Bioavailability of Eszopiclone 3.0 mg With Regards to Reference Product

Bioavailability of Two Formulations of Eszopiclone 3.0 mg Coated Tablets With Regards to the Marketed Reference Product

This study will investigate the bioavailability in fasting healthy, adult, human subjects of 1 tablet of two formulations containing Eszopiclone 3mg.

The study will be performed at a single site with 28 subjects. Participants will take 1 tablet of the test product 1, and 1 tablet of the test product 2, and reference product in 4 periods and 2 sequences (either test after reference or reference after test). There will be a washout of at least 2 days between each study period.

The primary objective of the study is to investigate the relative bioavailability of Eszopiclone 3mg of 1 tablet of 2 formulations with Eszopiclone 3mg and to demonstrate bioequivalence of the three formulations in terms of rate and extent of absorption:

• Test Product T-1: Product manufactured by Laboratorios Silesia S.A.
• Test Product T-2: Product manufactured by Laboratorios Andromaco S.A.
• Reference Product: Lunesta [Trademark], product of Sunovion Pharmaceuticals Inc. The 90% confidence intervals for the intra-subject coefficient of variation (Test products T1/T2 versus Reference Product) for the main pharmacokinetic parameters area under the plasma concentration-time curve from time zero to time t (AUC0-t), and maximum plasma concentration (Cmax) for total Eszopiclone will be determined.

Participants will be confined in the study site for approximately 9 days during the entire study (for 10 hours pre-dosing and for 24 hours post dosing after period IV) during which pharmacokinetic (PK) blood samples will be obtained. 24 blood samples will be taken up to 24 hours after the administration in each period. The washout period between the four study periods will be at least 2 days. The samples from each participant will be analyzed with validated LC-MS/MS method for estimation of Eszopiclone in plasma. The safety objective is to evaluate the tolerability of both formulations in subjects by collecting adverse events.

Inclusion Criteria:

1. Healthy male and/or non-pregnant, non-breast feeding female literate volunteers of 18 to 45 years (both years inclusive) with BMI of 18.50 - 29.99 Kg/m2 and weight > 50 Kg.
2. Healthy volunteers as evaluated by medical history, vitals and general clinical examination.
3. Normal or clinically insignificant biochemical, hematological, urine and serology parameters.
4. Normal or clinically insignificant ECG.
5. Negative urine test for drugs of abuse for both males and females and negative pregnancy test for females and do not plan to become pregnant during course of the study and for 03 months after completion of study.
6. Volunteers who are willing to use acceptable methods of contraception (barrier method/IUD/surgical) or abstinence, for the entire duration of the study and do not plan to be pregnant for at least 1 month after the last drug administration.
7. Volunteers who can give written informed consent and communicate effectively.

Exclusion Criteria:

1. History of any major surgical procedure in the past 03 months.

2. History of any clinically significant cardiac, gastrointestinal, respiratory, hepatic, renal, endocrine, neurological, metabolic, psychiatric and hematological disorders.

3. History of chronic alcoholism/ chronic smoking/ drug of abuse.

4. Volunteers with known hypersensitivity to Eszopiclone or any of the excipients.

5. History of consumption of tobacco containing products within 48 hours prior to proposed time of dosing

6. Volunteer who are positive for hepatitis B surface antigen, anti-hepatitis C antibody, treponemal antibodies and human immunodeficiency virus (HIV 1&2) antibodies.

7. Present or past history of intake of drugs or any prescription drug or over the counter (OTC) drugs within 14 days which potentially modify kinetics / dynamics of Eszopiclone or any other medication judged to be clinically significant by the investigator.

8. History of consumption of grapefruit and/or its products within 10 days prior to the start of study.

9. Volunteer who had participated in any other clinical study or who had bled during the last 03 months before check-in.

10. History of consumption of one or more of the below, 48 hours prior to dosing:

    Xanthine containing food or drinks such as cola, chocolate, coffee or tea, citrus fruits or items (lime, lemon and orange), alcohol and any other food/beverage known to have interactions as deemed by the investigator.

11. Volunteers who are dysphagic.