Study to Evaluate Single Inhaled Doses of PT001, PT003, PT005 and PT001 Plus PT005 in Healthy Subjects

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety of a single dose of PT003 compared with single doses of PT001 and PT005, and compared with PT001 plus PT005 delivered together as two separate single doses in healthy subjects.

Official Title
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A Randomized, Double-blind, Single Dose, Four-period, Four-treatment, Cross-over Study Evaluating the Safety of PT001, PT003, PT005 Administered Individually and PT001 + PT005 Delivered Together in Separate Inhalers in Healthy Subjects

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: PT001
* Drug: PT005
* Drug: PT003
* Drug: PT001 + PT005


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provide signed written informed consent 18-55 years of age Healthy subjects confirmed by medical history, physical examination, vital signs, pulmonary function tests, electrocardiogram and clinical laboratory tests Female subjects of child-bearing potential who are sexually active must be willing to undergo a pregnancy test and agree to use two forms of contraception Body mass index (BMI) between 18.5 and 30, inclusive Non-smokers for at least 6 months prior to screening Pulmonary function tests within normal limits Willing to remain at the study center for at least 12-24 hours on each test day Venous access in both arms to allow collection of numerous blood samples Exclusion Criteria: Women who are pregnant or lactating Clinically significant medical conditions Viral illness within the last 30 days Symptomatic prostatic hypertrophy or bladder neck obstruction Known narrow-angle glaucoma History of bowel obstruction Clinically significant abnormal electrocardiogram Positive Hepatitis B surface antigen or positive Hepatitis C antibody Positive screening test for HIV antibodies History of hypersensitivity to any beta2-agonists, anticholinergics, or any component of the MDI Known or suspected history of alcohol or drug abuse within the last 2-years Greater than normal alcohol consumption Ingestion of any poppy seeds within the 48 hours prior to the screening Ingestion of any poppy seeds within the 48 hours prior to, or any alcohol, xanthines or grapefruit-containing foods or beverages within the 24 hours prior to, or during, each confinement Positive breath alcohol result Positive urine drug screen Use of any beta2-agonists,or anticholinergics prior to the recruitment interview Lower respiratory tract infections requiring antibiotics in the previous 6 weeks Use of any other prescription medication Use of any over the counter product, herbal product, diet aid, hormone supplement Donation > 450 ml of blood within 8 weeks of first treatment dose Clinically significant vital sign abnormality Clinically significant biochemical, hematological or urinalysis abnormality Affiliations with investigator site Treatment with investigational study drug or participation in another clinical trial or study within the last 30 days or 5 half lives prior to screening, whichever is longer

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Inhaled PT001 18 μg | Drug: PT001<br>* Inhaled PT001, single dose<br>|
| Experimental: 2<br>Inhaled PT005 2.4 μg | Drug: PT005<br>* Inhaled PT005, single dose<br>|
| Experimental: 3<br>Inhaled PT003 (PT001 18 μg / 2.4 μg PT005) | Drug: PT003<br>* Inhaled PT003, single dose<br>|
| Experimental: 4<br>PT001 18 μg + PT005 2.4 μg | Drug: PT001 + PT005<br>* Inhaled PT001 + PT005, single dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Symptoms of Dry Mouth | Number of participants reporting dry mouth at 12 hours post-dose | 12 hours | 
| Symptoms of Tremor | Number of participants reporting tremor at 12 hours post-dose | 12 hours | 
| Blood Chemistry Change From Baseline | Series of 11 blood chemistries assessed throughout the study | 24 hours post dose for sentinel subjects, 12 hours post dose for subsequent subjects | 
| Hematology Change From Baseline | Hematology assessments taken throughout the study Hematocrit | 24 hours post dose for sentinel subjects, 12 hours post dose for subsequent subjects | 
| Hematology Change From Baseline | Hematology assessments taken throughout the study | 24 hours post dose for sentinel subjects, 12 hours post dose for subsequent subjects | 
| Hematology Change From Baseline | Hematology assessments taken throughout the study Hemoglobin | 24 hours post dose for sentinel subjects, 12 hours post dose for subsequent subjects | 
| Heart Rate Change From Baseline | Change from baseline for heart rate 12-hours post-dose Heart rate (bpm) | 12 hours | 
| Vital Sign Change Baseline; Blood Pressure | Vital sign change baseline; blood pressure | 12 hours | 
| Vital Sign Change From Baseline, SpO2 | Vital Sign Change from baseline 12-hours post-dose SpO2 (%) | 12 hours | 
| ECG Change From Baseline | Change from baseline for ECG parameters 12-hours post-dose Ventricular rate (bpm) | 12 hours | 
| ECG Change From Baseline | Change from baseline for ECG parameters 12-hours post-dose | 12 hours | 
| Spirometry Change From Baseline | Change from baseline for spirometery measures 12-hours post-dose | 12 hours | 
| Spirometry Change From Baseline | Change from baseline for spirometery measures 12-hours post-dose (FEV1 % predicted) | 12 hours | 
| Spirometry Change From Baseline | Change from baseline for spirometery measures 12-hours post-dose FEV/FVC (%) | 12 hours | 
| Spirometry Change From Baseline | Change from baseline for spirometery measures 12-hours post-dose PEFR (L/min) | 12 hours | 
| Serum Potassium Change From Baseline |  | 12 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma Glycopyrrolate PK Parameters | Various pharmacokinetic parameters for plasma glycopyrrolate | Concentrations were measured at pre-dose and 2,5,15, and 30 minutes post dose as well as 1,2,4,6,8, and 12 hours post dose | 
| Plasma Glycopyrrolate PK Parameters AUC0-inf (h*pg/mL) | Various pharmacokinetic parameters for plasma glycopyrrolate | Concentrations were measured at pre-dose and 2,5,15, and 30 minutes post dose as well as 1,2,4,6,8, and 12 hours post dose | 
| Plasma Glycopyrrolate PK Parameters (Tmax) | Various pharmacokinetic parameters for plasma glycopyrrolate | Concentrations were measured at pre-dose and 2,5,15, and 30 minutes post dose as well as 1,2,4,6,8, and 12 hours post dose | 
| Plasma Glycopyrrolate PK Parameters (t1/2) | Various pharmacokinetic parameters for plasma glycopyrrolate | Concentrations were measured at pre-dose and 2,5,15, and 30 minutes post dose as well as 1,2,4,6,8, and 12 hours post dose | 
| Plasma Glycopyrrolate PK Parameters Cmax (pg/mL) | Various pharmacokinetic parameters for plasma glycopyrrolate | Concentrations were measured at pre-dose and 2,5,15, and 30 minutes post dose as well as 1,2,4,6,8, and 12 hours post dose | 
| Plasma Glycopyrrolate PK Parameters (ke) | Various pharmacokinetic parameters for plasma glycopyrrolate | Concentrations were measured at pre-dose and 2,5,15, and 30 minutes post dose as well as 1,2,4,6,8, and 12 hours post dose | 
| Plasma Formoterol PK Parameters | Various pharmacokinetic parameters for plasma formoterol | Concentrations were measured at pre-dose and 2,5,15, and 30 minutes post dose as well as 1,2,4,6,8, and 12 hours post dose | 
| Plasma Formoterol PK Parameters AUC0-inf (h*pg/mL) | Various pharmacokinetic parameters for plasma formoterol | Concentrations were measured at pre-dose and 2,5,15, and 30 minutes post dose as well as 1,2,4,6,8, and 12 hours post dose | 
| Plasma Formoterol PK Parameters (Tmax) | Various pharmacokinetic parameters for plasma formoterol | Concentrations were measured at pre-dose and 2,5,15, and 30 minutes post dose as well as 1,2,4,6,8, and 12 hours post dose | 
| Plasma Formoterol PK Parameters (t1/2) | Various pharmacokinetic parameters for plasma formoterol | Concentrations were measured at pre-dose and 2,5,15, and 30 minutes post dose as well as 1,2,4,6,8, and 12 hours post dose | 
| Plasma Formoterol PK Parameters (Cmax) | Pharmacokinetic parameters for plasma formoterol Cmax | Concentrations were measured at pre-dose and 2,5,15, and 30 minutes post dose as well as 1,2,4,6,8, and 12 hours post dose | 
| Plasma Formoterol PK Parameters (ke) | Pharmacokinetic parameters for plasma formoterol ke | Concentrations were measured at pre-dose and 2,5,15, and 30 minutes post dose as well as 1,2,4,6,8, and 12 hours post dose | 

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