Bioavailability of Oseltamivir Phosphate 75 mg With Regards to Reference Product

Bioavailability of a Formulation of Oseltamivir Phosphate 75 mg Capsules With Regards to the Reference Product

This study will investigate the bioavailability in fasting male and/or non-pregnant and non- breast feeding female subjects of 1 capsule formulation containing Oseltamivir Phosphate 75 mg.

The study will be performed at a single site with 36 subjects. Participants will take 1 capsule of the test product and reference product in 2 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.

Study Overview

• Status: Completed
• Conditions: Bioequivalence
• Intervention / Treatment: Drug: Oseltamivir 75mg Test Drug capsules; Drug: Oseltamivir 75mg capsules Reference Product capsules

Detailed Description

The primary objective of the study is to investigate the relative bioavailability of Oseltamivir Phosphate 75 mg of 1 capsule formulations with Oseltamivir Phosphate 75 mg and to demonstrate bioequivalence of both formulations in terms of rate and extent of absorption:

• Test Product: Product manufactured by Laboratorios Silesia S.A.
• Reference Product: Tamiflu [Trademark], product of Roche Pharma AG, Switzerland.

The 90% confidence intervals for the intra-subject coefficient of variation (Test versus Reference Product) for the main pharmacokinetic parameters area under the plasma concentration-time curve from time zero to time t (AUC0 0-t) and from time zero to infinite (AUC0 0-∞), and maximum plasma concentration (Cmax) for total Oseltamivir Phosphate will be determined. Participants will be confined in the study site for approximately 68 hours during the entire study (for 10 hours pre-dosing and for 10 hours post dosing in period II) during which pharmacokinetic (PK) blood samples will be obtained. 20 blood samples will be taken up to 10 hours after the administration in each period.

The washout period between the two 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 Oseltamivir in plasma.

The safety objective is to evaluate the tolerability of both formulations in subjects by collecting adverse events.

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• India
  • Tamil Nadu
    • Chennai, Tamil Nadu, India, 600048
      • Azidus laboratories Ltd.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 41 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Oseltamivir phosphate or any of the excipients.
5. History of consumption of tobacco containing products within 48 hours prior to proposed time of dosing
6. Volunteers 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 Oseltamivir phosphate 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Oseltamivir Phosphate Test Product; Participants will receive one capsule of the test formulation containing Oseltamivir 75 mg. The capsules will be taken with water and in a fasting condition.	Drug: Oseltamivir 75mg Test Drug capsules; Investigational Medicinal Product
Active Comparator: Oseltamivir Phosphate Referent Product; Participants will receive one capsule of the marketed reference containing Oseltamivir 75 mg. The capsules will be taken with water and in a fasting condition.	Drug: Oseltamivir 75mg capsules Reference Product capsules; Tamiflu (Roche Pharma (Switzerland) AG, Basel)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Total Oseltamivir Phosphate: area under the plasma concentration-time curve from 0 to time t (AUC0-t)	20 samples up to 10 hours will be taken after the administration in each period.
Total Oseltamivir Phosphate: area under the plasma concentration-time curve from 0 to time infinite (AUC0-∞)	20 samples up to 10 hours will be taken after the administration in each period.
Total Oseltamivir Phosphate: Maximum plasma concentration (Cmax)	20 samples up to 10 hours will be taken after the administration in each period.
Total Oseltamivir Phosphate: Time to achieve maximum plasma concentration (tmax)	20 samples up to 10 hours will be taken after the administration in each period.

Collaborators and Investigators

• Sponsor: Laboratorios Andromaco S.A.

Study record dates

Study Major Dates

• Study Start (Actual): October 8, 2021
• Primary Completion (Actual): October 10, 2021
• Study Completion (Actual): October 10, 2021

Study Registration Dates

• First Submitted: October 6, 2021
• First Submitted That Met QC Criteria: October 6, 2021
• First Posted (Actual): October 19, 2021

Study Record Updates

• Last Update Posted (Actual): October 28, 2021
• Last Update Submitted That Met QC Criteria: October 27, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Oseltamivir
• Other Study ID Numbers: HP8835-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No