Pharmacokinetics and Safety Study of PT010 in Healthy Subjects

A Phase I, Randomized, Double-Blind, Single-Dose, Three-Period, Three-Treatment, Cross-Over Study Evaluating the Pharmacokinetics and Safety of a Single Dose of PT010, a Single Dose of PT009, and a Single Dose of Open-Label Symbicort® Turbohaler® in Healthy Subjects

This is a single-center, Phase I, healthy adult subject study with a randomized, double blind, three period, three-treatment, cross-over design.

Study Overview

• Status: Completed
• Conditions: COPD
• Intervention / Treatment: Drug: PT009; Drug: Symbicort Turbohaler; Drug: PT010

• Study Type: Interventional
• Enrollment (Actual): 59
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • SNBL Clinical Pharmacology Center

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:

• Informed Consent Form (ICF) prior to any study related procedures
• Male and female subjects 18 to 55 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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PT010; PT010; Budesonide, Glycopyrrolate, and Formoterol Fumarate Inhalation Aerosol. Administered as 2 inhalations	Drug: PT009; PT009 administered as 2 inhalations; Other Names: PT009; Budesonide and Formoterol Fumarate Inhalation Aerosol. Administered as 2 inhalations; Drug: Symbicort Turbohaler; Symbicort Turbohaler taken as 2 inhalations; Other Names: Symbicort Turbohaler; Budesonide and Formoterol Fumarate Inhalation Powder
Experimental: PT009; PT009; Budesonide and Formoterol Fumarate Inhalation Aerosol. Administered as 2 inhalations	Drug: Symbicort Turbohaler; Symbicort Turbohaler taken as 2 inhalations; Other Names: Symbicort Turbohaler; Budesonide and Formoterol Fumarate Inhalation Powder; Drug: PT010; PT010; Budesonide, Glycopyrrolate, and Formoterol Fumarate Inhalation Aerosol. Administered as 2 inhalations; Other Names: PT010; Budesonide, Glycopyrrolate, and Formoterol Fumarate Inhalation Aerosol
Active Comparator: Symbicort Turbohaler; Symbicort Turbohaler; Budesonide and Formoterol Fumarate Inhalation Powder taken as 2 inhalations	Drug: PT009; PT009 administered as 2 inhalations; Other Names: PT009; Budesonide and Formoterol Fumarate Inhalation Aerosol. Administered as 2 inhalations; Drug: PT010; PT010; Budesonide, Glycopyrrolate, and Formoterol Fumarate Inhalation Aerosol. Administered as 2 inhalations; Other Names: PT010; Budesonide, Glycopyrrolate, and Formoterol Fumarate Inhalation Aerosol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Safety of PT010, PT009 and Symbicort Turbohaler	The safety of PT010 and PT009 and Symbicort Turbohaler will be assessed based on physical examination, adverse events, vital signs, clinical laboratory values, and electrocardiogram	12 hours post dose

Secondary Outcome Measures

Outcome Measure	Time Frame
◦Maximum plasma concentration (Cmax) of PT010, PT009 and Symbicort Turbohaler	12 Hour post dose
◦Area under the curve from 0 to 12 hours (AUC0 12) of PT010, PT009 and Symbicort Turbohaler	12 Hour post dose
◦Area under the curve from 0 to the time of the last measureable plasma concentration (AUC0 t) of PT010, PT009 and Symbicort Turbohaler	12 Hour post dose
◦Area under the curve from 0 extrapolated to infinity (AUC0-∞) of PT010, PT009, and Symbicort Turbohaler	12 Hour post dose
◦Time to maximum plasma concentration (tmax) of PT010, PT009, and Symbicort Turbohaler	12 Hour post dose
◦Apparent terminal elimination half life (t½) of PT010, PT009, and Symbicort Turbohaler	12 Hour post dose
◦Apparent total body clearance (CL/F) of PT010, PT009, and Symbicort Turbohaler	12 Hour post dose
◦Apparent volume of distribution (Vd/F) of PT010, PT009, and Symbicort Turbohaler	12 Hour post dose
◦Termination elimination rate constant (λz) of PT010, PT009, and Symbicort Turbohaler	12 Hour post dose

Collaborators and Investigators

• Sponsor: Pearl Therapeutics, Inc.
• Investigators: Study Chair: Chadwick Orevillo, Pearl Therapeutics

Publications and helpful links

General Publications

• Huang Y, Assam PN, Feng C, Su R, Dorinsky P, Gillen M. Ethnic pharmacokinetic comparison of budesonide/glycopyrrolate/formoterol fumarate metered dose inhaler (BGF MDI) between Asian and Western healthy subjects. Pulm Pharmacol Ther. 2020 Oct;64:101976. doi: 10.1016/j.pupt.2020.101976. Epub 2020 Nov 2.
• Maes A, DePetrillo P, Siddiqui S, Reisner C, Dorinsky P. Pharmacokinetics of Co-Suspension Delivery Technology Budesonide/Glycopyrronium/Formoterol Fumarate Dihydrate (BGF MDI) and Budesonide/Formoterol Fumarate Dihydrate (BFF MDI) Fixed-Dose Combinations Compared With an Active Control: A Phase 1, Randomized, Single-Dose, Crossover Study in Healthy Adults. Clin Pharmacol Drug Dev. 2019 Feb;8(2):223-233. doi: 10.1002/cpdd.585. Epub 2018 Jun 14.

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2014
• Primary Completion (Actual): September 1, 2014
• Study Completion (Actual): September 1, 2014

Study Registration Dates

• First Submitted: July 9, 2014
• First Submitted That Met QC Criteria: July 10, 2014
• First Posted (Estimate): July 14, 2014

Study Record Updates

• Last Update Posted (Actual): June 13, 2018
• Last Update Submitted That Met QC Criteria: June 11, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Keywords: Healthy volunteers
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Adrenergic Agonists; Adjuvants, Anesthesia; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Budesonide; Glycopyrrolate; Formoterol Fumarate; Budesonide, Formoterol Fumarate Drug Combination
• Other Study ID Numbers: PT010002-00

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No