Clinical trial NCT06292091: A Study to Investigate the Effect of Urine Acid-base Disequilibrium on the Pharmacokinetics of Captopril
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hypertension
Lead sponsor: Seoul National University Hospital
Sponsor class: OTHER
First posted: 2024-03-04
Enrollment: 12
Sex: MALE
Minimum age (years): 19
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: OTHER

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.

Detailed description: * Pharmacokinetic analysis of captopril before and after urine acid-base imbalance
* Safety analysis

Eligibility criteria: 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

Primary outcomes:
measure: AUClast of captopril
timeFrame: Pre-dose (0 hour) and up to 12 hours in each period
measure: Cmax of captopril
timeFrame: Observed value among pre-dose (0 hour) and up to 12 hours in each period
Secondary outcomes:
measure: AUCinf of captopril
timeFrame: Pre-dose (0 hour) and up to 12 hours in each period
measure: Tmax of captopril
timeFrame: Observed time point among pre-dose (0 hour) and up to 12 hours in each period
measure: t1/2 of captopril
timeFrame: Pre-dose (0 hour) and up to 12 hours in each period
measure: CL/F of captopril
timeFrame: Pre-dose (0 hour) and up to 12 hours in each period
measure: Vd/F of captopril
timeFrame: Pre-dose (0 hour) and up to 12 hours in each period
measure: fe of captopril
timeFrame: Pre-dose (0 hour) and up to 12 hours in each period
measure: urine pH
timeFrame: Pre-dose (0 hour) and up to 12 hours in each period
measure: Safety parameters
timeFrame: Through study completion, an average of 3 months
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
Study officials:
References: