Asthma
Conditions
Brief summary
Study Comparing the Efficacy and Safety of PT001 to Placebo and Open-label Spiriva® Respimat® in Subjects With Persistent Asthma
Detailed description
A Randomized, Double-Blind, Parallel Group, Multi-Center 24-Week Study Comparing the Efficacy and Safety of Three Doses of PT001 to Placebo and Open-label Spiriva® Respimat® in Subjects With Persistent Asthma
Interventions
DRUGGP MDI 28.8 μg
GP MDI (PT001)14.4 μg per actuation taken as 2 inhalations BID
DRUGGP MDI 14.4 μg
GP MDI (PT001) 7.2 μg per actuation taken as 2 inhalations BID
DRUGGP MDI 7.2 μg
GP MDI (PT001) 3.6 μg per actuation taken as 2 inhalations BID
DRUGPlacebo MDI
Placebo taken as 2 inhalations BID
DRUGSpiriva Respimat 2.5 μg
Spiriva Respimat 2.5 μg QD (open-label)
Sponsors
Pearl Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Double Blind vs Placebo, Open Label Spiriva Respimat
Intervention model description
Linear repeated measures model
Eligibility
Sex/Gender
ALL
Age
12 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Have a documented history of physician-diagnosed asthma * Require inhaled asthma maintenance therapy: has been regularly using an ICS/LABA on a stable regimen for at least 4 weeks * Documented reversibility to albuterol * A pre-bronchodilator FEV1 \>40% and \<85% of predicted normal value for subjects 18 to 80 years of age or \>40% and \<90% of predicted for subjects 12 to \<18 years of age * Demonstrate acceptable spirometry performance * Willing and, in the opinion of the Investigator, able to adjust current asthma therapy, as required by the protocol * Compliance: must be willing to remain at the study center as required per protocol to complete all visit assessments
Exclusion criteria
* Oral corticosteroid use (any dose) within 4 weeks * Current smokers, former smokers with \>10 pack-years history, or former smokers who stopped smoking \<6 months (including all forms of tobacco, e-cigarettes, and marijuana) * Life-threatening asthma as defined as a history of significant asthma episode(s) requiring intubation associated with hypercapnia, respiratory arrest, hypoxic seizures, or asthma-related syncopal episode(s) * Completed treatment for lower respiratory infection or asthma exacerbation within 4 weeks * Hospitalizations for asthma within 3 months * Historical or current evidence of a clinically significant disease * Cancer not in complete remission for at least 5 years * Treatment with investigational study drug (or device) in another clinical study within the last 30 days or 5 half-lives, whichever is longer * Previously randomized in any PT001 study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve From 0 to 4 Hours (AUC0-4) | Week 24 | Change from baseline in forced expiratory volume in 1 second (FEV1) area under the curve from 0 to 4 hours (AUC0-4)AUC was normalized for length of follow up (e.g. typically 4 hours). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Morning Pre-dose Trough FEV1 | Week 24 | — |
| Rate of Moderate to Severe Asthma Exacerbations | over 24 Weeks (timepoints of 4, 12 & 20 weeks) | Rate of moderate to severe Asthma exacerbations (A deterioration of asthma requiring a new or increased dose of ICS for at least 3 days) or severe Asthma exacerbation (Use of systemic corticosteroids (tablets, suspension, or injection) for at least 3 days OR a hospitalization or ER visit because of asthma) |
| Change From Baseline in ACQ-7 (Asthma Control Questionnaire) | Week 24 | ACQ-7: The ACQ, comprising 7 questions, is completed in the clinic and requires subjects to recall their experiences during the previous week (7 days) prior to the study visit. 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 ACQ-6 is these symptom measurements plus daily rescue medication use as recalled by the subject; and the ACQ 7 is the ACQ 6 plus airway caliber as measured by pre-bronchodilator FEV1 percent predicted. Each question is scored on a 7-point scale (generally, 0=no impairment, 6=maximum impairment), the questions are equally weighted, and the ACQ score is the mean of the item responses and therefore ranges from 0 (totally controlled) to 6 (severely uncontrolled. |
| Change From Baseline in ACQ-5 (Asthma Control Questionnaire) | Week 24 | ACQ-5: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). Each question is scored on a 7-point scale (generally, 0=no impairment, 6=maximum impairment), the questions are equally weighted, and the ACQ score is the mean of the item responses and therefore ranges from 0 (totally controlled) to 6 (severely uncontrolled). |
| Change From Baseline in Asthma Quality of Life Questionnaire for 12 Years and Older (AQLQ +12) | Week 24 | AQLQ +12 - Asthma Quality of Life Questionnaire The AQLQ +12 is a 32-item validated subject-administered questionnaire that was developed to measure the functional problems (physical, emotional, social and occupational) that are most troublesome to adults (≥18 years of age) and adolescents (12 to 17 years of age) with asthma. The 32 questions in the AQLQ +12 are in 4 domains (symptoms, activity limitation, emotional function, and environmental stimuli). All 4 domains contain standard specific questions relating to each domain. Subjects are asked to think about how they have been during the previous 2 weeks. Responses to each of the 32 questions are on a 7-point scale (7=no impairment to 1=severe impairment). The overall AQLQ +12 score is the mean of all 32 responses. Overall scores range from 1=severe impairment to 7=no impairment. |
Countries
United States
Participant flow
Recruitment details
The study randomized subjects at 194 sites in the United States from December 2017 to September 2019. The entire study period was scheduled to take up to approximately 26 weeks for each individual subject from the time of screening through the follow up period.
Pre-assignment details
Subjects were randomized in a 2:2:2:2:1 Scheme to follow 1 of the 5 treatment groups.
Participants by arm
| Arm | Count |
|---|---|
| GP MDI 28.8 μg Glycopyrronium Metered Dose Inhalation 28.8 μg | 235 |
| GP MDI 14.4 μg Glycopyrronium Metered Dose Inhalation 14.4 μg | 240 |
| GP MDI 7.2 μg Glycopyrronium Metered Dose Inhalation 7.2μg | 240 |
| Placebo MDI Placebo Metered Dose Inhalation | 237 |
| Spiriva Respimat 2.5 μg Spiriva Respimat 2.5 μg | 119 |
| Total | 1,071 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Administrative reasons | 0 | 1 | 0 | 3 | 0 |
| Overall Study | Adverse Event | 3 | 9 | 7 | 5 | 2 |
| Overall Study | Lack of Efficacy | 0 | 1 | 1 | 0 | 0 |
| Overall Study | Lost to Follow-up | 4 | 3 | 7 | 6 | 4 |
| Overall Study | Major Protocol Deviation | 11 | 3 | 2 | 3 | 1 |
| Overall Study | Physician Decision | 1 | 0 | 1 | 6 | 1 |
| Overall Study | Protocol specified criteria | 2 | 3 | 0 | 3 | 1 |
| Overall Study | Withdrawal by Subject | 13 | 19 | 16 | 10 | 5 |
Baseline characteristics
| Characteristic | Placebo MDI | GP MDI 28.8 μg | GP MDI 14.4 μg | GP MDI 7.2 μg | Spiriva Respimat 2.5 μg | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 47.1 Years STANDARD_DEVIATION 16.2 | 48.4 Years STANDARD_DEVIATION 15.1 | 47.7 Years STANDARD_DEVIATION 16.8 | 46.7 Years STANDARD_DEVIATION 15.5 | 49.8 Years STANDARD_DEVIATION 15.3 | 47.7 Years STANDARD_DEVIATION 15.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 51 Participants | 36 Participants | 61 Participants | 52 Participants | 21 Participants | 221 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 186 Participants | 198 Participants | 179 Participants | 186 Participants | 98 Participants | 847 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 2 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 1 Participants | 3 Participants | 1 Participants | 5 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 6 Participants | 1 Participants | 6 Participants | 0 Participants | 15 Participants |
| Race (NIH/OMB) Black or African American | 52 Participants | 62 Participants | 68 Participants | 52 Participants | 25 Participants | 259 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants | 1 Participants | 2 Participants | 2 Participants | 0 Participants | 9 Participants |
| Race (NIH/OMB) White | 179 Participants | 165 Participants | 168 Participants | 177 Participants | 93 Participants | 782 Participants |
| Sex: Female, Male Female | 134 Participants | 146 Participants | 153 Participants | 151 Participants | 76 Participants | 660 Participants |
| Sex: Female, Male Male | 103 Participants | 89 Participants | 87 Participants | 89 Participants | 43 Participants | 411 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 | 0 / 235 | 0 / 240 | 0 / 240 | 0 / 237 | 0 / 119 |
| other Total, other adverse events | 33 / 235 | 35 / 240 | 33 / 240 | 29 / 237 | 14 / 119 |
| serious Total, serious adverse events | 9 / 235 | 7 / 240 | 6 / 240 | 7 / 237 | 2 / 119 |
Outcome results
Primary
Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve From 0 to 4 Hours (AUC0-4)
Change from baseline in forced expiratory volume in 1 second (FEV1) area under the curve from 0 to 4 hours (AUC0-4)AUC was normalized for length of follow up (e.g. typically 4 hours).
Time frame: Week 24
Population: mITT Population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| GP MDI 28.8 μg | Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve From 0 to 4 Hours (AUC0-4) | 0.294 Liter |
| GP MDI 14.4 μg | Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve From 0 to 4 Hours (AUC0-4) | 0.284 Liter |
| GP MDI 7.2 μg | Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve From 0 to 4 Hours (AUC0-4) | 0.308 Liter |
| Placebo MDI | Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve From 0 to 4 Hours (AUC0-4) | 0.240 Liter |
| Spiriva Respimat 2.5 μg | Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve From 0 to 4 Hours (AUC0-4) | 0.347 Liter |
Secondary
Change From Baseline in ACQ-5 (Asthma Control Questionnaire)
ACQ-5: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). Each question is scored on a 7-point scale (generally, 0=no impairment, 6=maximum impairment), the questions are equally weighted, and the ACQ score is the mean of the item responses and therefore ranges from 0 (totally controlled) to 6 (severely uncontrolled).
Time frame: Week 24
Population: mITT Population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| GP MDI 28.8 μg | Change From Baseline in ACQ-5 (Asthma Control Questionnaire) | -0.87 Scores on a scale |
| GP MDI 14.4 μg | Change From Baseline in ACQ-5 (Asthma Control Questionnaire) | -0.80 Scores on a scale |
| GP MDI 7.2 μg | Change From Baseline in ACQ-5 (Asthma Control Questionnaire) | -1.02 Scores on a scale |
| Placebo MDI | Change From Baseline in ACQ-5 (Asthma Control Questionnaire) | -0.93 Scores on a scale |
| Spiriva Respimat 2.5 μg | Change From Baseline in ACQ-5 (Asthma Control Questionnaire) | -1.03 Scores on a scale |
Secondary
Change From Baseline in ACQ-7 (Asthma Control Questionnaire)
ACQ-7: The ACQ, comprising 7 questions, is completed in the clinic and requires subjects to recall their experiences during the previous week (7 days) prior to the study visit. 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 ACQ-6 is these symptom measurements plus daily rescue medication use as recalled by the subject; and the ACQ 7 is the ACQ 6 plus airway caliber as measured by pre-bronchodilator FEV1 percent predicted. Each question is scored on a 7-point scale (generally, 0=no impairment, 6=maximum impairment), the questions are equally weighted, and the ACQ score is the mean of the item responses and therefore ranges from 0 (totally controlled) to 6 (severely uncontrolled.
Time frame: Week 24
Population: mITT Population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| GP MDI 28.8 μg | Change From Baseline in ACQ-7 (Asthma Control Questionnaire) | -0.78 Scores on a scale |
| GP MDI 14.4 μg | Change From Baseline in ACQ-7 (Asthma Control Questionnaire) | -0.73 Scores on a scale |
| GP MDI 7.2 μg | Change From Baseline in ACQ-7 (Asthma Control Questionnaire) | -0.90 Scores on a scale |
| Placebo MDI | Change From Baseline in ACQ-7 (Asthma Control Questionnaire) | -0.80 Scores on a scale |
| Spiriva Respimat 2.5 μg | Change From Baseline in ACQ-7 (Asthma Control Questionnaire) | -0.90 Scores on a scale |
Secondary
Change From Baseline in Asthma Quality of Life Questionnaire for 12 Years and Older (AQLQ +12)
AQLQ +12 - Asthma Quality of Life Questionnaire The AQLQ +12 is a 32-item validated subject-administered questionnaire that was developed to measure the functional problems (physical, emotional, social and occupational) that are most troublesome to adults (≥18 years of age) and adolescents (12 to 17 years of age) with asthma. The 32 questions in the AQLQ +12 are in 4 domains (symptoms, activity limitation, emotional function, and environmental stimuli). All 4 domains contain standard specific questions relating to each domain. Subjects are asked to think about how they have been during the previous 2 weeks. Responses to each of the 32 questions are on a 7-point scale (7=no impairment to 1=severe impairment). The overall AQLQ +12 score is the mean of all 32 responses. Overall scores range from 1=severe impairment to 7=no impairment.
Time frame: Week 24
Population: mITT Population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| GP MDI 28.8 μg | Change From Baseline in Asthma Quality of Life Questionnaire for 12 Years and Older (AQLQ +12) | 0.89 Scores on a scale |
| GP MDI 14.4 μg | Change From Baseline in Asthma Quality of Life Questionnaire for 12 Years and Older (AQLQ +12) | 0.90 Scores on a scale |
| GP MDI 7.2 μg | Change From Baseline in Asthma Quality of Life Questionnaire for 12 Years and Older (AQLQ +12) | 1.02 Scores on a scale |
| Placebo MDI | Change From Baseline in Asthma Quality of Life Questionnaire for 12 Years and Older (AQLQ +12) | 0.96 Scores on a scale |
| Spiriva Respimat 2.5 μg | Change From Baseline in Asthma Quality of Life Questionnaire for 12 Years and Older (AQLQ +12) | 1.04 Scores on a scale |
Secondary
Change From Baseline in Morning Pre-dose Trough FEV1
Time frame: Week 24
Population: mITT Population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| GP MDI 28.8 μg | Change From Baseline in Morning Pre-dose Trough FEV1 | 0.142 Liter |
| GP MDI 14.4 μg | Change From Baseline in Morning Pre-dose Trough FEV1 | 0.108 Liter |
| GP MDI 7.2 μg | Change From Baseline in Morning Pre-dose Trough FEV1 | 0.142 Liter |
| Placebo MDI | Change From Baseline in Morning Pre-dose Trough FEV1 | 0.129 Liter |
| Spiriva Respimat 2.5 μg | Change From Baseline in Morning Pre-dose Trough FEV1 | 0.150 Liter |
Secondary
Rate of Moderate to Severe Asthma Exacerbations
Rate of moderate to severe Asthma exacerbations (A deterioration of asthma requiring a new or increased dose of ICS for at least 3 days) or severe Asthma exacerbation (Use of systemic corticosteroids (tablets, suspension, or injection) for at least 3 days OR a hospitalization or ER visit because of asthma)
Time frame: over 24 Weeks (timepoints of 4, 12 & 20 weeks)
Population: mITT Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GP MDI 28.8 μg | Rate of Moderate to Severe Asthma Exacerbations | 0.43 Events per year | Standard Error 0.078 |
| GP MDI 14.4 μg | Rate of Moderate to Severe Asthma Exacerbations | 0.44 Events per year | Standard Error 0.08 |
| GP MDI 7.2 μg | Rate of Moderate to Severe Asthma Exacerbations | 0.41 Events per year | Standard Error 0.076 |
| Placebo MDI | Rate of Moderate to Severe Asthma Exacerbations | 0.55 Events per year | Standard Error 0.092 |
| Spiriva Respimat 2.5 μg | Rate of Moderate to Severe Asthma Exacerbations | 0.50 Events per year | Standard Error 0.123 |