Study to Assess the Efficacy and Safety of Budesonide (PT008) in Adult Subjects With Mild to Moderate Persistent Asthma

Study Overview
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Brief Summary
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Study to assess the efficacy and safety of four doses of budesonide inhalation aerosol (BD MDI, PT008) relative to placebo MDI in adult subjects with mild to moderate persistent asthma.

Detailed Description
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This is a randomized, double-blind, chronic dosing (4 weeks), four-period, five-treatment, incomplete block, cross-over, multicenter study to assess the efficacy and safety of four doses of budesonide inhalation aerosol (BD MDI, PT008) relative to placebo MDI in adult subjects with mild to moderate persistent asthma.

Official Title
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Randomized, Double-Blind, Chronic Dosing (4 Weeks), Four-Period, Five-Treatment, Incomplete Block, Cross-Over, Multi-Center Study to Assess the Efficacy and Safety of Four Doses of Budesonide Inhalation Aerosol (BD MDI, PT008) Relative to Placebo MDI in Adult Subjects With Mild to Moderate Persistent Asthma

Conditions
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Asthma

Intervention / Treatment
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* Drug: BD MDI 320 µg
* Drug: BD MDI 160 µg
* Drug: BD MDI 80 µg
* Drug: BD MDI 40 µg
* Drug: Placebo MDI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥ 18 - 65 years of age Diagnosis of mild to moderate persistent asthma, diagnosed at least 6 months prior to screening Currently receiving treatment with a low to medium dose of an inhaled corticosteroid (ICS) OR a combination of controller medications for at least 4 weeks preceding screening Pre-albuterol FEV1 of > 60% and < 85% of predicted normal value Reversibility: Increase in FEV1 of ≥ 12% and ≥ 200 mL over the pre-albuterol FEV1 within 30 - 60 minutes after the inhalation of 4 puffs of Ventolin hydrofluoroalkane (HFA) Asthma Symptom Criteria: Have required albuterol use on at least two of the last seven days and have an Asthma Control Questionnaire (ACQ) total score ≥ 1.5 prior to Randomization Exclusion Criteria: Life-Threatening Asthma: A subject must not have life-threatening asthma defined as a history of significant asthma episode(s) requiring intubation associated with hypercapnia, respiratory arrest, hypoxic seizures, or asthma-related syncopal episode(s) within the 12 months prior to screening Worsening of Asthma: A subject must not have experienced a worsening of asthma which involved an emergency department visit, hospitalization or use of oral/parenteral corticosteroids within 6 weeks of screening Intermittent, Seasonal, or Exercise-Induced Asthma Alone: Subjects with only intermittent, seasonal or exercise-induced asthma are excluded from participation in this study Concurrent Respiratory Disease Pregnant women or nursing mothers A current diagnosis of Chronic Obstructive Pulmonary Disease (COPD Current smokers or subjects with a > 10 pack year history of cigarettes, cigars, or pipe smoking Respiratory tract infection within 6 weeks prior to Visit 1 Subjects with documented myocardial infarction within a year from screening visit Clinically significant abnormal ECG Abnormal liver function tests defined as aspartate aminotransferase (AST), alanine aminotransferace (ALT), alkaline phosphatase or total bilirubin ≥ 1.5 times upper limit of normal on repeat testing Subjects who have cancer that has not been in complete remission for at least 5 years Drug Allergy: Subjects who have a history of hypersensitivity to any component of the metered-dose inhaler (MDI)

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: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BD MDI 320 µg<br>Budesonide metered dose inhaler (BD MDI) 320 µg (PT008) administered as 2 inhalations BID | Drug: BD MDI 320 µg<br>* Budesonide Inhalation Aerosol administered as 2 inhalations BID<br>* Other names: PT008;|
| Experimental: BD MDI 160 µg<br>BD MDI 160 µg (PT008) administered as 2 inhalations BID | Drug: BD MDI 160 µg<br>* Budesonide Inhalation Aerosol administered as 2 inhalations BID<br>* Other names: PT008;|
| Experimental: BD MDI 80 µg<br>BD MDI 80 µg (PT008) administered as 2 inhalations BID | Drug: BD MDI 80 µg<br>* Budesonide Inhalation Aerosol administered as 2 inhalations BID<br>* Other names: PT008;|
| Experimental: BD MDI 40 µg<br>BD MDI 40 µg (PT008) administered as 2 inhalations BID | Drug: BD MDI 40 µg<br>* Budesonide Inhalation Aerosol administered as 2 inhalations BID<br>* Other names: PT008;|
| Placebo Comparator: Placebo MDI<br>Placebo MDI administered as 2 inhalations BID | Drug: Placebo MDI<br>* Placebo MDI administered as 2 inhalations BID<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Morning Pre-dose Trough Forced Expiratory Volume in 1 Second (FEV1) at the End of the Treatment Period | Change from baseline in morning pre-dose trough Forced Expiratory Volume in 1 second (FEV1) at the end of the Treatment Period. | Baseline to End of Treatment Period (Day 29 or Day 15 if Day 29 is missing) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Mean Morning Pre-dose Diary Peak Expiratory Flow Rate (PEFR) | Change From Baseline in Mean Morning Pre-dose Diary Peak Expiratory Flow Rate (PEFR) | Baseline to Last 7 Days of Treatment Period | 
| Change From Baseline in Mean Evening Pre-dose Diary Peak Expiratory Flow Rate (PEFR) | Change From Baseline in Mean Evening Pre-dose Diary Peak Expiratory Flow Rate (PEFR) | Baseline to Last 7 Days of Treatment Period | 
| Change From Baseline in Mean Number of Puffs of Rescue Ventolin HFA | Change from baseline in mean number of puffs of rescue Ventolin HFA | Baseline to Last 7 Days of Treatment | 
| Change From Baseline in Asthma Control Questionnaire (ACQ-5) Score | The ACQ-5 measures 5 symptoms (woken at night by symptoms, wake in the morning with symptoms, limitation of daily activities, shortness of breath, and wheeze). The scale is 0-6, where 0=minimum and 6=maximum | Baseline to End of Treatment Period (Day 29 or Day 15 if Day 29 is missing) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mild, moderate persistent, Adult