Bioequivalence Study of Ramipril 10 mg Capsules Under Fed Conditions

An Open Label, Balanced, Randomized, Two-Treatment, Two-Period, Two-Sequence, Single-Dose, Crossover Bioavailability Study Comparing Ramipril 10 mg Capsules of Ohm Laboratories Inc. (A Subsidiary of Ranbaxy Pharmaceuticals Inc.), With Altace® Capsule 10 mg (Containing Ramipril 10 mg) of Monarch Pharmaceuticals Inc, USA in Healthy, Adult, Male, Human Subjects Under Fed Conditions.

The study was conducted as an open label, balanced, randomized, two-treatment, two-period, two-sequence, single-dose, crossover bioavailability study comparing ramipril 10 mg capsules of Ohm Laboratories Inc., with Altace® capsule 10 mg (containing ramipril 10 mg) manufactured by King Pharmaceuticals Inc, Bristol and Distributed by Monarch Pharmaceuticals Inc, Bristol in healthy, adult, male, human subjects under fed condition.

A single oral dose of ramipril 10 mg capsule was administered with 240 mL of drinking water at ambient temperature 30 minutes after start of a high-fat high-caloric breakfast under the supervision of trained study personnel.

A total of thirty-two (32) subjects were randomized to receive a single oral dose of the test (T) and reference (R) formulation of ramipril 10 mg capsule. One subject (subject No. 18) was withdrawn and one dropped out (subject No. 10) from the study in period I. One subject (subject No. 20) dropped out and two subjects were withdrawn (subject No. 27, 29) from the study in period II.

A total of twenty-seven (27) subjects completed both the periods of the study.

Inclusion Criteria:

1. Were in the age range of 18-45 years.
2. Were neither overweight nor underweight for the corresponding height as per the Life Insurance Corporation of India height/weight chart for non-medical cases.
3. Had voluntarily given written informed consent to participate in this study.
4. Were of normal health as determined by medical history and physical examination of the subjects performed within 21 days prior to the commencement of the study.
5. Had a non-vegetarian diet habit.

Exclusion Criteria:

1. Hypersensitivity, allergy to ramipril or related group of drugs.
2. History of anaphylaxis/anaphylactoid reactions.
3. History of fever in the week preceding the study.
4. History of seizures and sleep disorders.
5. History of chronic cough, bronchial asthma.
6. Subject who had sitting systolic blood pressure of less than 90 mmHg or >140 mmHg and diastolic blood pressure of less than 60 mmHg or > 90 mmHg at predose.
7. History of frequent syncopal attacks, frequent palpitations.
8. History of angina, myocardial infarction or angioedema.
9. History of severe diarrhea or vomiting in the week preceding the study.
10. History of dry cough.
11. History of congestive heart failure.
12. Any evidence of organ dysfunction or any clinically significant deviation from the normal, in physical or clinical determinations.
13. Presence of disease markers of HIV 1 or 2, Hepatitis B or C viruses or syphilis infection.
14. Presence of values which were significantly different from normal reference ranges and/or judged clinically significant for hemoglobin, total white blood cells count, differential WBC count or platelet count.
15. Positive for urinary screen testing of drugs of abuse (opiates or cannabinoids).
16. Presence of values which were significantly different from normal reference ranges and/or judged clinically significant for serum creatinine, blood urea nitrogen, serum aspartate aminotransferase (AST), serum alanine aminotransferase (ALT), serum alkaline phosphatase, serum bilirubin, plasma glucose or serum cholesterol.
17. Clinically abnormal chemical and microscopic examination of urine defined as presence of RBC, WBC (>4/HPF), glucose (positive) or protein (positive).
18. Clinically abnormal ECG or Chest X-ray.
19. History of serious gastrointestinal, hepatic, renal, cardiovascular, pulmonary, neurological or hematological disease, diabetes or glaucoma.
20. History of any psychiatric illness, which might impair the ability to provide written informed consent.
21. Regular smokers who smoked more than 10 cigarettes daily or had difficulty abstaining from smoking for the duration of each study period.
22. History of drug dependence or excessive alcohol intake on a habitual basis of more than 2 units of alcoholic beverages per day (1 unit equivalent to half pint of beer or 1 glass of wine or 1 measure of spirit) or had difficulty in abstaining for the duration of each study period.
23. Use of any enzyme modifying drugs within 30 days prior to Day 1 of this study.
24. Participation in any clinical trial within 12 weeks preceding Day 1 of this study.
25. Subjects who, through completion of this study, had donated and/or lost more than 350 mL of blood in the past 3 months.