A Single Center, Open Label, Randomized, Single-dose, Two Period Two Way Cross-over Study to Explore the Bioequivalence of Xaroban 20mg (Rivaroxaban) Tablet and Xarelto 20mg (Rivaroxaban) Tablet Under Fed Conditions in Healthy Male Pakistani Subjects.
Overview
- Phase
- Phase 1
- Intervention
- Rivaroxaban 20 MG Oral Tablet
- Conditions
- Bioequivalence
- Sponsor
- University of Karachi
- Enrollment
- 26
- Locations
- 1
- Primary Endpoint
- Peak Plasma Concentration (Cmax)
- Status
- Completed
- Last Updated
- 3 years ago
Overview
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.
Detailed Description
Single oral administrations of study drug in two periods separated by a washout period of 07 days. Subjects will take their assigned study medication orally, together with 240 mL of ambient temperature water, at least 1 hour after start of the meal at their scheduled dosing time-point. Total duration of treatment of study drug will be of 58 hours comprising 10 hours prior drug administration until 48 hours post dose in each study period. Pharmacokinetic parameters include Rivaroxaban plasma concentrations at the given sampling times. In each period 16 blood samples for plasma Rivaroxaban concentrations will be taken on Day 2, Day 3 and Day 4 including 0.00 hour pre dose and post dose at 0.25, 0.5, 1.00, 1.50, 2.00, 2.50, 3.00, 3.5, 4.00, 6.00, 8.00, 12.00, 24.00, 36.00 and 48.00 hours.
Investigators
Dr. Muhammad Raza Shah
Professor
University of Karachi
Eligibility Criteria
Inclusion Criteria
- •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.
Exclusion Criteria
- •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.
Arms & Interventions
Reference Group [Xarelto 20mg (Rivaroxaban) Tablet]
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
Intervention: Rivaroxaban 20 MG Oral Tablet
Test Group [Xaroban 20mg (Rivaroxaban) Tablet]
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
Intervention: Rivaroxaban 20 MG Oral Tablet
Outcomes
Primary Outcomes
Peak Plasma Concentration (Cmax)
Time Frame: 2 weeks
Evaluation of Peak Plasma Concentration (Cmax)
Area under the plasma concentration versus time curve (AUC) 0-t
Time Frame: 2 weeks
plasma concentration-time curve from zero to the time of the last measurable time point t
Area under the plasma concentration versus time curve (AUC)0-∞
Time Frame: 2 weeks
area under the plasma concentration-time curve from zero to infinity