COPD
Conditions
Brief summary
Randomized, Phase IIIb, Two-period, Two-treatment Double-blind, Multi-center, Crossover Study to Evaluate the 24-hour Lung Function Profile in Subjects with Moderate to Very Severe COPD after 4 Weeks of Treatment with PT003 and Placebo MDI
Interventions
DRUGGFF MDI (PT003)
DRUGPlacebo MDI
Sponsors
Pearl Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* At least 40 years of age and no older than 80 at Screening * Women of non-child bearing potential or negative serum pregnancy test at Screening, and agrees to acceptable contraceptive methods used consistently and correctly Screening until 14 days after final visit * Subjects with an established clinical history of COPD as defined by the American Thoracic Society (ATS)/European Respiratory Society (ERS) * Current or former smokers with a history of at least 10 pack-years of cigarette smoking * Pre- and post-bronchodilator FEV1/FVC ratio of \<0.70 * Post-bronchodilator FEV1 must be \<80% predicted normal value, calculated using NHANES III reference equations, and the measured FEV1 must also be ≥750 mL if FEV1 \<30% of predicted normal value
Exclusion criteria
* Significant diseases other than COPD, i.e., disease or condition which, in the opinion of the Investigator, may put the subject at risk because of participation in the study or may influence either the results of the study or the subject's ability to participate in the study * Women who are pregnant or lactating * Subjects, who in the opinion of the Investigator, have a current diagnosis of asthma * Subjects who have been hospitalized due to poorly controlled COPD within 3 months prior to Screening or during the Screening Period * Subjects who have poorly controlled COPD, defined as acute worsening of COPD that requires treatment with oral corticosteroids or antibiotics within 6 weeks prior to Screening or during the Screening Period * Subjects who have clinically significant uncontrolled hypertension. * Subjects who have cancer that has not been in complete remission for at least five years * Subjects with abnormal liver function tests defined as AST, ALT, or total bilirubin ≥1.5 times upper limit of normal at Screening and on repeat testing * Subjects with a diagnosis of angle closure glaucoma will be excluded, regardless of whether or not they have been treated. Subjects with a diagnosis of open angle glaucoma who have intraocular pressure controlled with medication(s) are eligible * Subjects with symptomatic prostatic hypertrophy that is clinically significant in the opinion of the Investigator. Subjects with a trans-urethral resection of prostate (TURP) or full resection of the prostate within 6 months prior to Screening are excluded from the study * Subjects with bladder neck obstruction or urinary retention that is clinically significant in the opinion of the Investigator
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| FEV1 AUC0-24 on Day 29 | Day 29 | Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC)0-24 on Day 29 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| FEV1 AUC0-12 on Day 29 | Day 29 | FEV1 AUC0-12 on Day 29 |
| Peak Change From Baseline in FEV1 on Day 29 | Day 29 | Peak Change From Baseline in FEV1 following evening Dose on Day 29 |
| Morning Pre-Dose Trough FEV1 on Day 29 | Day 29 | Morning Pre-Dose Trough FEV on Day 29 |
| FEV1 AUC12-24 on Day 29 | Day 29 | FEV1 AUC12-24 on Day 29 |
| Peak Change From Baseline in Inspiratory Capacity (IC) Following the Evening Dose on Day 29 | Day 29 | Peak Change from Baseline in Inspiratory Capacity (IC) following the evening dose on Day 29 |
| Peak Change From Baseline in IC Following the Morning Dose on Day 29 | Day 29 | Peak Change from Baseline in IC following the morning dose on Day 29 |
| Morning Pre-Dose Trough FEV1 on Day 30 | Day 30 | Morning Pre-Dose Trough FEV1 on Day 30 |
Participant flow
Recruitment details
This study was conducted at 5 sites in the US from March 2015 to Jun 2015. The study was anticipated to run for approximately 6 months but not to expected to exceed 9 months.The study period was 11 to 17 weeks for each subject.
Pre-assignment details
Complete crossover study to assess the efficacy and safety of GFF MDI vs. Placebo MDI. Each subject received 28 days of study treatment in each assigned treatment, with a minimum 7 day washout period between each of the 2 periods. By-treatment sequence tabulations of the data were not pre-specified.
Participants by arm
| Arm | Count |
|---|---|
| All Subjects | 35 |
| Total | 35 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
| Overall Study | Lack of Efficacy | 1 |
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Protocol Criteria | 2 |
| Overall Study | Withdrawal by Subject | 4 |
Baseline characteristics
| Characteristic | All Subjects |
|---|---|
| Age, Continuous | 61.3 Years STANDARD_DEVIATION 9.2 |
| Sex: Female, Male Female | 15 Participants |
| Sex: Female, Male Male | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 1 / 40 | 6 / 40 |
| serious Total, serious adverse events | 1 / 40 | 1 / 40 |
Outcome results
Primary
FEV1 AUC0-24 on Day 29
Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC)0-24 on Day 29
Time frame: Day 29
Population: Modified-Intent-to-Treat (MITT) Population
| Arm | Measure | Value (MEAN) |
|---|---|---|
| GFF MD (PT003) | FEV1 AUC0-24 on Day 29 | 0.166 Liters |
| Placebo | FEV1 AUC0-24 on Day 29 | -0.083 Liters |
Secondary
FEV1 AUC0-12 on Day 29
FEV1 AUC0-12 on Day 29
Time frame: Day 29
Population: MITT Population
| Arm | Measure | Value (MEAN) |
|---|---|---|
| GFF MD (PT003) | FEV1 AUC0-12 on Day 29 | 0.216 Liters |
| Placebo | FEV1 AUC0-12 on Day 29 | -0.039 Liters |
Secondary
FEV1 AUC12-24 on Day 29
FEV1 AUC12-24 on Day 29
Time frame: Day 29
Population: MITT Population
| Arm | Measure | Value (MEAN) |
|---|---|---|
| GFF MD (PT003) | FEV1 AUC12-24 on Day 29 | 0.115 Liters |
| Placebo | FEV1 AUC12-24 on Day 29 | -0.127 Liters |
Secondary
Morning Pre-Dose Trough FEV1 on Day 29
Morning Pre-Dose Trough FEV on Day 29
Time frame: Day 29
Population: MITT Population
| Arm | Measure | Value (MEAN) |
|---|---|---|
| GFF MD (PT003) | Morning Pre-Dose Trough FEV1 on Day 29 | 0.130 Liters |
| Placebo | Morning Pre-Dose Trough FEV1 on Day 29 | -0.012 Liters |
Secondary
Morning Pre-Dose Trough FEV1 on Day 30
Morning Pre-Dose Trough FEV1 on Day 30
Time frame: Day 30
Population: MITT Population
| Arm | Measure | Value (MEAN) |
|---|---|---|
| GFF MD (PT003) | Morning Pre-Dose Trough FEV1 on Day 30 | 0.090 Liters |
| Placebo | Morning Pre-Dose Trough FEV1 on Day 30 | -0.064 Liters |
Secondary
Peak Change From Baseline in FEV1 on Day 29
Peak Change From Baseline in FEV1 following the morning dose on Day 29
Time frame: Day 29
Population: MITT Population
| Arm | Measure | Value (MEAN) |
|---|---|---|
| GFF MD (PT003) | Peak Change From Baseline in FEV1 on Day 29 | 0.410 Liters |
| Placebo | Peak Change From Baseline in FEV1 on Day 29 | 0.134 Liters |
Secondary
Peak Change From Baseline in FEV1 on Day 29
Peak Change From Baseline in FEV1 following evening Dose on Day 29
Time frame: Day 29
Population: MITT Population
| Arm | Measure | Value (MEAN) |
|---|---|---|
| GFF MD (PT003) | Peak Change From Baseline in FEV1 on Day 29 | 0.344 Liters |
| Placebo | Peak Change From Baseline in FEV1 on Day 29 | 0.050 Liters |
Secondary
Peak Change From Baseline in IC Following the Morning Dose on Day 29
Peak Change from Baseline in IC following the morning dose on Day 29
Time frame: Day 29
Population: MITT Population
| Arm | Measure | Value (MEAN) |
|---|---|---|
| GFF MD (PT003) | Peak Change From Baseline in IC Following the Morning Dose on Day 29 | 0.543 Liters |
| Placebo | Peak Change From Baseline in IC Following the Morning Dose on Day 29 | 0.208 Liters |
Secondary
Peak Change From Baseline in Inspiratory Capacity (IC) Following the Evening Dose on Day 29
Peak Change from Baseline in Inspiratory Capacity (IC) following the evening dose on Day 29
Time frame: Day 29
Population: MITT Population
| Arm | Measure | Value (MEAN) |
|---|---|---|
| GFF MD (PT003) | Peak Change From Baseline in Inspiratory Capacity (IC) Following the Evening Dose on Day 29 | 0.486 Liters |
| Placebo | Peak Change From Baseline in Inspiratory Capacity (IC) Following the Evening Dose on Day 29 | 0.105 Liters |