Clinical trial NCT03657550: Bioavailability of 5 mg of Levamlodipine Maleate Tablets Versus 10 mg of Amlodipine Besylate Tablet in Healthy Subjects
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hypertension
Lead sponsor: Conjupro Biotherapeutics, Inc.
Sponsor class: INDUSTRY
Collaborators: name: CSPC Ouyi Pharmaceutical Co., Ltd.
First posted: 2018-09-05
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention 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.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: The plasma concentration of study drugs
timeFrame: 6 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Long Beach
country: United States
facility: Collaborative Neuroscience Network, LLC
state: California
Study officials:
affiliation: Conjupro Biotherapeutics, Inc.
name: Study Officials
role: STUDY_DIRECTOR
References: