COPD
Conditions
Brief summary
Randomized, Phase IIIb, Three-period, Three-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, Open-Label Spiriva® Respimat® (Tiotropium Bromide) as an Active Control, and Placebo.
Interventions
DRUGGFF MDI (PT003)
DRUGPlacebo MDI
DRUGSpiriva® Respimat® (Tiotropium Bromide)
Tiotropium Bromide Inhalation Solution; Spiriva® Respimat® (Spiriva)
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 |
|---|---|---|
| Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC) 0-24 | Pre dose, 15 and 30 minutes, 1, 2, 4, 8, 12, 12.25, 12.5, 13, 14, 16, 22, and 24 hours post the morning dose on Day 29 | Normalized Forced Expiratory Volume in 1 second (FEV1) Area Under the Curve (AUC) 0-24 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Peak Change From Baseline in FEV1 Morning | Baseline and Day 29 | Peak Change From Baseline in FEV1 Morning |
| FEV1 AUC12-24 | Pre dose, 15 and 30 minutes, 1, 2, 4, 8, and 12 hours post the evening dose on Day 29 | Normalized FEV1 AUC12-24 |
| FEV1 AUC0-12 | Pre dose, 15 and 30 minutes, 1, 2, 4, 8, and 12 hours post the morning dose on Day 29 | Normalized FEV1 AUC0-12 |
| Morning Pre-Dose Trough FEV1 on Day 29 | Day 29 | Morning Pre-Dose Trough FEV1 on Day 29 |
| Morning Pre-Dose Trough FEV1 on Day 30 | Day 30 | Morning Pre-Dose Trough FEV1 on Day 30 |
| Peak Change From Baseline in IC (Inspiratory Capacity) Evening | Baseline and Day 29 | Peak Change From Baseline in IC Evening |
| Peak Change From Baseline in IC Morning | Baseline and Day 29 | Peak Change From Baseline in IC Morning |
| Peak Change From Baseline in FEV1 Evening | Baseline and Day 29 | Peak Change From Baseline in FEV1 Evening |
Participant flow
Recruitment details
This study was conducted at 10 sites in the US from February 2015 to August 2015. The study was anticipated to run for approximately 9 months but not expected to exceed 12 months.
Pre-assignment details
Study to assess the efficacy and safety of GFF MDI 14.4/9.6µg relative to either Placebo MDI or Spiriva Respimat 5µg. Subjects were randomized into 1 of 6 treatment sequences, and all treatment sequences included all 3 treatments. By-treatment sequence tabulations of the data were not pre-specified.
Participants by arm
| Arm | Count |
|---|---|
| All Subjects | 75 |
| Total | 75 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
| Overall Study | Disc due to Protocol-specified Criteria | 6 |
| Overall Study | Lost to Follow-up | 2 |
| Overall Study | Physician Decision | 1 |
| Overall Study | Protocol Violation | 1 |
| Overall Study | Withdrawal by Subject | 6 |
Baseline characteristics
| Characteristic | All Subjects |
|---|---|
| Age, Continuous | 61.8 Years STANDARD_DEVIATION 9.1 |
| Sex: Female, Male Female | 48 Participants |
| Sex: Female, Male Male | 27 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 5 / 75 | 5 / 73 | 6 / 72 |
| serious Total, serious adverse events | 2 / 75 | 2 / 73 | 2 / 72 |
Outcome results
Primary
Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC) 0-24
Normalized Forced Expiratory Volume in 1 second (FEV1) Area Under the Curve (AUC) 0-24
Time frame: Pre dose, 15 and 30 minutes, 1, 2, 4, 8, 12, 12.25, 12.5, 13, 14, 16, 22, and 24 hours post the morning dose on Day 29
Population: Subjects in the Modified Intent to Treat (MITT) Population who had a sufficient number of post dose FEV1 measurements
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| GFF MDI | Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC) 0-24 | 0.192 Liters |
| Spiriva Respimat | Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC) 0-24 | 0.112 Liters |
| Placebo | Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC) 0-24 | -0.072 Liters |
Secondary
FEV1 AUC0-12
Normalized FEV1 AUC0-12
Time frame: Pre dose, 15 and 30 minutes, 1, 2, 4, 8, and 12 hours post the morning dose on Day 29
Population: Subjects in the MITT Population who had a sufficient number of post dose FEV1 measurements
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| GFF MDI | FEV1 AUC0-12 | 0.226 Liters |
| Spiriva Respimat | FEV1 AUC0-12 | 0.178 Liters |
| Placebo | FEV1 AUC0-12 | -0.026 Liters |
Secondary
FEV1 AUC12-24
Normalized FEV1 AUC12-24
Time frame: Pre dose, 15 and 30 minutes, 1, 2, 4, 8, and 12 hours post the evening dose on Day 29
Population: Subjects in the MITT Population who had a sufficient number of post dose FEV1 measurements
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| GFF MDI | FEV1 AUC12-24 | 0.159 Liters |
| Spiriva Respimat | FEV1 AUC12-24 | 0.039 Liters |
| Placebo | FEV1 AUC12-24 | -0.118 Liters |
Secondary
Morning Pre-Dose Trough FEV1 on Day 29
Morning Pre-Dose Trough FEV1 on Day 29
Time frame: Day 29
Population: Subjects in the MITT Population who had a sufficient number of post dose FEV1 measurements
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| GFF MDI | Morning Pre-Dose Trough FEV1 on Day 29 | 0.140 Liters |
| Spiriva Respimat | Morning Pre-Dose Trough FEV1 on Day 29 | 0.097 Liters |
| Placebo | Morning Pre-Dose Trough FEV1 on Day 29 | -0.020 Liters |
Secondary
Morning Pre-Dose Trough FEV1 on Day 30
Morning Pre-Dose Trough FEV1 on Day 30
Time frame: Day 30
Population: Subjects in the MITT Population who had a sufficient number of post dose FEV1 measurements
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| GFF MDI | Morning Pre-Dose Trough FEV1 on Day 30 | 0.129 Liters |
| Spiriva Respimat | Morning Pre-Dose Trough FEV1 on Day 30 | 0.072 Liters |
| Placebo | Morning Pre-Dose Trough FEV1 on Day 30 | -0.073 Liters |
Secondary
Peak Change From Baseline in FEV1 Evening
Peak Change From Baseline in FEV1 Evening
Time frame: Baseline and Day 29
Population: MITT Population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| GFF MDI | Peak Change From Baseline in FEV1 Evening | 0.395 Liters |
| Spiriva Respimat | Peak Change From Baseline in FEV1 Evening | 0.230 Liters |
| Placebo | Peak Change From Baseline in FEV1 Evening | 0.058 Liters |
Secondary
Peak Change From Baseline in FEV1 Morning
Peak Change From Baseline in FEV1 Morning
Time frame: Baseline and Day 29
Population: Subjects in the MITT Population who had a sufficient number of post dose FEV1 measurements
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| GFF MDI | Peak Change From Baseline in FEV1 Morning | 0.406 Liters |
| Spiriva Respimat | Peak Change From Baseline in FEV1 Morning | 0.325 Liters |
| Placebo | Peak Change From Baseline in FEV1 Morning | 0.129 Liters |
Secondary
Peak Change From Baseline in IC (Inspiratory Capacity) Evening
Peak Change From Baseline in IC Evening
Time frame: Baseline and Day 29
Population: Subjects in the MITT Population who had a sufficient number of post dose FEV1 measurements
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| GFF MDI | Peak Change From Baseline in IC (Inspiratory Capacity) Evening | 0.421 Liters |
| Spiriva Respimat | Peak Change From Baseline in IC (Inspiratory Capacity) Evening | 0.297 Liters |
| Placebo | Peak Change From Baseline in IC (Inspiratory Capacity) Evening | 0.109 Liters |
Secondary
Peak Change From Baseline in IC Morning
Peak Change From Baseline in IC Morning
Time frame: Baseline and Day 29
Population: Subjects in the MITT Population who had a sufficient number of post dose FEV1 measurements
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| GFF MDI | Peak Change From Baseline in IC Morning | 0.454 Liters |
| Spiriva Respimat | Peak Change From Baseline in IC Morning | 0.374 Liters |
| Placebo | Peak Change From Baseline in IC Morning | 0.206 Liters |