Clinical trial NCT05083325: Bioavailability of Oseltamivir Phosphate 75 mg With Regards to Reference Product
Official title: Bioavailability of a Formulation of Oseltamivir Phosphate 75 mg Capsules With Regards to the Reference Product
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Bioequivalence
Lead sponsor: Laboratorios Andromaco S.A.
Sponsor class: INDUSTRY
First posted: 2021-10-19
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Total Oseltamivir Phosphate: area under the plasma concentration-time curve from 0 to time t (AUC0-t)
timeFrame: 20 samples up to 10 hours will be taken after the administration in each period.
measure: Total Oseltamivir Phosphate: area under the plasma concentration-time curve from 0 to time infinite (AUC0-∞)
timeFrame: 20 samples up to 10 hours will be taken after the administration in each period.
measure: Total Oseltamivir Phosphate: Maximum plasma concentration (Cmax)
timeFrame: 20 samples up to 10 hours will be taken after the administration in each period.
measure: Total Oseltamivir Phosphate: Time to achieve maximum plasma concentration (tmax)
timeFrame: 20 samples up to 10 hours will be taken after the administration in each period.
Secondary outcomes:
Other outcomes:
Locations:
city: Chennai
country: India
facility: Azidus Laboratories Ltd.
state: Tamil Nadu
Study officials:
References: