Study to Evaluate the Influence of Tegoprazan on the Pharmacokinetics of Proguanil in Healthy Volunteers

A Randomized, Open-label, Three-period Crossover Clinical Trial to Evaluate the Influence of Tegoprazan on the Pharmacokinetics of Proguanil in Healthy Volunteers

The aim of this study is to evaluate the influence of tegoprazan on the pharmacokinetics of proguanil in healthy volunteers.

Study Overview

• Status: Completed
• Conditions: Gastroesophageal Reflux Disease
• Intervention / Treatment: Drug: Tegoprazan 50 mg; Drug: Atovaquone / Proguanil 250/100 mg; Drug: Esomeprazole 40 mg; Drug: Vonoprazan 20 mg

Detailed Description

Evaluation criteria

• Pharmacokinetic assessment with plasma concentrations of proguanil and cycloguanil
• Safety assessments with adverse event monitoring including subjective/objective symptoms, physical examination, vital signs, electrocardiogram, and laboratory tests

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Seoul National University Hospital, Clinical Trial Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 17 years to 48 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy adult aged ≥ 19 years and ≤ 50 years at the time of screening
• Body weight of ≥ 55.0 kg and ≤ 90.0 kg, with body mass index (BMI) of ≥ 19.0 kg/m2 and ≤ 30.0 kg/m2 at the time of screening
• Extensive metabolizer (*1/*1) by CYP2C19 genotyping
• A subject without any congenital or chronic disease, and has no medical examination result as pathological symptoms or signs
• A subject who listened to sufficient explanation and fully understood this study, and voluntarily decided to participate and agreed in writing to comply with the precautions
• A subject determined eligible for this study by investigator based physical examination, clinical laboratory tests, interview, etc.

Exclusion Criteria:

• A subject with clinically significant hepatobiliary (severe hepatic impairment, etc.), renal (severe renal impairment, etc.), neurologic, immunologic, respiratory, gastrointestinal, endocrine, blood•oncology, cardiovascular (heart failure, Torsades de pointes, etc.), urinary, or, psychical diseases (except for simple dental past history such as tartar, impacted tooth, or wisdom tooth) or a history
• A subject who has hypersensitivity to the investigational products, drugs containing the same class, or other drugs (penicillin and antibiotics, etc.), or a history of clinically significant hypersensitivity
• A subject with a history of gastrointestinal disorders (gastrointestinal ulcer, gastritis, gastrospasm, gastroesophageal reflux disease, Crohn's disease, etc.) or surgery (except for simple appendectomy and herniotomy) that may affect the safety and pharmacokinetics of the investigational products
• A subject with the following results in the screening test:
• Blood AST (GOT), ALT (GPT): > Normal range upper × 1.5
• Creatinine clearance calculated by MDRD equation: < 80mL/min
• QTc interval: > 450 ms
• Fasting serum glucose: > 126 mg/dL
• Positive serological test (syphilis test, hepatitis B test, hepatitis C test, human immunodeficiency virus (HIV) test)
• A subject with systolic blood pressure < 90 mmHg or > 150 mmHg, or diastolic blood pressure < 50 mmHg or > 100 mmHg when vital signs are measured in sitting position after resting for at least 3 minutes
• A subject with a history of or positive urine screening for drug abuse
• A subject who administered any prescription drugs or herbal medicine within 2 weeks prior to the expected date of the first dose, or any over-the-counter drug (OTC drug, health functional food or vitamin within 1 week prior to the expected date of the first dose (However, can participate in the study if otherwise decided eligible by the investigator), or is expected to administer it
• A subject who administered drugs that induce or inhibit the drug metabolizing enzymes, such as barbitals, within 1 week prior to the expected date of the first dose
• A subject who participated in other clinical trial or bioequivalence study within 6 months prior to the expected date of the first dose
• A subject who donated whole blood within 2 months or the component blood within 1 month prior to the expected date of the first dose, or received blood transfusion within 1 month prior to the expected date of the first dose
• A subject with persistent alcohol intake (> 21 units/week, 1 unit = 10 g of pure alcohol), or inability to abstain from drinking from 3 days before the expected date of the first dose until the last discharge
• A subject who is a currently smoker (But, can be eligible if he or she quitted smoking 3 months ago), or is not able to cease smoking from 3 months before the expected date of the first dose until the last discharge
• A subject with inability to refrain from grapefruit-containing food from 3 days before the expected date of the first dose until the last discharge
• A subject with excessive caffeine intake (> 5 units/day), or inability to refrain from caffeine or caffeine-containing food from 3 days before the expected date of the first dose until the last discharge
• A subject with inability to use a medically acceptable double contraception or contraception throughout the study and for at least 4 weeks after the last dose, and with inability to agree to donate sperm until the period

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Atovaquone/Proguanil 250/100 mg; A single oral administration of atovaquone/proguanil 250/100 mg	Drug: Atovaquone / Proguanil 250/100 mg; Atovaquone / Proguanil 250/100 mg tablet; Other Names: Malarone
Experimental: Tegoprazan 50 mg + Atovaquone/Proguanil 250/100 mg; Oral administration of tegoprazan 50 mg once daily for 6 days and then co-administration of tegoprazan 50 mg and atovaquone/proguanil 250/100 mg at 7 day	Drug: Tegoprazan 50 mg; Tegoprazan 50 mg tablet; Other Names: K-cab; Drug: Atovaquone / Proguanil 250/100 mg; Atovaquone / Proguanil 250/100 mg tablet; Other Names: Malarone
Experimental: Esomeprazole 40 mg + Atovaquone/Proguanil 250/100 mg; Oral administration of esomeprazole 40 mg once daily for 6 days and then co-administration of esomeprazole 40 mg and atovaquone/proguanil 250/100 mg at 7 day	Drug: Atovaquone / Proguanil 250/100 mg; Atovaquone / Proguanil 250/100 mg tablet; Other Names: Malarone; Drug: Esomeprazole 40 mg; Esomeprazole 40 mg tablet; Other Names: Nexium
Experimental: Vonoprazan 20 mg + Atovaquone/Proguanil 250/100 mg; Oral administration of vonoprazan 20 mg once daily for 6 days and then co-administration of vonoprazan 20 mg and atovaquone/proguanil 250/100 mg at 7 day	Drug: Atovaquone / Proguanil 250/100 mg; Atovaquone / Proguanil 250/100 mg tablet; Other Names: Malarone; Drug: Vonoprazan 20 mg; Vonoprazan 20 mg tablet; Other Names: Takecab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUClast of proguanil, cycloguanil	Systemic exposure of proguanil and cycloguanil	Pre-dose(0 hour) and up to 48 hours in each period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax of proguanil	Secondary pharmacokinetic parameters of proguanil	Pre-dose(0 hour) and up to 48 hours in each period
AUCinf of proguanil	Secondary pharmacokinetic parameters of proguanil	Pre-dose(0 hour) and up to 48 hours in each period
Tmax of proguanil	Secondary pharmacokinetic parameters of proguanil	Pre-dose(0 hour) and up to 48 hours in each period
t1/2 of proguanil	Secondary pharmacokinetic parameters of proguanil	Pre-dose(0 hour) and up to 48 hours in each period
CL/F of proguanil	Secondary pharmacokinetic parameters of proguanil	Pre-dose(0 hour) and up to 48 hours in each period
Vz/F of proguanil	Secondary pharmacokinetic parameters of proguanil	Pre-dose(0 hour) and up to 48 hours in each period
fe of proguanil	Secondary pharmacokinetic parameters of proguanil	Pre-dose(0 hour) and up to 48 hours in each period
CLR of proguanil	Secondary pharmacokinetic parameters of proguanil	Pre-dose(0 hour) and up to 48 hours in each period

Collaborators and Investigators

• Sponsor: Seoul National University Hospital
• Investigators: Principal Investigator: SeungHwan Lee, MD, PhD, Seoul National University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): November 25, 2020
• Primary Completion (Actual): July 8, 2021
• Study Completion (Actual): August 3, 2021

Study Registration Dates

• First Submitted: September 15, 2020
• First Submitted That Met QC Criteria: September 24, 2020
• First Posted (Actual): September 29, 2020

Study Record Updates

• Last Update Posted (Actual): September 27, 2021
• Last Update Submitted That Met QC Criteria: September 23, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Esophageal Motility Disorders; Deglutition Disorders; Esophageal Diseases; Gastroesophageal Reflux; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antimetabolites; Gastrointestinal Agents; Antiprotozoal Agents; Antiparasitic Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Antimalarials; Atovaquone; Proguanil; Esomeprazole; Atovaquone, proguanil drug combination
• Other Study ID Numbers: Tegoprazan_CYP2C19_DDI

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

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