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

HK inno.N

Status and phase: Completed; Phase 1

Conditions: Healthy

Treatments: Drug: Tegoprazan 50mg; Drug: Apixaban 5mg; Drug: Rivaroxaban 20mg; Drug: Edoxaban 60mg

Study type: Interventional

Funder types: Industry

Identifiers

NCT05723510

IN_APA_121

Details and patient eligibility

About

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.

Full description

A randomized, open-label, multiple-dose, two-arm, two-period crossover study

[Cohort 1] To evaluate the effects of combination therapy of tegoprazan and edoxaban on the pharmacokinetic and pharmacodynamic properties of edoxaban in healthy adults.

[Cohort 2] To evaluate the effects of combination therapy of tegoprazan and apixaban on the pharmacokinetic and pharmacodynamic properties of apixaban in healthy adults.

[Cohort 3] To evaluate the effects of combination therapy of tegoprazan and rivaroxaban on the pharmacokinetic and pharmacodynamic properties of rivaroxaban in healthy adults.

Enrollment: 87 patients

Sex: All

Ages: 19 to 54 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

1. Healthy adults aged ≥ 19 years to < 55 years at the time of screening

2. 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

3. Those who have neither congenital/chronic disease (within recent 3 years) nor pathological symptoms/findings as a result of medical examination

4. 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

5. 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

6. Those with a capability/willingness to participate throughout the study

Exclusion criteria

1. 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

2. 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

3. Following findings of clinical laboratory tests:

   ☞ ALT or AST value > twice the upper limit of normal (ULN)

4. 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)

5. Administration of another investigational product within 6 months prior to the first dose of the investigational product

6. History of serious alcohol or drug misuse and abuse within 1 year prior to screening

7. Administration of drugs known to markedly induce or inhibit drug metabolizing enzymes within 30 days prior to the first dose of the investigational product

8. History of smoked cigarettes ≥ 20 cigarettes/day within 6 months prior to screening

9. Administration of a prescription or non-prescription drug within 10 days prior to the first dose of the investigational product

10. 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

11. 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

12. Patients with hypersensitivity to tegoprazan, edoxaban, apixaban, rivaroxaban, etc. (e.g., asthma, acute rhinitis, nasal polyp, angioedema, urticaria, allergic reactions, etc.)

13. Patients with a clinically significant bleeding

14. Patients with hemostatic disorder and hepatic disease related to a clinically significant risk of bleeding

15. Severe hepatic impairment

16. Renal impairment (eGFR <60 ml/min/1.73m2)

17. Hereditary problems such as galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption

18. Pregnant/breast-feeding women

19. Those who cannot use medically acceptable contraceptive methods throughout the study

    ▶ Medically acceptable contraceptive methods

    • Use of intrauterine device (IUD) showing a demonstrated pregnancy failure rate
    • Combined use of barrier contraceptive method (for male or female) and spermicide
    • Use of vasectomy, tubectomy/tubal ligation, or hysterectomy

20. Those who are not eligible for the study in the judgment of the investigator

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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87 participants in 6 patient groups

Edoxaban 60mg

Experimental group

Description:

Multiple dosing of edoxaban alone once daily for 5 days

Treatment:

Drug: Edoxaban 60mg

Edoxaban 60mg + Tegoprazan 50mg

Experimental group

Description:

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

Treatment:

Drug: Edoxaban 60mg

Drug: Tegoprazan 50mg

Apixaban 5mg

Experimental group

Description:

Multiple dosing of apixaban alone twice daily for 5 days

Treatment:

Drug: Apixaban 5mg

Apixaban 5mg + Tegoprazan 50mg

Experimental group

Description:

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

Treatment:

Drug: Apixaban 5mg

Drug: Tegoprazan 50mg

Rivaroxaban 20mg

Experimental group

Description:

Multiple dosing of rivaroxaban alone once daily for 5 days

Treatment:

Drug: Rivaroxaban 20mg

Rivaroxaban 20mg + Tegoprazan 50mg

Experimental group

Description:

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

Treatment:

Drug: Rivaroxaban 20mg

Drug: Tegoprazan 50mg