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

Pearl Therapeutics, Inc.96 enrolled

Overview

A study to assess the pharmacokinetics and safety of two doses of PT010 and a single dose of 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 Administration and After Chronic Administration for 7 Days

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

Chronic Obstructive Pulmonary Disease

Interventions

PT010 (BGF MDI) 320/14.4/9.6 µgDRUG

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.

PT010 (BGF MDI) 160/14.4/9.6 µgDRUG

PT003 (GFF MDI) 14.4/9.6 µgDRUG

Eligibility

Sex: ALLMin age: 18 YearsMax age: 45 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Locations (1)

Research Site

Shanghai, China

Outcomes

Primary Outcomes

Maximum Plasma Concentration (Cmax) - Budesonide

Maximum plasma concentration (Cmax) of Budesonide Day 1

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: Day 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose

Data from ClinicalTrials.gov

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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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: Day 8

Time to Maximum Plasma Concentration (Tmax) - Budesonide

Time to maximum plasma concentration (tmax) - Budesonide Day 1

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: Day 1

Elimination Half-life (t½) - Budesonide

Elimination half-life (t½) - Budesonide Day 1

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: Day 1 and Day 8

Secondary Outcomes

Physical Exam Findings

Number of subjects with clinically significant changes in post baseline physical exam findings

Time frame: Visit 4, Day 8

Laboratory Tests

Number of subjects with clinically significant changes in post baseline laboratory tests

Time frame: Visit 4, Day 8

Electrocardiogram

Number of subjects with clinically significant changes in post baseline electrocardiogram

Time frame: 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

Time frame: Visit 4, Day 8

Vital Signs

Number of subjects with clinically significant changes in post baseline vital signs

Time frame: Visit 4, Day 8