A Randomized, Open-label, Single-dose, Single-center, Crossover Study in Healthy Subjects to Assess the Relative Bioavailability of PT010

A Randomized, Open-label, Single-dose, Single-center, Crossover Study in Healthy Subjects to Assess the Relative Bioavailability of PT010 Administered With and Without a Spacer, and With and Without Oral Charcoal

Randomized, Open-label, Single-dose, Single-center, Crossover Study in Healthy Subjects to Assess the Relative Bioavailability of PT010

Study Overview

• Status: Completed
• Conditions: Chronic Obstructive Pulmonary Disease
• Intervention / Treatment: Drug: Regimen A; Drug: Regimen B; Drug: Regimen C; Drug: Regimen D

Detailed Description

A Randomized, Open-label, Single-dose, Single-center, Crossover Study in Healthy Subjects to Assess the Relative Bioavailability of PT010 Administered With and Without a Spacer, and With and Without Oral Charcoal

• Study Type: Interventional
• Enrollment (Actual): 56
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Pearl Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

• Signed and dated Independent Ethics Committee (IEC)/Institutional Review Board (IRB)-approved Informed Consent Form (ICF) before any protocol-specific screening procedures are performed
• Male and female subjects 18 to 40 years of age, inclusive
• Be in good general health as determined by a thorough medical history and physical examination, ECG, vital signs, and clinical laboratory evaluation
• Non-childbearing potential (ie, physiologically incapable of becoming pregnant, including any female who is 2 years post-menopausal, or surgically sterile
• Male subjects who are sexually active must agree to use a double-barrier method of contraception (condom with spermicide) from the first dose of randomized study drug until 2 weeks after their last dose, and must not donate sperm during their study participation period
• Screening laboratory tests must be within normal range or determined to not be clinically significant by the Investigator.
• Demonstrate correct MDI administration technique

Key Exclusion Criteria:

• For female subjects, a positive serum human chorionic gonadotropin (hCG) test at screening or a positive urine hCG at admission for any of the 4 Treatment Periods
• 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 who have cancer that has not been in complete remission for at least 5 years
• Male subjects with a trans-urethral resection of the prostate or full resection of the prostate within 6 months prior to screening
• Subjects with bladder neck obstruction or urinary retention that is clinically significant in the opinion of the Investigator
• History of substance-related disorders (with the exception of caffeine-related and nicotine-related disorders) within 1 year of screening
• History of smoking or the use of nicotine-containing products within 3 months of screening by self-reporting
• A positive alcohol breathalyzer or urine drug screen for drugs of abuse at screening or at the beginning of each Treatment Period
• Treatment with any prescription or non-prescription drugs including vitamins, herbal, and dietary supplements for 28 days or 5 half-lives, whichever is longer, before study drug use
• Treatment with an investigational drug within 30 days or 5 half-lives (whichever is longer) prior to the beginning of the screening Period
• Subjects with any flu-like syndrome or other respiratory infections within 2 weeks of drug administration or who have been vaccinated with an attenuated live virus within 4 weeks of drug administration
• Any other condition and/or situation that causes the Investigator to deem a subject unsuitable for the study (eg, inability to medically tolerate the study procedures, or a subject's unwillingness to comply with study-related procedures)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment Period 1; Test Formulation (Regimen B or D) or Reference Formulation (Regimen A or C)	Drug: Regimen A; 2 inhalations BGF MDI; no spacer device; no oral charcoal - reference formulation/total systemic exposure; Drug: Regimen B; 2 inhalations BGF MDI; AeroChamber Plus Flow-Vu spacer device; no oral charcoal - test formulation/total systemic exposure; Drug: Regimen C; 2 inhalations BGF MDI; no spacer device; with oral charcoal - reference formulation/lung exposure; Drug: Regimen D; 2 inhalations BGF MDI; AeroChamber Plus Flow-Vu spacer device; with oral charcoal - test formulation/lung exposure
Experimental: Treatment Period 2; Test Formulation (Regimen (B or D) or Reference Formulation (Regimen A or C)	Drug: Regimen A; 2 inhalations BGF MDI; no spacer device; no oral charcoal - reference formulation/total systemic exposure; Drug: Regimen B; 2 inhalations BGF MDI; AeroChamber Plus Flow-Vu spacer device; no oral charcoal - test formulation/total systemic exposure; Drug: Regimen C; 2 inhalations BGF MDI; no spacer device; with oral charcoal - reference formulation/lung exposure; Drug: Regimen D; 2 inhalations BGF MDI; AeroChamber Plus Flow-Vu spacer device; with oral charcoal - test formulation/lung exposure
Experimental: Treatment Period 3; Test Formulation (Regimen (B or D) or Reference Formulation (Regimen A or C)	Drug: Regimen A; 2 inhalations BGF MDI; no spacer device; no oral charcoal - reference formulation/total systemic exposure; Drug: Regimen B; 2 inhalations BGF MDI; AeroChamber Plus Flow-Vu spacer device; no oral charcoal - test formulation/total systemic exposure; Drug: Regimen C; 2 inhalations BGF MDI; no spacer device; with oral charcoal - reference formulation/lung exposure; Drug: Regimen D; 2 inhalations BGF MDI; AeroChamber Plus Flow-Vu spacer device; with oral charcoal - test formulation/lung exposure
Experimental: Treatment Period 4; Test Formulation (Regimen (B or D) or Reference Formulation (Regimen A or C)	Drug: Regimen A; 2 inhalations BGF MDI; no spacer device; no oral charcoal - reference formulation/total systemic exposure; Drug: Regimen B; 2 inhalations BGF MDI; AeroChamber Plus Flow-Vu spacer device; no oral charcoal - test formulation/total systemic exposure; Drug: Regimen C; 2 inhalations BGF MDI; no spacer device; with oral charcoal - reference formulation/lung exposure; Drug: Regimen D; 2 inhalations BGF MDI; AeroChamber Plus Flow-Vu spacer device; with oral charcoal - test formulation/lung exposure

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Plasma Concentration (Cmax)-Budesonide	Maximum plasma concentration (Cmax) per Regimen	Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 12 and 24 h post-dose
Maximum Plasma Concentration (Cmax)-Glycopyrronium	Maximum plasma concentration (Cmax) per Regimen	Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 12 and 24 h post-dose
Maximum Plasma Concentration (Cmax)-Formoterol	Maximum plasma concentration (Cmax) per Regimen	Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 12 and 24 h post-dose
Area Under the Plasma Concentration-time Curve From 0 the Time of the Last Measurable Plasma Concentration (AUC0-tlast)-Budesonide	Each treatment period is equal to assigned regimen	Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 12 and 24 h post-dose
Area Under the Plasma Concentration-time Curve From 0 the Time of the Last Measurable Plasma Concentration (AUC0-tlast)-Glycopyrronium	Each treatment period is equal to assigned regimen	Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 12 and 24 h post-dose
Area Under the Plasma Concentration-time Curve From 0 the Time of the Last Measurable Plasma Concentration (AUC0-tlast)-Formoterol	Each treatment period is equal to assigned regimen	Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 12 and 24 h post-dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Maximum Plasma Concentration (Tmax)-Budesonide	Each treatment period is equal to assigned regimen	Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 12 and 24 h post-dose
Time to Maximum Plasma Concentration (Tmax)-Glycopyrronium	Each treatment period is equal to assigned regimen	Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 12 and 24 h post-dose
Time to Maximum Plasma Concentration (Tmax)-Formoterol	Each treatment period is equal to assigned regimen	Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 12 and 24 h post-dose
Area Under the Plasma Concentration-time Curve From 0 Extrapolated to Infinity (AUC0-∞);-Budesonide	Each treatment period is equal to assigned regimen	Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 12 and 24 h post-dose
Area Under the Plasma Concentration-time Curve From 0 Extrapolated to Infinity (AUC0-∞);-Glycopyrronium	Each treatment period is equal to assigned regimen	Pre-dose and 2, 6, 20, 40 min, 1, 2, 4, 8, 12 and 24 h post-dose
Area Under the Plasma Concentration-time Curve From 0 Extrapolated to Infinity (AUC0-∞);-Formoterol	Each treatment period is equal to assigned regimen	24 hrs

Collaborators and Investigators

• Sponsor: Pearl Therapeutics, Inc.
• Investigators: Study Director: Paul M. Dorinsky, MD, Pearl Therapeutics, Inc.

Publications and helpful links

General Publications

• Dorinsky P, DePetrillo P, DeAngelis K, Trivedi R, Darken P, Gillen M. Relative Bioavailability of Budesonide/Glycopyrrolate/Formoterol Fumarate Metered Dose Inhaler Administered With and Without a Spacer: Results of a Phase I, Randomized, Crossover Trial in Healthy Adults. Clin Ther. 2020 Apr;42(4):634-648. doi: 10.1016/j.clinthera.2020.02.012. Epub 2020 Apr 3.

Helpful Links

• Related Info
• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): October 17, 2017
• Primary Completion (Actual): December 15, 2017
• Study Completion (Actual): December 15, 2017

Study Registration Dates

• First Submitted: October 11, 2017
• First Submitted That Met QC Criteria: October 11, 2017
• First Posted (Actual): October 17, 2017

Study Record Updates

• Last Update Posted (Actual): June 11, 2020
• Last Update Submitted That Met QC Criteria: June 8, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: COPD
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: PT010011

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

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