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

Study Overview
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Brief Summary
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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
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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

Official Title
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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

Conditions
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Chronic Obstructive Pulmonary Disease

Intervention / Treatment
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* 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


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PT010 (BGF MDI) 320/14.4/9.6 µg<br>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<br>* 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.<br>* Other names: Budesonide, Glycopyrronium, Formoterol Metered Dose Inhaler;|
| Experimental: PT010 (BGF MDI) 160/14.4/9.6 µg<br>PT010 (BGF MDI) 160/14.4/9.6 µg | Drug: PT010 (BGF MDI) 160/14.4/9.6 µg<br>* 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.<br>* Other names: Budesonide, Glycopyrronium, Formoterol Metered Dose Inhaler;|
| Experimental: PT003 (GFF MDI) 14.4/9.6 µg<br>PT003 (GFF MDI) 14.4/9.6 µg | Drug: PT003 (GFF MDI) 14.4/9.6 µg<br>* 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.<br>* Other names: Glycopyrronium and Formoterol Fumurate Metered Dose Inhaler;|

What is the study measuring?
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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 |