Chronic Obstructive Pulmonary Disease
Conditions
Brief summary
The overall objective of this study was to assess the efficacy and safety of GP MDI relative to placebo in Japanese subjects with moderate to severe COPD. Each subject received the 4 separate study treatments, scheduled as four, 7-day, treatment periods for a total treatment duration of 28 days.
Detailed description
This was a randomized, double-blind, chronic-dosing (7-day), four-period, four-treatment, placebo-controlled, crossover, multi-center study to assess the efficacy and safety of 3 doses of GP MDI (28.8, 14.4, and 7.2 μg ex-actuator, BID) in Japanese subjects with moderate to severe COPD. Subjects who met the entry criteria had their maintenance therapy for COPD adjusted, as specified in the protocol. To allow for an adequate washout of previous maintenance medications, subjects underwent a washout period of at least 7 days, but not greater than 28 days duration prior to returning to the clinic for Visit 2 (Randomization Visit; Day 1 of Treatment Period 1). The 4 study treatments were GP MDI 28.8, 14.4, and 7.2 μg ex-actuator, and Placebo MDI BID. Subjects were randomly assigned to 1 of the following 4 treatment sequences (ABCD, BDAC, CADB, DCBA) in a 1:1:1:1 ratio using an Interactive Web Response System where each letter represented 1 of the 4 treatments included in the study by random assignment. Subjects were to complete 7 days of dosing in each of the 4 Treatment Periods, with each Treatment Period separated by a washout period of 5 to 21 days.
Interventions
DRUGGlycopyrronium MDI 28.8 micrograms
Glycopyrronium MDI 28.8 micrograms
DRUGGlycopyrronium MDI 14.4 micrograms
Glycopyrronium MDI 14.4 micrograms
DRUGGlycopyrronium MDI 7.2 micrograms
Glycopyrronium MDI 7.2 micrograms
DRUGPlacebo MDI
Placebo Inhalation Aerosol
Sponsors
Pearl Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
randomized, double-blind, chronic-dosing (7-day), four-period, four-treatment, placebo-controlled, crossover, multi-center
Eligibility
Sex/Gender
ALL
Age
40 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Clinical history of COPD with a moderate to severe classification * Current and former smokers with a history of at least 10 pack-years of cigarette smoking. -Post-bronchodilator FEV1 must be ≥30% and \<80% predicted normal value-
Exclusion criteria
* Pregnancy * Primary asthma diagnosis; Poorly controlled COPD defined as acute worsening of COPD that required treatment with corticosteroids or antibiotics in the 6-week interval prior to Screening or between Screening and Visit 2; * Clinically significant abnormal ECG * Other active pulmonary disease such as active tuberculosis, lung cancer, bronchiectasis, sarcoidosis, lung fibrosis, primary pulmonary hypertension, interstitial lung disease, and uncontrolled sleep apnea; Cancer that was not in complete remission for at least 5 years; * Diagnosis of angle closure glaucoma * A documented myocardial infarction within 1 year of Screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Morning Pre-dose Trough FEV1 | Baseline, Day 8 | Change from Baseline in Morning Pre-dose Trough FEV1 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| FEV1 AUC0-2 | Day 1 and Day 8 | Change from Baseline in FEV1 AUC0-2 normalized for length of follow-up. FEV1 was measured at 15 min, 30 min, 1 hour, and 2 hours post dose. |
| Peak Change in FEV1 | Day 1 and Day 8 | Peak Change from Baseline in FEV1 |
| FVC AUC0-2 | Baseline, Day 8 | Change from Baseline in FVC AUC0-2 on Day 8 normalized for length of follow-up. FVC was measured at 15 min, 30 min, 1 hour, and 2 hours post dose. |
Countries
Japan
Participant flow
Recruitment details
Conducted at 20 sites in Japan from January-September 2015. Entire period of study participation per subject was a maximum of 19 weeks. Planned target enrollment of 60 subjects.
Pre-assignment details
This was a chronic dosing (7 days), 4-period, 4-treatment, placebo-controlled, crossover study. Each subject was randomized to 1 of 4 sequences. Each sequence included the four treatment groups. By-treatment sequence tabulations of the data were not pre-specified.
Participants by arm
| Arm | Count |
|---|---|
| All Subjects All Subjects in the MITT Population | 62 |
| Total | 62 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Physician Decision | 1 |
| Overall Study | Protocol Violation | 1 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | All Subjects |
|---|---|
| Age, Continuous | 67.5 Years STANDARD_DEVIATION 7 |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 59 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 2 / 61 | 2 / 63 | 1 / 62 | 1 / 65 |
| serious Total, serious adverse events | 0 / 61 | 0 / 63 | 0 / 62 | 1 / 65 |
Outcome results
Primary
Morning Pre-dose Trough FEV1
Change from Baseline in Morning Pre-dose Trough FEV1
Time frame: Baseline, Day 8
Population: MITT Population defined as all subjects who received treatment and had post-treatment efficacy data from at least two treatment periods.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| GP MDI 28.8 µg | Morning Pre-dose Trough FEV1 | 0.101 Liters |
| GP MDI 14.4 µg | Morning Pre-dose Trough FEV1 | 0.098 Liters |
| GP MDI 7.2 µg | Morning Pre-dose Trough FEV1 | 0.077 Liters |
| Placebo MDI | Morning Pre-dose Trough FEV1 | -0.031 Liters |
Secondary
FEV1 AUC0-2
Change from Baseline in FEV1 AUC0-2 normalized for length of follow-up. FEV1 was measured at 15 min, 30 min, 1 hour, and 2 hours post dose.
Time frame: Day 1 and Day 8
Population: MITT Population defined as all subjects who received treatment and had post-treatment efficacy data from at least two treatment periods.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| GP MDI 28.8 µg | FEV1 AUC0-2 | Day 1 | 0.176 Liters |
| GP MDI 28.8 µg | FEV1 AUC0-2 | Day 8 | 0.194 Liters |
| GP MDI 14.4 µg | FEV1 AUC0-2 | Day 8 | 0.199 Liters |
| GP MDI 14.4 µg | FEV1 AUC0-2 | Day 1 | 0.140 Liters |
| GP MDI 7.2 µg | FEV1 AUC0-2 | Day 1 | 0.127 Liters |
| GP MDI 7.2 µg | FEV1 AUC0-2 | Day 8 | 0.170 Liters |
| Placebo MDI | FEV1 AUC0-2 | Day 1 | 0.043 Liters |
| Placebo MDI | FEV1 AUC0-2 | Day 8 | 0.019 Liters |
Secondary
FVC AUC0-2
Change from Baseline in FVC AUC0-2 on Day 8 normalized for length of follow-up. FVC was measured at 15 min, 30 min, 1 hour, and 2 hours post dose.
Time frame: Baseline, Day 8
Population: MITT Population defined as all subjects who received treatment and had post-treatment efficacy data from at least two treatment periods.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| GP MDI 28.8 µg | FVC AUC0-2 | 0.273 Liters |
| GP MDI 14.4 µg | FVC AUC0-2 | 0.265 Liters |
| GP MDI 7.2 µg | FVC AUC0-2 | 0.223 Liters |
| Placebo MDI | FVC AUC0-2 | 0.047 Liters |
Secondary
Peak Change in FEV1
Peak Change from Baseline in FEV1
Time frame: Day 1 and Day 8
Population: MITT Population defined as all subjects who received treatment and had post-treatment efficacy data from at least two treatment periods.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| GP MDI 28.8 µg | Peak Change in FEV1 | Day 8 | 0.260 Liters |
| GP MDI 28.8 µg | Peak Change in FEV1 | Day 1 | 0.254 Liters |
| GP MDI 14.4 µg | Peak Change in FEV1 | Day 8 | 0.265 Liters |
| GP MDI 14.4 µg | Peak Change in FEV1 | Day 1 | 0.212 Liters |
| GP MDI 7.2 µg | Peak Change in FEV1 | Day 8 | 0.238 Liters |
| GP MDI 7.2 µg | Peak Change in FEV1 | Day 1 | 0.192 Liters |
| Placebo MDI | Peak Change in FEV1 | Day 8 | 0.082 Liters |
| Placebo MDI | Peak Change in FEV1 | Day 1 | 0.104 Liters |