A Drug Interaction Study to Evaluate the Pharmacokinetics of ASP015K and Metformin

ASP015K Pharmacokinetic Study: Evaluation of Drug-Drug Interaction Between ASP015K and Metformin

The objective of this study is to evaluate the pharmacokinetic interactions between ASP015K and metformin in healthy non-elderly male subjects.

Study Overview

• Status: Completed
• Conditions: Healthy Subjects
• Intervention / Treatment: Drug: peficitinib; Drug: Metformin

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

Contacts and Locations

Study Locations

• Japan
  • Kagoshima, Japan
    • Site JP00001

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 44 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Body weight at screening: ≥ 50.0 kg, < 80.0 kg
• BMI at screening: ≥ 17.6, < 26.4
• Subjects who agree to use highly effective contraception as consisting of two forms of birth control (at least one of which must be a barrier method) from getting informed consent through 90 days after the final study drug administration.
• Subjects who agree NOT to donate sperm from getting informed consent through 90 days after the final study drug administration.

Exclusion Criteria:

• Subjects who received or are scheduled to receive any investigational drugs in other clinical trials or post-marketing studies within 120 days before screening test or during the screening test to the hospital admission (Day -1).
• Subjects who received or is scheduled to receive any medications (including over-the-counter drugs) within seven days before the hospital admission (Day -1).
• Subjects who received ASP015K or metformin previously.
• Subjects who have a habit of excessive alcohol drinking or smoking.
• Any deviation from the normal range of blood pressure, pulse, body temperature, or 12-lead ECG at screening or on the day of hospital admission (Day -1).
• Subjects who meet any of the following criterion for laboratory tests at screening or on the day of hospital admission (Day -1). Normal ranges of each test specified at the study site or test/assay organization will be used as the normal ranges in this study.
• Subjects with a complication or history of drug allergies.
• Subjects who have a history of clinically serious allergy, which induces generalized urticaria or anaphylactic shock requiring hospital admission.
• Subjects with a complication or history of hepatic disease, renal disease, cardiac disease, congenital short QT syndrome, respiratory disease , gastrointestinal disease.
• Subjects with a history of gastrointestinal resection.
• Subjects who developed upper gastrointestinal symptoms within seven days before the hospital admission (Day -1).
• Subjects with a complication or history of endocrine disease, cerebrovascular disease, malignant tumor, lymphatic disease , lactic acidosis.
• Subjects who apply to any of the concerns with regard to tuberculosis.
• Subjects who apply to any of the concerns with regard to infection other than tuberculosis.
• Subjects with vaccination of live vaccines or live attenuated vaccines within 56 days before the hospital admission (Day -1).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ASP015K and Metformin; Subjects will receive a single oral dose of metformin on Days 1 and 10, a single dose of ASP015K on Day 3 and multiple doses of ASP015K once daily Day 5 to Day 11. Subjects will receive a single dose of metformin and ASP015K concurrently on Day 10.	Drug: peficitinib; Oral; Other Names: ASP015K; Drug: Metformin; Oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics (PK) parameter of metformin in plasma: AUCinf	AUCinf: Area under the concentration-time curve from the time of dosing extrapolated to time infinity	Up to Day 12
PK parameter of metformin in plasma: Cmax	Cmax: Maximum concentration	Up to Day 12
PK parameter of metformin in plasma: AUClast	AUClast: Area under the concentration-time curve from the time of dosing to the last measurable concentration	Up to Day 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PK parameter of metformin in plasma: CL/F	CL/F: Apparent total systemic clearance	Up to Day 12
PK parameter of metformin in plasma: t1/2	t1/2: Terminal elimination half-life	Up to Day 12
PK parameter of metformin in plasma: tmax	tmax: Time of Cmax	Up to Day 12
PK parameter of metformin in plasma: Vz/F	Vz/F: Apparent volume of distribution during the terminal elimination phase	Up to Day 12
PK parameter of metformin in urine: Aelast	Aelast: Amount of metformin excreted into the urine from the time of dosing to the last measurable concentration	Up to Day 12
PK parameter of metformin in urine: Aelast%	Aelast%: Percent of metformin excreted into the urine from the time of dosing to the last measurable concentration	Up to Day 12
PK parameter of metformin in urine: CLR	CLR: Renal clearance	Up to Day 12
PK parameter of ASP015K in plasma: AUCinf		Up to Day 12
PK parameter of ASP015K in plasma: AUClast		Up to Day 12
PK parameter of ASP015K in plasma: AUCtau	AUCtau: Area under the concentration-time curve from the time of dosing to the start of the next dosing interval	Up to Day 12
PK parameter of ASP015K in plasma: CL/F		Up to Day 12
PK parameter of ASP015K in plasma: Cmax		Up to Day 12
PK parameter of ASP015K in plasma: Ctrough	Ctrough: Concentration immediately prior to dosing at multiple dosing	Up to Day 12
PK parameter of ASP015K in plasma: PTR	PTR: Peak trough ratio	Up to Day 12
PK parameter of ASP015K in plasma: Rac	Rac: accumulation ratio	Up to Day 12
PK parameter of ASP015K in plasma: t1/2		Up to Day 12
PK parameter of ASP015K in plasma: tmax		Up to Day 12
PK parameter of ASP015K in plasma: Vz/F		Up to Day 12
PK parameter of metabolites of ASP015K in plasma: AUCinf		Up to Day 12
PK parameter of metabolites of ASP015K in plasma: AUClast		Up to Day 12
PK parameter of metabolites of ASP015K in plasma: AUCtau		Up to Day 12
PK parameter of metabolites of ASP015K in plasma: Cmax		Up to Day 12
PK parameter of metabolites of ASP015K in plasma: Ctrough		Up to Day 12
PK parameter of metabolites of ASP015K in plasma: PTR		Up to Day 12
PK parameter of metabolites of ASP015K in plasma: Rac		Up to Day 12
PK parameter of metabolites of ASP015K in plasma: t1/2		Up to Day 12
PK parameter of metabolites of ASP015K in plasma: tmax		Up to Day 12
Safety assessed by Adverse events		Up to 17 days after first study drug dosing
Number of participants with abnormal vital signs and/or adverse events related to treatment		Up to 17 days after first study drug dosing
Number of participants with abnormal laboratory values and/or adverse events related to treatment		Up to 17 days after first study drug dosing
Number of participants with abnormal standard 12-lead ECG and/or adverse events related to treatment	ECG: Electrocardiogram	Up to 17 days after first study drug dosing

Collaborators and Investigators

• Sponsor: Astellas Pharma Inc

Publications and helpful links

General Publications

• Toyoshima J, Shibata M, Kaibara A, Kaneko Y, Izutsu H, Nishimura T. Population pharmacokinetic analysis of peficitinib in patients with rheumatoid arthritis. Br J Clin Pharmacol. 2021 Apr;87(4):2014-2022. doi: 10.1111/bcp.14605. Epub 2020 Dec 1.

Study record dates

Study Major Dates

• Study Start (Actual): May 15, 2016
• Primary Completion (Actual): June 26, 2016
• Study Completion (Actual): June 26, 2016

Study Registration Dates

• First Submitted: May 1, 2016
• First Submitted That Met QC Criteria: May 1, 2016
• First Posted (Estimate): May 3, 2016

Study Record Updates

• Last Update Posted (Actual): September 20, 2019
• Last Update Submitted That Met QC Criteria: September 19, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Metformin; ASP015K; Drug-drug interaction
• Additional Relevant MeSH Terms: Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Immunosuppressive Agents; Immunologic Factors; Metformin; Peficitinib
• Other Study ID Numbers: 015K-CL-PK20

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Access to anonymized individual participant level data will not be provided for this trial as it meets one or more of the exceptions described on www.clinicalstudydatarequest.com under "Sponsor Specific Details for Astellas."