Bioequivalence of Levamlodipine Besylate Tablets in Healthy Chinese Subjects

Study Overview
=================
Brief Summary
-----------------
The single-dose randomized, open-label, two-period crossover study was executed in the Phase I Clinical Research Center of the Affiliated Hospital of Qingdao University. According to the random table generate by SAS 9.4, the subjects were divided into two groups at the ratio of 1:1. The select qualified volunteers were hospitalized in the Phase I Clinical Research Center, and fasted for 10 hours overnight until administration. The medicine was swallowed with 240 ml water at room temperature. Blood samples were taken before administration and at 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 24, 36, 48, 72, 96, 120, 144, 168 hours after administration. The samples were centrifuged at 1,800 g for 10 min at 4 °C to separate the plasma. The plasma samples were divided into two aliquots and stored at -80 °C until bioanalysis. The half-life of levamlodipine is 30   50 hours. Washout period, the interval between two administration, is 21 days. In the two periods, the operation was kept the same. Moreover, in high fat meal group, the high-fat breakfast was arranged within half an hour before taking the medicine. Other procedures were the same as those in the fasting group.

Official Title
-----------------
Bioequivalence of Levamlodipine Besylate Tablets in Healthy Chinese Subjects: A Single-dose and Two-period Crossover Study

Conditions
-----------------
Healthy Subjects

Intervention / Treatment
-----------------
* Drug: Amlodipine 10 mg
* Drug: Levamlodipine 5 mg


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy male or female aged 18 and above. The body mass index is in the range of 18.6-28.5 kg/m2 (including the critical value). The weight of male is not less than 50.0 kg, and that of female is not less than 45.0 kg. The following examination show that the indicators are normal or abnormal without clinical significance. The examination including: Vital signs, physical examination, blood routine, blood biochemistry, urinalysis, pregnancy test for female, serological tests for hepatitis B virus, hepatitis C virus, human immunodeficiency virus (HIV), and syphilis virus, 12 lead ECG, breath test for alcohol, drug abuse test. The subjects have no family planning within 3 months and could select contraceptive method. Before the study, all subjects have been informed of the study's purpose, protocal, benefits, and risks, and signed the informed consent voluntarily. Exclusion Criteria: Being allergy to the study medications, smoking, alcohol abuse. Participation in another clinical trial within 3 months.

Ages Eligible for Study
-----------------
Minimum Age: 19 Years
Maximum Age: 48 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Amlodipine<br>amlodipine reference formulation at a single dose of 10 mg | Drug: Amlodipine 10 mg<br>* The subjects randomly received single oral administration of amlodipine 10 mg.<br>|
| Experimental: Levamlodipine<br>levamlodipine test formulation at a single dose of 5 mg | Drug: Levamlodipine 5 mg<br>* The subjects randomly received single oral administration of levamlodipine 5 mg.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak Plasma Concentration (Cmax) | Evaluation of Peak Plasma Concentration (Cmax) | 64 days | 
| Area under the plasma concentration versus time curve (AUC)0-t | Evaluation of Area under the plasma concentration versus time curve (AUC)0-t | 64 days | 
| Area under the plasma concentration versus time curve (AUC)0-∞ | Evaluation of Area under the plasma concentration versus time curve (AUC)0-∞ | 64 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment-Emergent Adverse Events | Collection of adverse events | 64 days | 
| Incidence of abnormal blood pressure | Monitor both systolic and diastolic blood pressure | 64 days | 
| Incidence of abnormal temperature | Monitor the temperature | 64 days | 
| Incidence of abnormal pulse | Temperature the pulse | 64 days | 
| Incidence of abnormal electrocardiogram waveform | Electrocardiogram inspection | 64 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
levamlodipine, bioequivalence, pharmacokinetics