Bioequivalence Study of Two Formulations of Rivaroxaban Tablets 10 mg in Healthy Male Volunteers in Fasting Conditions

NCT04753489 | Unknown Phase 1

• 1 other identifier: RVRX_10-2020-CPD-FRMT
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-labeled, laboratory-blinded, randomized, two period, single-center, crossover, comparative study, where each participant will be randomly assigned to the reference (Xarelto®, 10 mg film-coated tablets) or the test (Rivaroxaban, 10 mg film-coated tablets) formulation in each period of study (sequences Test-Reference (TR) or Reference-Test (RT)), in order to evaluate if both formulations are bioequivalent.

Conditions

Bioequivalence

Keywords

Rivaroxaban; Bioequivalence; Xarelto

Outcome Measures

Primary Outcomes (2)

• Cmax of rivaroxaban in plasma after administration of the test and the reference products.

  Maximum observed concentration in plasma.

  Time points 0.00 (prior to each drug administration) and 0.17, 0.33, 0.67, 1.00, 1.33, 1.67, 2.00, 2.33, 2.67, 3.00, 3.33, 3.67, 4.00, 4.50, 5.00, 6.00, 8.00, 12.00, 16.00, 24.00, 36.00. 48.00 hours after each drug administration.

• AUC0-t of rivaroxaban in plasma after administration of the test and the reference.

  Cumulative area under the concentration time curve calculated from 0 to time of last observed quantifiable concentration using the linear trapezoidal method

  Time points 0.00 (prior to each drug administration) and 0.17, 0.33, 0.67, 1.00, 1.33, 1.67, 2.00, 2.33, 2.67, 3.00, 3.33, 3.67, 4.00, 4.50, 5.00, 6.00, 8.00, 12.00, 16.00, 24.00, 36.00. 48.00 hours after each drug administration.

Secondary Outcomes (5)

• Tmax of rivaroxaban in plasma after administration of the test and the reference products.

  Time points 0.00 (prior to each drug administration) and 0.17, 0.33, 0.67, 1.00, 1.33, 1.67, 2.00, 2.33, 2.67, 3.00, 3.33, 3.67, 4.00, 4.50, 5.00, 6.00, 8.00, 12.00, 16.00, 24.00, 36.00. 48.00 hours after each drug administration.

• AUC0-INF of rivaroxaban in plasma after administration of the test and the reference products.

  Time points 0.00 (prior to each drug administration) and 0.17, 0.33, 0.67, 1.00, 1.33, 1.67, 2.00, 2.33, 2.67, 3.00, 3.33, 3.67, 4.00, 4.50, 5.00, 6.00, 8.00, 12.00, 16.00, 24.00, 36.00. 48.00 hours after each drug administration.

• Residual area of rivaroxaban in plasma after administration of the test and the reference products.

  Time points 0.00 (prior to each drug administration) and 0.17, 0.33, 0.67, 1.00, 1.33, 1.67, 2.00, 2.33, 2.67, 3.00, 3.33, 3.67, 4.00, 4.50, 5.00, 6.00, 8.00, 12.00, 16.00, 24.00, 36.00. 48.00 hours after each drug administration.

• λZ of rivaroxaban in plasma after administration of the test and the reference products.

  Time points 0.00 (prior to each drug administration) and 0.17, 0.33, 0.67, 1.00, 1.33, 1.67, 2.00, 2.33, 2.67, 3.00, 3.33, 3.67, 4.00, 4.50, 5.00, 6.00, 8.00, 12.00, 16.00, 24.00, 36.00. 48.00 hours after each drug administration.

• Terminal elimination half-life (T1/2) of rivaroxaban in plasma after administration of the test and the reference products.

  Time points 0.00 (prior to each drug administration) and 0.17, 0.33, 0.67, 1.00, 1.33, 1.67, 2.00, 2.33, 2.67, 3.00, 3.33, 3.67, 4.00, 4.50, 5.00, 6.00, 8.00, 12.00, 16.00, 24.00, 36.00. 48.00 hours after each drug administration.

Study Arms (2)

Sequence TR

OTHER

17 subjects assigned to the sequence TR will receive a single 10 mg dose of the test product Rivaroxaban (1 x 10 mg tablet), marked as T in the sequence, in Period 1 and a single 10 mg dose of the reference product Xarelto® (1 x 10 mg tablet), marked as R in the sequence, in period 2. These treatments will be administered orally with approximately 200 mL of water, in the morning, after overnight fasting. The tablet must be swallowed whole and must not be chewed or broken.

Drug: Rivaroxaban film-coated tablet 10 mg; Drug: Xarelto® film-coated tablet 10 mg

Sequence RT

OTHER

17 subjects assigned to the sequence RT will receive a single 10 mg dose of the reference product Xarelto® (1 x 10 mg tablet), marked as R in the sequence, in Period 1 and a single 10 mg dose of the test product Rivaroxaban (1 x 10 mg tablet), marked as T in the sequence, in period 2. These treatments will be administered orally with approximately 200 mL of water, in the morning, after overnight fasting. The tablet must be swallowed whole and must not be chewed or broken.

Drug: Rivaroxaban film-coated tablet 10 mg; Drug: Xarelto® film-coated tablet 10 mg

Interventions

Rivaroxaban film-coated tablet 10 mg DRUG

Rivaroxaban is manufactured by Pharmtechnology LLC, Republic of Belarus. Each tablet contains 10 mg of rivaroxaban.

Also known as: The test product

Sequence RT; Sequence TR

Xarelto® film-coated tablet 10 mg DRUG

Xarelto® is manufactured by Bayer AG, Germany. Each tablet contains 10 mg of rivaroxaban.

Also known as: The reference product

Sequence RT; Sequence TR

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• healthy caucasian men aged between 18 to 45 years;
• verified diagnosis "healthy" according to the anamnesis data and the results of standard clinical, laboratory and instrumental examination methods, physical examination and anamnestic examination;
• body mass index 18.5-30 kg/m²;
• the results of an X-ray or fluorographic examination of the chest organs within the normal range (the results of an examination carried out within 12 months before the start of the study may be provided);
• consent to use a double barrier method of contraception (condom + spermicide) or complete sexual abstinence, as well as consent not to take part in sperm donation from the moment of taking the drug in the first period, during the entire study and within 14 days after taking the drug in the second period research;
• subjects are able to understand the requirements of the study, to sign a written informed consent, and also to accept all the restrictions imposed during the course of the study, and to agree to return for the required investigations.

You may not qualify if:

• burdened allergic history, hypersensitivity to rivaroxaban or excipients that are part of any of the investigational drugs, or intolerance to these components;
• clinically significant pathologies of the cardiovascular, bronchopulmonary, neuroendocrine systems, as well as diseases of the gastrointestinal tract, liver, kidneys and blood;
• other diseases that, in the opinion of the researcher, may affect the absorption, distribution, metabolism or excretion of both drugs, or increase the risk of negative consequences for the volunteer;
• a history of brain or spinal cord injury, recent surgery on the brain, spinal cord or eyes;
• history of internal bleeding of any genesis;
• a history of coagulation disorders (eg, von Willebrand disease, hemophilia);
• hereditary intolerance to lactose or galactose (for example, congenital lactase deficiency or glucose-galactose malabsorption), since the composition of the tested and reference drugs includes lactose monohydrate;
• the presence of mental disorders, including a history;
• seizures, epilepsy and any other neurological disorders in history;
• surgical interventions on the gastrointestinal tract, with the exception of appendectomy;
• acute infectious diseases that ended less than 4 weeks before taking the drug in the first period;
• dehydration due to diarrhea, vomiting or other reason within the last 24 hours before taking the drug in the first period of the study. Moreover, if vomiting or diarrhea was a manifestation of an infectious disease, then participation in the study is possible only 4 weeks after the last symptom.
• Clinically significant abnormalities on the ECG, the level of systolic blood pressure (SBP) measured in the sitting position at the time of screening \<100 mm Hg or ≥ 130 mm Hg and / or diastolic blood pressure (DBP) \<60 mm Hg or ≥ 85 mm Hg;
• Heart rate less than 60 beats/min or more than 90 beats/min at the time of screening, respiratory rate less than 12 or more than 18 per minute at the time of screening, body temperature below 36.0 ° C or above 37.0 ° C at the time of screening;
• use of any prescription and ATC drugs:

Sponsors & Collaborators

• Pharmtechnology LLC: lead
• ClinPharmInvest, LLC: collaborator

Study Sites (1)

Private healthcare institution "Clinical Hospital "RZD-Medicine" of the city of Yaroslavl"

Yaroslavl, 150047, Russia

Location

Study Officials

• Alexander Khokhlov

  ClinPharmInvest, LLC

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Veronika Kumpel

CONTACT

80173094418; specialist.fs@ft.by

Andrei Yaremchuk

CONTACT

80291268246; development@ft.by

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 10, 2021
• First Posted: February 15, 2021
• Study Start: February 13, 2021
• Primary Completion: March 1, 2021
• Study Completion: March 1, 2021
• Last Updated: February 15, 2021

Record last verified: 2021-02

Locations

RU (1)