24-hour Lung Function in Subjects With Moderate to Very Severe COPD After Treatment With PT003, Open-Label Spiriva® Respimat® as an Active Control, and Placebo

A Randomized, Phase IIIb, Three-period, Three-treatment, Double-blind, Multi-center, Crossover Study to Evaluate the 24-hour Lung Function Profile in Subjects With Moderate to Very Severe COPD After 4 Weeks of Treatment With PT003, Open-Label Spiriva® Respimat® (Tiotropium Bromide) as an Active Control, and Placebo

Randomized, Phase IIIb, Three-period, Three-treatment, Double-blind, Multi-center, Crossover Study to Evaluate the 24-hour Lung Function Profile in Subjects with Moderate to Very Severe COPD after 4 Weeks of Treatment with PT003, Open-Label Spiriva® Respimat® (Tiotropium Bromide) as an Active Control, and Placebo.

Study Overview

• Status: Completed
• Conditions: COPD
• Intervention / Treatment: Drug: Placebo MDI; Drug: GFF MDI (PT003); Drug: Spiriva® Respimat® (Tiotropium Bromide)

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Phase 3

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:

• At least 40 years of age and no older than 80 at Screening
• Women of non-child bearing potential or negative serum pregnancy test at Screening, and agrees to acceptable contraceptive methods used consistently and correctly Screening until 14 days after final visit.
• Subjects with an established clinical history of COPD as defined by the American Thoracic Society (ATS)/European Respiratory Society (ERS)
• Current or former smokers with a history of at least 10 pack-years of cigarette smoking
• Pre- and post-bronchodilator FEV1/FVC ratio of <0.70
• Post-bronchodilator FEV1 must be <80% predicted normal value, calculated using NHANES III reference equations, and the measured FEV1 must also be ≥750 mL if FEV1 <30% of predicted normal value.

Exclusion Criteria:

• Significant diseases other than COPD, i.e., disease or condition which, in the opinion of the Investigator, may put the subject at risk because of participation in the study or may influence either the results of the study or the subject's ability to participate in the study.
• Women who are pregnant or lactating.
• Subjects, who in the opinion of the Investigator, have a current diagnosis of asthma.
• Subjects who have been hospitalized due to poorly controlled COPD within 3 months prior to Screening or during the Screening Period.
• Subjects who have poorly controlled COPD, defined as acute worsening of COPD that requires treatment with oral corticosteroids or antibiotics within 6 weeks prior to Screening or during the Screening Period.
• Subjects who have clinically significant uncontrolled hypertension.
• Subjects who have cancer that has not been in complete remission for at least five years.
• Subjects with abnormal liver function tests defined as AST, ALT, or total bilirubin ≥1.5 times upper limit of normal at Screening and on repeat testing.
• Subjects with a diagnosis of angle closure glaucoma will be excluded, regardless of whether or not they have been treated. Subjects with a diagnosis of open angle glaucoma who have intraocular pressure controlled with medication(s) are eligible.
• Subjects with symptomatic prostatic hypertrophy that is clinically significant in the opinion of the Investigator. Subjects with a trans-urethral resection of prostate (TURP) or full resection of the prostate within 6 months prior to Screening are excluded from the study.
• Subjects with bladder neck obstruction or urinary retention that is clinically significant in the opinion of the Investigator.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: GFF MDI (PT003); Glycopyrronium and Formoterol Fumarate Inhalation Aerosol; PT003, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (GFF MDI)	Drug: GFF MDI (PT003); Other Names: Glycopyrronium and Formoterol Fumarate Inhalation Aerosol; PT003, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (GFF MDI)
Placebo Comparator: Placebo MDI; Placebo Metered Dose Inhaler (MDI) for Glycopyrronium and Formoterol Fumarate Inhalation Aerosol	Drug: Placebo MDI; Other Names: Placebo Metered Dose Inhaler (MDI) for Glycopyrronium and Formoterol Fumarate Inhalation Aerosol
Active Comparator: Spiriva® Respimat® (Tiotropium Bromide); Tiotropium Bromide Inhalation Solution; Spiriva® Respimat® (Spiriva)	Drug: Spiriva® Respimat® (Tiotropium Bromide); Tiotropium Bromide Inhalation Solution; Spiriva® Respimat® (Spiriva)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC) 0-24	Normalized Forced Expiratory Volume in 1 second (FEV1) Area Under the Curve (AUC) 0-24	Pre dose, 15 and 30 minutes, 1, 2, 4, 8, 12, 12.25, 12.5, 13, 14, 16, 22, and 24 hours post the morning dose on Day 29

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
FEV1 AUC12-24	Normalized FEV1 AUC12-24	Pre dose, 15 and 30 minutes, 1, 2, 4, 8, and 12 hours post the evening dose on Day 29
FEV1 AUC0-12	Normalized FEV1 AUC0-12	Pre dose, 15 and 30 minutes, 1, 2, 4, 8, and 12 hours post the morning dose on Day 29
Peak Change From Baseline in FEV1 Evening	Peak Change From Baseline in FEV1 Evening	Baseline and Day 29
Peak Change From Baseline in FEV1 Morning	Peak Change From Baseline in FEV1 Morning	Baseline and Day 29
Morning Pre-Dose Trough FEV1 on Day 29	Morning Pre-Dose Trough FEV1 on Day 29	Day 29
Morning Pre-Dose Trough FEV1 on Day 30	Morning Pre-Dose Trough FEV1 on Day 30	Day 30
Peak Change From Baseline in IC (Inspiratory Capacity) Evening	Peak Change From Baseline in IC Evening	Baseline and Day 29
Peak Change From Baseline in IC Morning	Peak Change From Baseline in IC Morning	Baseline and Day 29

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Reisner C, Gottschlich G, Fakih F, Koser A, Krainson J, Delacruz L, Arora S, Feldman G, Pudi K, Siddiqui S, Orevillo C, Maes A, St Rose E, Martin U. 24-h bronchodilation and inspiratory capacity improvements with glycopyrrolate/formoterol fumarate via co-suspension delivery technology in COPD. Respir Res. 2017 Aug 18;18(1):157. doi: 10.1186/s12931-017-0636-4.

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2015
• Primary Completion (Actual): August 1, 2015
• Study Completion (Actual): March 1, 2016

Study Registration Dates

• First Submitted: January 21, 2015
• First Submitted That Met QC Criteria: January 21, 2015
• First Posted (Estimate): January 27, 2015

Study Record Updates

• Last Update Posted (Actual): April 19, 2017
• Last Update Submitted That Met QC Criteria: March 7, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Parasympatholytics; Autonomic Agents; Peripheral Nervous System Agents; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Adrenergic Agonists; Adjuvants, Anesthesia; Anticonvulsants; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Glycopyrrolate; Tiotropium Bromide; Bromides; Formoterol Fumarate
• Other Study ID Numbers: PT003011-00