Asthma
Conditions
Keywords
Mild, moderate persistent, Adult
Brief summary
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
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.
Interventions
DRUGBD MDI 320 µg
Budesonide Inhalation Aerosol administered as 2 inhalations BID
DRUGBD MDI 160 µg
Budesonide Inhalation Aerosol administered as 2 inhalations BID
DRUGBD MDI 80 µg
Budesonide Inhalation Aerosol administered as 2 inhalations BID
DRUGBD MDI 40 µg
Budesonide Inhalation Aerosol administered as 2 inhalations BID
DRUGPlacebo MDI
Placebo MDI administered as 2 inhalations BID
Sponsors
Pearl Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Double Blind
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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) | Change from baseline in morning pre-dose trough Forced Expiratory Volume in 1 second (FEV1) at the end of the Treatment Period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 Morning 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 Evening Pre-dose Diary Peak Expiratory Flow Rate (PEFR) |
| Change From Baseline in Mean Number of Puffs of Rescue Ventolin HFA | Baseline to Last 7 Days of Treatment | Change from baseline in mean number of puffs of rescue Ventolin HFA |
| Change From Baseline in Asthma Control Questionnaire (ACQ-5) Score | Baseline to End of Treatment Period (Day 29 or Day 15 if Day 29 is missing) | 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 |
Countries
United States
Participant flow
Recruitment details
Conducted at 44 sites in the US from May 2015 to September 2015. Study participation maximum of 32 weeks.
Pre-assignment details
A 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
Participants by arm
| Arm | Count |
|---|---|
| All Subjects | 147 |
| Total | 147 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Lack of Efficacy | 1 |
| Overall Study | Lost to Follow-up | 4 |
| Overall Study | Physician Decision | 3 |
| Overall Study | Protocol Specified Criteria | 9 |
| Overall Study | Protocol Violation | 4 |
| Overall Study | Withdrawal by Subject | 11 |
Baseline characteristics
| Characteristic | All Subjects |
|---|---|
| Age, Continuous | 45.7 Years STANDARD_DEVIATION 11.2 |
| Sex: Female, Male Female | 102 Participants |
| Sex: Female, Male Male | 45 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 7 / 124 | 7 / 132 | 1 / 64 | 2 / 63 | 12 / 127 |
| serious Total, serious adverse events | 0 / 124 | 0 / 132 | 2 / 64 | 0 / 63 | 0 / 127 |
Outcome results
Primary
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.
Time frame: Baseline to End of Treatment Period (Day 29 or Day 15 if Day 29 is missing)
Population: Modified Intent to Treat Population (MITT)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| BD MDI 320 µg | Change From Baseline in Morning Pre-dose Trough Forced Expiratory Volume in 1 Second (FEV1) at the End of the Treatment Period | -0.002 Liters |
| BD MDI 160 µg | Change From Baseline in Morning Pre-dose Trough Forced Expiratory Volume in 1 Second (FEV1) at the End of the Treatment Period | -0.001 Liters |
| BD MDI 80 µg | Change From Baseline in Morning Pre-dose Trough Forced Expiratory Volume in 1 Second (FEV1) at the End of the Treatment Period | -0.034 Liters |
| BD MDI 40 µg | Change From Baseline in Morning Pre-dose Trough Forced Expiratory Volume in 1 Second (FEV1) at the End of the Treatment Period | -0.031 Liters |
| Placebo MDI | Change From Baseline in Morning Pre-dose Trough Forced Expiratory Volume in 1 Second (FEV1) at the End of the Treatment Period | -0.116 Liters |
Secondary
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
Time frame: Baseline to End of Treatment Period (Day 29 or Day 15 if Day 29 is missing)
Population: MITT
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| BD MDI 320 µg | Change From Baseline in Asthma Control Questionnaire (ACQ-5) Score | -0.575 Scores on a scale |
| BD MDI 160 µg | Change From Baseline in Asthma Control Questionnaire (ACQ-5) Score | -0.565 Scores on a scale |
| BD MDI 80 µg | Change From Baseline in Asthma Control Questionnaire (ACQ-5) Score | -0.515 Scores on a scale |
| BD MDI 40 µg | Change From Baseline in Asthma Control Questionnaire (ACQ-5) Score | -0.407 Scores on a scale |
| Placebo MDI | Change From Baseline in Asthma Control Questionnaire (ACQ-5) Score | -0.100 Scores on a scale |
Secondary
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)
Time frame: Baseline to Last 7 Days of Treatment Period
Population: MITT
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| BD MDI 320 µg | Change From Baseline in Mean Evening Pre-dose Diary Peak Expiratory Flow Rate (PEFR) | -7.345 Liters/min |
| BD MDI 160 µg | Change From Baseline in Mean Evening Pre-dose Diary Peak Expiratory Flow Rate (PEFR) | -11.791 Liters/min |
| BD MDI 80 µg | Change From Baseline in Mean Evening Pre-dose Diary Peak Expiratory Flow Rate (PEFR) | -14.403 Liters/min |
| BD MDI 40 µg | Change From Baseline in Mean Evening Pre-dose Diary Peak Expiratory Flow Rate (PEFR) | -1.896 Liters/min |
| Placebo MDI | Change From Baseline in Mean Evening Pre-dose Diary Peak Expiratory Flow Rate (PEFR) | -32.807 Liters/min |
Secondary
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)
Time frame: Baseline to Last 7 Days of Treatment Period
Population: MITT
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| BD MDI 320 µg | Change From Baseline in Mean Morning Pre-dose Diary Peak Expiratory Flow Rate (PEFR) | -5.802 Liters/min |
| BD MDI 160 µg | Change From Baseline in Mean Morning Pre-dose Diary Peak Expiratory Flow Rate (PEFR) | -7.461 Liters/min |
| BD MDI 80 µg | Change From Baseline in Mean Morning Pre-dose Diary Peak Expiratory Flow Rate (PEFR) | -9.992 Liters/min |
| BD MDI 40 µg | Change From Baseline in Mean Morning Pre-dose Diary Peak Expiratory Flow Rate (PEFR) | -5.653 Liters/min |
| Placebo MDI | Change From Baseline in Mean Morning Pre-dose Diary Peak Expiratory Flow Rate (PEFR) | -29.933 Liters/min |
Secondary
Change From Baseline in Mean Number of Puffs of Rescue Ventolin HFA
Change from baseline in mean number of puffs of rescue Ventolin HFA
Time frame: Baseline to Last 7 Days of Treatment
Population: MITT
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| BD MDI 320 µg | Change From Baseline in Mean Number of Puffs of Rescue Ventolin HFA | -0.140 Puffs/Day |
| BD MDI 160 µg | Change From Baseline in Mean Number of Puffs of Rescue Ventolin HFA | -0.268 Puffs/Day |
| BD MDI 80 µg | Change From Baseline in Mean Number of Puffs of Rescue Ventolin HFA | -0.312 Puffs/Day |
| BD MDI 40 µg | Change From Baseline in Mean Number of Puffs of Rescue Ventolin HFA | -0.095 Puffs/Day |
| Placebo MDI | Change From Baseline in Mean Number of Puffs of Rescue Ventolin HFA | 0.606 Puffs/Day |