Clinical Trial Results:
A Randomized, Double-Blind, Placebo-Controlled 2-Way Crossover Study to Evaluate the Efficacy, Safety and Tolerability of PF-03715455 Administered Twice Daily by Inhalation for 4 Weeks in Subjects with Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD)
Summary
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EudraCT number |
2014-002340-40 |
Trial protocol |
GB |
Global end of trial date |
01 May 2015
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Results information
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Results version number |
v1(current) |
This version publication date |
23 Apr 2016
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First version publication date |
23 Apr 2016
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
A9111004
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
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WHO universal trial number (UTN) |
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Sponsors
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Sponsor organisation name |
Pfizer, Inc.
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Sponsor organisation address |
235 E 42nd Street, New York, United States, 10017
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Public contact |
Pfizer ClinicalTrials.gov Call Center, Pfizer Inc., 001 800-718-1021, ClinicalTrials.gov_Inquiries@pfizer.com
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Scientific contact |
Pfizer ClinicalTrials.gov Call Center, Pfizer Inc., 001 800-718-1021, ClinicalTrials.gov_Inquiries@pfizer.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
28 May 2015
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
01 May 2015
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Global end of trial reached? |
Yes
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Global end of trial date |
01 May 2015
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
The main objective was to determine the effect, at Week 4, of orally inhlaed PF-03715455 680 mcg twice daily on trough forced expiratory volume in 1 second (FEV1) in subjects with moderate to severe chronic obstructive pulmonary disease (COPD) on a stable regimen of short or long acting bronchodilators.
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Protection of trial subjects |
The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Conference on Harmonization (ICH) Good Clinical Practice (GCP) Guidelines. All the local regulatory requirements pertinent to safety of trial subjects were followed.
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Background therapy |
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Evidence for comparator |
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Actual start date of recruitment |
14 Jan 2015
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United Kingdom: 13
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Worldwide total number of subjects |
13
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EEA total number of subjects |
13
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
7
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From 65 to 84 years |
6
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85 years and over |
0
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Recruitment
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Recruitment details |
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Pre-assignment
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Screening details |
Participants were randomly assigned in a 1:1 ratio to receive either PF-03715455 680 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. | ||||||||||||||||||
Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | ||||||||||||||||||
Roles blinded |
Subject, Investigator | ||||||||||||||||||
Arms
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Are arms mutually exclusive |
No
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Arm title
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PF-03715455 680 mcg Twice Daily | ||||||||||||||||||
Arm description |
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. | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
PF-03715455
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Inhalation powder
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Routes of administration |
Inhalation use
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Dosage and administration details |
inhaled orally twice daily
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Arm title
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Placebo | ||||||||||||||||||
Arm description |
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. | ||||||||||||||||||
Arm type |
Placebo | ||||||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Inhalation powder
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Routes of administration |
Inhalation use
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Dosage and administration details |
inhaled orally twice daily
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Baseline characteristics reporting groups
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Reporting group title |
Overall Study
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
PF-03715455 680 mcg Twice Daily
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Reporting group description |
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. | ||
Reporting group title |
Placebo
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Reporting group description |
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. |
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End point title |
Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) at Week 4 [1] | ||||||||||||||||||
End point description |
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.
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End point type |
Primary
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End point timeframe |
Baseline (Day 1), Day 29 (Week 4)
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Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Statistical analyses were not planned and were not performed due to the limited number of subjects. |
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No statistical analyses for this end point |
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End point title |
Change From Baseline in Sputum Cell Counts | |||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Baseline, Day 7 (Week 1), Day 21 (Week 3), Day 29 (Week 4)
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Notes [2] - As the study was prematurely terminated, efficacy analyses were not performed. [3] - As the study was prematurely terminated, efficacy analyses were not performed. |
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No statistical analyses for this end point |
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End point title |
Change From Baseline in Trough FEV1 and Forced Vital Capacity (FVC) at Weeks 1, 3, and 4 | ||||||||||||||||||||||||||||||
End point description |
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.
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End point type |
Secondary
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End point timeframe |
Baseline, Day 7 (Week 1), Day 21 (Week 3), Day 29 (Week 4)
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No statistical analyses for this end point |
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End point title |
Maximum Observed Plasma Concentrations (Cmax) of PF-03715455 | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Day 7 (Week 1), Day 21 (Week 3), Day 29 (Week 4)
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Notes [4] - As the study was prematurely terminated, PK analysis was not conducted. [5] - As the study was prematurely terminated, PK analysis was not conducted. |
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No statistical analyses for this end point |
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End point title |
Trough Plasma Concentration (Ctrough) of PF-03715455 | ||||||||||||
End point description |
Ctrough is the concentration prior to study drug administration.
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End point type |
Secondary
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End point timeframe |
Day 7 (Week 1), Day 21 (Week 3), Day 29 (Week 4)
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Notes [6] - As the study was prematurely terminated, PK analysis was not conducted. [7] - As the study was prematurely terminated, PK analysis was not conducted. |
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No statistical analyses for this end point |
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End point title |
Change From Baseline in Trough FEV1 and Forced Vital Capacity (FVC) Over 4 Weeks | ||||||||||||||||||
End point description |
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.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 1 to Week 4
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No statistical analyses for this end point |
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End point title |
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | |||||||||||||||
End point description |
An AE was any untoward medical occurrence in a participant who received study drug. 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 49 that were absent before treatment or that worsened relative to pre-treatment state. AEs included both SAEs and non-SAEs.
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End point type |
Other pre-specified
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End point timeframe |
Baseline up to Day 29 (Week 4)
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No statistical analyses for this end point |
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End point title |
Number of Participants with Clinically Significant Treatment Emergent Electrocardiogram (ECG) Findings | |||||||||||||||||||||||||||||||||||||||
End point description |
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.
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End point type |
Other pre-specified
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End point timeframe |
Baseline up to Day 29 (Week 4)
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No statistical analyses for this end point |
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End point title |
Change From Baseline in Systolic and Diastolic Blood Pressure | ||||||||||||||||||||||||||||||||||||||||||
End point description |
Systolic blood pressure (SBP) and diastolic pressure (DBP) were evaluated in the supine position.
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End point type |
Other pre-specified
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End point timeframe |
Baseline, Day 7 (Week 1), Day 21 (Week 3), Day 29 (Week 4), Day 49 (follow-up)
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No statistical analyses for this end point |
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End point title |
Change From Baseline in Pulse Rate | |||||||||||||||||||||||||||
End point description |
Pulse rate was evaluated in the supine position.
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End point type |
Other pre-specified
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End point timeframe |
Baseline, Day 7 (Week 1), Day 21 (Week 3), Day 29 (Week 4), Day 49 (follow-up)
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No statistical analyses for this end point |
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End point title |
Number of Participants With Laboratory Abnormalities Meeting the Criteria for Potential Clinical Concern | |||||||||
End point description |
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]).
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End point type |
Other pre-specified
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End point timeframe |
Baseline up to Week 4
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No statistical analyses for this end point |
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Adverse events information
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Timeframe for reporting adverse events |
Baseline up to follow-up period (Day 49)
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Assessment type |
Non-systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
18.0
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Reporting groups
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Reporting group title |
Placebo
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Reporting group description |
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. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
PF-03715455 680 mcg Twice Daily
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Reporting group description |
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. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 0% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
As this study was prematurely terminated by the sponsor, no formal safety or efficacy conclusions can be drawn due to insufficient participant numbers. In addition, PK analysis was not conducted. |