PT001 MDI Versus Spiriva® in Patients With Moderate to Severe COPD

A Randomized, Double Blind (Test Products and Placebo), Chronic Dosing (14 Days), Four Period, Eight Treatment, Placebo-Controlled, Incomplete Block, Cross Over, Multi Center Study to Assess Efficacy and Safety of Six Doses of PT001 in Patients With Moderate to Severe COPD, Compared With Spiriva® Handihaler® (Tiotropium Bromide, 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: PT001 Placebo MDI; Drug: Tiotropium Bromide

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 140
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Fullerton, California, United States, 92835
      • Pearl Investigative Site
  • Florida
    • Clearwater, Florida, United States, 33765
      • Pearl Investigative Site
    • Panama City, Florida, United States, 32405
      • Pearl Investigative Site
    • Tampa, Florida, United States, 33603
      • Pearl Investigative Site
    • Winter Park, Florida, United States, 32789
      • Pearl Investigative Site
  • North Carolina
    • Charlotte, North Carolina, United States, 28207
      • Pearl Investigative Site
  • Oregon
    • Medford, Oregon, United States, 97504
      • Pearl Investigative Site
  • South Carolina
    • Spartanburg, South Carolina, United States, 29303
      • Pearl Investigative Site
  • Texas
    • Longview, Texas, United States, 75605
      • Pearl Investigative Site
  • Virginia
    • Richmond, Virginia, United States, 23225
      • 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:

• 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

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

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PT001 MDI (Dose 1)	Drug: PT001 MDI; Administered as two puffs BID for 14 days
Experimental: PT001 MDI (Dose 2)	Drug: PT001 MDI; Administered as two puffs BID for 14 days
Experimental: PT001 MDI (Dose 3)	Drug: PT001 MDI; Administered as two puffs BID for 14 days
Experimental: PT001 MDI (Dose 4)	Drug: PT001 MDI; Administered as two puffs BID for 14 days
Experimental: PT001 MDI (Dose 5)	Drug: PT001 MDI; Administered as two puffs BID for 14 days
Experimental: PT001 MDI (Dose 6)	Drug: PT001 MDI; Administered as two puffs BID for 14 days
Placebo Comparator: PT001 Placebo MDI	Drug: PT001 Placebo MDI
Active Comparator: Spiriva® Handihaler® (Tiotropium Bromide)	Drug: Tiotropium Bromide; Taken as 1 capsule containing 18 µg of tiotropium via the Handihaler DPI; Other Names: Spiriva® Handihaler®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
FEV1 AUC0-12	Forced expiratory volume in 1 second (FEV1) normalized area under the curve 0-12 hours (AUC0-12) following chronic dosing for 14 days.	Day 14 (-1 hr, -30 min, 15 min, 30 min, 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 10 hr, 11.5 hr, 12 hr)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak Change From Baseline in FEV1	Highest value of FEV1 post dose on day 1	Day 1
Time to Onset of Action (>10% Improvement in FEV1) on Day 1	Time to Onset of Action (>10% Improvement in FEV1) on Day 1.	Day 1 (15 min, 30 min, 1 hr, 2 hrs, no onset within 2 hrs)
Percentage of Subjects Achieving at Least 12% Improvement in FEV1	Percentage of subjects achieving at least 12% improvement in FEV1.	Day 1
Peak Change From Baseline in Inspiratory Capacity (IC)	Peak change in Inspiratory Capacity (IC) mean of 1 and 2 hour post-dose assessments minus the baseline	Day 1 (1 hr and 2 hr post-dose )
Change From Baseline in Morning Pre-dose Trough FEV1	Change from baseline in morning pre-dose trough FEV1 (average of the 60 and 30-minute pre-dose values on Treatment Day 7 minus the baseline)	Day 7 (average of the 60 and 30-minute pre-dose values on Treatment Day 7 minus the baseline)
Peak Change From Baseline in FEV1	Peak change from baseline in FEV1 (defined as the change at the highest value of FEV1 post-dose minus the baseline)	Day 7
Change From Baseline in Morning Pre-dose Trough Inspiratory Capacity (IC)	Change from baseline in morning pre-dose trough IC (average of the 60 and 30-minute pre-dose assessments minus the baseline)	Day 7
Peak Change From Baseline in IC	Peak change from baseline in IC (mean of 1 hr and 2 hr post-dose assessments)	Day 7 (mean of 1 hr and 2 hr post-dose assessments)
Change From Baseline in Mean Morning Pre-dose Daily PEFR	Change from baseline in mean morning pre-dose daily PEFR (peak expiratory flow rate) taken by subjects and recorded in subject diaries, up through Diary Day 7 of each treatment period (excluding reading taken pre-dose on Visit 2 [Treatment Day 1])	Day 7 (60 minutes pre-dose, 30 minutes pre-dose)
Change From Baseline in Morning Post-dose Daily PEFR	Change from baseline in morning post-dose daily PEFR (peak expiratory flow rate) taken by subjects and recorded in subject diaries, up through Diary Day 7 of each treatment period (excluding reading taken pre-dose on Visit 2 [Treatment Day 1])	Day 7 (30 minutes post-dose)
Change From Baseline in Mean Evening Pre-dose PEFR	Change from baseline in mean evening pre-dose daily peak flow readings taken by subjects and recorded in subject diaries, up through Diary Day 7 of each treatment period (subjects taking Spiriva performed a single evening assessment)	Day 7
Change From Baseline in Mean Evening Post-dose PEFR	Change from baseline in mean evening post-dose daily peak flow readings taken by subjects and recorded in subject diaries, up through Diary Day 7 of each treatment period (subjects taking Spiriva performed a single evening assessment)	Day 7
Mean Number of Puffs of Rescue Medication	Mean number of puffs of rescue medication recorded in subject diaries during each treatment period and by treatment and numbers of days treated	Day 7
Change From Baseline in Morning Pre-dose Trough FEV1	Change from baseline in morning pre-dose trough FEV1 (average of the 60 and 30-minute pre-dose values on Treatment Day 14 minus the baseline)	Day 14 (average of the 60 and 30-minute pre-dose values on Treatment Day 14 minus the baseline)
Peak Change From Baseline in FEV1	Peak change from baseline in FEV1 (defined as the change at the highest value of FEV1 post-dose minus the baseline)	Day 14
Change From Baseline for Mean Morning Pre-dose Trough IC	Change from baseline for mean morning pre-dose trough IC (average of the 60 and 30-minute pre-dose assessments minus the baseline)	Day 14 (average of the 60 and 30-minute pre-dose assessments minus the baseline)
Peak Change From Baseline in IC	Peak change from baseline in IC (mean of 1 and 2 hour post-dose assessments minus the baseline)	Day 14 (mean of 1 and 2 hour post-dose assessments minus the baseline)
Change From Baseline in 12-hour Post-dose Trough FEV1	12-hour post-dose trough FEV1 was defined as the mean of the FEV1 assessments taken at 11.5 and 12 hours post-dose minus the baseline	Day 14 (Baseline, 11.5 and 12 hours post dose)
Change From Baseline in Mean Morning Pre-dose Daily PEFR	Change from baseline in mean morning pre-dose daily peak flow readings taken by subjects and recorded in subject diaries during each treatment period for subjects with more than 7 days of diary data (mean reading excluded reading taken pre-dose on Visit 2 [Treatment 1 Day 1]	Baseline, Treatment Day 1 and every day, to the end of the 14-Day Treatment period before dosing, values were averaged for the end of treatment value (all subjects with diary data after Diary day 7)
Change From Baseline in Mean Morning Post-dose Daily PEFR	Change from baseline in mean morning post-dose daily peak flow readings taken by subjects and recorded in subject diaries during each treatment period for subjects with more than 7 days of diary data (mean reading excluded reading taken pre-dose on Visit 2 [Treatment 1 Day 1]	Baseline, Treatment Day 1 and every day, to the end of the 14-Day Treatment period 30 minutes post dosing, values were averaged for the end of treatment value (all subjects with diary data after Diary day 7)
Change From Baseline in Mean Evening Pre-dose Daily PEFR	Change from baseline in mean evening pre-dose daily peak flow readings taken by subjects and recorded in subject diaries during each treatment period for subjects with more than 7 days of diary data (subjects taking Spiriva performed a single evening assessment)	Treatment Day 1 to the end of the 14-Day Treatment, values were averaged for the end of treatment value (all subjects with diary data after Diary day 7)
Change From Baseline in Mean Evening Post-dose Daily PEFR	Change from baseline in mean evening post-dose daily peak flow readings taken by subjects and recorded in subject diaries during each treatment period for subjects with more than 7 days of diary data (subjects taking Spiriva performed a single evening assessment)	Through the end of the 14-Day Treatment
Mean Number of Puffs of Rescue Medication (End of Treatment)	Mean number of puffs of rescue medication recorded in subject diaries during each treatment period and by treatment and numbers of days treated	Day 14 (End of treatment)
Change From Baseline in Morning Pre-dose Trough FEV1 (mL) Averaging Treatment Day 7 and Day 14	Change from Baseline in Morning Pre-dose Trough FEV1 (mL) Averaging Treatment Day 7 and Day 14	Day 1 through Day 14

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Fabbri LM, Kerwin EM, Spangenthal S, Ferguson GT, Rodriguez-Roisin R, Pearle J, Sethi S, Orevillo C, Darken P, St Rose E, Fischer T, Golden M, Dwivedi S, Reisner C. Dose-response to inhaled glycopyrrolate delivered with a novel Co-Suspension Delivery Technology metered dose inhaler (MDI) in patients with moderate-to-severe COPD. Respir Res. 2016 Sep 2;17(1):109. doi: 10.1186/s12931-016-0426-4.

Helpful Links

• protocol-pt001003_FINAL_Redacted

Study record dates

Study Major Dates

• Study Start: March 1, 2012
• Primary Completion (Actual): August 1, 2012
• Study Completion (Actual): August 1, 2012

Study Registration Dates

• First Submitted: March 27, 2012
• First Submitted That Met QC Criteria: March 27, 2012
• First Posted (Estimate): March 29, 2012

Study Record Updates

• Last Update Posted (Actual): October 12, 2017
• Last Update Submitted That Met QC Criteria: October 10, 2017
• Last Verified: October 1, 2017

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; Parasympatholytics; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Antagonists; Cholinergic Agents; Anticonvulsants; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Tiotropium Bromide; Bromides
• Other Study ID Numbers: PT001003