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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Hypertension

Intervention / Treatment
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* Drug: Levamlodipine, Amlodipine
* Drug: Amlodipine, Levamlodipine


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: 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. Considered healthy by the Principal Investigator, based on a detailed medical history, full physical examination, clinical laboratory tests, 12-lead ECG and vital signs; Nonsmoker, defined as not having smoked or used any form of tobacco in more than 6 months before screening; Body mass index (BMI) of 19 to 30 kg/m2 inclusive and body weight not less than 50 kg; Exclusion Criteria: Clinically significant history of gastrointestinal, cardiovascular, musculoskeletal, endocrine, hematologic, psychiatric, renal, hepatic, bronchopulmonary, neurologic, immunologic, lipid metabolism disorders, or drug hypersensitivity; Mean systolic blood pressure of three measurements >140 mmHg, or a mean diastolic blood pressure of three measurements >90 mmHg at screening. Known or suspected malignancy; Positive blood screen for human immunodeficiency virus (HIV), or hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV); A history of seizure. However, a history of febrile seizure is allowed; Positive pregnancy test result, or plan to become pregnant if female; A hospital admission or major surgery within 30 days prior to screening; Participation in any other investigational drug trial within 30 days prior to screening; DSM-V substance use disorder within 6 months prior to screening; A positive result for alcohol or drugs of abuse at screening or admission; Tobacco use within 6 months prior to screening; An unwillingness or inability to comply with food and beverage restrictions during study participation; 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; 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; 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; A history of intolerance or hypersensitivity to amlodipine or any excipients; 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Interventional Model 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 versus Amlodipine Besylate Tablet NORVASC® from Pfizer Inc. after a single oral administration under fasted conditions in male and female healthy 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.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Test Drug - Reference Product - Test Drug (Food Effect)<br>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<br>* 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.<br>* Other names: Xuanning®, NORVASC®;Drug: Amlodipine, Levamlodipine<br>* 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.<br>* Other names: NORVASC®, Xuanning®;|
| Other: Reference Product - Test Drug - Test Drug (Food Effect)<br>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<br>* 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.<br>* Other names: Xuanning®, NORVASC®;Drug: Amlodipine, Levamlodipine<br>* 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.<br>* Other names: NORVASC®, Xuanning®;|

What is the study measuring?
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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 |