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

NCT02220725 | Completed Phase 3 Results DMC

• 1 other identifier: 14-504
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Bleeding

Keywords

Andexanet alpha; Anticoagulation; Antidote; Rivaroxaban; Anti-fXa inhibitor; PRT4445; Xarelto; Reversal agent

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• 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)

• 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 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)

• 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)

Study Arms (2)

Andexanet 800mg bolus (Part I)

EXPERIMENTAL

Andexanet (antidote) - 800 mg bolus

Biological: Andexanet; Other: Placebo

Andexanet 800mg + 960mg (Part II)

EXPERIMENTAL

800 mg bolus + 960 mg infusion (8 mg/min)

Biological: Andexanet; Other: Placebo

Interventions

Andexanet BIOLOGICAL

Also known as: Andexanet alpha, PRT4445

Andexanet 800mg + 960mg (Part II); Andexanet 800mg bolus (Part I)

Placebo OTHER

Andexanet 800mg + 960mg (Part II); Andexanet 800mg bolus (Part I)

Eligibility Criteria

• Age: 50 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Reasonably healthy men and women aged 50 to 75

You may not qualify if:

• 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

Sponsors & Collaborators

• Portola Pharmaceuticals: lead

Study Sites (1)

West Coast Clinical Trials

Cypress, California, 90630, United States

Location

Related Publications (1)

• 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.

  PMID: 26559317 DERIVED

MeSH Terms

Conditions

Hemorrhage

Interventions

PRT064445

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Head of Clinical Development
• Organization: Portola Pharmaceuticals, Inc.

650-246-7000

Study Officials

• Vandana Mathur, M.D.

  Portola Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 18, 2014
• First Posted: August 20, 2014
• Study Start: May 1, 2014
• Primary Completion: August 1, 2015
• Study Completion: August 1, 2015
• Last Updated: February 10, 2023
• Results First Posted: September 25, 2018

Record last verified: 2023-02

Locations

US (1)