Clinical trial NCT04556058: A Study on the Bioequivalence of Perindopril Tert-butylamine Tablets Taken on an Empty Stomach in Healthy Subjects
Official title: Bioequivalence Study of Fasting Oral Perindopril Tert-butylamine Tablets in Healthy Subjects With a Single-dose, Randomized, Open, Two-cycle, Crossover Trial Design
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: perindopril tert-butylamine
Bioequivalence study
fasting
Lead sponsor: Haisco Pharmaceutical Group Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2020-09-21
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

Brief summary: In order to evaluate the bioequivalence of the test preparations and reference preparations of perindopril tert-butylamine tablets after meal and their safety in Chinese adult healthy subjects.

Detailed description: This single-center, randomized, open-lable, single-dose, two-cycle,cross-over design bioequivalence test was conducted in subjects under fasting conditions. Subjects were fasted for at least 10 hours overnight in each cycle，but can't ban their from drinking water.The next morning according to test-reference (TR) or Reference-test (RT) sequential oral perindopril tert-butylamine tablets (4 mg, 240 mL warm water) . Each period was separated with a 14-day washout period in fasted trials. The blood concentrations of perindopril and perindoprilat in qualified subjects were tested. Safety assessment includes vital signs examination, physical examination, laboratory safety examination, coagulation examination, electrocardiogram and adverse event reports.

Eligibility criteria: Inclusion Criteria:

1. Healthy volunteers between the ages of 18 and 50 (including cut-off values), both male and female;
2. Male weight ≥50kg, female weight ≥45kg, and body mass index (BMI) 19-26kg/m2 (including cut-off values);
3. Sign the informed consent form voluntarily;
4. Be able to maintain good communication with researchers and comply with various requirements of clinical trials.

Exclusion Criteria:

1. People who is addicted to alcohol, tobacco,(drink 14 units of alcohol per week within the first month of enrollment: 1 unit = 285 ml of beer, or 25 ml of spirits, or 1 glass of wine; average daily smoking in the 3 months before screening ≥5) and/or those who cannot ban smoking and alcohol during the trial; or those who have a positive result alcohol breath trial;
2. Use any prescription drugs (such as antihypertensive drugs) within 4 weeks before screening, or use any over-the-counter drugs (vitamins, Chinese herbal tonics) within 2 weeks before screening, or take foods that affect metabolism within 2 weeks before screening, such as grapefruit or a drink containing grapefruit (acetaminophen can be used, but it must be recorded in the concomitant medication of CRF); or the subject refused to stop using foods that affect CYP1A2 during the trial, such as coffee, tea, cola, chocolate, etc.
3. Those who have used any drugs with a long half-life that may affect this study, or have participated in any drug clinical trials as subjects in the past 3 months;
4. Blood donation or blood loss ≥ 400mL within 8 weeks before the first administration;
5. People with a history of food or drug allergy, or allergies;
6. Any clinically significant physical examination, vital signs, electrocardiogram or clinical laboratory measurement abnormalities during screening;
7. Suffer from blood system, circulatory system, digestive system, urinary system, respiratory system, nervous system, immune system, endocrine system, mental abnormality, metabolic abnormality or any other chronic or serious disease history or existing disease that may affect the results of the study Those with the aforementioned systemic diseases;
8. Human immunodeficiency virus (HIV) antibody, hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, or Treponema pallidum antibody (TPPA) has a positive result;
9. Those who have a history of drug abuse or drug dependence;
10. People who have a history of fainting needles and blood, or who cannot tolerate venipuncture blood sampling and known serious bleeding tendency;
11. Patients with resting systolic blood pressure ≤90 mmHg, ≥140mmHg, or diastolic blood pressure ≤60 mmHg, ≥90mmHg, or pulse (HR) ≤50bpm, ≥100bpm;
12. Pregnant or lactating women, or female subjects whose pregnancy test results are positive; subjects (or their partners) have birth plans or sperm and egg donors during the entire trial period and within 3 months after the end of the study; trial Those who are unwilling to take one or more physical contraceptive measures during the period and within 3 months after the end of the study;
13. Patients with congenital galactosemia, glucose and galactose malabsorption syndrome, or lack of lactase;
14. Subjects who have poor compliance or who the researcher thinks are not suitable for inclusion in the group.

Primary outcomes:
measure: Maximum drug concentration (Cmax) of Perindopril
timeFrame: Before administration (within 2 hours) and 10 minutes to 72 hours after administration
measure: Area under the plasma concentration versus time curve （AUC0-∞、AUC0-t）of Perindopril
timeFrame: Before administration (within 2 hours) and 10 minutes to 72 hours after administration
Secondary outcomes:
measure: Time to reach maximum plasma concentration(Tmax) of Perindopril and Perindoprilat
timeFrame: Before administration (within 2 hours) and 10 minutes to 72 hours after administration
measure: Terminal elimination half-life（t1/2 ）of Perindopril and Perindoprilat
timeFrame: Before administration (within 2 hours) and 10 minutes to 72 hours after administration
measure: Maximum drug concentration (Cmax) of Perindoprilat
timeFrame: fore administration (within 2 hours) and 10 minutes to 72 hours after administration
measure: Area under the plasma concentration versus time curve （AUC0-∞、AUC0-t）of Perindoprilat
timeFrame: Before administration (within 2 hours) and 10 minutes to 72 hours after administration
Other outcomes:
measure: Adverse event rate
timeFrame: from the screening to 18 days post-dose
Locations:
city: Shenyang
country: China
facility: General Hospital of the northern theater of the Chinese people's Liberation Army
state: Liaoning
Study officials:
References: