An Evaluation Of PF-03715455 In Moderate To Severe Uncontrolled Asthma

A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PARALLEL GROUP STUDY TO ASSESS THE EFFICACY, SAFETY, AND TOLERABILITY OF PF-03715455 ADMINISTERED TWICE DAILY BY INHALATION FOR 12 WEEKS IN SUBJECTS WITH PERSISTENT MODERATE TO SEVERE ASTHMA WHO REMAIN UNCONTROLLED DESPITE TREATMENT WITH INHALED CORTICOSTEROIDS (ICS) AND LONG-ACTING BETA2 AGONISTS (LABA)

The study proposes to evaluate the safety and efficacy of PF-03715455 in moderate to severe asthma when added to standard of care and during staged withdrawal of background therapy.

Study Overview

• Status: Terminated
• Conditions: Asthma
• Intervention / Treatment: Drug: Placebo; Drug: PF-03715455

Detailed Description

Study terminated on 7th April 2015. The termination was due to business reasons. No safety or efficacy concerns contributed to the termination of the study

• Study Type: Interventional
• Enrollment (Actual): 51
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35209
      • Clinical Research Center of Alabama
  • Arizona
    • Phoenix, Arizona, United States, 85006
      • Pulmonary Associates, PA
  • Arkansas
    • Little Rock, Arkansas, United States, 72205-4565
      • Little Rock Allergy & Asthma Clinical Research Center
  • California
    • Fullerton, California, United States, 92835
      • California Research Medical Group, Inc
    • Los Angeles, California, United States, 90025
      • Jonathan Corren MD, Inc.
    • Los Angeles, California, United States, 90025
      • California Allergy and Asthma Medical Group, Inc.
    • Riverside, California, United States, 92506
      • Integrated Research Group, Incorporated
    • Rolling Hills Estates, California, United States, 90274
      • Peninsula Research Associates
    • San Diego, California, United States, 92108
      • Allergy Associates Medical Group
  • Colorado
    • Colorado Springs, Colorado, United States, 80907
      • Asthma and Allergy Associates, PC
    • Denver, Colorado, United States, 80230
      • Colorado Allergy and Asthma Centers, PC
  • Florida
    • Tampa, Florida, United States, 33613
      • University of South Florida - Asthma, Allergy and Immunology Clinical Research Unit
    • Winter Park, Florida, United States, 32789
      • Florida Pulmonary Research Institute, LLC
  • Maryland
    • Baltimore, Maryland, United States, 21236
      • Chesapeake Clinical Research, Inc.
  • Massachusetts
    • North Dartmouth, Massachusetts, United States, 02747
      • Northeast Medical Research Associates, Inc.
  • Minnesota
    • Minneapolis, Minnesota, United States, 55402
      • Clinical Research Institute
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
    • Saint Louis, Missouri, United States, 63141
      • Associated Specialists in Medicine, PC
    • Saint Louis, Missouri, United States, 63141
      • The Clinical Research Center, L.L.C.
  • Nebraska
    • Bellevue, Nebraska, United States, 68123
      • The Asthma and Allergy Center
  • New York
    • New Hyde Park, New York, United States, 11040
      • North Shore Long Island Jewish Health System
  • North Carolina
    • Charlotte, North Carolina, United States, 28277
      • American Health Research
    • Winston-Salem, North Carolina, United States, 27103
      • Wake Forest University School of Medicine
  • Ohio
    • Cincinnati, Ohio, United States, 45231
      • Bernstein Clinical Research Center
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Asthma Institute
  • South Carolina
    • Greenville, South Carolina, United States, 29615
      • Upstate Pharmaceutical Research
  • Texas
    • Killeen, Texas, United States, 76542
      • The Allergy & Asthma Clinic of Central Texas
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin School of Medicine & Public Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects with a physician documented history or diagnosis of persistent asthma (according to GINA, 2014 definition of asthma),
• Pre bronchodilator FEV1 of greater than or equal to 50 and less that 80% of predicted.
• Subjects defined as GINA Step 4 on a stable dose of either fluticasone/salmeterol combination therapy, or budesonide/formoterol combination therapy or mometasone/formoterol combination therapy.
• Subjects who are defined as uncontrolled as evidenced by; Juniper Asthma Control Questionnaire (5 item version, ACQ) score greater than or equal to 1.5 and less than or equal to 3.0)

Exclusion Criteria:

• Subjects diagnosed with chronic pulmonary disease (COPD) and/or other chronic pulmonary diseases (eg, Occupational asthma, pulmonary fibrosis, bronchiectasis, Allergic bronchopulmonary aspergillosis (ABPA), pneumoconiosis, sarcoidosis, tuberculosis).
• Subjects who are current smokers.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Matched blinded placebo	Drug: Placebo; 680 micrograms BID, Orally inhaled placebo for 12 weeks
Experimental: PF-03715455	Drug: PF-03715455; 680 micrograms BID, Orally inhaled PF-03715455 for 12 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Asthma Worsening Events	Asthma worsening was defined as one of the following events: greater than or equal to (>=) 30% reduction from baseline in morning peak expiratory flow (PEF) on 2 consecutive days; >=6 additional rescue puffs of albuterol or levalbuterol in a 24-hour period (compared to baseline) on 2 consecutive days; deterioration of asthma (as determined by the Investigator) requiring systemic steroid treatment, an increase in inhaled corticosteroids >=4 times the last dose received prior to discontinuation from the study, or hospitalization due to asthma.	Baseline up to follow-up period (Week 16)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Asthma Worsening Event	The time post randomization that the first asthma worsening event occurred (defined above).	Baseline up to follow-up period (Week 16)
Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1)	FEV1 is the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration. Baseline was defined as the latest measurement before first dosing.	Baseline, Week 1, Week 2, Week 3, and Week 4
Change From Baseline in Forced Vital Capacity (FVC)	FVC is the volume of air which can be forcibly exhaled from the lungs after taking the deepest breath possible.	Baseline, Week 1, Week 2, Week 3, and Week 4
Change From Baseline in Forced Expiratory Volume in 6 Seconds (FEV6)	FEV6 is the maximal volume of air exhaled in the first 6 seconds of a forced expiration from a position of full inspiration.	Baseline, Week 1, Week 2, Week 3, and Week 4
Change From Baseline in Asthma Symptom Scores	Participants used a daily diary assessment to record overall asthma symptom scores twice a day (morning and evening). Questions included extent of albuterol use, symptoms of wheezing, breathlessness, chest tightness, and cough. The visit dependent asthma symptom scores were calculated based on the item in the daily diary assessment. A participant summarized her/his daily frequency of asthma symptoms during the last 24 hours by the assignment of an integer score (0,1,2,3 or 4). The score=0 value denoted the day without symptoms and the score=4 value denoted the day where symptoms occurred all of the time. The asthma symptom scores were calculated by averaging the values of the daily scores within visit-dependent time window. Higher score indicates asthma worsening	Baseline, Week 1, Week 2, Week 3, and Week 4
Number of Night Time Awakenings Per Week	The number of nocturnal awakenings due to asthma symptoms was recorded by the participant.	Baseline, Week 1, Week 2, Week 3, and Week 4
Change From Baseline in Morning and Evening Peak Expiratory Flow (PEF)	The PEF is a participant's maximum speed of expiration, as measured with a peak flow meter. The changes from baseline (CFB) at each week and over 4 weeks were analyzed.	Baseline, Week 1, Week 2, Week 3, and Week 4
Change From Baseline in Asthma Control Questionnaire (ACQ)-5 Score at Week 1, Week 2, Week 3, and Week 4	The 5-question version of the Juniper ACQ is a validated questionnaire to evaluate asthma control. Questions were weighted equally and scored from 0 (totally controlled) to 6 (severely uncontrolled). The mean ACQ score was the mean of the responses. Mean scores of <= 0.75 indicate well-controlled asthma, scores between 0.76 and less than (<) 1.5 indicate partly controlled asthma, and a score >= 1.5 indicates uncontrolled asthma.	Baseline, Week 1, Week 2, Week 3, and Week 4
Number of Daily Puffs of Rescue Medication	The use of rescue bronchodilators (albuterol or levalbuterol) for symptomatic relief of asthma in a 24-hour period was recorded by the participant.	Baseline, Week 1, Week 2, Week 3, and 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 (Actual): November 1, 2014
• Primary Completion (Actual): May 1, 2015
• Study Completion (Actual): May 1, 2015

Study Registration Dates

• First Submitted: August 14, 2014
• First Submitted That Met QC Criteria: August 14, 2014
• First Posted (Estimate): August 18, 2014

Study Record Updates

• Last Update Posted (Actual): June 12, 2019
• Last Update Submitted That Met QC Criteria: May 23, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Keywords: Asthma; Staged withdrawal of background therapy
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma
• Other Study ID Numbers: A9111007; INHALED P38I ASTHMA (Other Identifier: Alias Study Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.