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

Gastroesophageal Reflux Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04568772
• Other study ID #: Tegoprazan_CYP2C19_DDI
• Status: Completed
• Phase: Phase 1
• Start date: November 25, 2020
• Est. completion date: August 3, 2021

Study information

• Verified date: September 2021
• Source: Seoul National University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 19
• Est. completion date: August 3, 2021
• Est. primary completion date: July 8, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years to 50 Years

Eligibility

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

Related Conditions & MeSH terms

• Gastroesophageal Reflux
• Gastroesophageal Reflux Disease

Intervention

Drug:
• Atovaquone / Proguanil 250/100 mg
Atovaquone / Proguanil 250/100 mg tablet
• Tegoprazan 50 mg
Tegoprazan 50 mg tablet
• Esomeprazole 40 mg
Esomeprazole 40 mg tablet
• Vonoprazan 20 mg
Vonoprazan 20 mg tablet

Locations

Country	Name	City	State
Korea, Republic of	Seoul National University Hospital, Clinical Trial Center	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
Seoul National University Hospital

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	AUClast of proguanil, cycloguanil	Systemic exposure of proguanil and cycloguanil	Pre-dose(0 hour) and up to 48 hours in each period
Secondary	Cmax of proguanil	Secondary pharmacokinetic parameters of proguanil	Pre-dose(0 hour) and up to 48 hours in each period
Secondary	AUCinf of proguanil	Secondary pharmacokinetic parameters of proguanil	Pre-dose(0 hour) and up to 48 hours in each period
Secondary	Tmax of proguanil	Secondary pharmacokinetic parameters of proguanil	Pre-dose(0 hour) and up to 48 hours in each period
Secondary	t1/2 of proguanil	Secondary pharmacokinetic parameters of proguanil	Pre-dose(0 hour) and up to 48 hours in each period
Secondary	CL/F of proguanil	Secondary pharmacokinetic parameters of proguanil	Pre-dose(0 hour) and up to 48 hours in each period
Secondary	Vz/F of proguanil	Secondary pharmacokinetic parameters of proguanil	Pre-dose(0 hour) and up to 48 hours in each period
Secondary	fe of proguanil	Secondary pharmacokinetic parameters of proguanil	Pre-dose(0 hour) and up to 48 hours in each period
Secondary	CLR of proguanil	Secondary pharmacokinetic parameters of proguanil	Pre-dose(0 hour) and up to 48 hours in each period