Evaluate the PK of Multiple Oral Doses of Tegoprazan, Metronidazole, Tetracycline and Bismuth in Healthy Volunteers

An Open-Label, Randomized, Crossover Study to Evaluate the Pharmacokinetic Interaction After Multiple Oral Doses of Tegoprazan, Metronidazole, Tetracycline and Bismuth in Healthy Volunteers

This study aims to evaluate the pharmacokinetic interaction between tegoprazan and combination of metronidazole, tetracycline and bismuth in healthy adult volunteers.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Tegoprazan; Drug: Metronidazole; Drug: Tetracycline; Drug: Bismuth

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Jeonju, Korea, Republic of
    • Chonbuk National University Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Healthy adult aged ≥ 19 and < 55 year-old on the day of obtaining the informed consent.
• Body mass index (BMI) ≥ 17.5 kg/m2 and < 28.0 kg/m2 with a body weight ≥ 55 kg at screening.
• H. pylori negative.

Exclusion Criteria:

• Medical History

  1. History or evidence of clinically significant disease
  2. History of gastrointestinal disease (e.g., esophageal disease such as esophageal achalasia or stenosis, and Crohn's disease) or surgery that may affect the absorption of a drug.
  3. History or presence of hypersensitivity to IMPs, components of IMPs, benzimidazoles, imidazole derivatives or tetracycline antibiotics

• Laboratory tests(in blood)

  1) Total bilirubin, AST (GOT), ALT (GPT) > 1.5 X upper limit of normal (ULN) at screening

• History of drug/alcohol abuse
• Participated in other study and received investigational product within 3 months prior to the first study dose.
• taken a medication known to substantially induce or inhibit a drug metabolizing enzyme
• Not able to use a medically acceptable contraceptive method throughout the study.

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: Tegoprazan 50 mg; Oral administration of Tegoprazan 50 mg twice daily for 7 days	Drug: Tegoprazan; Tegoprazan 50 mg tablet; Other Names: K-CAB
Active Comparator: Tegoprazan 50 mg+MTN 500 mg+TCL 500 mg+BIS 300 mg; Oral administration of Tegoprazan 50 mg twice daily, Metronidazole 500 mg three times daily, and Tetracycline hydrochloride 500 mg & Tripotassium bismuth dicitrate 300 mg four times daily for 7 days	Drug: Tegoprazan; Tegoprazan 50 mg tablet; Other Names: K-CAB; Drug: Metronidazole; Metronidazole 250 mg tablet; Other Names: Flasinyl; Drug: Tetracycline; Tetracycline hydrochloride 250 mg capsule; Other Names: Teracyclin; Drug: Bismuth; Tripotassium bismuth dicitrate 300 mg tablet; Other Names: Denol
Active Comparator: MTN 500 mg+TCL 500 mg+BIS 300 mg; Oral administration of Metronidazole 500 mg twice daily, Tetracycline hydrochloride 500 mg & Tripotassium bismuth dicitrate 300 mg four times daily for 7 days	Drug: Metronidazole; Metronidazole 250 mg tablet; Other Names: Flasinyl; Drug: Tetracycline; Tetracycline hydrochloride 250 mg capsule; Other Names: Teracyclin; Drug: Bismuth; Tripotassium bismuth dicitrate 300 mg tablet; Other Names: Denol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC0-12 of tegaprazan and metabolite M1	Area under the plasma concentration versus time curve of tegoprazan	pre-dose on Day 1,5,6,7 and post-dose up to 24 hours on Day 7 in period1 ,2.
Cmax of tegaprazan and metabolite M1	Peak Plasma Concentration of tegoprazan and metabolite M1	pre-dose on Day 1,5,6,7 and post-dose up to 24 hours on Day 7 in period1 ,2.
AUC0-6 of metronidazole, tetracycline and bismuth	Area under the plasma concentration versus time curve of metronidazole, tetracycline and bismuth	pre-dose on Day 1,5,6,7 and post-dose up to 24 hours on Day 7 in period1 ,2.
Cmax of metronidazole, tetracycline and bismuth	Peak Plasma Concentration of metronidazole, tetracycline and bismuth	pre-dose on Day 1,5,6,7 and post-dose up to 24 hours on Day 7 in period1 ,2.

Collaborators and Investigators

• Sponsor: HK inno.N Corporation
• Investigators: Principal Investigator: Min-Gul Kim, MD, Chonbuk university hospital

Publications and helpful links

General Publications

• Jeon JY, Kim SY, Moon SJ, Oh K, Lee J, Kim B, Song GS, Kim MG. Pharmacokinetic Interactions between Tegoprazan and Metronidazole/Tetracycline/Bismuth and Safety Assessment in Healthy Korean Male Subjects. Clin Ther. 2021 Apr;43(4):722-734. doi: 10.1016/j.clinthera.2021.01.026. Epub 2021 Feb 23.

Study record dates

Study Major Dates

• Study Start (Actual): January 17, 2019
• Primary Completion (Actual): February 22, 2019
• Study Completion (Actual): April 25, 2019

Study Registration Dates

• First Submitted: August 20, 2019
• First Submitted That Met QC Criteria: August 21, 2019
• First Posted (Actual): August 26, 2019

Study Record Updates

• Last Update Posted (Actual): August 28, 2019
• Last Update Submitted That Met QC Criteria: August 22, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: pharmacokinetic; Drug-Drug interaction
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Gastrointestinal Agents; Anti-Bacterial Agents; Protein Synthesis Inhibitors; Antiprotozoal Agents; Antiparasitic Agents; Antacids; Metronidazole; Bismuth; Tetracycline
• Other Study ID Numbers: CJ_APA_111

Drug and device information, study documents

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