Clinical trial NCT02220725: A Study in Older Subject to Evaluate the Safety and Ability of Andexanet Alfa to Reverse the Anticoagulation Effect of Rivaroxaban
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Bleeding
Keywords: Andexanet alpha
Anticoagulation
Antidote
Rivaroxaban
Anti-fXa inhibitor
PRT4445
Xarelto
Reversal agent
Lead sponsor: Alexion Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2014-08-20
Enrollment: 80
Sex: ALL
Minimum age (years): 50
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: 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

Primary outcomes:
measure: Efficacy: Percent Change From Baseline in Anti-fXa Activity at the Nadir (Parts I and II)
timeFrame: 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:
measure: Efficacy: Percent Change in Anti-fXa Activity (Part II)
timeFrame: Baseline to +2 minutes or +5 minutes following the end of andexanet/placebo bolus (Part II)
measure: Efficacy: Number of Participants With ≥80% Reduction in the Anti-fXa Activity From Baseline to Nadir
timeFrame: 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)
measure: Efficacy: Change From Baseline in Free Rivaroxaban Concentration at the Nadir
timeFrame: 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)
measure: Efficacy: Change in Thrombin Generation (ETP) From Baseline to Its Peak [Parts I and II]
timeFrame: 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)
measure: Efficacy: Number of Participants With Thrombin Generation (ETP) Above the Lower Limit of the Derived Normal Range at Its Peak (mITT Population)
timeFrame: 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)
Other outcomes:
Locations:
city: Cypress
country: United States
facility: West Coast Clinical Trials
state: California
Study officials:
affiliation: Portola Pharmaceuticals
name: Vandana Mathur, M.D.
role: STUDY_DIRECTOR
References:
citation: Siegal DM, Curnutte JT, Connolly SJ, Lu G, Conley PB, Wiens BL, Mathur VS, Castillo J, Bronson MD, Leeds JM, Mar FA, Gold A, Crowther MA. Andexanet Alfa for the Reversal of Factor Xa Inhibitor Activity. N Engl J Med. 2015 Dec 17;373(25):2413-24. doi: 10.1056/NEJMoa1510991. Epub 2015 Nov 11.