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

Phase 2

Completed

Interventions: Drug: Glycopyrronium MDI 28.8 micrograms
Drug: Glycopyrronium MDI 14.4 micrograms
Drug: Glycopyrronium MDI 7.2 micrograms
Drug: Placebo MDI

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.

Recruitment & Eligibility

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.

Arm && Interventions

Group	Intervention	Description
GP MDI 28.8 micrograms	Glycopyrronium MDI 28.8 micrograms	Glycopyrronium Metered Dose Inhaler 28.8 micrograms
GP MDI 14.4 micrograms	Glycopyrronium MDI 14.4 micrograms	Glycopyrronium Metered Dose Inhaler 14.4 micrograms
GP MDI 7.2 micrograms	Glycopyrronium MDI 7.2 micrograms	Glycopyrronium Metered Dose Inhaler 7.2 micrograms
Placebo MDI	Placebo MDI	Placebo Inhalation Aerosol

Primary Outcome Measures

Name	Time	Method
Morning Pre-dose Trough FEV1	Baseline, Day 8	Change from Baseline in Morning Pre-dose Trough FEV1

Secondary Outcome Measures

Name	Time	Method
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.
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