Bioequivalence of Levamlodipine Besylate Tablets in Healthy Chinese Subjects

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy Subjects
• Intervention / Treatment: Drug: Amlodipine 10 mg; Drug: Levamlodipine 5 mg

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Shandong
    • Qingdao, Shandong, China, 266003
      • Phase I Clinical Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 48 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

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

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

Collaborators and Investigators

• Sponsor: The Affiliated Hospital of Qingdao University

Publications and helpful links

General Publications

• Li X, Wang C, Li T, Liu Y, Liu S, Tao Y, Ma Y, Gao X, Cao Y. Bioequivalence of levamlodipine besylate tablets in healthy Chinese subjects: a single-dose and two-period crossover randomized study. BMC Pharmacol Toxicol. 2020 Nov 19;21(1):80. doi: 10.1186/s40360-020-00459-6.

Study record dates

Study Major Dates

• Study Start (Actual): November 13, 2018
• Primary Completion (Actual): January 15, 2019
• Study Completion (Actual): February 15, 2019

Study Registration Dates

• First Submitted: May 19, 2020
• First Submitted That Met QC Criteria: May 28, 2020
• First Posted (Actual): June 2, 2020

Study Record Updates

• Last Update Posted (Actual): June 5, 2020
• Last Update Submitted That Met QC Criteria: June 3, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: pharmacokinetics; bioequivalence; levamlodipine
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Vasodilator Agents; Membrane Transport Modulators; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Amlodipine
• Other Study ID Numbers: 180815-ALDP-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: The technical achievements (including but not limited to patent right and thesis publishing right) involved in this trial, clinical research materials and achievements are owned by Zhejiang onlycom Pharmaceutical Co., Ltd. With the written consent of Zhejiang onlycom Pharmaceutical Co., Ltd., all partners have the right to publish academic papers, and the Affiliated Hospital of Qingdao University, a clinical research institution, has the right to exchange research results in academic conferences or journals.
• IPD Sharing Time Frame: The data have been available on February 15, 2019. The duration has not been determined.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No