The EINSTEIN CYP Cohort Study Oral Direct Factor Xa Inhibitor Rivaroxaban in Patients With Acute Symptomatic Deep-vein Thrombosis or Pulmonary Embolism Using a Strong CYP 3A4 Inducer

Percentage of Participants With Clinically Relevant Bleeding (i.e. Major Bleeding and Clinically Relevant Non-major Bleeding)

时间窗: Up to 3 months treatment and during subsequent 2 days

All events were adjudicated and confirmed by a central independent adjudication committee. Clinically relevant bleeding included major bleeding (overt bleeding associated with 2 g/dL or greater fall in hemoglobin, leading to a transfusion of 2 or more units of packed red blood cells or whole blood, occurring in a critical site or contributing to death) and non-major bleeding associated with medical intervention, unscheduled physician contact, (temporary) cessation of study treatment, discomfort for the participants such as pain, or impairment of activities of daily life.

Pharmacodynamics - Prothrombin Time (PT), Baseline Value

时间窗: The baseline value of prothrombin time is measured or calculated at a rivaroxaban concentration of 0 µg/L and is based on the observations that were made during the 3 months treatment period

Prothrombin time (PT) is a global clotting test assessing the extrinsic pathway of the blood coagulation cascade. The test is sensitive for deficiencies of Factors II, V, VII, and X, with sensitivity being best for Factors V, VII, and X and less pronounced for Factor II. The initial read-out is in seconds. Mean and standard deviation (SD) values are presented for PT baseline.

Pharmacodynamics - Prothrombin Time (PT), Slope

时间窗: Up to 3 months treatment

Prothrombin time (PT) is a global clotting test assessing the extrinsic pathway of the blood coagulation cascade. The test is sensitive for deficiencies of Factors II, V, VII, and X, with sensitivity being best for Factors V, VII, and X and less pronounced for Factor II. The initial read-out of PT is in seconds. The PT slope describes the linear increase of PT for one unit increase in concentration, thus the unit of PT slope is s\*(µg/L)\^-1. The final population PK/PD model included a fixed slope that was fitted to the data of the 19 patients that were eligible for evaluation. The estimated mean value (fixed/ the same for all patients in this study) is presented for PT slope.

Pharmacokinetics - Cmin,ss (Minimum Observed Drug Concentration in Measured Matrix at Steady State During a Dosage Interval) of Rivaroxaban

时间窗: 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban

Cmin,ss was predicted for each individual participant from rivaroxaban plasma concentrations and was only considered for the time period during which participants concomitantly received rivaroxaban and a strong CYP3A4 inducer.

Pharmacokinetics - AUC(0-24)ss (Area Under the Measurement Versus Time Curve From Time 0 to 24 Hours After First Dosing on a Day at Steady State) of Rivaroxaban

时间窗: 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban

AUC(0-24)ss was predicted from rivaroxaban plasma concentrations for each individual participant and was only considered for the time period during which participants concomitantly received rivaroxaban and a strong cytochrome P450 isoenzyme 3A4 (CYP3A4) inducer.

Pharmacokinetics - Cmax,ss (Maximum Observed Drug Concentration in Measured Matrix at Steady State During a Dosage Interval) of Rivaroxaban

时间窗: 0 (predose), 1, 2, 3, 4, 6, 8, 12, and 24 h after first administration of rivaroxaban

Cmax,ss was predicted from rivaroxaban plasma concentrations for each individual participant and was only considered for the time period during which participants concomitantly received rivaroxaban and a strong CYP3A4 inducer.