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

Healthy Clinical Trial

Official title:

An Open-label, Randomized, Crossover Study to Evaluate the Pharmacokinetic and Pharmacodynamic Interaction Between Tegoprazan and Novel Oral Anticoagulants (NOACs) After Multiple Oral Dosing in Healthy Volunteers

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05723510
• Other study ID #: IN_APA_121
• Status: Completed
• Phase: Phase 1
• Start date: March 6, 2023
• Est. completion date: July 24, 2023

Study information

• Verified date: December 2023
• Source: HK inno.N Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 87
• Est. completion date: July 24, 2023
• Est. primary completion date: July 17, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 19 Years to 54 Years

Eligibility

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

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• Tegoprazan 50mg
Oral administration of one tablet of tegoprazan 50 mg once daily
• Edoxaban 60mg
Oral administration of one tablet of edoxaban 60 mg once daily
• Apixaban 5mg
Oral administration of one tablet of apixaban 5 mg twice daily
• Rivaroxaban 20mg
Oral administration of one tablet of rivaroxaban 20 mg once daily

Locations

Country	Name	City	State
Korea, Republic of	Jeonbuk National University Hospital	Jeonju

Sponsors (1)

Lead Sponsor	Collaborator
HK inno.N Corporation

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	AUCt and Css,max of edoxaban	Area under the plasma concentration-time curve during a steady-state dosing interval (t) 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
Primary	AUCt and Css,max of apixaban	Area under the plasma concentration-time curve during a steady-state dosing interval (t) 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
Primary	AUCt and Css,max of rivaroxaban	Area under the plasma concentration-time curve during a steady-state dosing interval (t) 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
Primary	AUECt and Emax of Anti-Factor Xa activity, PT, aPTT, and Prothrombin (INR)	Area under the effect-time curve over the dosing interval (t) 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