Clinical trial NCT03250182: A Study to Assess the PK and Safety of PT010 in Subjects With COPD Following Single and Repeat Dose
Official title: A Study to Assess the Pharmacokinetics and Safety of PT010 in Subjects With Moderate to Severe COPD Following Single and Repeat Dose Administration
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Chronic Obstructive Pulmonary Disease
Lead sponsor: Pearl Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2017-08-15
Enrollment: 30
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Maximum Plasma Concentration (Cmax) - Budesonide
timeFrame: Day 1
measure: Maximum Plasma Concentration (Cmax) - Budesonide
timeFrame: Day 8 (pre-dose and 2,6,20,40 minutes, 1,2,4,8,10,12 hours post-dose
measure: Maximum Plasma Concentration (Cmax) - Glycopyrronium
timeFrame: Day 1 (pre-dose 2,6,20,40 minutes, 1,2,4,8,10,12,18,24 hours post-dose)
measure: Maximum Plasma Concentration (Cmax) - Glycopyrronium
timeFrame: Day 8 (pre-dose and 2,6,20,40 minutes, 1,2,4,8,10,12 hours post-dose)
measure: Maximum Plasma Concentration (Cmax) - Formoterol
timeFrame: Day 1 (pre-dose 2,6,20,40 minutes, 1,2,4,8,10,12,18,24 hours post-dose)
measure: Maximum Plasma Concentration (Cmax) - Formoterol
timeFrame: Day 8 (pre-dose and 2,6,20,40 minutes, 1,2,4,8,10,12 hours post-dose)
measure: Area Under the Plasma Concentration-time Curve (AUC 0-12) - Budesonide
timeFrame: Day 1
measure: Area Under the Plasma Concentration-time Curve (AUC 0-12) - Budesonide
timeFrame: Day 8
measure: Area Under the Plasma Concentration-time Curve (AUC 0-12) - Glycopyrronium
timeFrame: Day 1
measure: Area Under the Plasma Concentration-time Curve (AUC 0-12) - Glycopyrronium
timeFrame: Day 8
measure: Area Under the Plasma Concentration-time Curve (AUC 0-12) - Formoterol
timeFrame: Day 1
measure: Area Under the Plasma Concentration-time Curve (AUC 0-12) - Formoterol
timeFrame: Day 8
measure: Area Under the Plasma Concentration-time Curve (AUC 0-tlast) - Budesonide
timeFrame: Day 1
measure: Area Under the Plasma Concentration-time Curve (AUC 0-tlast) - Glycopyrronium
timeFrame: Day 1
measure: Area Under the Plasma Concentration-time Curve (AUC 0-tlast) - Formoterol
timeFrame: Day 1
Secondary outcomes:
measure: Time to Maximum Plasma Concentration (Tmax) - Budesonide
timeFrame: 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)
measure: Time to Maximum Plasma Concentration (Tmax) - Glycopyrronium
timeFrame: 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)
measure: Time to Maximum Plasma Concentration (Tmax) - Formoterol
timeFrame: 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)
measure: Area Under the Plasma Concentration-time Curve From 0 Extrapolated to Infinity (AUC0-∞) - Budesonide
timeFrame: Day 1
measure: Area Under the Plasma Concentration-time Curve From 0 Extrapolated to Infinity (AUC0-∞) - Glycopyrronium
timeFrame: Day 1
measure: Area Under the Plasma Concentration-time Curve From 0 Extrapolated to Infinity (AUC0-∞) - Formoterol
timeFrame: Day 1
Other outcomes:
Locations:
city: Clearwater
country: United States
facility: Research Site
state: Florida
Study officials:
affiliation: Pearl Therapeutics, Inc.
name: Paul M Dorinsky, MD
role: STUDY_DIRECTOR
References:
citation: 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.