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

• ClinicalTrials.gov Identifier: NCT02366637
• Recruitment Status: Terminated
• First Posted: February 19, 2015
• Results First Posted: July 6, 2016
• Last Update Posted: July 6, 2016
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Pulmonary Disease, Chronic Obstructive	Drug: Placebo; Drug: PF-03715455	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 13 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: 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)
• Study Start Date: January 2015
• Actual Primary Completion Date: May 2015
• Actual Study Completion Date: May 2015

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

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

Other Outcome Measures:

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

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United Kingdom

Medicines Evaluation Unit Ltd

Wythenshawe, Manchester, United Kingdom, M23 9QZ

Nottingham University Hospital NHS Trust

Nottingham, Nottinghamshire, United Kingdom, NG5 1PB

University Hospitals Birmingham NHS Foundation Trust

Birmingham, United Kingdom, B15 2WB

Heart of England NHS Foundation Trust

Birmingham, United Kingdom, B9 5SS

Respiratory Medicine, Bradford Institute of Health Research

Bradford, United Kingdom, BD9 6RJ

Sponsors and Collaborators

Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

More Information

Additional Information:

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

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT02366637
• Other Study ID Numbers: A9111004; INHALED p38i COPD; 2014-002340-40 ( EudraCT Number )
• First Posted: February 19, 2015
• Results First Posted: July 6, 2016
• Last Update Posted: July 6, 2016
• Last Verified: May 2016

Keywords provided by Pfizer:

COPD; Sputum

Additional relevant MeSH terms:

Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Respiratory Tract Diseases