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

Phase 1

Completed

Conditions: Chronic Obstructive Pulmonary Disease

Interventions: Drug: PT010

Registration Number: NCT03250182

Lead Sponsor: Pearl Therapeutics, Inc.

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 30

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
PT010	PT010	PT010; Budesonide, Glycopyrrolate, and Formoterol Fumarate Inhalation Aerosol per protocol. Administered as 2 inhalations per use as instructed in the protocol.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
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) - Budesonide
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) - Glycopyrronium
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-∞) - Budesonide
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-∞) - Glycopyrronium
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)	Time to maximum plasma concentration (tmax) - Formoterol
Area Under the Plasma Concentration-time Curve From 0 Extrapolated to Infinity (AUC0-∞) - Formoterol	Day 1	Area under the plasma concentration-time curve from 0 extrapolated to infinity (AUC0-∞) - Formoterol