Effect of Tegoprazan or RAPA113 on Pharmacodynamics/Pharmacokinetics of Clopidogrel in Healthy Male Volunteers

A Randomized, Open-label, Multiple-dose, Crossover Clinical Trial to Explore the Drug Interaction of Tegoprazan or RAPA113 and Clopidogrel After Oral Administration in Healthy Male Volunteers

This study aims to evaluate the influence of tegoprazan or RAPA113 on the pharmacodynamics/Pharmacokinetics of following co-administration of tegoprazan or RAPA113 and clopidogrel in healthy male volunteers.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Clopidogrel 75mg; Drug: Tegoprazan 50 mg; Drug: RAPA113

Detailed Description

Evaluation Criteria:

• Primary outcome Pharmacodynamic assessments using P2Y12 assay
• Secondary outcome Pharmacokinetics assessments on Cmax,ss, AUCτ,ss, tmax,ss, Cmin,ss , CLss/F of Clopidogrel
• Safety assessments with adverse event monitoring including subjective/objective symptoms, physical examination, vital signs, electrocardiogram, and laboratory test

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Severance Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 17 years to 53 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Healthy adult males aged ≥ 19 years and ≤ 50 years on the date of the written informed consent
• Body weight of ≥ 55.0 kg and ≤ 90.0 kg, with body mass index (BMI) of ≥ 18.5 kg/m2 and ≤ 27.0 kg/m2 at the time of screening
• Helicobacter pylori negative
• Voluntarily decided to participate in the study and provided written informed consent before any screening procedure

Exclusion Criteria:

• Has a history of or currently has clinically significant liver, kidney, nervous system, immune system, respiratory system, endocrine system, blood, tumor, cardiovascular system or psychiatric disease
• Has a history of gastrointestinal diseases (such as Crohn's disease, ulcer, etc.) or surgery (except for simple appendectomy or hernia) that can affect the absorption of drugs
• Has a genetic problems such as galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption
• Has a clinically significant history of hemorrhage (e.g. Gastric ulcers, intracranial bleeding, haemophilia, gastrointestinal bleeding, urinary tract bleeding, vitreous hemorrhage, etc.)
• P2Y12 Reaction Unit (PRU) by P2Y12 assay outside the upper/lower limit of normal range by 10% at screening

• Considered ineligible to participate in the study based on screening test(by asking condition, vital sign, 12-lead ECG, physical exam, laboratory test etc.) results :

  1. Platelet, PT and aPTT levels outside the upper/lower limit of normal range by 10%
  2. AST (GOT), and ALT (GPT) levels greater than 1.25x of the upper limit of normal range
  3. Blood total bilirubin levels greater than 1.5x of the upper limit of normal range
  4. Hemoglobin levels less than 12.0 g/dL

  5. eGFR (estimated Glomerular Filtration Rate) using MDRD (Modification of Diet in Renal Disaster) < 60 mL/min/1.73 m2

     : eGFR (estimated glomerular filtration rate) (mL/min/1.73m2) = 175 x [serum creatinine (mg/dL)]-1.154 x [age]-0.203

  6. positive as a result of serum examination (B-type hepatitis test, hepatitis C test, human immunodeficiency virus test, syphilis test)
  7. Systolic blood pressure < 90 mmHg or > 150 mmHg, diastolic blood pressure < 50 mmHg or > 100 mmHg, or pulse rate < 45 beats/minute or > 100 beats/minute when vital signs are measured in sitting position after resting for at least 5 minutes during screening

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

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Clopidogrel 75 mg; Oral administration of clopidogrel 75 mg tablet once daily for 7 days	Drug: Clopidogrel 75mg; Clopidogrel 75 mg tablet; Other Names: Plavix
Experimental: Clopidogrel 75 mg + Tegoprazan 50 mg; Oral administration of clopidogrel 75 mg tablet and Tegoprazan 50mg tablet once daily for 7 days	Drug: Clopidogrel 75mg; Clopidogrel 75 mg tablet; Other Names: Plavix; Drug: Tegoprazan 50 mg; Tegoprazan 50 mg tablet; Other Names: K-CAB
Experimental: Clopidogrel 75 mg + RAPA113; Oral administration of clopidogrel 75 mg tablet and RAPA113 tablet once daily for 7 days	Drug: Clopidogrel 75mg; Clopidogrel 75 mg tablet; Other Names: Plavix; Drug: RAPA113; RAPA113 tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in P2Y12 Reaction Unit (PRU) from baseline	Pharmacodynamics blood sampling to measure PRU using VerifyNow® system	Pre-dose(0h) on days 1, 3, 5, 7 and 8 in each period

Collaborators and Investigators

• Sponsor: HK inno.N Corporation
• Investigators: Principal Investigator: Min Soo Park, Severance Hospital, Dept of Clinical Pharmacology

Study record dates

Study Major Dates

• Study Start (Actual): October 21, 2019
• Primary Completion (Actual): February 7, 2020
• Study Completion (Actual): April 9, 2020

Study Registration Dates

• First Submitted: November 19, 2019
• First Submitted That Met QC Criteria: November 19, 2019
• First Posted (Actual): November 21, 2019

Study Record Updates

• Last Update Posted (Actual): May 8, 2020
• Last Update Submitted That Met QC Criteria: May 6, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Clopidogrel
• Other Study ID Numbers: CJ_APA_113

Drug and device information, study documents

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