Last reviewed · How we verify

NCT03310021

A Healthy Volunteer Pharmacokinetics (PK)/Pharmacodynamics (PD), Safety and Tolerability Study of Andexanet in Healthy Japanese and Caucasian Subjects

Completed Phase 2 Results posted Last updated 24 February 2023
What this trial tests

Phase 2 trial testing Andexanet alfa in Bleeding in 108 participants. Completed in 13 August 2019.

Timeline
28 August 2017
Primary endpoint
13 August 2019
13 August 2019

Quick facts

Lead sponsorPortola Pharmaceuticals
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingtriple
Primary purposetreatment
Enrollment108
Start date28 August 2017
Primary completion13 August 2019
Estimated completion13 August 2019
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

Portola Pharmaceuticals — full company profile →

Who can join

Adults 18 to 75, any sex, with Bleeding. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percent Change in Anti-Fxa Activity From Baseline to the End of Infusion (EOI) Nadir. Primary · Baseline to the end of infusion (EOI) nadir, approximately 2.5 hours

The primary efficacy endpoint is the percent change in the anti-FXa activity from baseline to the end of infusion (EOI) nadir.

GroupValue95% CI
Cohort 1 Apixaban 5 mg BID/Low Dose Andexanet-94.50-96.00 – -90.00
Cohort 1 Apixaban 5 mg BID/Placebo-29.00-32.00 – -18.00
Cohort 2 Rivaroxaban15 mg BID/High Dose Andexanet-98.00-99.00 – -97.00
Cohort 2 Rivaroxaban 15 mg BID/Placebo-37.00-53.00 – -34.00
Cohort 3 Edoxaban 60 mg QD/High Dose Andexanet-81.00-89.00 – -51.00
Cohort 3 Edooxaban 60 mg QD/Placebo-47.50-62.00 – -34.00
Cohort 4 Edoxaban 60 mg QD/High Dose Andexanet-75.50-82.00 – -45.00
Cohort 4 Edooxaban 60 mg QD/Placebo-37.00-46.00 – -16.00
Cohort 5 Apixaban 5 mg BID/Low Dose Andexanet-93.00-94.00 – -91.00
Cohort 5 Apixaban 5 mg BID/Placebo-34.00-53.00 – -24.00
Cohort 6 Apixaban 10 mg BID/High Dose Andexanet-97.00-98.00 – -96.00
Cohort 6 Apixaban 10 mg BID/Placebo-31.00-35.00 – -30.00
Percent Change in Anti-Fxa Activity From Baseline to the End of Bolus (EOB) Nadir. Secondary · Baseline to the end of bolus (EOB) nadir, approximately 2.5 hours

The percent change from baseline in anti-FXa activity at its end of bolus (EOB) nadir.

GroupValue95% CI
Cohort 1 Apixaban 5 mg BID/Low Dose Andexanet-94.50-95.00 – -92.00
Cohort 1 Apixaban 5 mg BID/Placebo-14.00-15.00 – -12.00
Cohort 2 Rivaroxaban15 mg BID/High Dose Andexanet-97.50-98.00 – -96.00
Cohort 2 Rivaroxaban 15 mg BID/Placebo-18.00-29.00 – -1.00
Cohort 3 Edoxaban 60 mg QD/High Dose Andexanet-65.50-87.00 – -8.00
Cohort 3 Edooxaban 60 mg QD/Placebo-16.00-46.00 – -13.00
Cohort 4 Edoxaban 60 mg QD/High Dose Andexanet-22.50-78.00 – 0.00
Cohort 4 Edooxaban 60 mg QD/Placebo-15.00-19.00 – 7.00
Cohort 5 Apixaban 5 mg BID/Low Dose Andexanet-94.00-94.00 – -92.00
Cohort 5 Apixaban 5 mg BID/Placebo-10.00-21.00 – -7.00
Cohort 6 Apixaban 10 mg BID/High Dose Andexanet-96.00-97.00 – -95.00
Cohort 6 Apixaban 10 mg BID/Placebo-18.00-21.00 – -14.00
Percent Change in Free Fxa Inhibitor Concentration From Baseline to the End of Bolus (EOB) Nadir. Secondary · Baseline to the end of bolus (EOB) nadir, approximately 2.5 hours

The percent change from baseline in free FXa inhibitors concentration (ng/mL) at its EOB nadir.

GroupValue95% CI
Cohort 1 Apixaban 5 mg BID/Low Dose Andexanet-93.00-94.70 – -90.38
Cohort 1 Apixaban 5 mg BID/Placebo-11.94-18.42 – -1.71
Cohort 2 Rivaroxaban15 mg BID/High Dose Andexanet-97.72-97.97 – -95.70
Cohort 2 Rivaroxaban 15 mg BID/Placebo-28.57-47.06 – -1.06
Cohort 3 Edoxaban 60 mg QD/High Dose Andexanet-78.20-86.17 – -59.17
Cohort 3 Edooxaban 60 mg QD/Placebo-17.60-27.95 – -10.15
Cohort 4 Edoxaban 60 mg QD/High Dose Andexanet-56.05-77.92 – -40.69
Cohort 4 Edooxaban 60 mg QD/Placebo-2.49-28.57 – 12.48
Cohort 5 Apixaban 5 mg BID/Low Dose Andexanet-94.45-96.56 – -93.04
Cohort 5 Apixaban 5 mg BID/Placebo5.80-8.56 – 36.52
Cohort 6 Apixaban 10 mg BID/High Dose Andexanet-93.57-97.30 – -90.08
Cohort 6 Apixaban 10 mg BID/Placebo-12.94-24.34 – -10.94
Percent Change in Free Fxa Inhibitor Concentration From Baseline to the End of Infusion (EOI) Nadir. Secondary · Baseline to the end of infusion (EOI) nadir, approximately 2.5 hours

The percent change from baseline in free FXa inhibitors concentration (ng/mL) at its EOI nadir.

GroupValue95% CI
Cohort 1 Apixaban 5 mg BID/Low Dose Andexanet-92.940-94.610 – -90.400
Cohort 1 Apixaban 5 mg BID/Placebo-33.550-37.780 – -28.130
Cohort 2 Rivaroxaban15 mg BID/High Dose Andexanet-98.650-99.060 – -97.610
Cohort 2 Rivaroxaban 15 mg BID/Placebo-39.390-70.670 – -28.720
Cohort 3 Edoxaban 60 mg QD/High Dose Andexanet-85.005-93.140 – -68.740
Cohort 3 Edooxaban 60 mg QD/Placebo-48.710-49.790 – -38.980
Cohort 4 Edoxaban 60 mg QD/High Dose Andexanet-81.040-89.300 – -67.660
Cohort 4 Edooxaban 60 mg QD/Placebo-42.755-53.330 – -25.890
Cohort 5 Apixaban 5 mg BID/Low Dose Andexanet-93.495-96.180 – -91.240
Cohort 5 Apixaban 5 mg BID/Placebo-31.830-47.460 – -20.360
Cohort 6 Apixaban 10 mg BID/High Dose Andexanet-96.65-97.62 – -94.80
Cohort 6 Apixaban 10 mg BID/Placebo-29.02-32.81 – -20.22
Change in Thrombin Generation From Baseline to the End of Bolus (EOB) Nadir. Secondary · Baseline to the end of bolus (EOB) nadir, approximately 2.5 hours

The change in thrombin generation from baseline to its EOB peak.

GroupValue95% CI
Cohort 1 Apixaban 5 mg BID/Low Dose Andexanet1145.03708.92 – 1538.44
Cohort 1 Apixaban 5 mg BID/Placebo179.94161.09 – 234.44
Cohort 2 Rivaroxaban15 mg BID/High Dose Andexanet1337.281155.95 – 1632.28
Cohort 2 Rivaroxaban 15 mg BID/Placebo209.9957.26 – 386.49
Cohort 3 Edoxaban 60 mg QD/High Dose Andexanet758.92560.66 – 1494.51
Cohort 3 Edooxaban 60 mg QD/Placebo215.71-15.75 – 319.23
Cohort 4 Edoxaban 60 mg QD/High Dose Andexanet815.07603.90 – 949.73
Cohort 4 Edooxaban 60 mg QD/Placebo48.5922.87 – 165.84
Cohort 5 Apixaban 5 mg BID/Low Dose Andexanet1244.301106.36 – 1714.52
Cohort 5 Apixaban 5 mg BID/Placebo103.13-22.26 – 142.33
Cohort 6 Apixaban 10 mg BID/High Dose Andexanet1177.471081.47 – 1564.10
Cohort 6 Apixaban 10 mg BID/Placebo0.16-106.20 – 92.65
Change in Thrombin Generation From Baseline to the End of Infusion (EOI) Nadir. Secondary · Baseline to the end of infusion (EOI) nadir, approximately 2.5 hours

The change in thrombin generation from baseline to its EOI peak.

GroupValue95% CI
Cohort 1 Apixaban 5 mg BID/Low Dose Andexanet1000.630695.120 – 1519.850
Cohort 1 Apixaban 5 mg BID/Placebo171.220157.740 – 189.720
Cohort 2 Rivaroxaban15 mg BID/High Dose Andexanet1329.5801161.360 – 1679.680
Cohort 2 Rivaroxaban 15 mg BID/Placebo207.590126.910 – 287.490
Cohort 3 Edoxaban 60 mg QD/High Dose Andexanet804.405692.880 – 1560.300
Cohort 3 Edooxaban 60 mg QD/Placebo347.535107.360 – 482.840
Cohort 4 Edoxaban 60 mg QD/High Dose Andexanet910.935775.950 – 1108.160
Cohort 4 Edooxaban 60 mg QD/Placebo236.610126.010 – 295.710
Cohort 5 Apixaban 5 mg BID/Low Dose Andexanet1130.5751022.120 – 1460.710
Cohort 5 Apixaban 5 mg BID/Placebo118.130108.660 – 163.040
Cohort 6 Apixaban 10 mg BID/High Dose Andexanet1119.41969.95 – 1567.02
Cohort 6 Apixaban 10 mg BID/Placebo108.67-67.28 – 150.99

Adverse events — posted to ClinicalTrials.gov

Time frame: Study day 1 to 39. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Cohort 1 Apixaban 5 mg BID/Low Dose Andexanet
Serious: 0/6 (0%)
Deaths: 0/6
Cohort 1 Apixaban 5 mg BID/Placebo
Serious: 0/3 (0%)
Deaths: 0/3
Cohort 2 Rivaroxaban15 mg BID/High Dose Andexanet
Serious: 0/6 (0%)
Deaths: 0/6
Cohort 2 Rivaroxaban 15 mg BID/Placebo
Serious: 0/3 (0%)
Deaths: 0/3
Cohort 3 Edoxaban 60 mg QD/High Dose Andexanet
Serious: 0/8 (0%)
Deaths: 0/8
Cohort 3 Edooxaban 60 mg QD/Placebo
Serious: 0/4 (0%)
Deaths: 0/4
Cohort 4 Edoxaban 60 mg QD/High Dose Andexanet
Serious: 0/8 (0%)
Deaths: 0/8
Cohort 4 Edooxaban 60 mg QD/Placebo
Serious: 0/4 (0%)
Deaths: 0/4
Cohort 5 Apixaban 5 mg BID/Low Dose Andexanet
Serious: 1/6 (17%)
Deaths: 0/6
Cohort 5 Apixaban 5 mg BID/Placebo
Serious: 0/3 (0%)
Deaths: 0/3
Cohort 6 Apixaban 10 mg BID/High Dose Andexanet
Serious: 0/6 (0%)
Deaths: 0/6
Cohort 6 Apixaban 10 mg BID/Placebo
Serious: 0/3 (0%)
Deaths: 0/3
Cohort 7 Edoxaban 30 mg QD/Low Dose Andexanet
Serious: 0/8 (0%)
Deaths: 0/8
Cohort 7 Edoxaban 30 mg QD/Placebo
Serious: 0/4 (0%)
Deaths: 0/4
Cohort 8 Apixaban 10 mg BID/Low Dose Andexanet
Serious: 0/6 (0%)
Deaths: 0/6
Cohort 8 Apixaban 10 mg BID/Placebo
Serious: 0/3 (0%)
Deaths: 0/3
Cohort 9 Rivaroxaban 15 mg BID/Low Dose Andexanet
Serious: 0/10 (0%)
Deaths: 0/10
Cohort 9 Rivaroxaban 15 mg BID/Placebo
Serious: 0/5 (0%)
Deaths: 0/5
Cohort 10 Edoxaban 60 mg QD /Low Dose Andexanet
Serious: 0/8 (0%)
Deaths: 0/8
Cohort 10 Edoxaban 60 mg QD/Placebo
Serious: 0/3 (0%)
Deaths: 0/3

Serious adverse events (1 terms)

ReactionSystemCohort 1 Apixaban 5 mg BID…Cohort 1 Apixaban 5 mg BID…Cohort 2 Rivaroxaban15 mg …Cohort 2 Rivaroxaban 15 mg…Cohort 3 Edoxaban 60 mg QD…Cohort 3 Edooxaban 60 mg Q…Cohort 4 Edoxaban 60 mg QD…Cohort 4 Edooxaban 60 mg Q…Cohort 5 Apixaban 5 mg BID…Cohort 5 Apixaban 5 mg BID…Cohort 6 Apixaban 10 mg BI…Cohort 6 Apixaban 10 mg BI…Cohort 7 Edoxaban 30 mg QD…Cohort 7 Edoxaban 30 mg QD…Cohort 8 Apixaban 10 mg BI…Cohort 8 Apixaban 10 mg BI…Cohort 9 Rivaroxaban 15 mg…Cohort 9 Rivaroxaban 15 mg…Cohort 10 Edoxaban 60 mg Q…Cohort 10 Edoxaban 60 mg Q…
NephrolithiasisRenal and urinary disorders
Other adverse events (32 terms — click to expand)

ReactionSystemCohort 1 Apixaban 5 mg BID…Cohort 1 Apixaban 5 mg BID…Cohort 2 Rivaroxaban15 mg …Cohort 2 Rivaroxaban 15 mg…Cohort 3 Edoxaban 60 mg QD…Cohort 3 Edooxaban 60 mg Q…Cohort 4 Edoxaban 60 mg QD…Cohort 4 Edooxaban 60 mg Q…Cohort 5 Apixaban 5 mg BID…Cohort 5 Apixaban 5 mg BID…Cohort 6 Apixaban 10 mg BI…Cohort 6 Apixaban 10 mg BI…Cohort 7 Edoxaban 30 mg QD…Cohort 7 Edoxaban 30 mg QD…Cohort 8 Apixaban 10 mg BI…Cohort 8 Apixaban 10 mg BI…Cohort 9 Rivaroxaban 15 mg…Cohort 9 Rivaroxaban 15 mg…Cohort 10 Edoxaban 60 mg Q…Cohort 10 Edoxaban 60 mg Q…
DiarrhoeaGastrointestinal disorders
HeadacheNervous system disorders
Abdominal Pain UpperGastrointestinal disorders
Aphthous UlcerGastrointestinal disorders
VomitingGastrointestinal disorders
Catheter Site PainGeneral disorders
Infusion Site PainGeneral disorders
Vessel Puncture Site HaemorrhageGeneral disorders
NasopharyngitisInfections and infestations
Oral HerpesInfections and infestations
PharyngitisInfections and infestations
Rash PustularInfections and infestations
SinusitisInfections and infestations
Upper Respiratory Tract InfectionInfections and infestations
Foot FractureInjury, poisoning and procedural complications
Muscle StrainInjury, poisoning and procedural complications
ArthralgiaMusculoskeletal and connective tissue disorders
CostochondritisMusculoskeletal and connective tissue disorders
MyalgiaMusculoskeletal and connective tissue disorders
Muscle SpasmsMusculoskeletal and connective tissue disorders
OsteoarthritisMusculoskeletal and connective tissue disorders
Pain in ExtremityMusculoskeletal and connective tissue disorders
DizzinessNervous system disorders
MigraineNervous system disorders
Neuropathy PeripheralNervous system disorders
Oropharyngeal PainRespiratory, thoracic and mediastinal disorders
Dermatitis ContactSkin and subcutaneous tissue disorders
Dry SkinSkin and subcutaneous tissue disorders
EczemaSkin and subcutaneous tissue disorders
PetechiaeSkin and subcutaneous tissue disorders
RashSkin and subcutaneous tissue disorders
PhlebitisVascular disorders

Most-reported serious reactions: Nephrolithiasis.

Data from ClinicalTrials.gov NCT03310021 adverse events section.

Sponsor's own description

"This is a single-center, randomized, double-blind, and placebo-controlled trial designed to: 1) demonstrate the degree to which administered andexanet doses can reverse Factor Ten A (FXa)-inhibitor induced anticoagulation; and 2) evaluate the safety and PK/PD of andexanet in healthy Japanese subjects taking direct FXa inhibitors at therapeutic doses."

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

  1. Andexanet Alfa: First Global Approval.
    Heo YA. · · 2018 · cited 77× · PMID 29926311 · DOI 10.1007/s40265-018-0940-4

Verify or expand the search:

Other trials of Andexanet alfa

Trials testing the same drug.

Other recruiting trials for Bleeding

Currently open trials in the same condition.

Other Portola Pharmaceuticals trials

Trials by the same sponsor.

Verify against primary sources

Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT03310021.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing