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

Bleeding Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02207725
• Other study ID #: 14-503
• Status: Completed
• Phase: Phase 3
• Start date: March 2014
• Est. completion date: September 2015

Study information

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

Clinical Trial Summary

The purpose of this stuy is to evaluate the ability of Andexanet Alfa to reverse the anticoagulation effect of Apixaban.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 68
• Est. completion date: September 2015
• Est. primary completion date: April 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	Celerion	Tempe	Arizona

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 I, 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 II, 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, 3 hours following the Day 4 dose of apixaban. 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 From Baseline in Anti-fXa Activity at the Nadir (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	Occurrence of =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 Apixaban Concentration at the Nadir	Change from baseline in free apixaban concentration (ng/mL) at the nadir, when nadir was defined as the smaller value for free apixaban 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 apixaban 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)