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

Phase 1
Completed
Conditions
Chronic Obstructive Pulmonary Disease
Interventions
Drug: PT003 (GFF MDI) 14.4/9.6 µg
Drug: PT010 (BGF MDI) 320/14.4/9.6 µg
Drug: PT010 (BGF MDI) 160/14.4/9.6 µg
Registration Number
NCT03075267
Lead Sponsor
Pearl Therapeutics, Inc.
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

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
96
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PT003 (GFF MDI) 14.4/9.6 µgPT003 (GFF MDI) 14.4/9.6 µgPT003 (GFF MDI) 14.4/9.6 µg
PT010 (BGF MDI) 320/14.4/9.6 µgPT010 (BGF MDI) 320/14.4/9.6 µgPT010 Budesonide, Glycopyrronium and Formoterol Fumurate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg
PT010 (BGF MDI) 160/14.4/9.6 µgPT010 (BGF MDI) 160/14.4/9.6 µgPT010 (BGF MDI) 160/14.4/9.6 µg
Primary Outcome Measures
NameTimeMethod
Maximum Plasma Concentration (Cmax) - FormoterolDay 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) of Formoterol Day 8

Area Under the Plasma Concentration-time Curve From 0 to the Time of the Last Measurable Plasma Concentration (AUC 0-t) - GlycopyrroniumDay 1

Area under the plasma concentration-time curve from 0 to the time of the last measurable plasma concentration (AUC 0-t) - Glycopyrronium Day 1

Area Under the Plasma Concentration-time Curve From 0 Extrapolated to Infinity (AUC 0-∞) - GlycopyrroniumDay 1

Area under the plasma concentration-time curve from 0 extrapolated to infinity (AUC 0-∞) - Glycopyrronium Day 1

Area Under the Plasma Concentration-time Curve From 0 Extrapolated to Infinity (AUC 0-∞) - FormoterolDay 1

Area under the plasma concentration-time curve from 0 extrapolated to infinity (AUC 0-∞) - Formoterol Day 1

Area Under the Plasma Concentration-time Curve From 0-12 Hours (AUC 0-12) - GlycopyrroniumDay 8

Area under the plasma concentration-time curve from 0-12 hours (AUC 0-12) - Glycopyrronium Day 8

Area Under the Plasma Concentration-time Curve From 0 to the Time of the Last Measurable Plasma Concentration (AUC 0-t) - BudesonideDay 1

Area under the plasma concentration-time curve from 0 to the time of the last measurable plasma concentration (AUC 0-t) - Budesonide Day 1

Area Under the Plasma Concentration-time Curve From 0-12 Hours (AUC 0-12) - FormoterolDay 8

Area under the plasma concentration-time curve from 0-12 hours (AUC 0-12) - Formoterol Day 8

Area Under the Plasma Concentration-time Curve From 0 to the Time of the Last Measurable Plasma Concentration (AUC 0-t) - FormoterolDay 1

Area under the plasma concentration-time curve from 0 to the time of the last measurable plasma concentration (AUC 0-t) - Formoterol Day 1

Apparent Total Body Clearance (CL/F) - GlycopyrroniumDay 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 Day 1

Apparent Volume of Distribution (Vd/F) - FormoterolDay 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 - Day 1

Terminal Elimination Rate Constant (λz) - BudesonideDay 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 - Day 1

Maximum Plasma Concentration (Cmax) - BudesonideDay 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) of Budesonide Day 8

Maximum Plasma Concentration (Cmax) - GlycopyrroniumDay 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) of Glycopyrronium Day 8

Area Under the Plasma Concentration-time Curve From 0-12 Hours (AUC 0-12) - BudesonideDay 8

Area under the plasma concentration-time curve from 0-12 hours (AUC 0-12) - Budesonide Day 8

Time to Maximum Plasma Concentration (Tmax) - BudesonideDay 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) - Budesonide Day 8

Time to Maximum Plasma Concentration (Tmax) - GlycopyrroniumDay 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 Day 8

Area Under the Plasma Concentration-time Curve From 0 Extrapolated to Infinity (AUC 0-∞) - BudesonideDay 1

Area under the plasma concentration-time curve from 0 extrapolated to infinity (AUC 0-∞) - Budesonide Day 1

Time to Maximum Plasma Concentration (Tmax) - FormoterolDay 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 Day 8

Elimination Half-life (t½) - BudesonideDay 1 Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 10, 12 and 24 h post-dose

Elimination half-life (t½) - Budesonide Day 1

Elimination Half-life (t½) - GlycopyrroniumDay 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 Day 1

Apparent Total Body Clearance (CL/F) - FormoterolDay 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 Day 1

Apparent Volume of Distribution (Vd/F) - BudesonideDay 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 - Day 1

Elimination Half-life (t½) - FormoterolDay 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 Day 1

Apparent Total Body Clearance (CL/F) - BudesonideDay 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 Day 1

Apparent Volume of Distribution (Vd/F) - GlycopyrroniumDay 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 - Day 1

Terminal Elimination Rate Constant (λz) - GlycopyrroniumDay 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 - Day 1

Terminal Elimination Rate Constant (λz) - FormoterolDay 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 - Day 1

Accumulation Ratio for Cmax (RAC [Cmax]) - BudesonideDay 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 \[Cmax\]) - Budesonide

Accumulation Ratio for Cmax (RAC [Cmax]) - GlycopyrroniumDay 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 AUC 0-12 (RAC [AUC 0-12]) - BudesonideDay 1 and Day 8

Accumulation ratio for AUC 0-12 (RAC \[AUC 0-12\]) - Budesonide

Accumulation Ratio for Cmax (RAC [Cmax]) - FormoterolDay 1 and Day 8

Accumulation ratio for Cmax (RAC \[Cmax\]) - Formoterol

Accumulation Ratio for AUC 0-12 (RAC [AUC 0-12]) - GlycopyrroniumDay 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]) - FormoterolDay 1 and Day 8

Accumulation ratio for AUC 0-12 (RAC \[AUC 0-12\]) - Formoterol

Secondary Outcome Measures
NameTimeMethod
ElectrocardiogramVisit 4, Day 8

Number of subjects with clinically significant changes in post baseline electrocardiogram

Physical Exam FindingsVisit 4, Day 8

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

Serious Adverse Events/Adverse EventsVisit 4, Day 8

Number of subjects with clinically significant changes in post baseline serious TEAEs (treatment-emergent adverse events) or TEAEs leading to withdrawal

Vital SignsVisit 4, Day 8

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

Laboratory TestsVisit 4, Day 8

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

Trial Locations

Locations (1)

Research Site

🇨🇳

Shanghai, China

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