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

Study Overview
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Brief Summary
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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.

Detailed Description
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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

Official Title
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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)

Conditions
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Asthma

Intervention / Treatment
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* Drug: Placebo
* Drug: PF-03715455


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Asthma, Staged withdrawal of background therapy