Study to Assess the Efficacy and Safety of Three Doses of PT001 in Japanese Subjects With Moderate to Severe COPD

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Randomized, Double-Blind, Chronic Dosing (7-Day), Four-Period, Four-Treatment, Placebo-Controlled, Cross-Over, Multi-Center Study to Assess the Efficacy and Safety of Three Doses of PT001 in Japanese Subjects With Moderate to Severe COPD

Conditions
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Chronic Obstructive Pulmonary Disease

Intervention / Treatment
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* Drug: Glycopyrronium MDI 28.8 micrograms
* Drug: Glycopyrronium MDI 14.4 micrograms
* Drug: Glycopyrronium MDI 7.2 micrograms
* Drug: Placebo MDI


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: randomized, double-blind, chronic-dosing (7-day), four-period, four-treatment, placebo-controlled, crossover, multi-center
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: GP MDI 28.8 micrograms<br>Glycopyrronium Metered Dose Inhaler 28.8 micrograms | Drug: Glycopyrronium MDI 28.8 micrograms<br>* Glycopyrronium MDI 28.8 micrograms<br>|
| Active Comparator: GP MDI 14.4 micrograms<br>Glycopyrronium Metered Dose Inhaler 14.4 micrograms | Drug: Glycopyrronium MDI 14.4 micrograms<br>* Glycopyrronium MDI 14.4 micrograms<br>|
| Active Comparator: GP MDI 7.2 micrograms<br>Glycopyrronium Metered Dose Inhaler 7.2 micrograms | Drug: Glycopyrronium MDI 7.2 micrograms<br>* Glycopyrronium MDI 7.2 micrograms<br>|
| Placebo Comparator: Placebo MDI<br>Placebo Inhalation Aerosol | Drug: Placebo MDI<br>* Placebo Inhalation Aerosol<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Morning Pre-dose Trough FEV1 | Change from Baseline in Morning Pre-dose Trough FEV1 | Baseline, Day 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Day 1 and Day 8 | 
| Peak Change in FEV1 | Peak Change from Baseline in FEV1 | Day 1 and Day 8 | 
| 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. | Baseline, Day 8 |