PK and PD Interaction Between Tegoprazan and NOACs After Multiple Oral Dosing in Healthy Volunteers

NCT05723510 | Completed Phase 1

• 1 other identifier: IN_APA_121
• Study Type: interventional
• Target: 87
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to evaluate the effects of combination therapy of tegoprazan and novel oral anticoagulants (NOACs) on the pharmacokinetic and pharmacodynamic properties of NOACs in healthy adults.

Conditions

Healthy

Outcome Measures

Primary Outcomes (4)

• AUCτ and Css,max of edoxaban

  Area under the plasma concentration-time curve during a steady-state dosing interval (τ) and maximum plasma concentration at steady state of edoxaban

  Pre-dose(0 hour) on 1D, 3D, and 4D for each period; pre-dose(0 hour) up to 48 hours after treatment on 5D for each period

• AUCτ and Css,max of apixaban

  Area under the plasma concentration-time curve during a steady-state dosing interval (τ) and maximum plasma concentration at steady state of apixaban

  Pre-dose (0 hour) in the morning on 1D and in the morning and afternoon on 4D for each period; pre-dose(0 hour) in the morning up to 48 hours after treatment on 5D for each period

• AUCτ and Css,max of rivaroxaban

  Area under the plasma concentration-time curve during a steady-state dosing interval (τ) and maximum plasma concentration at steady state of rivaroxaban

  Pre-dose (0 hour) on 1D, 3D, and 4D for each period; pre-dose(0 hour) up to 48 hours after treatment on 5D for each period

• AUECτ and Emax of Anti-Factor Xa activity, PT, aPTT, and Prothrombin (INR)

  Area under the effect-time curve over the dosing interval (τ) at steady state and maximum effect of Anti-Factor Xa activity, PT, aPTT, and Prothrombin (INR)

  Pre-dose (0 hour) up to 24 hours after treatment on 5D for each period

Study Arms (6)

Edoxaban 60mg

EXPERIMENTAL

Multiple dosing of edoxaban alone once daily for 5 days

Drug: Edoxaban 60mg

Edoxaban 60mg + Tegoprazan 50mg

EXPERIMENTAL

Multiple dosing of edoxaban once daily in combination with tegoprazan once daily for 5 days

Drug: Tegoprazan 50mg; Drug: Edoxaban 60mg

Apixaban 5mg

EXPERIMENTAL

Multiple dosing of apixaban alone twice daily for 5 days

Drug: Apixaban 5mg

Apixaban 5mg + Tegoprazan 50mg

EXPERIMENTAL

Multiple dosing of apixaban twice daily in combination with tegoprazan once daily for 5 days

Drug: Tegoprazan 50mg; Drug: Apixaban 5mg

Rivaroxaban 20mg

EXPERIMENTAL

Multiple dosing of rivaroxaban alone once daily for 5 days

Drug: Rivaroxaban 20mg

Rivaroxaban 20mg + Tegoprazan 50mg

EXPERIMENTAL

Multiple dosing of rivaroxaban once daily in combination with tegoprazan once daily for 5 days

Drug: Tegoprazan 50mg; Drug: Rivaroxaban 20mg

Interventions

Tegoprazan 50mg DRUG

Oral administration of one tablet of tegoprazan 50 mg once daily

Also known as: K-CAB Tab. 50 mg

Apixaban 5mg + Tegoprazan 50mg; Edoxaban 60mg + Tegoprazan 50mg; Rivaroxaban 20mg + Tegoprazan 50mg

Edoxaban 60mg DRUG

Oral administration of one tablet of edoxaban 60 mg once daily

Also known as: Lixiana Tab. 60mg

Edoxaban 60mg; Edoxaban 60mg + Tegoprazan 50mg

Apixaban 5mg DRUG

Oral administration of one tablet of apixaban 5 mg twice daily

Also known as: Eliquis Tab. 5 mg

Apixaban 5mg; Apixaban 5mg + Tegoprazan 50mg

Rivaroxaban 20mg DRUG

Oral administration of one tablet of rivaroxaban 20 mg once daily

Also known as: Xarelto Tab. 20 mg

Rivaroxaban 20mg; Rivaroxaban 20mg + Tegoprazan 50mg

Eligibility Criteria

• Age: 19 Years - 54 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy adults aged ≥ 19 years to \< 55 years at the time of screening
• Those with body weight ≥ 45 kg (but ≥ 60 kg for cohort 1 and cohort 2) and body mass index (BMI) in the range of 19.0 kg/m2 to 27.0 kg/m2 at the time of screening
• ☞ BMI = weight (kg) / height (m)2
• Those who have neither congenital/chronic disease (within recent 3 years) nor pathological symptoms/findings as a result of medical examination
• Those determined to be eligible for this study based on the findings of screening such as clinical laboratory tests (hematological test, blood chemistry test, blood coagulation test, urinalysis, test for viruses/bacteria, etc.), vital signs, and electrocardiogram (ECG) which are performed by the investigator according to the properties of medicines
• Those who are fully informed of study purpose, procedures, etc., voluntarily decide to participate in this study, and sign an informed consent form (ICF) approved by the Institutional Review Board (IRB) of Jeonbuk National University Hospital, prior to participation in the study
• Those with a capability/willingness to participate throughout the study

You may not qualify if:

• Medical history of clinically significant blood, renal, endocrine, respiratory, gastrointestinal (peptic ulcer, etc.), urinary, cardiovascular, hepatic, psychiatric, neurological or immune disease (but except for history of simple dental treatment such as tartar, impacted teeth, and third molar teeth) or evidence thereof
• Previous history of gastrointestinal disease (except for esophageal disease such as esophageal achalasia or esophageal stricture, inflammatory bowel disease (Crohn's disease, ulcerative colitis)) or surgery (not including simple appendectomy, hernia surgery, tooth extraction, etc.) which may affect drug absorption
• Following findings of clinical laboratory tests:
• ☞ ALT or AST value \> twice the upper limit of normal (ULN)
• History of periodic alcohol consumption exceeding 210 g/week within 6 months prior to screening (beer (5%) 1 glass (250 mL) = 10 g, soju (20%) 1 glass (50 mL) = 8 g, wine (12%) 1 glass (125 mL) = 12 g)
• Administration of another investigational product within 6 months prior to the first dose of the investigational product
• History of serious alcohol or drug misuse and abuse within 1 year prior to screening
• Administration of drugs known to markedly induce or inhibit drug metabolizing enzymes within 30 days prior to the first dose of the investigational product
• History of smoked cigarettes ≥ 20 cigarettes/day within 6 months prior to screening
• Administration of a prescription or non-prescription drug within 10 days prior to the first dose of the investigational product
• Whole blood donation within 2 months prior to the first dose of the investigational product or apheresis donation within 1 month prior to the first dose of the investigational product
• Those who may be put at an increased risk due to the adminisration of the investigational product and study participation or have a severe acute/chronic medical or mental condition which may interfere with the interpretation of study results
• Patients with hypersensitivity to tegoprazan, edoxaban, apixaban, rivaroxaban, etc. (e.g., asthma, acute rhinitis, nasal polyp, angioedema, urticaria, allergic reactions, etc.)
• Patients with a clinically significant bleeding
• Patients with hemostatic disorder and hepatic disease related to a clinically significant risk of bleeding

Sponsors & Collaborators

• HK inno.N Corporation: lead

Study Sites (1)

Jeonbuk National University Hospital

Jeonju, South Korea

Location

MeSH Terms

Interventions

tegoprazan; edoxaban; apixaban; Rivaroxaban

Intervention Hierarchy (Ancestors)

Thiophenes; Sulfur Compounds; Organic Chemicals; Morpholines; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Min-Gul Kim

  Clinical Pharmacology Center, Jeonbuk National University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: two-arm, two-period crossover

Study Record Dates

• First Submitted: February 2, 2023
• First Posted: February 10, 2023
• Study Start: March 6, 2023
• Primary Completion: July 17, 2023
• Study Completion: July 24, 2023
• Last Updated: December 11, 2023

Record last verified: 2023-12

Locations

KR (1)