The Study of Pharmacokinetic Interactions Between HL237 and Tacrolimus

An Open-label, Multiple-dose, Fixed-sequence, 3-Period Study to Evaluate the Pharmacokinetic Interactions Between HL237 and Tacrolimus in Healthy Male Subjects

This study aims to evaluate the pharmacokinetic interaction between HL237 and tacrolimus in healthy male subjects.

Study Overview

• Status: Unknown
• Conditions: Healthy Male Volunteers
• Intervention / Treatment: Drug: HL237 tablet; Drug: tacrolimus capsule

Detailed Description

To evaluate the pharmacokinetic interaction by comparing of pharmacokinetic parameters when administered HL237(or tacrolimus) between with tacrolimus(or HL237) and without tacrolimus(or HL237).

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

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • The Korea Univertisy Anam Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Healthy male, 19 years ≤ age ≤ 45
• Body weight ≥ 50kg and 18.5 ≤ BMI ≤ 29.9kg/m2
• Subjects are agree to use contraceptives that protocol suggest and not provide sperm for up to 2 months after the last administration of the investigational drug
• Volunteer

Exclusion Criteria:

• Subject with serious cardiovascular, respiratory, hepatology, renal, hematologic, gastrointestinal, immunologic, dermal, neurologic, or psychological disease or history of such disease
• Subject with symptoms of acute disease within 28 days prior to investigational products dosing
• Subject with medical history which able to affect absorption, distribution, metabolism and excretion of drug

• Subject with hypersensitive reaction to following drug or history of clinically significant hypersensitive reaction to following drug

  • Calcineurin inhibitor or Macrolides
  • HL237
• Subject with clinically significant active chronic disease
• Subject with genetic deficiency such as galactose intolerance, Lapp lactose deficiency or glucosegalactose malabsorption

• Subjects who showed one or more of the following in a screening test including a retest

  • AST, ALT > UNL (upper normal limit) x 2.5
  • Creatinine clearance =< 80mL/min (Cockcroft-Gault GFR = (140-age) * (Wt in kg) / (72 * Cr))
  • Results of ECG, QTc > 450 msec
• Positive test results for hepatitis B virus surface antigen, anti-hepatitis C virus antibody, anti-Human Immunodeficiency virus antibody or venereal disease research laboratory test
• Use of any prescription medication within 14 days prior to study medication dosing
• Use of any over-the-counter(OTC) medication within 7 days prior to study medication dosing
• Subject with clinically significant allergic disease (except for mild allergic rhinitis and mild allergic dermatitis that are not needed to administer drug)
• Subject who is not able to taking standard meals provided by the institution
• Subject with whole blood donation within 60 days, component blood donation within 20 days
• Subjects receiving blood transfusion within 30 days prior to study medication dosing
• Participation in any clinical investigation within 6 months prior to study medication dosing
• Use of any medication effected on drug enzyme induction or inhibition such as barbitals within 30 days prior to study medication dosing
• Subjects who have continuously consumed grapefruit juice or caffeine (grapefruit juice or caffeine > 5 cups/day), or who can't refrain from intake during hospitalization
• Subjects who have continued to drink alcohol (alcohol> 30 g/day) or who can't quit drinking during hospitalization
• Severe heavy smoker(cigarette > 10 cigarettes per day) or subjects who can't quit smoking during hospitalization
• Subjects that the investigator deems unsuitable for participation in the clinical trial due to laboratory test results or other excuse such as non-responding to request or instruction by investigator

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single arm; This single arm is conducted in fixed-sequence(Treatment A ->(washout period) -> Treatment B -> Treatment C -> Maintenance treatment). Treatment A : tacrolimus 5mg po single dose, Treatment B : HL237 400mg bid for 4 days, Treatment C: tacrolimus 5mg po single dose and HL237 400 mg bid, Maintenance treatment : HL237 400mg bid for 2 days	Drug: HL237 tablet; HL237 400mg will be administered orally twice a day.; Drug: tacrolimus capsule; tacrolimus 5mg will be administered orally once a day.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak plasma concentration at steady state(Cmax,ss) of HL237	Comparison of pharmacokinetic parameters between when administered tacrolimus with HL237 and without HL237	0(before dosing), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12 hour(after dosing) on day 21 and day 22
Area under the plasma concentration versus time curve during a dosage interval(AUCτ) of HL237	Comparison of pharmacokinetic parameters between when administered tacrolimus with HL237 and without HL237	0(before dosing), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12 hour(after dosing) on day 21 and day 22
Peak whole-blood concentration(Cmax) of tacrolimus	Comparison of pharmacokinetic parameters between when administered tacrolimus with HL237 and without HL237	0(before dosing), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, 72hour(after dosing) on day 1 and day 22
Area under the whole-blood concentration versus time curve from time zero to time of last measurable concentration(AUClast) of tacrolimus	Comparison of pharmacokinetic parameters between when administered tacrolimus with HL237 and without HL237	0(before dosing), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, 72hour(after dosing) on day 1 and day 22

Collaborators and Investigators

• Sponsor: Hanlim Pharm. Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): August 22, 2020
• Primary Completion (Actual): September 24, 2020
• Study Completion (Anticipated): January 1, 2021

Study Registration Dates

• First Submitted: November 13, 2020
• First Submitted That Met QC Criteria: November 16, 2020
• First Posted (Actual): November 18, 2020

Study Record Updates

• Last Update Posted (Actual): November 18, 2020
• Last Update Submitted That Met QC Criteria: November 16, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Immunosuppressive Agents; Immunologic Factors; Calcineurin Inhibitors; Tacrolimus
• Other Study ID Numbers: HL237-103

Drug and device information, study documents

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