Clinical trial NCT04568772: Study to Evaluate the Influence of Tegoprazan on the Pharmacokinetics of Proguanil in Healthy Volunteers
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Gastroesophageal Reflux Disease
Lead sponsor: Seoul National University Hospital
Sponsor class: OTHER
First posted: 2020-09-29
Enrollment: 19
Sex: ALL
Minimum age (years): 19
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

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

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

Eligibility criteria: 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

Primary outcomes:
measure: AUClast of proguanil, cycloguanil
timeFrame: Pre-dose(0 hour) and up to 48 hours in each period
Secondary outcomes:
measure: Cmax of proguanil
timeFrame: Pre-dose(0 hour) and up to 48 hours in each period
measure: AUCinf of proguanil
timeFrame: Pre-dose(0 hour) and up to 48 hours in each period
measure: Tmax of proguanil
timeFrame: Pre-dose(0 hour) and up to 48 hours in each period
measure: t1/2 of proguanil
timeFrame: Pre-dose(0 hour) and up to 48 hours in each period
measure: CL/F of proguanil
timeFrame: Pre-dose(0 hour) and up to 48 hours in each period
measure: Vz/F of proguanil
timeFrame: Pre-dose(0 hour) and up to 48 hours in each period
measure: fe of proguanil
timeFrame: Pre-dose(0 hour) and up to 48 hours in each period
measure: CLR of proguanil
timeFrame: Pre-dose(0 hour) and up to 48 hours in each period
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital, Clinical Trial Center
Study officials:
affiliation: Seoul National University Hospital
name: SeungHwan Lee, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: