Bioequivalence Study of Etodolac Tablet USP 500 mg Under Fasting Condition

An Open Label, Balanced, Randomized, Single-dose, Two-treatment, Two-sequence, Two-period, Crossover, Oral Bioequivalence Study of Etodolac Tablets USP 500mg of Ipca Laboratories Limited, India and Etodolac Tablets USP 500mg of Taro Pharmaceutical Industries Ltd., USA in Healthy, Adult, Human Subjects Under Fasting Condition.

This is a open Label, balanced, randomized, single dose, two-treatment, two-sequence, two-period, crossover pivotal study. The purpose of this study is to assess the bioequivalence between Test Product and the corresponding Reference Product under fasting condition in healthy, adult human subjects.

Objective of this pivotal study was to assess the bioequivalence between Test Product: Etodolac Tablets USP 500 mg of Ipca Laboratories Limited, India and the corresponding Reference Product: Etodolac Tablets USP 500mg of Taro Pharmaceutical Industries Ltd., USA, under fasting condition in healthy, adult, human subjects in a randomized crossover study.

The study was conducted with 36 healthy adult subjects. In each study period, a single 500 mg dose of either test or reference was administered to the subjects as per the randomization schedule in each study period with about 240 mL of water at ambient temperature in sitting position.

The duration of the clinical phase was approximately 12 days including washout period of 9 days between administrations of study drug in each study period.

Inclusion Criteria:

1. Healthy male and non-pregnant female subjects within the age range of 18 to 45 years (both inclusive), at the time of dosing.

2. Subjects' weight within normal range according to normal values for Body Mass Index (18.5 to 24.9 kg/m2) with minimum of 50 kg weight.

3. Subjects with normal health as determined by personal medical and medication history, clinical examination and laboratory examinations within the clinically acceptable reference range.

4. Subjects having normal 12-lead electrocardiogram (ECG).

5. Subjects having normal chest X-Ray (P/A view) whose X-Ray was taken within 6 months prior to the dosing of Period 01.

6. Subjects having negative urine screen for drugs of abuse (including amphetamines, barbiturates, benzodiazepines, marijuana, cocaine, and morphine).

7. Subjects having negative alcohol breath test.

8. Subjects willing to adhere to protocol requirements and to provide written informed consent.

9. Subjects having negative Beta-hCG Pregnancy test (only for female subjects).

10. For Female Subjects:

    • Female of child bearing potential practicing an acceptable method of birth control for the duration of the study as judged by the investigator(s), such as condoms, foams, jellies, diaphragm, intrauterine device (IUD), or abstinence, or
    • Postmenopausal for at least 1 years, or if less than 1 years, then following acceptable contraceptive measures as mentioned above
    • Surgically sterile (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy has been performed on the subject).

Exclusion Criteria:

1. Hypersensitivity to Etodolac or related class of drugs.
2. History or presence of significant cardiovascular, pulmonary, hepatic, renal, gastrointestinal, endocrine, immunological, dermatological, neurological or psychiatric disease or disorder.
3. History or presence of significant alcoholism or drug abuse.
4. History or presence of significant smoking (more than 10 cigarettes or beedi's/day).
5. History or presence of significant asthma, urticaria or other allergic reactions.
6. History or presence of significant gastric and/or duodenal ulceration.
7. History or presence of significant thyroid disease, adrenal dysfunction, organic intracranial lesion such as pituitary tumour.
8. History or presence of cancer.
9. Difficulty with donating blood.
10. Difficulty in swallowing solids like tablets or capsules.
11. Use of any prescribed medication or OTC medical products during last two weeks prior to dosing in period 01.
12. Major illness during 3 months before screening.
13. Participation in a drug research study within past 3 months.
14. Donation of blood in the past 3 months before screening.
15. Consumption of grapefruit juice, xanthine-containing products, tobacco containing products or alcohol within 48 hours prior to dosing.
16. Positive screening test for any one or more: HIV, Hepatitis B and Hepatitis C.
17. History or presence of significant easy bruising or bleeding.
18. History or presence of significant recent trauma.
19. Subjects who have been on an abnormal diet (for whatever reason) during the four weeks preceding the study.
20. Female subjects who are currently on breast feeding.