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

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)

This study proposes to evaluate the safety and efficacy of PF-03715455 in subjects with moderate to severe Chronic Obstructive Pulmonary Disorder.

Study Overview

• Status: Terminated
• Conditions: Pulmonary Disease, Chronic Obstructive
• Intervention / Treatment: Drug: Placebo; Drug: PF-03715455

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 2

Contacts and Locations

Study Locations

• United Kingdom
  • Birmingham, United Kingdom, B9 5SS
    • Heart of England Nhs Foundation Trust
  • Birmingham, United Kingdom, B15 2WB
    • University Hospitals Birmingham NHS Foundation Trust
  • Bradford, United Kingdom, BD9 6RJ
    • Respiratory Medicine, Bradford Institute of Health Research
  • Manchester
    • Wythenshawe, Manchester, United Kingdom, M23 9QZ
      • Medicines Evaluation Unit Ltd
  • Nottinghamshire
    • Nottingham, Nottinghamshire, United Kingdom, NG5 1PB
      • Nottingham University Hospital NHS Trust

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Female subjects of non-childbearing potential and male subjects between the ages of 40 and 80 years, inclusive
• Subjects with a diagnosis, for at least 6 months, of moderate to severe COPD and who meet the criteria for Stage II-III disease
• Subjects must have a smoking history of at least 10 pack-years

Exclusion Criteria:

• Current evidence or history within the previous 6 months of any clinically significant disease (other than COPD) or abnormality in the opinion of the Investigator that would put the subject at risk or which would compromise the quality of the study data
• A COPD exacerbation requiring treatment with oral steroids or hospitalization for the treatment of COPD within 3 months of Screening

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Double blind placebo for PF-03715455	Drug: Placebo; Orally inhaled placebo twice a day (BID) for 4 weeks
Experimental: PF-03715455	Drug: PF-03715455; 680 micrograms BID, Orally inhaled PF-03715455 for 4 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) at Week 4	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.	Baseline (Day 1), Day 29 (Week 4)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Sputum Cell Counts Over 4 Weeks	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.	Baseline, Week 1 to Week 4
Change From Baseline in Trough FEV1 and Forced Vital Capacity (FVC) at Weeks 1, 3, and 4	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.	Baseline, Day 7 (Week 1), Day 21 (Week 3), Day 29 (Week 4)
Change From Baseline in Trough FEV1 and Forced Vital Capacity (FVC) Over 4 Weeks	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.	Baseline, Week 1 to Week 4
Maximum Observed Plasma Concentrations (Cmax) of PF-03715455		Pre-dose on Day 7 and Day 21; post-dose on Day 7 (10 minutes and 1 hour post-dose) and Day 29
Trough Plasma Concentration (Ctrough) of PF-03715455	Ctrough is the concentration prior to study drug administration.	Pre-dose on Day 7 and Day 21; post-dose on Day 7 (10 minutes and 1 hour post-dose) and Day 29

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)	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.	Baseline up to Day 29 (Week 4)
Number of Participants With Clinically Significant Treatment Emergent Electrocardiogram (ECG) Findings	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.	Baseline up to Day 29 (Week 4)
Change From Baseline in Systolic and Diastolic Blood Pressure	Systolic blood pressure (SBP) and diastolic pressure (DBP) were evaluated in the supine position.	Baseline, Day 7 (Week 1), Day 21 (Week 3), Day 29 (Week 4), Day 49 (follow-up)
Change From Baseline in Pulse Rate	Pulse rate was evaluated in the supine position.	Baseline, Day 7 (Week 1), Day 21 (Week 3), Day 29 (Week 4), Day 49 (follow-up)
Number of Participants With Laboratory Abnormalities	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]).	Baseline up to Week 4

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start: January 1, 2015
• Primary Completion (Actual): May 1, 2015
• Study Completion (Actual): May 1, 2015

Study Registration Dates

• First Submitted: September 2, 2014
• First Submitted That Met QC Criteria: February 11, 2015
• First Posted (Estimate): February 19, 2015

Study Record Updates

• Last Update Posted (Estimate): July 6, 2016
• Last Update Submitted That Met QC Criteria: May 24, 2016
• Last Verified: May 1, 2016

More Information

Terms related to this study

• Keywords: COPD; Sputum
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: A9111004; INHALED p38i COPD; 2014-002340-40 (EudraCT Number)