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

An Open-label, Fixed-sequence, 3-period Crossover Exploratory Study to Investigate the Effect of Urine Acid-base Disequilibrium on the Pharmacokinetics of Captopril in Healthy Male Volunteers

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

Study Overview

• Status: Completed
• Conditions: Hypertension
• Intervention / Treatment: Drug: Captopril 12.5 Mg; Drug: Sodium bicarbonate 4 G; Drug: Torsemide 20 MG

Detailed Description

• Pharmacokinetic analysis of captopril before and after urine acid-base imbalance
• Safety analysis

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Captopril; Single dose of captopril 12.5 mg	Drug: Captopril 12.5 Mg; 12.5 mg of captopril
Experimental: Sodium bicarbonate+captopril; Single dose of captopril 12.5 mg during multiple doses of sodium bicarbonate 1 g every 4-6 hours	Drug: Captopril 12.5 Mg; 12.5 mg of captopril; Drug: Sodium bicarbonate 4 G; 4 g of sodium bicarbonate
Experimental: Torsemide+captopril; Single dose of captopril 12.5 mg during multiple doses of torsemide 20 mg every 6-12 hours	Drug: Captopril 12.5 Mg; 12.5 mg of captopril; Drug: Torsemide 20 MG; 20 mg of torsemide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
urine pH	urine pH	Pre-dose (0 hour) and up to 12 hours in each period
Safety parameters	Number and frequency of participants observed adverse events in each period	Through study completion, an average of 3 months
AUCinf of captopril	Area under the concentration-time curve from 0 to infinite (AUCinf)	Pre-dose (0 hour) and up to 12 hours in each period
Tmax of captopril	Time to Cmax (Tmax)	Observed time point among pre-dose (0 hour) and up to 12 hours in each period
t1/2 of captopril	half-life (t1/2)	Pre-dose (0 hour) and up to 12 hours in each period
CL/F of captopril	Apparent clearance (CL/F)	Pre-dose (0 hour) and up to 12 hours in each period
Vd/F of captopril	Apparent volume of distribution (Vd/F)	Pre-dose (0 hour) and up to 12 hours in each period
fe of captopril	Fraction of urinary excretion (fe)	Pre-dose (0 hour) and up to 12 hours in each period

Collaborators and Investigators

• Sponsor: Seoul National University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): February 28, 2024
• Primary Completion (Actual): March 27, 2024
• Study Completion (Actual): April 1, 2024

Study Registration Dates

• First Submitted: February 13, 2024
• First Submitted That Met QC Criteria: February 27, 2024
• First Posted (Actual): March 4, 2024

Study Record Updates

• Last Update Posted (Actual): May 30, 2025
• Last Update Submitted That Met QC Criteria: May 25, 2025
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Protease Inhibitors; Enzyme Inhibitors; Membrane Transport Modulators; Diuretics; Natriuretic Agents; Sodium Potassium Chloride Symporter Inhibitors; Antihypertensive Agents; Angiotensin-Converting Enzyme Inhibitors; Torsemide; Captopril
• Other Study ID Numbers: Ur_ABD_PK

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No