.026 liters
Standard Deviation 0.1033
Change From Baseline in Trough FEV1 and Forced Vital Capacity (FVC) at Weeks 1, 3, and 4
FVC: Baseline (n=8,7)
2.535 liters
Standard Deviation 0.8639
3.263 liters
Standard Deviation 1.2571
Change From Baseline in Trough FEV1 and Forced Vital Capacity (FVC) at Weeks 1, 3, and 4
FVC: Change at Week 1 (n=8,7)
-0.019 liters
Standard Deviation 0.1336
0.090 liters
Standard Deviation 0.1630
Change From Baseline in Trough FEV1 and Forced Vital Capacity (FVC) at Weeks 1, 3, and 4
FVC: Change at Week 3 (n=8,7)
0.049 liters
Standard Deviation 0.2100
-0.079 liters
Standard Deviation 0.1893
Change From Baseline in Trough FEV1 and Forced Vital Capacity (FVC) at Weeks 1, 3, and 4
FVC: Change at Week 4 (n=6,6)
0.091 liters
Standard Deviation 0.1661
0.233 liters
Standard Deviation 0.3014

SECONDARY outcome

Timeframe: Baseline, Week 1 to Week 4

Population: The mITT analysis set included all randomized participants who received at least 1 dose of study drug; n=number of participants analyzed in respective arms for category.

FEV1 is the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration. FVC is the volume of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. Change over 4 weeks is presented.

Outcome measures

Outcome measures
Measure
PF-03715455 680 mcg Twice Daily
n=8 Participants
PF-03715455 680 mcg dry powder capsule was administered by oral inhalation twice daily via a Miat mondose inhaler device for 4 weeks in each treatment period. Dosing in each treatment period was separated by a washout period of 28 to 49 days.
Placebo
n=7 Participants
Matching placebo was administered by oral inhalation twice daily via a Miat mondose inhaler device for 4 weeks in each treatment period. Dosing in each treatment period was separated by a washout period of 28 to 49 days.
Change From Baseline in Trough FEV1 and Forced Vital Capacity (FVC) Over 4 Weeks
FEV1: Change Over 4 Weeks (n=6,6)
-0.047 liters
Standard Deviation 0.0983
0.080 liters
Standard Deviation 0.2310
Change From Baseline in Trough FEV1 and Forced Vital Capacity (FVC) Over 4 Weeks
FVC: Change Over 4 Weeks (n=6,6)
0.091 liters
Standard Deviation 0.1661
0.233 liters
Standard Deviation 0.3014

SECONDARY outcome

Timeframe: Pre-dose on Day 7 and Day 21; post-dose on Day 7 (10 minutes and 1 hour post-dose) and Day 29

Population: As pharmacokinetics (PK) was not a primary objective of the study, only sparse PK sampling was performed to allow for a population PK analysis. As the study was prematurely terminated, there were too few subjects to perform this analysis. Therefore, the PK was not analyzed.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Pre-dose on Day 7 and Day 21; post-dose on Day 7 (10 minutes and 1 hour post-dose) and Day 29

Population: As PK was not a primary objective of the study, only sparse PK sampling was performed to allow for a population PK analysis. As the study was prematurely terminated, there were too few subjects to perform this analysis. Therefore, the PK was not analyzed.

Ctrough is the concentration prior to study drug administration.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline up to Day 29 (Week 4)

Population: The mITT analysis set included all randomized participants who received at least 1 dose of study drug.

An AE was any untoward medical occurrence in a participant who received study drug without regard to causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to Day 29 that were absent before treatment or that worsened relative to pre-treatment state. AEs included both SAEs and non-SAEs.

Outcome measures

Outcome measures
Measure
PF-03715455 680 mcg Twice Daily
n=8 Participants
PF-03715455 680 mcg dry powder capsule was administered by oral inhalation twice daily via a Miat mondose inhaler device for 4 weeks in each treatment period. Dosing in each treatment period was separated by a washout period of 28 to 49 days.
Placebo
n=7 Participants
Matching placebo was administered by oral inhalation twice daily via a Miat mondose inhaler device for 4 weeks in each treatment period. Dosing in each treatment period was separated by a washout period of 28 to 49 days.
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
AEs
3 participants
4 participants
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
SAEs
0 participants
0 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline up to Day 29 (Week 4)

Population: The mITT analysis set included all randomized participants who received at least 1 dose of study drug.

Clinically significant ECG findings include: PR interval \>=300 milliseconds (msec) or \>=25% increase when baseline is \>200 msec and \>=50% increase when baseline is less than or equal to 200 msec; QRS interval \>=200 msec or \>=25/50% increase from baseline; QT interval \>=500 msec; corrected QT interval using Fridericia's formula (QTcF) \>=450 msec or \>=30 msec increase.

Outcome measures

Outcome measures
Measure
PF-03715455 680 mcg Twice Daily
n=8 Participants
PF-03715455 680 mcg dry powder capsule was administered by oral inhalation twice daily via a Miat mondose inhaler device for 4 weeks in each treatment period. Dosing in each treatment period was separated by a washout period of 28 to 49 days.
Placebo
n=7 Participants
Matching placebo was administered by oral inhalation twice daily via a Miat mondose inhaler device for 4 weeks in each treatment period. Dosing in each treatment period was separated by a washout period of 28 to 49 days.
Number of Participants With Clinically Significant Treatment Emergent Electrocardiogram (ECG) Findings
PR Interval >=300 msec
0 participants
0 participants
Number of Participants With Clinically Significant Treatment Emergent Electrocardiogram (ECG) Findings
QRS Complex >=200 msec
0 participants
0 participants
Number of Participants With Clinically Significant Treatment Emergent Electrocardiogram (ECG) Findings
QT Interval >=500 msec
0 participants
0 participants
Number of Participants With Clinically Significant Treatment Emergent Electrocardiogram (ECG) Findings
QTcF Interval 450-<480 msec
0 participants
0 participants
Number of Participants With Clinically Significant Treatment Emergent Electrocardiogram (ECG) Findings
QTcF Interval 480-<500 msec
0 participants
0 participants
Number of Participants With Clinically Significant Treatment Emergent Electrocardiogram (ECG) Findings
QTcF Interval >=500 msec
0 participants
0 participants
Number of Participants With Clinically Significant Treatment Emergent Electrocardiogram (ECG) Findings
PR Interval >=25/50% Increase From Baseline
0 participants
0 participants
Number of Participants With Clinically Significant Treatment Emergent Electrocardiogram (ECG) Findings
QRS Complex >=25/50% Increase From Baseline
0 participants
0 participants
Number of Participants With Clinically Significant Treatment Emergent Electrocardiogram (ECG) Findings
QTcF Interval 30-<60 msec Increase From Baseline
0 participants
0 participants
Number of Participants With Clinically Significant Treatment Emergent Electrocardiogram (ECG) Findings
QTcF Interval >=60 msec Increase From Baseline
0 participants
0 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Day 7 (Week 1), Day 21 (Week 3), Day 29 (Week 4), Day 49 (follow-up)

Population: The mITT analysis set included all randomized participants who received at least 1 dose of study drug; n=number of participants analyzed in respective arms for category.

Systolic blood pressure (SBP) and diastolic pressure (DBP) were evaluated in the supine position.

Outcome measures

Outcome measures
Measure
PF-03715455 680 mcg Twice Daily
n=8 Participants
PF-03715455 680 mcg dry powder capsule was administered by oral inhalation twice daily via a Miat mondose inhaler device for 4 weeks in each treatment period. Dosing in each treatment period was separated by a washout period of 28 to 49 days.
Placebo
n=7 Participants
Matching placebo was administered by oral inhalation twice daily via a Miat mondose inhaler device for 4 weeks in each treatment period. Dosing in each treatment period was separated by a washout period of 28 to 49 days.
Change From Baseline in Systolic and Diastolic Blood Pressure
DBP: Baseline (n=8,7)
69.9 millimeters of mercury (mmHg)
Standard Deviation 9.72
65.1 millimeters of mercury (mmHg)
Standard Deviation 9.01
Change From Baseline in Systolic and Diastolic Blood Pressure
DBP: Change at Week 1 (n=7,6)
0.6 millimeters of mercury (mmHg)
Standard Deviation 6.95
8.7 millimeters of mercury (mmHg)
Standard Deviation 8.69
Change From Baseline in Systolic and Diastolic Blood Pressure
SBP: Baseline (n=8,7)
130.0 millimeters of mercury (mmHg)
Standard Deviation 19.16
122.7 millimeters of mercury (mmHg)
Standard Deviation 13.92
Change From Baseline in Systolic and Diastolic Blood Pressure
SBP: Change at Week 1 (n=7,6)
-7.4 millimeters of mercury (mmHg)
Standard Deviation 13.24
1.3 millimeters of mercury (mmHg)
Standard Deviation 3.01
Change From Baseline in Systolic and Diastolic Blood Pressure
SBP: Change at Week 3 (n=5,5)
-3.4 millimeters of mercury (mmHg)
Standard Deviation 12.03
-0.6 millimeters of mercury (mmHg)
Standard Deviation 9.02
Change From Baseline in Systolic and Diastolic Blood Pressure
SBP: Change at Week 4 (n=8,7)
-2.0 millimeters of mercury (mmHg)
Standard Deviation 15.34
8.1 millimeters of mercury (mmHg)
Standard Deviation 7.06
Change From Baseline in Systolic and Diastolic Blood Pressure
SBP: Change at Follow-Up (n=7,6)
1.4 millimeters of mercury (mmHg)
Standard Deviation 13.49
4.7 millimeters of mercury (mmHg)
Standard Deviation 11.24
Change From Baseline in Systolic and Diastolic Blood Pressure
DBP: Change at Week 3 (n=5,5)
2.4 millimeters of mercury (mmHg)
Standard Deviation 7.09
4.4 millimeters of mercury (mmHg)
Standard Deviation 5.13
Change From Baseline in Systolic and Diastolic Blood Pressure
DBP: Change at Week 4 (n=8,7)
2.1 millimeters of mercury (mmHg)
Standard Deviation 3.91
2.4 millimeters of mercury (mmHg)
Standard Deviation 8.46
Change From Baseline in Systolic and Diastolic Blood Pressure
DBP: Change at Follow-Up (n=7,6)
5.4 millimeters of mercury (mmHg)
Standard Deviation 6.63
2.8 millimeters of mercury (mmHg)
Standard Deviation 5.04

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Day 7 (Week 1), Day 21 (Week 3), Day 29 (Week 4), Day 49 (follow-up)

Population: The mITT analysis set included all randomized participants who received at least 1 dose of study drug; n=number of participants analyzed in respective arms for category.

Pulse rate was evaluated in the supine position.

Outcome measures

Outcome measures
Measure
PF-03715455 680 mcg Twice Daily
n=8 Participants
PF-03715455 680 mcg dry powder capsule was administered by oral inhalation twice daily via a Miat mondose inhaler device for 4 weeks in each treatment period. Dosing in each treatment period was separated by a washout period of 28 to 49 days.
Placebo
n=7 Participants
Matching placebo was administered by oral inhalation twice daily via a Miat mondose inhaler device for 4 weeks in each treatment period. Dosing in each treatment period was separated by a washout period of 28 to 49 days.
Change From Baseline in Pulse Rate
Baseline (n=8,7)
66.5 beats per minute (bpm)
Standard Deviation 11.82
64.3 beats per minute (bpm)
Standard Deviation 9.71
Change From Baseline in Pulse Rate
Change at Week 1 (n=7,6)
3.6 beats per minute (bpm)
Standard Deviation 7.41
3.5 beats per minute (bpm)
Standard Deviation 3.56
Change From Baseline in Pulse Rate
Change at Week 3 (n=5,5)
-1.6 beats per minute (bpm)
Standard Deviation 3.36
0.0 beats per minute (bpm)
Standard Deviation 3.16
Change From Baseline in Pulse Rate
Change at Week 4 (n=8,7)
1.3 beats per minute (bpm)
Standard Deviation 2.96
1.3 beats per minute (bpm)
Standard Deviation 6.24
Change From Baseline in Pulse Rate
Change at Follow-Up (n=7,6)
2.0 beats per minute (bpm)
Standard Deviation 4.76
1.0 beats per minute (bpm)
Standard Deviation 3.35

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline up to Week 4

Population: The mITT analysis set included all randomized participants who received at least 1 dose of study drug.

The following laboratory parameters were analyzed: hematology (hemoglobin, hematocrit, red blood cell \[RBC\] count, RBC morphology, platelet count, white blood cell \[WBC\] count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes); blood chemistry (blood urea nitrogen \[BUN\], creatinine, glucose, calcium, sodium, potassium, chloride, total bicarbonate, aspartate aminotransferase \[AST\], alanine aminotransferase \[ALT\], total bilirubin, direct and indirect bilirubin, gamma-glutamyl transpeptidase \[GGT\], alkaline phosphatase, uric acid, albumin, total protein, high sensitivity C-reactive protein \[CRP\]); urinalysis (specific gravity, pH, glucose, protein, blood, ketones, nitrites, leukocyte esterase, microscopy \[only if urine dipstick was positive for blood or protein\]).

Outcome measures

Outcome measures
Measure
PF-03715455 680 mcg Twice Daily
n=8 Participants
PF-03715455 680 mcg dry powder capsule was administered by oral inhalation twice daily via a Miat mondose inhaler device for 4 weeks in each treatment period. Dosing in each treatment period was separated by a washout period of 28 to 49 days.
Placebo
n=7 Participants
Matching placebo was administered by oral inhalation twice daily via a Miat mondose inhaler device for 4 weeks in each treatment period. Dosing in each treatment period was separated by a washout period of 28 to 49 days.
Number of Participants With Laboratory Abnormalities
6 participants
4 participants

Adverse Events

PF-03715455 680 mcg Twice Daily

Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths

Placebo

Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
PF-03715455 680 mcg Twice Daily
n=8 participants at risk
PF-03715455 680 mcg dry powder capsule was administered by oral inhalation twice daily via a Miat mondose inhaler device for 4 weeks in each treatment period. Dosing in each treatment period was separated by a washout period of 28 to 49 days.
Placebo
n=7 participants at risk
Matching placebo was administered by oral inhalation twice daily via a Miat mondose inhaler device for 4 weeks in each treatment period. Dosing in each treatment period was separated by a washout period of 28 to 49 days.
Cardiac disorders
Palpitations
12.5%
1/8 • Baseline up to follow-up period (Day 49)
0.00%
0/7 • Baseline up to follow-up period (Day 49)
Gastrointestinal disorders
Dyspepsia
0.00%
0/8 • Baseline up to follow-up period (Day 49)
14.3%
1/7 • Baseline up to follow-up period (Day 49)
Infections and infestations
Bronchitis
12.5%
1/8 • Baseline up to follow-up period (Day 49)
0.00%
0/7 • Baseline up to follow-up period (Day 49)
Infections and infestations
Nasopharyngitis
0.00%
0/8 • Baseline up to follow-up period (Day 49)
28.6%
2/7 • Baseline up to follow-up period (Day 49)
Injury, poisoning and procedural complications
Arthropod bite
0.00%
0/8 • Baseline up to follow-up period (Day 49)
14.3%
1/7 • Baseline up to follow-up period (Day 49)
Injury, poisoning and procedural complications
Contusion
12.5%
1/8 • Baseline up to follow-up period (Day 49)
14.3%
1/7 • Baseline up to follow-up period (Day 49)
Musculoskeletal and connective tissue disorders
Haemarthrosis
0.00%
0/8 • Baseline up to follow-up period (Day 49)
14.3%
1/7 • Baseline up to follow-up period (Day 49)
Nervous system disorders
Headache
12.5%
1/8 • Baseline up to follow-up period (Day 49)
0.00%
0/7 • Baseline up to follow-up period (Day 49)
Reproductive system and breast disorders
Vulvovaginal pruritus
0.00%
0/8 • Baseline up to follow-up period (Day 49)
33.3%
1/3 • Baseline up to follow-up period (Day 49)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
0.00%
0/8 • Baseline up to follow-up period (Day 49)
14.3%
1/7 • Baseline up to follow-up period (Day 49)
Vascular disorders
Haematoma
12.5%
1/8 • Baseline up to follow-up period (Day 49)
0.00%
0/7 • Baseline up to follow-up period (Day 49)

Additional Information

Pfizer ClinicalTrials.gov Call Center

Pfizer, Inc.

Phone: 1-800-718-1021

Results disclosure agreements

  • Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
  • Publication restrictions are in place

Restriction type: OTHER