Study to Evaluate the Treatment Effect of PT003 on Cardiovascular Hemodynamics in Subjects With Moderate to Severe COPD

NCT02685293 | Terminated Phase 3 Results FDA Drug

• 1 other identifier: PT003017
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

This is a randomized, double-blind, placebo-controlled, single-center, chronic-dosing (7 days), two-period, two-treatment, cross-over study to evaluate the treatment effect of PT003 compared with that of Placebo MDI on Cardiovascular Hemodynamics following chronic-dosing (7 days) in subjects with moderate to severe COPD.

Conditions

COPD

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Right Ventricular End Diastolic Volume Index (RVEDVi) at 2-3 Hours Post-dose on Day 8

  Assessment of right ventricular (RV) volume was performed using magnetic resonance imaging (MRI) using RV end diastolic volume (RVEDV), 2-3 hours after dosing on Day 8 of each treatment period. RVEDV was normalized to body surface area (BSA) to provide the indexed counterpart (RVEDVi). Baseline was defined as the pre-dose value on Day 1 of treatment period 1.

  Baseline and Day 8 of either treatment period 1 or 2, as applicable.

Secondary Outcomes (14)

• Change From Baseline in Aortic Left Ventricular Stroke Volume (LVSV) at 2-3 Hours Post-dose on Day 8

  Baseline and Day 8 of either treatment period 1 or 2, as applicable.

• Change From Baseline in Right Ventricular Stroke Volume (RVSV) at 2-3 Hours Post-dose on Day 8

  Baseline and Day 8 of either treatment period 1 or 2, as applicable.

• Change From Baseline in Pulmonary Artery Velocity at 2-3 Hours Post-dose on Day 8

  Baseline and Day 8 of either treatment period 1 or 2, as applicable.

• Change From Baseline in Left Ventricular End Diastolic Volume Index (LVEDVi) at 2-3 Hours Post-dose on Day 8

  Baseline and Day 8 of either treatment period 1 or 2, as applicable.

• Change From Baseline in Cardiac Output at 2-3 Hours Post-dose on Day 8

  Baseline and Day 8 of either treatment period 1 or 2, as applicable.

Study Arms (2)

GFF MDI (PT003)

EXPERIMENTAL

Glycopyrronium and Formoterol Fumarate Inhalation Aerosol; PT003, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (GFF MDI)

Drug: GFF MDI (PT003)

Placebo MDI

PLACEBO COMPARATOR

Placebo Metered Dose Inhaler (MDI) for Glycopyrronium and Formoterol Fumarate Inhalation Aerosol

Drug: Placebo MDI

Interventions

GFF MDI (PT003) DRUG

Glycopyrronium and Formoterol Fumarate Inhalation Aerosol; PT003, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (GFF MDI)

GFF MDI (PT003)

Placebo MDI DRUG

Placebo Metered Dose Inhaler (MDI) for Glycopyrronium and Formoterol Fumarate Inhalation Aerosol

Placebo MDI

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• At least 40 years of age and no older than 80 at Visit 1.
• Women of non-child bearing potential,or negative serum pregnancy test at Screening, and agrees to acceptable contraceptive methods used consistently and correctly from Screening until 14 days after final visit
• Evidence of lung hyperinflation
• 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 must be \<0.70
• Post-bronchodilator FEV1 must be ≥30% to \<65% predicted normal value, calculated using NHANES III reference equations.

You may not qualify if:

• Significant diseases or conditions other than COPD which, in the opinion of the Investigator, may put the patient at risk
• Women who are pregnant or lactating or are planning to become pregnant during the course of the study
• Subjects, who in the opinion of the Investigator, have a current diagnosis of asthma or other active pulmonary disease
• Subjects who have been hospitalized due to poorly controlled COPD within 3 months prior to Screening
• 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 with symptomatic prostatic hypertrophy that is clinically significant and not adequately controlled with appropriate therapy, in the opinion of the Investigator.
• Subjects with bladder neck obstruction or urinary retention that is clinically significant in the opinion of the Investigator.
• Subjects with a calculated creatinine clearance ≤30 mL/minute using Chronic Kidney Disease Epidemiology Collaboration. (CKD-EPI) formula at Screening and on repeat testing prior to Visit 2.
• 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 prior to Visit 2
• Subjects who have cancer that has not been in complete remission for at least five years.
• Subjects with a diagnosis of glaucoma, who in the opinion of the Investigator, have not been adequately treated.
• Subjects with a clinically significant ECG
• Subjects who were previously enrolled in any previous PT001, PT003, or PT005 study conducted or sponsored by Pearl.

Sponsors & Collaborators

• Pearl Therapeutics, Inc.: lead

Study Sites (1)

Research Site

Birmingham, Alabama, 35294, United States

Location

Related Links

• Related Info

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

This study was terminated early on 20 June 2018 as target enrollment numbers were not met.

Results Point of Contact

• Title: Global Clinical Lead
• Organization: Pearl Therapeutics Inc.

ClinicalTrialTransparency@astrazeneca.com

+1 302 885 1180

Study Officials

• Colin Reisner, MD

  Pearl Therapeutics

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 28, 2016
• First Posted: February 18, 2016
• Study Start: December 9, 2016
• Primary Completion: June 6, 2018
• Study Completion: June 6, 2018
• Last Updated: August 28, 2019
• Results First Posted: August 28, 2019

Record last verified: 2019-08

Data Sharing

• IPD Sharing: Will share

Locations

US (1)