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

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

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.

Study Overview

• Status: Completed
• Conditions: Chronic Obstructive Pulmonary Disease
• Intervention / Treatment: Drug: Glycopyrronium MDI 28.8 micrograms; Drug: Glycopyrronium MDI 14.4 micrograms; Drug: Glycopyrronium MDI 7.2 micrograms; Drug: Placebo MDI

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.

• Study Type: Interventional
• Enrollment (Actual): 66
• Phase: Phase 2

Contacts and Locations

Study Locations

• Japan
  • Fukuoka-Ken
    • Fukuoka-shi, Fukuoka-Ken, Japan
      • Pearl Investigative Site
    • Iizuka-shi, Fukuoka-Ken, Japan
      • Pearl Investigative Site
  • Gifu-Ken
    • Mizunami-shi, Gifu-Ken, Japan
      • Pearl Investigative Site
  • Hokkaido
    • Sapporo-shi, Hokkaido, Japan
      • Pearl Investigative Site
  • Hyogo
    • Himeji-shi, Hyogo, Japan
      • Pearl Investigative Site
  • Hyogo-Ken
    • Ako-shi, Hyogo-Ken, Japan
      • Pearl Investigative Site
    • Kakogawa-shi, Hyogo-Ken, Japan
      • Pearl Investigative Site
    • Kobe-Shi, Hyogo-Ken, Japan
      • Pearl Investigative Site
    • Nishinomiya-shi, Hyogo-Ken, Japan
      • Pearl Investigative Site
  • Ibaraki-Ken
    • Naka-gun, Ibaraki-Ken, Japan
      • Pearl Investigative Site
  • Kanagawa-Ken
    • Kawasaki-shi, Kanagawa-Ken, Japan
      • Pearl Investigative Site
  • Kyoto-Fu
    • Kyoto-shi, Kyoto-Fu, Japan
      • Pearl Investigative Site
  • Okayama-Ken
    • Kasaoka-shi, Okayama-Ken, Japan
      • Pearl Investigative Site
  • Osaka-Fu
    • Kishiwada-shi, Osaka-Fu, Japan
      • Pearl Investigative Site
    • Osaka-shi, Osaka-Fu, Japan
      • Pearl Investigative Site
  • Shizuoka-Ken
    • Hamamatsu-shi, Shizuoka-Ken, Japan
      • Pearl Investigative Site
  • Tokyo-To
    • Chuo-ku, Tokyo-To, Japan
      • Pearl Investigative Site
    • Toshima-ku, Tokyo-To, Japan
      • Pearl Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: GP MDI 28.8 micrograms; Glycopyrronium Metered Dose Inhaler 28.8 micrograms	Drug: Glycopyrronium MDI 28.8 micrograms; Glycopyrronium MDI 28.8 micrograms
Active Comparator: GP MDI 14.4 micrograms; Glycopyrronium Metered Dose Inhaler 14.4 micrograms	Drug: Glycopyrronium MDI 14.4 micrograms; Glycopyrronium MDI 14.4 micrograms
Active Comparator: GP MDI 7.2 micrograms; Glycopyrronium Metered Dose Inhaler 7.2 micrograms	Drug: Glycopyrronium MDI 7.2 micrograms; Glycopyrronium MDI 7.2 micrograms
Placebo Comparator: Placebo MDI; Placebo Inhalation Aerosol	Drug: Placebo MDI; Placebo Inhalation Aerosol

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Pearl Therapeutics, Inc.

Publications and helpful links

General Publications

• Fukushima Y, Nakatani Y, Ide Y, Sekino H, St Rose E, Siddiqui S, Maes A, Reisner C. Randomized, double-blind, placebo-controlled trial to assess the efficacy and safety of three doses of co-suspension delivery technology glycopyrronium MDI in Japanese patients with moderate-to-severe COPD. Int J Chron Obstruct Pulmon Dis. 2018 Apr 13;13:1187-1194. doi: 10.2147/COPD.S159246. eCollection 2018.

Study record dates

Study Major Dates

• Study Start (Actual): January 28, 2015
• Primary Completion (Actual): September 5, 2015
• Study Completion (Actual): September 5, 2015

Study Registration Dates

• First Submitted: August 17, 2017
• First Submitted That Met QC Criteria: August 17, 2017
• First Posted (Actual): August 22, 2017

Study Record Updates

• Last Update Posted (Actual): January 23, 2018
• Last Update Submitted That Met QC Criteria: December 22, 2017
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Adjuvants, Anesthesia; Glycopyrrolate
• Other Study ID Numbers: PT001004

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes