PT001 MDI Versus Atrovent Study in Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD)

A Randomized, Double-Blind, Chronic Dosing (7 Days), Three-Period, Six-Treatment, Placebo-Controlled, Incomplete Block, Cross-Over, Multi-Center Study to Assess Efficacy and Safety of Four Doses of PT001 in Patients With Moderate to Severe COPD, Compared With Atrovent® HFA Inhalation Aerosol (Open-Label) as An Active Control

The overall objective of this study is to determine an optimal dose and dosing regimen of PT001 MDI for further evaluation in later stage studies.

Study Overview

• Status: Completed
• Conditions: Chronic Obstructive Pulmonary Disease
• Intervention / Treatment: Drug: PT001 MDI; Drug: Ipratropium Bromide HFA Inhalation Aerosol; Other: Placebo MDI

Detailed Description

The primary objective of this study is to demonstrate efficacy relative to placebo of PT001 MDI in patients with moderate to severe chronic obstructive pulmonary disease (COPD) within the range of doses evaluated in this protocol. To this end, each dose of PT001 MDI will be compared to placebo with respect to the primary efficacy endpoint, FEV1 AUC0-12 relative to baseline.

• Study Type: Interventional
• Enrollment (Actual): 103
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Florida
    • Panama City, Florida, United States
      • Pearl Investigative Site
    • Winter Park, Florida, United States
      • Pearl Investigative Site
  • New Jersey
    • Cherry Hill, New Jersey, United States
      • Pearl Investigative Site
    • Summit, New Jersey, United States
      • Pearl Investigative Site
  • North Carolina
    • Charlotte, North Carolina, United States
      • Pearl Investigative Site
  • Oregon
    • Medford, Oregon, United States
      • Pearl Investigative Site
  • Texas
    • Longview, Texas, United States
      • Pearl Investigative Site
  • Virginia
    • Richmond, Virginia, United States
      • Pearl Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 38 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

• Signed written informed consent
• 40 - 80 years of age
• Clinical history of COPD with airflow limitation that is not fully reversible
• Females of non-child bearing potential or females of child bearing potential with negative pregnancy test; and acceptable contraceptive methods
• Current/former smokers with at least a 10 pack-year history of cigarette smoking
• A measured post- bronchodilator FEV1/FVC ratio of < or = 0.70
• A measured post- bronchodilator FEV1 > or = 750ml or 30% predicted and < or = 80% of predicted normal values
• Able to change COPD treatment as required by protocol

Key Exclusion Criteria:

• Women who are pregnant or lactating
• Primary diagnosis of asthma
• Alpha-1 antitrypsin deficiency as the cause of COPD
• Active pulmonary diseases
• Prior lung volume reduction surgery
• Abnormal chest X-ray (or CT scan) not due to the presence of COPD
• Hospitalized due to poorly controlled COPD within 3 months of Screening
• Clinically significant medical conditions that preclude participation in the study (e.g. clinically significant abnormal ECG, uncontrolled hypertension, glaucoma, symptomatic prostatic hypertrophy)
• Cancer that has not been in complete remission for at least 5 years
• Treatment with investigational study drug or participation in another clinical trial or study within the last 30 days or 5 half lives

Other inclusion/exclusion criteria as defined in the protocol

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PT001 MDI (Dose 1); PT001 MDI	Drug: PT001 MDI; PT001 MDI administered as two puffs BID for 7 days
Experimental: PT001 MDI (Dose 2); PT001 MDI	Drug: PT001 MDI; PT001 MDI administered as two puffs BID for 7 days
Experimental: PT001 MDI (Dose 3); PT001 MDI	Drug: PT001 MDI; PT001 MDI administered as two puffs BID for 7 days
Experimental: PT001 MDI (Dose 4); PT001 MDI	Drug: PT001 MDI; PT001 MDI administered as two puffs BID for 7 days
Active Comparator: Ipratropium Bromide HFA Inhalation Aerosol	Drug: Ipratropium Bromide HFA Inhalation Aerosol; Taken as 2 inhalations of the 17 µg per actuation strength MDI QID; Other Names: Atrovent
Placebo Comparator: Placebo MDI; PT001 Placebo MDI	Other: Placebo MDI; Matching placebo to PT001 MDI administered as two puffs BID for 7 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
FEV1 AUC0-12	FEV1 AUC0-12 following chronic dosing (1 week), normalized.	Day 7 ( -1 hour, -30 min, 15 min, 30 min, 1 hour, 2 hours, 4 hours, 5.5 hours, 6.5 hours, 8 hours, 10 hours, 11.5 hours, and 12 hours)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak Change From Baseline in FEV1 on Day 1	Highest value of FEV1 post-dose minus baseline on Day 1 (baseline-adjusted)	Day 1
Time to Onset of Action ( ≥10% Improvement in FEV1) on Day 1	Time to onset of action ( ≥10% improvement in FEV1)	Day 1 (15 min, 30 min, 1 hour, 2 hours)
Proportion of Subjects Achieving at Least 12% Improvement in FEV1 on Day 1	Proportion of subjects achieving at least 12% improvement in FEV1 (relative to baseline)	Day 1
Peak Change From Baseline in IC on Day 1	Peak change from baseline in Inspiratory Capacity (IC) on Day 1 (mean of 1 and 2 hours post-dose minus baseline on Day 1)	Day 1
Change From Baseline in Morning Pre-dose FEV1 on Day 7	Change from baseline in morning pre-dose FEV1	Day 7
Peak Change From Baseline in FEV1 on Day 7	Peak change from baseline in FEV1	Day 7
Peak Change From Baseline in IC on Day 7	Peak change from baseline in IC	Day 7
Change From Baseline in 12-hour Post-dose Trough FEV1 on Day 7	Change from baseline in 12-hour post-dose trough FEV1	Day 7

Collaborators and Investigators

• Sponsor: Pearl Therapeutics, Inc.
• Investigators: Study Director: Colin Reisner, M.D., Pearl Therapeutics, Inc.

Publications and helpful links

General Publications

• Kerwin EM, Spangenthal S, Kollar C, St Rose E, Reisner C. A phase IIb randomized, chronic-dosing, incomplete block, cross-over study of glycopyrronium, delivered via metered dose inhaler, compared with a placebo and an active control in patients with moderate-to-severe COPD. Respir Res. 2018 Mar 5;19(1):38. doi: 10.1186/s12931-018-0739-6.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2011
• Primary Completion (Actual): October 1, 2011
• Study Completion (Actual): October 1, 2011

Study Registration Dates

• First Submitted: May 5, 2011
• First Submitted That Met QC Criteria: May 6, 2011
• First Posted (Estimate): May 9, 2011

Study Record Updates

• Last Update Posted (Actual): June 20, 2018
• Last Update Submitted That Met QC Criteria: May 23, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Keywords: COPD
• 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; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Antagonists; Cholinergic Agents; Anticonvulsants; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Bromides; Ipratropium
• Other Study ID Numbers: PT001002