Bioavailability of 5 mg of Levamlodipine Maleate Tablets Versus 10 mg of Amlodipine Besylate Tablet in Healthy Subjects

Randomized Open-label Single-Dose Two-Way Crossover Study to Assess the Relative Bioavailability of 5mg Levamlodipine Tablet vs. 10mg Amlodipine Besylate Tablet in Healthy Subjects Followed by a Phase to Study Food Effect on the PK of Levamlodipine

This study are (1) to assess the relative bioavailability (BA) of a single oral dose of either 5 mg of Levamlodipine Maleate Tablets from CSPC or 10 mg of Amlodipine Besylate Tablet (NORVASC®) from Pfizer Inc. under fasting condition in male and female healthy subjects; and (2) to evaluate food effect on the PK profile of Levamlodipine Maleate Tablets from CSPC.

Study Overview

• Status: Completed
• Conditions: Hypertension
• Intervention / Treatment: Drug: Levamlodipine, Amlodipine; Drug: Amlodipine, Levamlodipine

Detailed Description

This study consists of 2 parts:

Part 1 will be a randomized, open-label, single-dose, two-way crossover study to assess the relative BA of levamlodipine maleate tablets from CSPC (Test) versus Amlodipine Besylate Tablet NORVASC® from Pfizer Inc. (Reference) after a single oral administration under fasted conditions in male and female healthy subjects. Approximately 32 healthy subjects will be enrolled in the US to obtain 27 completed subjects.

Part 2 will be a single-arm, open-label, single-dose phase to assess food effect on the PK profile of levamlodipine maleate tablets from CSPC. Subjects who have completed Part 1 will be rolled over to Part 2 after a wash-out period for at least 14-days since the last dosing. Subjects will receive a single oral administration of study drug under a high-fat / high-calorie meal that should derive approximately 150, 250 and 500-600 calories from protein, carbohydrate and fat, respectively.

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Long Beach, California, United States, 90806
      • Collaborative Neuroscience Network, LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

1. Women of childbearing potential (WOCBP) must have a negative pregnancy test at Screening and be practicing a medically acceptable method of contraception with an annual failure rate of less than 1% during the study and 60 days after discontinuation of study treatment.
2. Considered healthy by the Principal Investigator, based on a detailed medical history, full physical examination, clinical laboratory tests, 12-lead ECG and vital signs;
3. Nonsmoker, defined as not having smoked or used any form of tobacco in more than 6 months before screening;
4. Body mass index (BMI) of 19 to 30 kg/m2 inclusive and body weight not less than 50 kg;

Exclusion Criteria:

1. Clinically significant history of gastrointestinal, cardiovascular, musculoskeletal, endocrine, hematologic, psychiatric, renal, hepatic, bronchopulmonary, neurologic, immunologic, lipid metabolism disorders, or drug hypersensitivity;
2. Mean systolic blood pressure of three measurements >140 mmHg, or a mean diastolic blood pressure of three measurements >90 mmHg at screening.
3. Known or suspected malignancy;
4. Positive blood screen for human immunodeficiency virus (HIV), or hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV);
5. A history of seizure. However, a history of febrile seizure is allowed;
6. Positive pregnancy test result, or plan to become pregnant if female;
7. A hospital admission or major surgery within 30 days prior to screening;
8. Participation in any other investigational drug trial within 30 days prior to screening;
9. DSM-V substance use disorder within 6 months prior to screening;
10. A positive result for alcohol or drugs of abuse at screening or admission;
11. Tobacco use within 6 months prior to screening;
12. An unwillingness or inability to comply with food and beverage restrictions during study participation;
13. Donation or blood collection of more than 1 unit (approximate 450 mL) of blood (or blood products) or acute loss of blood during the 90 days prior to screening;
14. Use of prescription or over-the-counter (OTC) medications, and herbal medicines (including St John's Wort, herbal teas, garlic extracts) within 14 days prior to dosing;
15. A history of suicide attempt in the past 12 months and/or seen by the investigator as having a significant history of risk of suicide or homicide;
16. A history of intolerance or hypersensitivity to amlodipine or any excipients;
17. An unwillingness of male participants to use appropriate contraceptive measures if engaging in sex intercourse with a female partner of childbearing potential during the study and 60 days after discontinuation of study treatment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Test Drug - Reference Product - Test Drug (Food Effect); In Part 1, this group of subjects were treated with a single dose of 5 mg levamlodipine maleate tablets (Test Product), then crossed over to receive a single dose of 10 mg Amlodipine Besylate Tablet NORVASC® (Reference Product) under fasted conditions. After a wash-out period for 14-days, all subjects were rolled over to Part 2 where they received a single dose of 5 mg levamlodipine maleate tablets under a high-fat/high-calorie meal to assess food effect.	Drug: Levamlodipine, Amlodipine; In Part 1, this group of subjects were treated with a single dose of 5 mg levamlodipine maleate tablets (Test Product), then crossed over to receive a single dose of 10 mg Amlodipine Besylate Tablet NORVASC® (Reference Product) under fasted conditions. After a wash-out period for 14-days, all subjects were rolled over to Part 2 where they received a single dose of 5 mg levamlodipine maleate tablets under a high-fat/high-calorie meal to assess food effect.; Other Names: Xuanning®, NORVASC®; Drug: Amlodipine, Levamlodipine; In Part 1, this group of subjects were treated with a single dose of 10 mg Amlodipine Besylate Tablet NORVASC® (Reference Product), and then crossed over to receive a single dose of 5 mg levamlodipine maleate tablets (Test Product) under fasted conditions. After a wash-out period for 14-days, all subjects were rolled over to Part 2 where they received a single dose of 5 mg levamlodipine maleate tablets under a high-fat/high-calorie meal to assess food effect.; Other Names: NORVASC®, Xuanning®
Other: Reference Product - Test Drug - Test Drug (Food Effect); In Part 1, this group of subjects were treated with a single dose of 10 mg Amlodipine Besylate Tablet NORVASC® (Reference Product), and then crossed over to receive a single dose of 5 mg levamlodipine maleate tablets (Test Product) under fasted conditions. After a wash-out period for 14-days, all subjects were rolled over to Part 2 where they received a single dose of 5 mg levamlodipine maleate tablets under a high-fat/high-calorie meal to assess food effect.	Drug: Levamlodipine, Amlodipine; In Part 1, this group of subjects were treated with a single dose of 5 mg levamlodipine maleate tablets (Test Product), then crossed over to receive a single dose of 10 mg Amlodipine Besylate Tablet NORVASC® (Reference Product) under fasted conditions. After a wash-out period for 14-days, all subjects were rolled over to Part 2 where they received a single dose of 5 mg levamlodipine maleate tablets under a high-fat/high-calorie meal to assess food effect.; Other Names: Xuanning®, NORVASC®; Drug: Amlodipine, Levamlodipine; In Part 1, this group of subjects were treated with a single dose of 10 mg Amlodipine Besylate Tablet NORVASC® (Reference Product), and then crossed over to receive a single dose of 5 mg levamlodipine maleate tablets (Test Product) under fasted conditions. After a wash-out period for 14-days, all subjects were rolled over to Part 2 where they received a single dose of 5 mg levamlodipine maleate tablets under a high-fat/high-calorie meal to assess food effect.; Other Names: NORVASC®, Xuanning®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The plasma concentration of study drugs	Plasma concentration of study drugs will be measured at all the time points.	6 weeks

Collaborators and Investigators

• Sponsor: Conjupro Biotherapeutics, Inc.
• Collaborators: CSPC Ouyi Pharmaceutical Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): May 31, 2018
• Primary Completion (Actual): September 6, 2018
• Study Completion (Actual): September 6, 2018

Study Registration Dates

• First Submitted: June 21, 2018
• First Submitted That Met QC Criteria: September 1, 2018
• First Posted (Actual): September 5, 2018

Study Record Updates

• Last Update Posted (Actual): September 16, 2021
• Last Update Submitted That Met QC Criteria: September 9, 2021
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Vasodilator Agents; Antimetabolites; Micronutrients; Hypolipidemic Agents; Lipid Regulating Agents; Membrane Transport Modulators; Vitamins; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Vitamin B Complex; Amlodipine; Niacin
• Other Study ID Numbers: LAM-US-101

Drug and device information, study documents

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