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

Phase 1

Completed

• Conditions: Hypertension
• Interventions: Drug: Levamlodipine, Amlodipine; Drug: Amlodipine, Levamlodipine

• Registration Number: NCT03657550
• Lead Sponsor: Conjupro Biotherapeutics, Inc.

Brief Summary

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

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 Timeline

• Study Start: 2018-05-31
• Study First Submitted: 2018-06-21
• Status Verified: 2018-09
• Study First Submitted QC: 2018-09-01
• Study First Posted: 2018-09-05
• Primary Completion: 2018-09-06
• Study Completion: 2018-09-06
• Last Update Submitted: 2021-09-09
• Last Update Posted: 2021-09-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 36

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Test Drug - Reference Product - Test Drug (Food Effect)	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.
Reference Product - Test Drug - Test Drug (Food Effect)	Levamlodipine, Amlodipine	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.
Test Drug - Reference Product - Test Drug (Food Effect)	Amlodipine, Levamlodipine	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.
Reference Product - Test Drug - Test Drug (Food Effect)	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.

Primary Outcome Measures

Name	Time	Method
The plasma concentration of study drugs	6 weeks	Plasma concentration of study drugs will be measured at all the time points.

Trial Locations

Locations (1)

Collaborative Neuroscience Network, LLC; 🇺🇸 Long Beach, California, United States