A Study to Investigate the Effect of Urine Acid-base Disequilibrium on the Pharmacokinetics of Captopril

NCT06292091 | Completed Phase 1

• 1 other identifier: Ur_ABD_PK
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of this study is to evaluate the effect of urine acid-base disequilibrium on the pharmacokinetics of captopril in healthy male volunteers.

Conditions

Hypertension

Outcome Measures

Primary Outcomes (2)

• AUClast of captopril

  Area under the concentration-time curve from 0 to last measurable concentration (AUClast)

  Pre-dose (0 hour) and up to 12 hours in each period

• Cmax of captopril

  Maximum concentration of captopril (Cmax)

  Observed value among pre-dose (0 hour) and up to 12 hours in each period

Secondary Outcomes (8)

• AUCinf of captopril

  Pre-dose (0 hour) and up to 12 hours in each period

• Tmax of captopril

  Observed time point among pre-dose (0 hour) and up to 12 hours in each period

• t1/2 of captopril

  Pre-dose (0 hour) and up to 12 hours in each period

• CL/F of captopril

  Pre-dose (0 hour) and up to 12 hours in each period

• Vd/F of captopril

  Pre-dose (0 hour) and up to 12 hours in each period

Study Arms (3)

Captopril

ACTIVE COMPARATOR

Single dose of captopril 12.5 mg

Drug: Captopril 12.5 Mg

Sodium bicarbonate+captopril

EXPERIMENTAL

Single dose of captopril 12.5 mg during multiple doses of sodium bicarbonate 1 g every 4-6 hours

Drug: Captopril 12.5 Mg; Drug: Sodium bicarbonate 4 G

Torsemide+captopril

EXPERIMENTAL

Single dose of captopril 12.5 mg during multiple doses of torsemide 20 mg every 6-12 hours

Drug: Captopril 12.5 Mg; Drug: Torsemide 20 MG

Interventions

Captopril 12.5 Mg DRUG

12.5 mg of captopril

Captopril; Sodium bicarbonate+captopril; Torsemide+captopril

Sodium bicarbonate 4 G DRUG

4 g of sodium bicarbonate

Sodium bicarbonate+captopril

Torsemide 20 MG DRUG

20 mg of torsemide

Torsemide+captopril

Eligibility Criteria

• Age: 19 Years - 50 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy male volunteer aged 19 to 50 years at screening
• Body weight between 50.0 kg and 90.0 kg and body mass index (BMI) between 18.5 kg/m2 and 29.9 kg/m2 at screening
• Body Mass Index (kg/m2) = Weight (kg)/{Height (m)}2
• Participants who voluntarily decided to participate and agreed in writing to comply with study instructions after receiving sufficient explanation and complete understanding of the study
• Participants who are suitable as test subjects for this test as determined by the investigator through physical examination, clinical laboratory tests, and interviews, etc.

You may not qualify if:

• Participants who have or have a history of clinically significant hepatobiliary system (severe liver failure, viral hepatitis, etc.), kidney (severe renal impairment, etc.), nervous system, immune system, respiratory system, digestive system, endocrine system, blood/tumor, cardiovascular system (heart failure, Torsades de pointes, etc.), urinary system, mental system (mood disorder, obsessive-compulsive disorder, etc.), and sexual dysfunction, etc.
• Evidence or past history of gastrointestinal disease (Crohn's disease, gastrointestinal ulcer, gastritis, gastroesophageal reflux disease, etc.) or past history of gastrointestinal surgery (except for simple appendectomy and hernia repair) that might affect the safety and PK assessment of the investigational product.
• Hypersensitivity to drugs including captopril, sodium bicarbonate, and torsemide or other drugs (aspirin, antibiotics, etc.) or history of clinically significant hypersensitivity reactions
• Participants with genetic problems such as lactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption
• Positive serum test (HBs antigen, HCV antibody, HIV antigen-antibody, and RPR) at screening
• Past history of alcohol and drug abuse or a positive urine test for drugs with abuse potential at screening
• Any abnormalities in vital signs after 3 minutes rest at screening
• Systolic blood pressure \< 90 mmHg or \> 150 mmHg, Diastolic blood pressure \< 60 mmHg or \> 100 mHg
• QT/QTcF \> 450 msec or any abnormalities on electrocardiogram (ECG) at screening
• Any abnormalities in blood tests at screening
• AST (SGOT), ALT (SGPT) \> 60 IU/L, creatinine clearance (CKD-EPI equation) \< 80 mL/min
• Past or planned treatment with any prescription drugs or herbal medicine within 2 weeks, or any over the counter drugs, health functional foods, or vitamin supplements within 1 week, prior to the first scheduled dose (individual who is eligible based on other criteria may participate in the study at the discretion of the investigator).
• Participants who have taken drugs that induce drug-metabolizing enzymes such as barbiturates or inhibit drug metabolism such as clarithromycin within 1 month prior to the first scheduled dose
• Treatment with any investigational product in another clinical trial within 6 months prior to the first scheduled dose

Sponsors & Collaborators

• Seoul National University Hospital: lead

Study Sites (1)

Seoul National University Hospital

Seoul, Seoul, 03080, South Korea

Location

MeSH Terms

Conditions

Hypertension

Interventions

Captopril; Sodium Bicarbonate; Torsemide

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Proline; Imino Acids; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Bicarbonates; Carbonates; Carbonic Acid; Carbon Compounds, Inorganic; Inorganic Chemicals; Sodium Compounds; Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

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

Study Record Dates

• First Submitted: February 13, 2024
• First Posted: March 4, 2024
• Study Start: February 28, 2024
• Primary Completion: March 27, 2024
• Study Completion: April 1, 2024
• Last Updated: May 30, 2025

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)