PK Study of PT003 and PT001 in Japanese Healthy Subjects

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

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.

Study Overview

• Status: Completed
• Conditions: COPD
• Intervention / Treatment: 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

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • SNBL

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Reisner C, Miller J, DePetrillo P, Maes A, Siddiqui S, Martin UJ. Pharmacokinetics and safety of a single dose of the novel LAMA/LABA fixed-dose combination of glycopyrronium/formoterol fumarate dihydrate metered dose inhaler, formulated using co-suspension delivery technology, in Japanese healthy subjects. Pulm Pharmacol Ther. 2018 Dec;53:33-38. doi: 10.1016/j.pupt.2018.09.005. Epub 2018 Sep 13.

Study record dates

Study Major Dates

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

Study Registration Dates

• First Submitted: July 18, 2014
• First Submitted That Met QC Criteria: July 18, 2014
• First Posted (Estimate): July 22, 2014

Study Record Updates

• Last Update Posted (Actual): April 26, 2017
• Last Update Submitted That Met QC Criteria: March 14, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: Japanese 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; Adrenergic Agonists; Adjuvants, Anesthesia; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Glycopyrrolate; Formoterol Fumarate
• Other Study ID Numbers: PT003010-00