A Study in Older Subject to Evaluate the Safety and Ability of Andexanet Alfa to Reverse the Anticoagulation Effect of Rivaroxaban

Phase 3CompletedNCT02220725

Portola Pharmaceuticals80 enrolled

Overview

The purpose of this study is to evaluate the ability of Andexanet Alfa to reverse the anticoagulation effect of Rivaroxaban.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Bleeding

Interventions

AndexanetBIOLOGICAL

PlaceboOTHER

Eligibility

Sex: ALLMin age: 50 YearsMax age: 75 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Reasonably healthy men and women aged 50 to 75 Exclusion Criteria: * History of abnormal bleeding, active bleeding or risk factors for bleeding * History of thrombosis or risk factors for thrombosis * History of adult asthma or use of inhaled medications

Locations (1)

West Coast Clinical Trials

Cypress, California, United States

Outcomes

Primary Outcomes

Efficacy: Percent Change From Baseline in Anti-fXa Activity at the Nadir (Parts I and II)

In Part 1, the primary endpoint was percent change from baseline in anti-fXa activity at the nadir, when nadir was defined as the smaller value for anti-fXa activity at the +2 minutes or +5 minutes time point following the end of the bolus. In Part 2, the primary endpoint was the percent change from baseline in anti-fXa activity from its baseline to nadir, when nadir was defined as the smaller value for anti-fXa activity between the 110-minute time point (10 minutes prior to the end of the continuous infusion) and the 5-minute time point after the end of the continuous infusion. The baseline for the primary endpoint in both parts was the anti-fXa activity just prior to administration of andexanet, 4 hours following the Day 4 dose of rivaroxaban. Anti-fXa activity was measured by a modified chromogenic assay.

Time frame: Baseline to +2 minutes or +5 minutes following the end of andexanet/placebo bolus (Part I), or 10 minutes prior to end of andexanet/placebo continuous infusion or 5 minutes after the end of andexanet/placebo continuous infusion (Part II)

Secondary Outcomes

Efficacy: Percent Change in Anti-fXa Activity (Part II)

The percent change from baseline in anti-fXa activity at the nadir, following the bolus, when nadir was defined as the smaller value for anti-fXa activity at the +2 minute or +5 minute time point after the completion of the andexanet bolus (Part II). Baseline was the last assessment obtained prior to the first dose of andexanet or placebo

Time frame: Baseline to +2 minutes or +5 minutes following the end of andexanet/placebo bolus (Part II)

Efficacy: Number of Participants With ≥80% Reduction in the Anti-fXa Activity From Baseline to Nadir

Number of participants with ≥80% reduction in anti-fXa activity from its baseline to nadir, when nadir was defined as the smaller value for anti-fXa activity at the +2 minute or +5 minute time point after the completion of the andexanet bolus (Part I) or between the 110-minute time point (10 minutes prior to the end of the continuous infusion) and the 5-minute time point after the end of the continuous infusion (inclusive) {Part II\]. Baseline was the last assessment obtained prior to the first dose of andexanet or placebo

Data from ClinicalTrials.gov

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Efficacy: Change From Baseline in Free Rivaroxaban Concentration at the Nadir

Change from baseline in free rivaroxaban concentration (ng/mL) at the nadir, when nadir was defined as the smaller value for free rivaroxaban at the +2 minute or +5 minute time point after the completion of the andexanet bolus (Part I) or between the 110-minute time point (10 minutes prior to the end of the continuous infusion) and the 5-minute time point after the end of the continuous infusion (inclusive) \[Part II\]. Free plasma concentrations of rivaroxaban was determined using a validated method that involved analysis of citrated human plasma with high-throughput equilibrium dialysis followed by liquid chromatography mass spectrometry.

Efficacy: Change in Thrombin Generation (ETP) From Baseline to Its Peak [Parts I and II]

Change in ETP from baseline to its peak, where peak was defined as the largest value for ETP between the +2 minute time point and the +10 minute time point after the end of the andexanet bolus (inclusive) {Part I\] or between the 110-minute time point (10 minutes prior to the end of the continuous infusion) and the 5-minute time point after the end of the continuous infusion (inclusive) \[Part II\]. Baseline was the last assessment obtained prior to the first dose of andexanet or placebo. ETP was measured using a tissue factor-initiated thrombin generation assay.

Time frame: Baseline to +2 minutes or +10 minutes following the end of andexanet/placebo bolus (Part I), or 10 minutes prior to end of andexanet/placebo continuous infusion or 5 minutes after the end of andexanet/placebo continuous infusion (Part II)

Efficacy: Number of Participants With Thrombin Generation (ETP) Above the Lower Limit of the Derived Normal Range at Its Peak (mITT Population)

Number of participants with ETP above the lower limit of the normal range at its peak, between the +2 minute time point and the +10 minute time point after the end of the andexanet bolus (inclusive) \[Part I\] or between the 110-minute time point (10 minutes prior to the end of the continuous infusion) and the 5-minute time point after the end of the continuous infusion (inclusive) \[Part II\]. ETP was measured using a tissue factor-initiated thrombin generation assay