Clinical trial NCT03075267: Pharmacokinetics and Safety Study of PT010 and PT003 in Healthy Chinese Adult Subjects
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Chronic Obstructive Pulmonary Disease
Lead sponsor: Pearl Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2017-03-09
Enrollment: 96
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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

Eligibility criteria: 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

Primary outcomes:
measure: Maximum Plasma Concentration (Cmax) - Budesonide
timeFrame: Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
measure: Maximum Plasma Concentration (Cmax) - Budesonide
timeFrame: Day 8 Pre-dose -60, and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
measure: Maximum Plasma Concentration (Cmax) - Glycopyrronium
timeFrame: Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
measure: Maximum Plasma Concentration (Cmax) - Glycopyrronium
timeFrame: Day 8 Pre-dose -60, and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
measure: Maximum Plasma Concentration (Cmax) - Formoterol
timeFrame: Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
measure: Maximum Plasma Concentration (Cmax) - Formoterol
timeFrame: Day 8 Pre-dose -60, and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
measure: Area Under the Plasma Concentration-time Curve From 0-12 Hours (AUC 0-12) - Budesonide
timeFrame: Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
measure: Area Under the Plasma Concentration-time Curve From 0-12 Hours (AUC 0-12) - Budesonide
timeFrame: Day 8
measure: Area Under the Plasma Concentration-time Curve From 0-12 Hours (AUC 0-12) - Glycopyrronium
timeFrame: Day 1
measure: Area Under the Plasma Concentration-time Curve From 0-12 Hours (AUC 0-12) - Glycopyrronium
timeFrame: Day 8
measure: Area Under the Plasma Concentration-time Curve From 0-12 Hours (AUC 0-12) - Formoterol
timeFrame: Day 1
measure: Area Under the Plasma Concentration-time Curve From 0-12 Hours (AUC 0-12) - Formoterol
timeFrame: Day 8
measure: Time to Maximum Plasma Concentration (Tmax) - Budesonide
timeFrame: Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
measure: Time to Maximum Plasma Concentration (Tmax) - Budesonide
timeFrame: Day 8 Pre-dose -60, and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
measure: Time to Maximum Plasma Concentration (Tmax) - Glycopyrronium
timeFrame: Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
measure: Time to Maximum Plasma Concentration (Tmax) - Glycopyrronium
timeFrame: Day 8 Pre-dose -60, and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
measure: Time to Maximum Plasma Concentration (Tmax) - Formoterol
timeFrame: Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
measure: Time to Maximum Plasma Concentration (Tmax) - Formoterol
timeFrame: Day 8 Pre-dose -60, and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
measure: Area Under the Plasma Concentration-time Curve From 0 to the Time of the Last Measurable Plasma Concentration (AUC 0-t) - Budesonide
timeFrame: Day 1
measure: Area Under the Plasma Concentration-time Curve From 0 to the Time of the Last Measurable Plasma Concentration (AUC 0-t) - Glycopyrronium
timeFrame: Day 1
measure: Area Under the Plasma Concentration-time Curve From 0 to the Time of the Last Measurable Plasma Concentration (AUC 0-t) - Formoterol
timeFrame: Day 1
measure: Area Under the Plasma Concentration-time Curve From 0 Extrapolated to Infinity (AUC 0-∞) - Budesonide
timeFrame: Day 1
measure: Area Under the Plasma Concentration-time Curve From 0 Extrapolated to Infinity (AUC 0-∞) - Glycopyrronium
timeFrame: Day 1
measure: Area Under the Plasma Concentration-time Curve From 0 Extrapolated to Infinity (AUC 0-∞) - Formoterol
timeFrame: Day 1
measure: Elimination Half-life (t½) - Budesonide
timeFrame: Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
measure: Elimination Half-life (t½) - Glycopyrronium
timeFrame: Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
measure: Elimination Half-life (t½) - Formoterol
timeFrame: Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
measure: Apparent Total Body Clearance (CL/F) - Budesonide
timeFrame: Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
measure: Apparent Total Body Clearance (CL/F) - Glycopyrronium
timeFrame: Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
measure: Apparent Total Body Clearance (CL/F) - Formoterol
timeFrame: Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
measure: Apparent Volume of Distribution (Vd/F) - Budesonide
timeFrame: Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
measure: Apparent Volume of Distribution (Vd/F) - Glycopyrronium
timeFrame: Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
measure: Apparent Volume of Distribution (Vd/F) - Formoterol
timeFrame: Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
measure: Terminal Elimination Rate Constant (λz) - Budesonide
timeFrame: Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
measure: Terminal Elimination Rate Constant (λz) - Glycopyrronium
timeFrame: Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
measure: Terminal Elimination Rate Constant (λz) - Formoterol
timeFrame: Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose
measure: Accumulation Ratio for Cmax (RAC [Cmax]) - Budesonide
timeFrame: 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
measure: Accumulation Ratio for Cmax (RAC [Cmax]) - Glycopyrronium
timeFrame: 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
measure: Accumulation Ratio for Cmax (RAC [Cmax]) - Formoterol
timeFrame: Day 1 and Day 8
measure: Accumulation Ratio for AUC 0-12 (RAC [AUC 0-12]) - Budesonide
timeFrame: Day 1 and Day 8
measure: Accumulation Ratio for AUC 0-12 (RAC [AUC 0-12]) - Glycopyrronium
timeFrame: Day 1 and Day 8
measure: Accumulation Ratio for AUC 0-12 (RAC [AUC 0-12]) - Formoterol
timeFrame: Day 1 and Day 8
Secondary outcomes:
measure: Physical Exam Findings
timeFrame: Visit 4, Day 8
measure: Laboratory Tests
timeFrame: Visit 4, Day 8
measure: Electrocardiogram
timeFrame: Visit 4, Day 8
measure: Serious Adverse Events/Adverse Events
timeFrame: Visit 4, Day 8
measure: Vital Signs
timeFrame: Visit 4, Day 8
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Research Site
Study officials:
affiliation: Pearl Therapeutics
name: Paul M. Dorinsky, MD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.