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

Hypertension Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT06292091
• Other study ID #: Ur_ABD_PK
• Status: Completed
• Phase: Phase 1
• Start date: February 28, 2024
• Est. completion date: April 1, 2024

Study information

• Verified date: April 2024
• 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 effect of urine acid-base disequilibrium on the pharmacokinetics of captopril in healthy male volunteers.

Description:

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

• Safety analysis

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: April 1, 2024
• Est. primary completion date: March 27, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 19 Years to 50 Years

Eligibility

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

Related Conditions & MeSH terms

• Hypertension

Intervention

Drug:
• Captopril 12.5 Mg
12.5 mg of captopril
• Sodium bicarbonate 4 G
4 g of sodium bicarbonate
• Torsemide 20 MG
20 mg of torsemide

Locations

Country	Name	City	State
Korea, Republic of	Seoul National University Hospital	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 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
Primary	Cmax of captopril	Maximum concentration of captopril (Cmax)	Observed value among pre-dose (0 hour) and up to 12 hours in each period
Secondary	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
Secondary	Tmax of captopril	Time to Cmax (Tmax)	Observed time point among pre-dose (0 hour) and up to 12 hours in each period
Secondary	t1/2 of captopril	half-life (t1/2)	Pre-dose (0 hour) and up to 12 hours in each period
Secondary	CL/F of captopril	Apparent clearance (CL/F)	Pre-dose (0 hour) and up to 12 hours in each period
Secondary	Vd/F of captopril	Apparent volume of distribution (Vd/F)	Pre-dose (0 hour) and up to 12 hours in each period
Secondary	fe of captopril	Fraction of urinary excretion (fe)	Pre-dose (0 hour) and up to 12 hours in each period
Secondary	urine pH	urine pH	Pre-dose (0 hour) and up to 12 hours in each period
Secondary	Safety parameters	Number and frequency of participants observed adverse events in each period	Through study completion, an average of 3 months