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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: PT001; Drug: PT005; Drug: PT003; Drug: PT001 + PT005

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Queensland
    • Herston, Queensland, Australia, 4006
      • Dr Joanne Marjason

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; Inhaled PT001 18 μg	Drug: PT001; Inhaled PT001, single dose
Experimental: 2; Inhaled PT005 2.4 μg	Drug: PT005; Inhaled PT005, single dose
Experimental: 3; Inhaled PT003 (PT001 18 μg / 2.4 μg PT005)	Drug: PT003; Inhaled PT003, single dose
Experimental: 4; PT001 18 μg + PT005 2.4 μg	Drug: PT001 + PT005; Inhaled PT001 + PT005, single dose

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Pearl Therapeutics, Inc.
• Investigators: Study Director: Colin Reisner, M.D., Pearl Therapeutics

Study record dates

Study Major Dates

• Study Start: May 1, 2009
• Primary Completion (Actual): July 1, 2009
• Study Completion (Actual): July 1, 2009

Study Registration Dates

• First Submitted: May 5, 2009
• First Submitted That Met QC Criteria: May 5, 2009
• First Posted (Estimate): May 6, 2009

Study Record Updates

• Last Update Posted (Actual): April 26, 2017
• Last Update Submitted That Met QC Criteria: March 16, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: Healthy Volunteers
• Other Study ID Numbers: PT0030901

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No