Bioequivalence of Xaroban 20mg (Rivaroxaban) Tablet and Xarelto 20mg (Rivaroxaban) Tablet Under Fed Conditions

NCT04689919 | Completed Phase 1 DMC

• 1 other identifier: CB-025-RIV-2018/Protocol/1.0
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

A single center, open label, randomized, single-dose, two period, Two way cross-over study to explore the Bioequivalence of Test Product Xaroban (Rivaroxaban) 20 mg Tablet with the reference product Xarelto (Rivaroxaban) 20 mg tablet under fed conditions in healthy Pakistani male subjects. Subjects will receive one single dose per treatment period separated by a wash-out period of 7 days. Blood samples will be taken up to 48hours post-dose.

Conditions

Bioequivalence

Outcome Measures

Primary Outcomes (3)

• Peak Plasma Concentration (Cmax)

  Evaluation of Peak Plasma Concentration (Cmax)

  2 weeks

• Area under the plasma concentration versus time curve (AUC) 0-t

  plasma concentration-time curve from zero to the time of the last measurable time point t

  2 weeks

• Area under the plasma concentration versus time curve (AUC)0-∞

  area under the plasma concentration-time curve from zero to infinity

  2 weeks

Other Outcomes (6)

• maximum plasma concentration (tmax)

  2 weeks

• Incidence of Treatment-Emergent Adverse Events

  During 2 weeks

• Incidence of abnormal blood pressure

  2 weeks

Study Arms (2)

Reference Group [Xarelto 20mg (Rivaroxaban) Tablet]

ACTIVE COMPARATOR

Subjects will take their assigned study medication, together with 240 mL of ambient temperature water, at least 1 hour after start of the meal at their scheduled dosing time-point

Drug: Rivaroxaban 20 MG Oral Tablet

Test Group [Xaroban 20mg (Rivaroxaban) Tablet]

EXPERIMENTAL

Subjects will take their assigned study medication, together with 240 mL of ambient temperature water, at least 1 hour after start of the meal at their scheduled dosing time-point

Drug: Rivaroxaban 20 MG Oral Tablet

Interventions

Rivaroxaban 20 MG Oral Tablet DRUG

The subjects randomly received single oral dose of Rivaroxaban 20 MG Tablet.

Reference Group [Xarelto 20mg (Rivaroxaban) Tablet]; Test Group [Xaroban 20mg (Rivaroxaban) Tablet]

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy male volunteers aged 18 to 55 years inclusive.
• Subjects with a body mass index from 18.5 to 30 kg/m2 (both inclusive).
• Subjects who are healthy as determined by routine physical examination, including vital sign monitoring (i.e., blood pressure, heart rate, and temperature), 12 Lead ECG, and laboratory analysis (i.e., hematology, blood biochemistry, and urinalysis), as determined by the investigator.
• Subjects should have negative urine test for drugs of abuse (Opiates, benzodiazepines, amphetamines, barbiturates, cannabinoids and cocaine will be tested) and alcohol breath analysis at screening and prior to each check-in.
• Subjects and their partners are willing to use reliable non-hormonal contraceptive methods (condoms, diaphragm, non-hormonal intra-uterine device (IUD), female or male sterilization or sexual abstinence) throughout the study and up to 30 days after the last administration of the study drug.
• All subjects should be free from any epidemic or contagious diseases (e.g. Malaria, Dengue, Covid-19).
• Subjects will be able to, understand and sign the Informed Consent Form for Medical Screening during their screening visit and Participation Informed Consent Form on study check-In day.

You may not qualify if:

• History of smoking (≤3cigarette/day), alcoholism, and test for drug of abuse, heavy pan or gutka user as judged by teeth / mouth inspection.
• Subjects with clinically relevant evidence of cardiovascular, gastrointestinal/hepatic, renal, psychiatric, respiratory, urogenital, hematologic/immunologic, HEENT (head, ears, eyes, nose, throat), dermatological/connective tissue, musculoskeletal, metabolic/nutritional, drug hypersensitivity, allergy, endocrine, major surgery or other relevant diseases as revealed by medical history, gastrointestinal (GI) bleeding within 6 months of randomization, history of intracranial, intraocular, spinal or atraumatic intra-articular bleeding, chronic hemorrhagic disorder, known intracranial neoplasm, arteriovenous malformation, physical examination, and laboratory assessments which may interfere with the absorption, distribution, metabolism or elimination of drugs or constitute a risk factor when taking study medication.
• Subjects receiving concomitant systemic treatment with azole-antimycotics (such as ketoconazole, itraconazole, voriconazole and posaconazole) or HIV protease inhibitors (e.g., ritonavir).
• Subjects receiving NSAIDs (including acetylsalicylic acid) and platelet aggregation inhibitors as these medicinal products typically increase the bleeding risk.
• Subjects receiving concomitant P-gp inhibitor (Erythromycin, Clarithromycin and Azithromycin).
• The concomitant use of rivaroxaban with other strong CYP3A4 inducers (e.g., phenytoin, carbamazepine, phenobarbital or St. John's Wort (Hypericum perforatum).
• Subject with known coagulation disorders (e.g. von Willebrand's disease, hemophilia)
• Subject with known disorders with increased bleeding risk (e.g. periodontosis, hemorrhoids, acute gastritis, peptic ulcer).
• Subject with known sensitivity to common causes of bleeding (e.g. nasal).
• Individuals with mild (creatinine clearance 50 - 80 ml/min), moderate (creatinine clearance 30 - 49 ml/min) and severe (creatinine clearance 15 - 29 ml/min) renal impairment.
• Subject is allergic to Rivaroxaban and/or other Factor Xa inhibitors.
• Subject has received any investigational drug within four weeks.
• Subjects with significant hepatic disease (including moderate to severe hepatic impairment, i.e. Child-Pugh B and C) which is associated with coagulopathy leading to a clinically relevant bleeding risk.
• Subjects with cardiac related conditions (hemodynamically significant mitral valve stenosis, prosthetic heart valve, planned cardioversion, transient atrial fibrillation caused by reversible disease Subjects with known presence of atrial myxoma or left ventricular thrombus and active endocarditis.\[8\]
• Subjects with salt imbalance in the blood (especially low levels of potassium or magnesium in the blood)

Sponsors & Collaborators

• University of Karachi: lead
• The Searle Company Limited Pakistan: collaborator
• Center for Bioequivalence Studies and Clinical Research (CBSCR), HEJ Research Institute of chemistry, University of Karachi: collaborator

Study Sites (1)

Center for Bioequivalence Studies and Clinical Research (CBSCR), ICCBS, university of Karachi

Karachi, 75270, Pakistan

Location

MeSH Terms

Interventions

Rivaroxaban

Intervention Hierarchy (Ancestors)

Thiophenes; Sulfur Compounds; Organic Chemicals; Morpholines; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Muhammad Raza Shah, PhD

  CBSCR , ICCBS, University of Karachi

  PRINCIPAL INVESTIGATOR

• Naghma Hashmi (Co-PI), PhD

  CBSCR, ICCBS, University of Karachi

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Two period Two way cross-over study

Study Record Dates

• First Submitted: December 17, 2020
• First Posted: December 30, 2020
• Study Start: February 19, 2022
• Primary Completion: March 7, 2022
• Study Completion: April 5, 2022
• Last Updated: September 7, 2022

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will not share

Locations

PA (1)