A Study to Assess the PK and Safety of PT010 in Subjects With COPD Following Single and Repeat Dose

A Study to Assess the Pharmacokinetics and Safety of PT010 in Subjects With Moderate to Severe COPD Following Single and Repeat Dose Administration

This is a Phase I open-label, single center study to assess the PK and safety of BGF MDI 320/14.4/9.6 µg in subjects with moderate to severe COPD. Pharmacokinetics will be assessed following a single dose administration on the first treatment day (Day 1) and will be assessed again after 7 days of repeat dosing. This study includes a Screening Period of up to 28 days and a single Treatment Period of 8 days. A follow-up phone call will be conducted at least 5 days but no longer than 7 days after the last dose of study drug.

Study Overview

• Status: Completed
• Conditions: Chronic Obstructive Pulmonary Disease
• Intervention / Treatment: Drug: PT010

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Clearwater, Florida, United States, 33765
      • Research 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

Key Inclusion Criteria:

• Given their signed written informed consent to participate.
• Non-child bearing potential (ie, physiologically incapable of becoming pregnant, including any female who is 2 years post-menopausal); or Child bearing potential, has a negative serum pregnancy test at Visit 1, and agrees to acceptable contraceptive methods used consistently and correctly for the duration of the study.
• Subjects with an established clinical history of COPD as defined by the American Thoracic Society (ATS)/European Respiratory Society (ERS), or other local applicable guidelines.
• Current or former smokers with a history of at least 10 pack-years of cigarette smoking.
• Pre-bronchodilator FEV1/FVC ratio must be <0.70 and pre-bronchodilator FEV1 must be ≥50% and <80% predicted normal value calculated using National Health and Nutrition Examination Survey (NHANES) III reference equations

Key Exclusion Criteria:

• Significant diseases or conditions to : other than COPD, active pulmonary disease such as active tuberculosis, lung cancer, bronchiectasis, sarcoidosis, lung fibrosis, primary pulmonary hypertension, interstitial lung disease and uncontrolled sleep apnea .
• Women who are pregnant or lactating, or are planning to become pregnant during the course of the study, or women of childbearing potential who are not using an acceptable method of contraception.
• Subjects, who in the opinion of the Investigator, have a current diagnosis of asthma.
• Subjects who have a history of hypersensitivity to any corticosteroid,
• β2-agonist, muscarinic anticholinergic, or any component of the MDI
• Alpha-1 antitrypsin deficiency as the cause of COPD

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PT010; PT010; Budesonide, Glycopyrrolate, and Formoterol Fumarate Inhalation Aerosol per protocol. Administered as 2 inhalations per use as instructed in the protocol.	Drug: PT010; PT010; Budesonide, Glycopyrrolate, and Formoterol Fumarate Inhalation Aerosol. Administered as 2 inhalations per use as instructed per the protocol.; Other Names: PT010; Budesonide, Glycopyrrolate, and Formoterol Fumarate Inhalation Aerosol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Plasma Concentration (Cmax) - Budesonide	Maximum plasma concentration (Cmax) - Budesonide	Day 1
Maximum Plasma Concentration (Cmax) - Budesonide	Maximum plasma concentration (Cmax) - Budesonide	Day 8 (pre-dose and 2,6,20,40 minutes, 1,2,4,8,10,12 hours post-dose
Maximum Plasma Concentration (Cmax) - Glycopyrronium	Maximum plasma concentration (Cmax) - Glycopyrronium	Day 1 (pre-dose 2,6,20,40 minutes, 1,2,4,8,10,12,18,24 hours post-dose)
Maximum Plasma Concentration (Cmax) - Glycopyrronium	Maximum plasma concentration (Cmax) - Glycopyrronium	Day 8 (pre-dose and 2,6,20,40 minutes, 1,2,4,8,10,12 hours post-dose)
Maximum Plasma Concentration (Cmax) - Formoterol	Maximum plasma concentration (Cmax) - Formoterol	Day 1 (pre-dose 2,6,20,40 minutes, 1,2,4,8,10,12,18,24 hours post-dose)
Maximum Plasma Concentration (Cmax) - Formoterol	Maximum plasma concentration (Cmax) - Formoterol	Day 8 (pre-dose and 2,6,20,40 minutes, 1,2,4,8,10,12 hours post-dose)
Area Under the Plasma Concentration-time Curve (AUC 0-12) - Budesonide	Area under the plasma concentration-time curve from 0 to 12 hours (AUC 0-12) - Budesonide	Day 1
Area Under the Plasma Concentration-time Curve (AUC 0-12) - Budesonide	Area under the plasma concentration-time curve from 0 to 12 hours (AUC 0-12) - Budesonide	Day 8
Area Under the Plasma Concentration-time Curve (AUC 0-12) - Glycopyrronium	Area under the plasma concentration-time curve from 0 to 12 hours (AUC 0-12) - Glycopyrronium	Day 1
Area Under the Plasma Concentration-time Curve (AUC 0-12) - Glycopyrronium	Area under the plasma concentration-time curve from 0 to 12 hours (AUC 0-12) - Glycopyrronium	Day 8
Area Under the Plasma Concentration-time Curve (AUC 0-12) - Formoterol	Area under the plasma concentration-time curve from 0 to 12 hours (AUC 0-12) - Formoterol	Day 1
Area Under the Plasma Concentration-time Curve (AUC 0-12) - Formoterol	Area under the plasma concentration-time curve from 0 to 12 hours (AUC 0-12) - Formoterol	Day 8
Area Under the Plasma Concentration-time Curve (AUC 0-tlast) - Budesonide	Area under the plasma concentration-time curve from 0 to the time of the last measurable plasma concentration (AUC 0-tlast) - Budesonide	Day 1
Area Under the Plasma Concentration-time Curve (AUC 0-tlast) - Glycopyrronium	Area under the plasma concentration-time curve from 0 to the time of the last measurable plasma concentration (AUC 0-tlast) - Glycopyrronium	Day 1
Area Under the Plasma Concentration-time Curve (AUC 0-tlast) - Formoterol	Area under the plasma concentration-time curve from 0 to the time of the last measurable plasma concentration (AUC 0-tlast) - Formoterol	Day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Maximum Plasma Concentration (Tmax) - Budesonide	Time to maximum plasma concentration (tmax) - Budesonide	Day 1 (pre-dose 2,6,20,40 minutes, 1,2,4,8,10,12,18,24 hours post-dose), Day 8 (pre-dose and 2,6,20,40 minutes, 1,2,4,8,10,12 hours post-dose)
Time to Maximum Plasma Concentration (Tmax) - Glycopyrronium	Time to maximum plasma concentration (tmax) - Glycopyrronium	Day 1 (pre-dose 2,6,20,40 minutes, 1,2,4,8,10,12,18,24 hours post-dose), Day 8 (pre-dose and 2,6,20,40 minutes, 1,2,4,8,10,12 hours post-dose)
Time to Maximum Plasma Concentration (Tmax) - Formoterol	Time to maximum plasma concentration (tmax) - Formoterol	Day 1 (pre-dose 2,6,20,40 minutes, 1,2,4,8,10,12,18,24 hours post-dose), Day 8 (pre-dose and 2,6,20,40 minutes, 1,2,4,8,10,12 hours post-dose)
Area Under the Plasma Concentration-time Curve From 0 Extrapolated to Infinity (AUC0-∞) - Budesonide	Area under the plasma concentration-time curve from 0 extrapolated to infinity (AUC0-∞) - Budesonide	Day 1
Area Under the Plasma Concentration-time Curve From 0 Extrapolated to Infinity (AUC0-∞) - Glycopyrronium	Area under the plasma concentration-time curve from 0 extrapolated to infinity (AUC0-∞) - Glycopyrronium	Day 1
Area Under the Plasma Concentration-time Curve From 0 Extrapolated to Infinity (AUC0-∞) - Formoterol	Area under the plasma concentration-time curve from 0 extrapolated to infinity (AUC0-∞) - Formoterol	Day 1

Collaborators and Investigators

• Sponsor: Pearl Therapeutics, Inc.
• Investigators: Study Director: Paul M Dorinsky, MD, Pearl Therapeutics, Inc.

Publications and helpful links

General Publications

• Dunn LJ, Kerwin EM, DeAngelis K, Darken P, Gillen M, Dorinsky P. Pharmacokinetics of budesonide/glycopyrrolate/formoterol fumarate metered dose inhaler formulated using co-suspension delivery technology after single and chronic dosing in patients with COPD. Pulm Pharmacol Ther. 2020 Feb;60:101873. doi: 10.1016/j.pupt.2019.101873. Epub 2019 Dec 10.

Study record dates

Study Major Dates

• Study Start (Actual): August 11, 2017
• Primary Completion (Actual): December 7, 2017
• Study Completion (Actual): December 7, 2017

Study Registration Dates

• First Submitted: August 11, 2017
• First Submitted That Met QC Criteria: August 14, 2017
• First Posted (Actual): August 15, 2017

Study Record Updates

• Last Update Posted (Actual): January 29, 2021
• Last Update Submitted That Met QC Criteria: January 12, 2021
• Last Verified: January 1, 2021

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; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Adrenergic Agonists; Adjuvants, Anesthesia; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Budesonide; Glycopyrrolate; Formoterol Fumarate
• Other Study ID Numbers: PT010018

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No