PK Study of PT003 and PT001 in Japanese Healthy Subjects

Study Overview
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Brief Summary
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A Randomized, Double-Blind, Single-Dose, Four-Period, Four-Treatment, Cross-Over, Single-Center, Phase I, Crossover Study in Healthy Japanese Adult Subjects to Evaluate the Safety and Pharmacokinetics of Two Doses of PT003 and Two Doses of PT001.

Official Title
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A Phase I, Randomized, Double-Blind, Single-Dose, Four-Period, Four-Treatment, Cross-Over Study Evaluating the Safety and Pharmacokinetics of Two Doses of PT003 and Two Doses of PT001 in Japanese Healthy Subjects

Conditions
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COPD

Intervention / Treatment
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* Drug: Glycopyrronium and Formoterol Fumarate (GFF) Dose 1
* Drug: Glycopyrronium and Formoterol Fumarate (GFF) Dose 2
* Drug: Glycopyrronium (GP) Dose 1
* Drug: Glycopyrronium (GP) Dose 2


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed Consent Form (ICF) prior to any study related procedures Male and female first generation Japanese subjects 18 to 45 years, inclusive Good general health Medically acceptable contraception for women of child-bearing potential and males with female partners of childbearing potential Clinical labs within normal ranges or determined to be not clinically significant by the Investigator Exclusion Criteria: Pregnancy, nursing female subjects, or subjects trying to conceive Clinically significant neurologic, cardiovascular, hepatic, renal, endocrinologic, pulmonary, hematological, psychiatric, or other medical illness that would interfere with participation in this study History of ECG abnormalities Cancer not in complete remission for at least 5 years Clinically significant, symptomatic prostatic hypertrophy Male subjects with a trans-urethral resection of the prostate or full resection of the prostate within 6 months prior to Screening Clinically significant bladder neck obstruction or urinary retention Inadequately treated glaucoma History of an allergic reaction or hypersensitivity to any drug or to any component of the formulations used in this study Subjects with pre-existing anemia and/or iron deficiency

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: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Glycopyrronium and Formoterol Fumarate (GFF) Dose 1<br>Glycopyrronium and Formoterol Fumarate metered-dose inhaler MDI (GFF MDI), Dose 1; PT003 administered as 2 inhalations twice-daily (BID) | Drug: Glycopyrronium and Formoterol Fumarate (GFF) Dose 1<br>* Glycopyrronium and Formoterol Fumarate metered-dose inhaler MDI (GFF MDI), Dose 1; PT003 administered as 2 inhalations twice-daily (BID)<br>|
| Experimental: Glycopyrronium and Formoterol Fumarate (GFF) Dose 2<br>Glycopyrronium and Formoterol Fumarate metered-dose inhaler MDI (GFF MDI), Dose 2; PT003 administered as 2 inhalations twice-daily (BID) | Drug: Glycopyrronium and Formoterol Fumarate (GFF) Dose 2<br>* Glycopyrronium and Formoterol Fumarate metered-dose inhaler MDI (GFF MDI), Dose 2; PT003 administered as 2 inhalations twice-daily (BID)<br>|
| Experimental: Glycopyrronium (GP) Dose 1<br>Glycopyrronium metered-dose inhaler MDI (GP MDI), Dose 1; PT001 administered as 2 inhalations twice-daily (BID) | Drug: Glycopyrronium (GP) Dose 1<br>* Glycopyrronium metered-dose inhaler MDI (GP MDI), Dose 1; PT001 administered as 2 inhalations twice-daily (BID)<br>|
| Experimental: Glycopyrronium (GP) Dose 2<br>Glycopyrronium metered-dose inhaler MDI (GP MDI), Dose 2; PT001 administered as 2 inhalations twice-daily (BID) | Drug: Glycopyrronium (GP) Dose 2<br>* Glycopyrronium metered-dose inhaler MDI (GP MDI), Dose 2; PT001 administered as 2 inhalations twice-daily (BID)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax | Descriptive Statistics for Pharmacokinetic Parameters of Glycopyrronium by Treatment (Cmax) | Day 1 | 
| Cmax | Descriptive Statistics for Pharmacokinetic Parameters of Formoterol by Treatment (Cmax) | Day 1 | 
| AUC 0-12 | Descriptive Statistics for Pharmacokinetic Parameters of Glycopyrronium by Treatment (AUC 0-12) | Day 1 | 
| AUC 0-12 | Descriptive Statistics for Pharmacokinetic Parameters of Formoterol by Treatment (AUC 0-12) | Day 1 | 
| AUC 0-t | Descriptive Statistics for Pharmacokinetic Parameters of Glycopyrronium by Treatment (AUC 0-t) | Day 1 | 
| AUC 0-t | Descriptive Statistics for Pharmacokinetic Parameters of Formoterol by Treatment (AUC 0-t) | Day 1 | 
| AUC 0-∞ | Descriptive Statistics for Pharmacokinetic Parameters of Glycopyrronium by Treatment (AUC 0-∞) | Day 1 | 
| AUC 0-∞ | Descriptive Statistics for Pharmacokinetic Parameters of Formoterol by Treatment (AUC 0-∞) | Day 1 | 
| Tmax | Descriptive Statistics for Pharmacokinetic Parameters of Glycopyrronium by Treatment (tmax) | Day 1 | 
| Tmax | Descriptive Statistics for Pharmacokinetic Parameters of Formoterol by Treatment (tmax) | Day 1 | 
| T 1/2 | Descriptive Statistics for Pharmacokinetic Parameters of Glycopyrronium by Treatment (T 1/2) | Day 1 | 
| T 1/2 | Descriptive Statistics for Pharmacokinetic Parameters of Formoterol by Treatment (T 1/2) | Day 1 | 
| CL/F | Descriptive Statistics for Pharmacokinetic Parameters of Glycopyrronium by Treatment | Day 1 | 
| CL/F | Descriptive Statistics for Pharmacokinetic Parameters of Formoterol by Treatment | Day 1 | 
| Vd/F | Descriptive Statistics for Pharmacokinetic Parameters of Glycopyrroniuml by Treatment | Day 1 | 
| Vd/F | Descriptive Statistics for Pharmacokinetic Parameters of Formoterol by Treatment | Day 1 | 
| Lambda z | Descriptive Statistics for Pharmacokinetic Parameters of Glycopyrronium by Treatment | Day 1 | 
| Lambda z | Descriptive Statistics for Pharmacokinetic Parameters of Formoterol by Treatment | Day 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Mean Hematology Parameters (±SD) From Pre-dose to 12 Hours Post-dose | Change in Mean Hematology Parameters (±SD) from Pre-dose to 12 Hours Post-dose | 12 Hours | 
| Change in Mean Hematology Parameters (±SD) From Pre-dose to 12 Hours Post-dose | Change in Mean Hematology Parameters (±SD) from Pre-dose to 12 Hours Post-dose (Ery. mean corpuscuar volume) | 12 Hours | 
| Change in Mean Hematology Parameters (±SD) From Pre-dose to 12 Hours Post-dose | Change in Mean Hematology Parameters (±SD) from Pre-dose to 12 Hours Post-dose (Ery. mean corpuscuar hemoglobin) | 12 Hours | 
| Change in Mean Hematology Parameters (±SD) From Pre-dose to 12 Hours Post-dose | Change in Mean Hematology Parameters (±SD) from Pre-dose to 12 Hours Post-dose (Erythrocytes) | 12 Hours | 
| Change in Mean Chemistry Parameters (±SD) From Pre-dose to 12 Hours Post-dose | Change in Mean Chemistry Parameters (±SD) from Pre-dose to 12 Hours Post-dose | 12 hours | 
| Change in Mean Chemistry Parameters (±SD) From Pre-dose to 12 Hours Post-dose | Change in Mean Chemistry Parameters (±SD) from Pre-dose to 12 Hours Post-dose (eGFR) | 12 hours | 
| Change in Mean Chemistry Parameters (±SD) From Pre-dose to 12 Hours Post-dose | Change in Mean Chemistry Parameters (±SD) from Pre-dose to 12 Hours Post-dose (Ferritin) | 12 hours | 
| Change in Mean Glucose and Potassium Results (±SD) From Pre-dose to 12 Hours Post-dose | Change in Mean Glucose and Potassium Results (±SD) from Pre-dose to 12 Hours Post-dose | 12 hours | 
| Change in Heart Rate From Pre-dose to 12 Hours Post Dose | Change in Heart Rate from Pre-dose to 12 hours Post dose | 12 hours | 
| Change in PR Interval From Pre-dose to 12 Hours Post Dose | Change in PR Interval from Pre-dose to 12 hours Post dose | 12 hours | 
| Change in QRS Axis From Pre-dose to 12 Hours Post Dose | Change in QRS axis from Pre-dose to 12 hours Post dose | 12 hours | 
| Change in QRS Duration From Pre-dose to 12 Hours Post Dose | Change in QRS duration from Pre-dose to 12 hours Post dose | 12 hours | 
| Change in QT Interval From Pre-dose to 12 Hours Post Dose | Change in QT Interval from Pre-dose to 12 hours Post dose | 12 hours | 
| Change in QTc Bazett Interval From Pre-dose to 12 Hours Post Dose | Change in QTc Bazett Interval from Pre-dose to 12 hours Post dose | 12 hours | 
| Change in QTc Fridericia's Interval From Pre-dose to 12 Hours Post Dose | Change in QTc Fridericia's Interval from Pre-dose to 12 hours Post dose | 12 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Japanese Healthy Volunteers