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

NCT04568772 | Completed Phase 1

• 1 other identifier: Tegoprazan_CYP2C19_DDI
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Gastroesophageal Reflux Disease

Outcome Measures

Primary Outcomes (1)

• AUClast of proguanil, cycloguanil

  Systemic exposure of proguanil and cycloguanil

  Pre-dose(0 hour) and up to 48 hours in each period

Secondary Outcomes (8)

• Cmax of proguanil

  Pre-dose(0 hour) and up to 48 hours in each period

• AUCinf of proguanil

  Pre-dose(0 hour) and up to 48 hours in each period

• Tmax of proguanil

  Pre-dose(0 hour) and up to 48 hours in each period

• t1/2 of proguanil

  Pre-dose(0 hour) and up to 48 hours in each period

• CL/F of proguanil

  Pre-dose(0 hour) and up to 48 hours in each period

Study Arms (4)

Atovaquone/Proguanil 250/100 mg

ACTIVE COMPARATOR

A single oral administration of atovaquone/proguanil 250/100 mg

Drug: Atovaquone / Proguanil 250/100 mg

Tegoprazan 50 mg + Atovaquone/Proguanil 250/100 mg

EXPERIMENTAL

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: Atovaquone / Proguanil 250/100 mg; Drug: Tegoprazan 50 mg

Esomeprazole 40 mg + Atovaquone/Proguanil 250/100 mg

EXPERIMENTAL

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; Drug: Esomeprazole 40 mg

Vonoprazan 20 mg + Atovaquone/Proguanil 250/100 mg

EXPERIMENTAL

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; Drug: Vonoprazan 20 mg

Interventions

Atovaquone / Proguanil 250/100 mg DRUG

Atovaquone / Proguanil 250/100 mg tablet

Also known as: Malarone

Atovaquone/Proguanil 250/100 mg; Esomeprazole 40 mg + Atovaquone/Proguanil 250/100 mg; Tegoprazan 50 mg + Atovaquone/Proguanil 250/100 mg; Vonoprazan 20 mg + Atovaquone/Proguanil 250/100 mg

Tegoprazan 50 mg DRUG

Tegoprazan 50 mg tablet

Also known as: K-cab

Tegoprazan 50 mg + Atovaquone/Proguanil 250/100 mg

Esomeprazole 40 mg DRUG

Esomeprazole 40 mg tablet

Also known as: Nexium

Esomeprazole 40 mg + Atovaquone/Proguanil 250/100 mg

Vonoprazan 20 mg DRUG

Vonoprazan 20 mg tablet

Also known as: Takecab

Vonoprazan 20 mg + Atovaquone/Proguanil 250/100 mg

Eligibility Criteria

• Age: 19 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Seoul National University Hospital: lead

Study Sites (1)

Seoul National University Hospital, Clinical Trial Center

Seoul, South Korea

Location

Related Publications (1)

• Yang E, Ji SC, Jang IJ, Lee S. Evaluation of CYP2C19-Mediated Pharmacokinetic Drug Interaction of Tegoprazan, Compared with Vonoprazan or Esomeprazole. Clin Pharmacokinet. 2023 Apr;62(4):599-608. doi: 10.1007/s40262-023-01228-4. Epub 2023 Mar 10.

  PMID: 36897544 DERIVED

MeSH Terms

Conditions

Gastroesophageal Reflux

Interventions

Atovaquone; Proguanil; atovaquone, proguanil drug combination; tegoprazan; Esomeprazole; 1-(5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl)-N-methylmethanamine

Condition Hierarchy (Ancestors)

Esophageal Motility Disorders; Deglutition Disorders; Esophageal Diseases; Gastrointestinal Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Naphthoquinones; Quinones; Organic Chemicals; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Biguanides; Guanidines; Amidines; Omeprazole; 2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• SeungHwan Lee, MD, PhD

  Seoul National University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Associate Professor

Study Record Dates

• First Submitted: September 15, 2020
• First Posted: September 29, 2020
• Study Start: November 25, 2020
• Primary Completion: July 8, 2021
• Study Completion: August 3, 2021
• Last Updated: September 27, 2021

Record last verified: 2021-09

Locations

KR (1)