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
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- Enrollment
- 68
- Locations
- 1
- Primary Endpoint
- Efficacy: Percent Change From Baseline in Anti-fXa Activity at the Nadir (Parts I and II)
Study Overview
Brief Summary
The purpose of this stuy is to evaluate the ability of Andexanet Alfa to reverse the anticoagulation effect of Apixaban.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 50 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
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
Arms & Interventions
Placebo
Placebo
Intervention: Placebo (Other)
Andexanet
Andexanet (antidote)
Intervention: Andexanet (Biological)
Outcomes
Primary Outcomes
Efficacy: Percent Change From Baseline in Anti-fXa Activity at the Nadir (Parts I and II)
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)
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.
Secondary Outcomes
- Efficacy: Percent Change From Baseline in Anti-fXa Activity at the Nadir (Part II)(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(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))
- Efficacy -Change From Baseline in Free Apixaban 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))
- 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))
- 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))