Pharmacokinetics and Safety Study of PT010 and PT003 in Healthy Chinese Adult Subjects

A Phase I, Randomized, Double-Blind, Parallel-Group, Study to Assess the Pharmacokinetics and Safety of Two Doses of PT010 and a Single Dose of PT003 in Healthy Chinese Adult Subjects Following A Single Administrations and After Chronic Administration for 7 Days

A study to assess the pharmacokinetics and safety of two doses of PT010 and a single dose of PT003 in healthy Chinese adult subjects

Study Overview

• Status: Completed
• Conditions: Chronic Obstructive Pulmonary Disease
• Intervention / Treatment: Drug: PT010 (BGF MDI) 320/14.4/9.6 µg; Drug: PT010 (BGF MDI) 160/14.4/9.6 µg; Drug: PT003 (GFF MDI) 14.4/9.6 µg

Detailed Description

A Phase I, Randomized, Double-Blind, Parallel Group, Study to Assess the Pharmacokinetics and Safety of Two Doses of PT010 and a Single Dose of PT003 in Healthy Chinese Adult Subjects Following a Single Administration and After Chronic Administration for 7 Days

• Study Type: Interventional
• Enrollment (Actual): 96
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Shanghai, China, 200031
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male and female Chinese subjects 18-45 years of age
• Females of childbearing potential must agree to be abstinent or else use one of the medically acceptable forms of contraception A female whose male partner has had a vasectomy must agree to use one additional form of medically acceptable contraception.

A male subject with female partner of child bearing potential must agree to use one additional form of medically acceptable contraception

-Be in good general health as assessed at Screening and have no clinically significant abnormal labs at Screening.

Exclusion Criteria:

• Pregnant or nursing female subjects or subjects who are trying to conceive
• Subjects with clinically significant neurologic, cardiovascular, hepatic, renal, endocrinologic, pulmonary, hematological, psychiatric, or other medical illness that would interfere with participation in this study
• Subjects with a history of ECG abnormalities
• Subjects who have cancer that has not been in complete remission for at least 5 years
• Male subjects with symptomatic prostatic hypertrophy that is clinically significant in the opinion of the Investigator
• Male subjects with a trans-urethral resection of the prostate or full resection of the prostate within 6 months prior to Screening
• Males with bladder neck obstruction or urinary retention that is clinically significant in the opinion of the Investigator
• Subjects with a diagnosis of glaucoma that in the opinion of the Investigator has not been adequately treated
• History of substance-related disorders within 1 year of Screening
• History of smoking or the use of nicotine containing products or electronic cigarettes within 3 months of Screening by self-reporting
• A positive alcohol breathalyzer or urine drug screen for drugs of abuse at the Screening Visit or at the beginning of each inpatient period
• Treatment with any prescription or non-prescription drugs (including vitamins, herbal, and dietary supplements) within 30 days
• Positivity for human immunodeficiency virus (HIV) or Hepatitis B surface antigen (HbsAg) or positive hepatitis C antibody at Screening
• Positive for Syphilis Antibody
• Subjects with any flu-like syndrome or other respiratory infections
• Recently vaccinated with an attenuated live virus

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: PT010 (BGF MDI) 320/14.4/9.6 µg; PT010 Budesonide, Glycopyrronium and Formoterol Fumurate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg	Drug: PT010 (BGF MDI) 320/14.4/9.6 µg; A single dose of study drug will be administered on Day 1 and BID doses will be administered Day 2 through Day 7 of the Treatment Period, with a final single administration of study drug occurring on the morning of Day 8.; Other Names: Budesonide, Glycopyrronium, Formoterol Metered Dose Inhaler
EXPERIMENTAL: PT010 (BGF MDI) 160/14.4/9.6 µg	Drug: PT010 (BGF MDI) 160/14.4/9.6 µg; A single dose of study drug will be administered on Day 1 and BID doses will be administered Day 2 through Day 7 of the Treatment Period, with a final single administration of study drug occurring on the morning of Day 8.; Other Names: Budesonide, Glycopyrronium, Formoterol Metered Dose Inhaler
EXPERIMENTAL: PT003 (GFF MDI) 14.4/9.6 µg	Drug: PT003 (GFF MDI) 14.4/9.6 µg; A single dose of study drug will be administered on Day 1 and BID doses will be administered Day 2 through Day 7 of the Treatment Period, with a final single administration of study drug occurring on the morning of Day 8.; Other Names: Glycopyrronium and Formoterol Fumurate Metered Dose Inhaler

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Plasma Concentration (Cmax) - Budesonide	Maximum plasma concentration (Cmax) of Budesonide Day 1	Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
Maximum Plasma Concentration (Cmax) - Budesonide	Maximum plasma concentration (Cmax) of Budesonide Day 8	Day 8 Pre-dose -60, and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
Maximum Plasma Concentration (Cmax) - Glycopyrronium	Maximum plasma concentration (Cmax) of Glycopyrronium Day 1	Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
Maximum Plasma Concentration (Cmax) - Glycopyrronium	Maximum plasma concentration (Cmax) of Glycopyrronium Day 8	Day 8 Pre-dose -60, and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
Maximum Plasma Concentration (Cmax) - Formoterol	Maximum plasma concentration (Cmax) of Formoterol Day 1	Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
Maximum Plasma Concentration (Cmax) - Formoterol	Maximum plasma concentration (Cmax) of Formoterol Day 8	Day 8 Pre-dose -60, and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
Area Under the Plasma Concentration-time Curve From 0-12 Hours (AUC 0-12) - Budesonide	Area under the plasma concentration-time curve from 0-12 hours (AUC 0-12) - Budesonide Day 1	Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
Area Under the Plasma Concentration-time Curve From 0-12 Hours (AUC 0-12) - Budesonide	Area under the plasma concentration-time curve from 0-12 hours (AUC 0-12) - Budesonide Day 8	Day 8
Area Under the Plasma Concentration-time Curve From 0-12 Hours (AUC 0-12) - Glycopyrronium	Area under the plasma concentration-time curve from 0-12 hours (AUC 0-12) - Glycopyrronium Day 1	Day 1
Area Under the Plasma Concentration-time Curve From 0-12 Hours (AUC 0-12) - Glycopyrronium	Area under the plasma concentration-time curve from 0-12 hours (AUC 0-12) - Glycopyrronium Day 8	Day 8
Area Under the Plasma Concentration-time Curve From 0-12 Hours (AUC 0-12) - Formoterol	Area under the plasma concentration-time curve from 0-12 hours (AUC 0-12) - Formoterol Day 1	Day 1
Area Under the Plasma Concentration-time Curve From 0-12 Hours (AUC 0-12) - Formoterol	Area under the plasma concentration-time curve from 0-12 hours (AUC 0-12) - Formoterol Day 8	Day 8
Time to Maximum Plasma Concentration (Tmax) - Budesonide	Time to maximum plasma concentration (tmax) - Budesonide Day 1	Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
Time to Maximum Plasma Concentration (Tmax) - Budesonide	Time to maximum plasma concentration (tmax) - Budesonide Day 8	Day 8 Pre-dose -60, and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
Time to Maximum Plasma Concentration (Tmax) - Glycopyrronium	Time to maximum plasma concentration (tmax) - Glycopyrronium Day 1	Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
Time to Maximum Plasma Concentration (Tmax) - Glycopyrronium	Time to maximum plasma concentration (tmax) - Glycopyrronium Day 8	Day 8 Pre-dose -60, and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
Time to Maximum Plasma Concentration (Tmax) - Formoterol	Time to maximum plasma concentration (tmax) - Formoterol Day 1	Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
Time to Maximum Plasma Concentration (Tmax) - Formoterol	Time to maximum plasma concentration (tmax) - Formoterol Day 8	Day 8 Pre-dose -60, and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
Area Under the Plasma Concentration-time Curve From 0 to the Time of the Last Measurable Plasma Concentration (AUC 0-t) - Budesonide	Area under the plasma concentration-time curve from 0 to the time of the last measurable plasma concentration (AUC 0-t) - Budesonide Day 1	Day 1
Area Under the Plasma Concentration-time Curve From 0 to the Time of the Last Measurable Plasma Concentration (AUC 0-t) - Glycopyrronium	Area under the plasma concentration-time curve from 0 to the time of the last measurable plasma concentration (AUC 0-t) - Glycopyrronium Day 1	Day 1
Area Under the Plasma Concentration-time Curve From 0 to the Time of the Last Measurable Plasma Concentration (AUC 0-t) - Formoterol	Area under the plasma concentration-time curve from 0 to the time of the last measurable plasma concentration (AUC 0-t) - Formoterol Day 1	Day 1
Area Under the Plasma Concentration-time Curve From 0 Extrapolated to Infinity (AUC 0-∞) - Budesonide	Area under the plasma concentration-time curve from 0 extrapolated to infinity (AUC 0-∞) - Budesonide Day 1	Day 1
Area Under the Plasma Concentration-time Curve From 0 Extrapolated to Infinity (AUC 0-∞) - Glycopyrronium	Area under the plasma concentration-time curve from 0 extrapolated to infinity (AUC 0-∞) - Glycopyrronium Day 1	Day 1
Area Under the Plasma Concentration-time Curve From 0 Extrapolated to Infinity (AUC 0-∞) - Formoterol	Area under the plasma concentration-time curve from 0 extrapolated to infinity (AUC 0-∞) - Formoterol Day 1	Day 1
Elimination Half-life (t½) - Budesonide	Elimination half-life (t½) - Budesonide Day 1	Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
Elimination Half-life (t½) - Glycopyrronium	Elimination half-life (t½) - Glycopyrronium Day 1	Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
Elimination Half-life (t½) - Formoterol	Elimination half-life (t½) - Formoterol Day 1	Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
Apparent Total Body Clearance (CL/F) - Budesonide	Apparent total body clearance (CL/F) - Budesonide Day 1	Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
Apparent Total Body Clearance (CL/F) - Glycopyrronium	Apparent total body clearance (CL/F) - Glycopyrronium Day 1	Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
Apparent Total Body Clearance (CL/F) - Formoterol	Apparent total body clearance (CL/F) - Formoterol Day 1	Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
Apparent Volume of Distribution (Vd/F) - Budesonide	Apparent volume of distribution (Vd/F) - Budesonide - Day 1	Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
Apparent Volume of Distribution (Vd/F) - Glycopyrronium	Apparent volume of distribution (Vd/F) - Glycopyrronium - Day 1	Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
Apparent Volume of Distribution (Vd/F) - Formoterol	Apparent volume of distribution (Vd/F) - Formoterol - Day 1	Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
Terminal Elimination Rate Constant (λz) - Budesonide	Terminal elimination rate constant (λz) - Budesonide - Day 1	Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
Terminal Elimination Rate Constant (λz) - Glycopyrronium	Terminal elimination rate constant (λz) - Glycopyrronium - Day 1	Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
Terminal Elimination Rate Constant (λz) - Formoterol	Terminal elimination rate constant (λz) - Formoterol - Day 1	Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
Accumulation Ratio for Cmax (RAC [Cmax]) - Budesonide	Accumulation ratio for Cmax (RAC [Cmax]) - Budesonide	Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose and Day 8 Pre-dose -60, and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
Accumulation Ratio for Cmax (RAC [Cmax]) - Glycopyrronium	Accumulation ratio for Cmax (RAC [Cmax]) - Glycopyrronium	Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose and Day 8 Pre-dose -60, and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
Accumulation Ratio for Cmax (RAC [Cmax]) - Formoterol	Accumulation ratio for Cmax (RAC [Cmax]) - Formoterol	Day 1 and Day 8
Accumulation Ratio for AUC 0-12 (RAC [AUC 0-12]) - Budesonide	Accumulation ratio for AUC 0-12 (RAC [AUC 0-12]) - Budesonide	Day 1 and Day 8
Accumulation Ratio for AUC 0-12 (RAC [AUC 0-12]) - Glycopyrronium	Accumulation ratio for AUC 0-12 (RAC [AUC 0-12]) - Glycopyrronium	Day 1 and Day 8
Accumulation Ratio for AUC 0-12 (RAC [AUC 0-12]) - Formoterol	Accumulation ratio for AUC 0-12 (RAC [AUC 0-12]) - Formoterol	Day 1 and Day 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Physical Exam Findings	Number of subjects with clinically significant changes in post baseline physical exam findings	Visit 4, Day 8
Laboratory Tests	Number of subjects with clinically significant changes in post baseline laboratory tests	Visit 4, Day 8
Electrocardiogram	Number of subjects with clinically significant changes in post baseline electrocardiogram	Visit 4, Day 8
Serious Adverse Events/Adverse Events	Number of subjects with clinically significant changes in post baseline serious TEAEs (treatment-emergent adverse events) or TEAEs leading to withdrawal	Visit 4, Day 8
Vital Signs	Number of subjects with clinically significant changes in post baseline vital signs	Visit 4, Day 8

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Huang Y, Assam PN, Feng C, Su R, Dorinsky P, Gillen M. Ethnic pharmacokinetic comparison of budesonide/glycopyrrolate/formoterol fumarate metered dose inhaler (BGF MDI) between Asian and Western healthy subjects. Pulm Pharmacol Ther. 2020 Oct;64:101976. doi: 10.1016/j.pupt.2020.101976. Epub 2020 Nov 2.
• Chen Q, Hu C, Yu H, Shen K, Assam PN, Gillen M, Liu Y, Dorinsky P. Pharmacokinetics and Tolerability of Budesonide/Glycopyrronium/Formoterol Fumarate Dihydrate and Glycopyrronium/Formoterol Fumarate Dihydrate Metered Dose Inhalers in Healthy Chinese Adults: A Randomized, Double-blind, Parallel-group Study. Clin Ther. 2019 May;41(5):897-909.e1. doi: 10.1016/j.clinthera.2019.03.007. Epub 2019 Apr 11.

Helpful Links

• Related Info
• Related Info

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 17, 2017
• Primary Completion (ACTUAL): September 5, 2017
• Study Completion (ACTUAL): September 5, 2017

Study Registration Dates

• First Submitted: March 6, 2017
• First Submitted That Met QC Criteria: March 6, 2017
• First Posted (ACTUAL): March 9, 2017

Study Record Updates

• Last Update Posted (ACTUAL): January 19, 2021
• Last Update Submitted That Met QC Criteria: December 23, 2020
• Last Verified: December 1, 2020

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: PT010010

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes