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

NCT03075267 | Completed Phase 1 Results FDA Drug

• 1 other identifier: PT010010
• Study Type: interventional
• Target: 96
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Chronic Obstructive Pulmonary Disease

Outcome Measures

Primary Outcomes (42)

• 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 Outcomes (5)

• Physical Exam Findings

  Visit 4, Day 8

• Laboratory Tests

  Visit 4, Day 8

• Electrocardiogram

  Visit 4, Day 8

• Serious Adverse Events/Adverse Events

  Visit 4, Day 8

• Vital Signs

  Visit 4, Day 8

Study Arms (3)

PT010 (BGF MDI) 320/14.4/9.6 µg

EXPERIMENTAL

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

PT010 (BGF MDI) 160/14.4/9.6 µg

EXPERIMENTAL

PT010 (BGF MDI) 160/14.4/9.6 µg

Drug: PT010 (BGF MDI) 160/14.4/9.6 µg

PT003 (GFF MDI) 14.4/9.6 µg

EXPERIMENTAL

PT003 (GFF MDI) 14.4/9.6 µg

Drug: PT003 (GFF MDI) 14.4/9.6 µg

Interventions

PT010 (BGF MDI) 320/14.4/9.6 µg DRUG

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.

Also known as: Budesonide, Glycopyrronium, Formoterol Metered Dose Inhaler

PT010 (BGF MDI) 320/14.4/9.6 µg

PT010 (BGF MDI) 160/14.4/9.6 µg DRUG

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.

Also known as: Budesonide, Glycopyrronium, Formoterol Metered Dose Inhaler

PT010 (BGF MDI) 160/14.4/9.6 µg

PT003 (GFF MDI) 14.4/9.6 µg DRUG

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.

Also known as: Glycopyrronium and Formoterol Fumurate Metered Dose Inhaler

PT003 (GFF MDI) 14.4/9.6 µg

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Pearl Therapeutics, Inc.: lead

Study Sites (1)

Research Site

Shanghai, 200031, China

Location

Related Publications (2)

• 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.

  PMID: 33152467 DERIVED

• 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.

  PMID: 30982547 DERIVED

Related Links

• Related Info
• Related Info

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

Budesonide; Glycopyrrolate

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Quaternary Ammonium Compounds; Amines; Organic Chemicals; Onium Compounds; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Pearl Therapeutics, Inc.
• Organization: Pearl Therapeutics, Inc.

information.center@astrazeneca.com

1-877-240-9479

Study Officials

• Paul M. Dorinsky, MD

  Pearl Therapeutics

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 6, 2017
• First Posted: March 9, 2017
• Study Start: April 17, 2017
• Primary Completion: September 5, 2017
• Study Completion: September 5, 2017
• Last Updated: January 19, 2021
• Results First Posted: January 19, 2021

Record last verified: 2020-12

Data Sharing

• IPD Sharing: Will share

Locations

CN (1)