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

Bleeding Clinical Trial

Official title:

A Phase 3 Randomized, Double-blind, Placebo-controlled Study in Older Subjects to Assess Safety and the Reversal of Rivaroxaban Anticoagulation With Intravenously Administered Andexanet Alpha

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02220725
• Other study ID #: 14-504
• Status: Completed
• Phase: Phase 3
• Start date: May 2014
• Est. completion date: August 2015

Study information

• Verified date: February 2023
• Source: Alexion Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 80
• Est. completion date: August 2015
• Est. primary completion date: August 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 50 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Bleeding

Intervention

Biological:
• Andexanet

Other:
• Placebo

Locations

Country	Name	City	State
United States	West Coast Clinical Trials	Cypress	California

Sponsors (1)

Lead Sponsor	Collaborator
Portola Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	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	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	Baseline to +2 minutes or +5 minutes following the end of andexanet/placebo bolus (Part II)
Secondary	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	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	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.	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	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.	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)
Secondary	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	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)