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

Phase 3

Completed

• Conditions: Bleeding
• Interventions: Biological: Andexanet; Other: Placebo

• Registration Number: NCT02220725
• Lead Sponsor: Portola Pharmaceuticals

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Study Start: 2014-05
• Study First Submitted: 2014-08-18
• Study First Submitted QC: 2014-08-18
• Study First Posted: 2014-08-20
• Primary Completion: 2015-08
• Study Completion: 2015-08
• Disposition First Submitted: 2017-09-19
• Disposition First Submitted QC: 2017-09-19
• Disposition First Posted: 2017-09-27
• Results First Submitted: 2018-05-18
• Results First Submitted QC: 2018-08-27
• Results First Posted: 2018-09-25
• Status Verified: 2023-02
• Last Update Submitted: 2023-02-08
• Last Update Posted: 2023-02-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 80

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Andexanet 800mg bolus (Part I)	Andexanet	Andexanet (antidote) - 800 mg bolus
Andexanet 800mg bolus (Part I)	Placebo	Andexanet (antidote) - 800 mg bolus
Andexanet 800mg + 960mg (Part II)	Andexanet	800 mg bolus + 960 mg infusion (8 mg/min)
Andexanet 800mg + 960mg (Part II)	Placebo	800 mg bolus + 960 mg infusion (8 mg/min)

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Efficacy: Number of Participants With ≥80% Reduction in the Anti-fXa Activity From Baseline to Nadir	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)	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
Efficacy: Change in Thrombin Generation (ETP) From Baseline to Its Peak [Parts I and II]	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)	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.
Efficacy: Percent Change in Anti-fXa Activity (Part II)	Baseline to +2 minutes or +5 minutes following the end of andexanet/placebo bolus (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
Efficacy: Number of Participants With Thrombin Generation (ETP) Above the Lower Limit of the Derived Normal Range at Its Peak (mITT Population)	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)	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
Efficacy: Change From Baseline in Free Rivaroxaban Concentration at the Nadir	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)	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.

Trial Locations

Locations (1)

West Coast Clinical Trials; 🇺🇸 Cypress, California, United States