Amlodipine-Benazepril 10mg-20mg Capsules in Healthy Subjects Under Fasting Conditions
Condition: Healthy
Intervention: Amlodipine-benazepril 10 mg-20 mg capsules; Lotrel® 10 mg-20 mg capsule
Intervention description: 1 x 10-20 mg; 1 x 10-20 mg
Intervention MeSH terms: Amlodipine; Benazepril
Phase: Phase 1
Study type: Interventional
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 48.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Bioequivalence; Healthy Subjects

Summary:

      The objective of this study is to compare the rate and extent of absorption of
      amlodipine-benzazepril 10 mg-20 mg capsules (test) versus Lotrel® (reference), administered
      as 1 x 10 mg capsule under fasting conditions.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male of non-child-bearing potential female, non-smoker, 18 years of age and older.

          -  Non-child-bearing potential female subjects is defined as follows:

          -  Post-menopausal state: absence of menses for 12 months prior to drug administration or
             hysterectomy woth bilateral oophorectomy at least 6 months prior to drug
             administration.

          -  Surgically sterile: hysterectomy, bilateral oophorectomy, or tubal ligation at least 6
             months prior to drug administration.

          -  Capable of consent

        Exclusion Criteria:

          -  Clinically significant illnesses within 4 weeks prior to the administration of the
             study medication.

          -  Clinically significant surgery within 4 weeks prior to the administration of the study
             medication

          -  Any clinically significant abnormality found during medical screening.

          -  Any reason which, in the opinion of the Medical Sub-Investigator, would prevent the
             subject from participating in the study.

          -  Abnormal laboratory tests judges clinically significant.

          -  Positive testing for hepatitis B, hepatitis C, or HIV at screening.

          -  EGC abnormalities (clinically significant) or vital sign abnormalities (systolic blood
             pressure lower than 100 ot over 140 nnHg, diastolic blood pressure lower than 60 or
             over 90 mmHg, or heart rate less that 60 or over 100 bpm) at screening.

          -  BMI ≥ 30.0

          -  History of significant alcohol abuse within six months prior to the screening visit or
             any indication of the regular use of more than fourteen units of alcohol per week ( 1
             Unit= 150 mL of wine, 360 mL of beer, or 45 mL ot 40% alcohol) or positive alcohol
             breath test at screening.

          -  History of drug abuse or use of illegal drugs: use of soft drugs (such as marijuana)
             within 3 months prior to the screening visit or hard drugs( such as cocaine,
             phencyclidine [PCP] and crack) within 1 year prior to the screening visit or positive
             urine drug screen at screening.

          -  History of allergic reactions to heparin,amlodipine,benazepril, or other ACE
             inhibitors, or other related drugs.

          -  Use of any drugs known to induce hepatic drug metabolism (examples of inducers:
             barbiturates, carbamazepine, phenytoin, glucocorticoids, omeprazole; examples of
             inhibitors: antidepressant (SSRI), cimetidine, diltiazem, macrolides, imidazoles,
             neuroleptics, verapamil, fluoroquinolones, antihistamines) within 30 days prior to
             administration of the study medication.

          -  Use of and investigational drug or participation in an investigational study within 30
             days prior to administration of the study medication.

          -  Clinically significant history or presence of any clinically significant
             gastrointestinal pathology (e.g. chronic diarrhea, inflammatory bowel diseases),
             unresolved gastrointestinal symptoms (e.g. diarrhea, vomiting), liver of kidney
             disease, or other conditions known to interfere with the absorption, distribution,
             metabolism, or excretion of the drug.

          -  Any clinically significant history or presence of clinically significant neurological,
             endocrinal, cardiovascular, pulmonary, hematologic, immunologic, psychiatric, or
             metabolic disease.

          -  Use of prescription medication ( including hormone replacement therapy) within 14 days
             prior to administration of study medication or over-the-counter products (including
             natural food supplements, vitamins, garlic as a supplement) within 7 days prior to
             administration of study medication, except for topical products without systemic
             absorption.

          -  Difficulty to swallow study medication. Subjects who have used tobacco in any form
             within the 90 days preceding study drug administration

          -  Any food allergy, intolerance, restriction or special diet that, in the opinion of the
             Medical Sub-Investigator, could contraindicate the subject's participation in this
             study.

          -  A depot injection or an implant of any drug within 3 months prior to administration of
             study medication.

          -  Donation of plasma (500 mL) within 30 days prior to drug administration. Donation or
             loss of whole blood (excluding the volume of blood that will be drawn during the
             screening procedures of this study) prior to administration of the study medication as
             follows:

          -  50 mL to 300 mL of whole blood within 30 days,

          -  301 mL to 500 mL of whole blood within 45 days, or

          -  more than 500 mL of whole blood within 56 days prior to drug administration.

          -  Consumption of food or beverages containing grapefruit ( e.g. fresh, canned, or
             frozen) within 7 days prior to administration of the study medication.

          -  Intolerance to venipunctures

          -  Unable to understand or unwilling to sign the Informed Consent Form.

          -  Clinically significant history of angioedema. Subjects with a clinically significant
             history or active hypotension. Subjects with a significant history of active
             neutropenia and/or agranulocytosis.

          -  Breast-feeding subject.

          -  Positive urine pregnancy test at screening.