Healthy VolunteersPhase 2NCT03578146

Phase 2 Healthy Volunteer Study to Evaluate the Ability of PRT064445 to Reverse the Effects of Several Blood Thinner Drugs on Laboratory Tests (Module 2 of 4)

A Phase 2 study testing PRT064445/Rivaroxaban in people with Healthy Volunteers, run by Portola Pharmaceuticals.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial summary

The purpose of this study is to evaluate the ability of PRT064445 to reverse the effects of several blood thinner drugs on laboratory tests. The study also is evaluating the blood levels of PRT064445 given at different doses. Read more about this study

Who is it for?: Ages 18 to 45 yearsHealthy volunteers can take part
Conditions the study is for: Healthy Volunteers
What is being tested?: PRT064445/Rivaroxaban
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 48 participants
Where: No sites listed yet
Study dates: Dec 2012to Sep 2015
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 45 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

Healthy men or women between the ages of 18 and 45 years old

Who cannot join

History (including family history) or symptoms of, or risk factors for bleeding
History (including family history) of or risk factors for a hypercoagulable or thrombotic condition
Absolute/relative contraindication to anticoagulation or treatment with specific anticoagulants
History of major surgery, severe trauma or bone fracture within 3 months prior to dosing; or planned surgery within 1 month after dosing.

About this study

Official title: A Randomized, Double-Blind, Vehicle-Controlled Multiple Dose Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Intravenously Administered PRT064445 After Dosing to Steady State With One of Four Direct/Indirect fXa Inhibitors in Healthy Volunteers

Read the detailed description

A randomized, double-blind, vehicle-controlled study to assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of intravenously administered PRT064445 after dosing to steady state with one of four direct/indirect factor Xa (fXa) inhibitors in healthy volunteers.

Conditions: Healthy Volunteers
Being tested: PRT064445/Rivaroxaban, Placebo/Rivaroxaban, Placebo

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

PRT064445/RivaroxabanCombination product
Also called Andexanet
Placebo/RivaroxabanCombination product
PlaceboDrug

Study groups in NCT03578146
Study group	Role	What they receive
Module 2 (210 mg)	Experimental	210 mg andexanet IV bolus administered over 7 minutes (~30 mg/min) Receives: Combination Product: PRT064445/Rivaroxaban; Combination Product: Placebo/Rivaroxaban
Module 2 (420 mg)	Experimental	420 mg andexanet IV bolus administered over 14 minutes (~30 mg/min) Receives: Combination Product: PRT064445/Rivaroxaban; Combination Product: Placebo/Rivaroxaban
Module 2 (600 mg)	Experimental	600 mg andexanet IV bolus administered over 20 minutes (~30 mg/min) Receives: Combination Product: PRT064445/Rivaroxaban; Combination Product: Placebo/Rivaroxaban
Module 2 (720 mg bolus + 240 mg infusion)	Experimental	720 mg IV bolus administered over 24 minutes [~30 mg/min] followed by 240 mg continuous IV infusion [4 mg/min over 60 min) Receives: Combination Product: PRT064445/Rivaroxaban; Combination Product: Placebo/Rivaroxaban
Module 2 (800 mg bolus + 960 mg infusion)	Experimental	800 mg IV bolus administered over 26.7 minutes [~30 mg/min] followed by 960 mg continuous IV infusion [8 mg/min over 120 min] Receives: Combination Product: PRT064445/Rivaroxaban; Combination Product: Placebo/Rivaroxaban
Module 2 Placebo	Experimental	Placebo administered intravenously (IV) as a bolus or a bolus followed by continuous fusion. Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Efficacy: Percent Change From Baseline in Anti-fXa Activity at 2 Mins Following Andexanet/Placebo Administration
Anti-fXa activity was measured immediately prior to (Baseline) and at 2 mins following andexanet/placebo administration. Anti-fXa activity was measured using a commercial kit (Coamatic Heparin-82 33 9363, DiaPharma)
Measured: Baseline to 2 minutes following the end of andexanet/placebo administration

Secondary outcomes (8)

Efficacy: Percent Change From Baseline in Thrombin Generation at 2 Mins Following Andexanet/Placebo Administration
Thrombin generation was measured immediately prior to (Baseline) and at 2 mins following andexanet/placebo administration. Thrombin generation was measured using a TF-initiated thrombin generation assay.
Measured: Baseline to 2 minutes following the end of andexanet/placebo administration
Efficacy: Percent Change From Baseline in Unbound Rivaroaxaban Plasma Concentration at 2 Mins Following Andexanet/Placebo Administration
Unbound rivaroxaban concentrations was measured immediately prior to (Baseline) and at 2 mins following andexanet/placebo administration. Unbound plasma concentrations for rivaroxaban were determined by a rapid equilibrium dialysis method followed by Liquid Chromatography-Mass Spectometry assay.
Measured: Baseline to 2 minutes following the end of andexanet/placebo administration
Andexanet Maximum Observed Plasma Concentration (Cmax)
Plasma concentrations of andexanet was determined using a validated method that involved analysis of citrated human plasma by an electrochemiluminescent assay.
Measured: Blood was collected at predose, 0.033, 0.2, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4.5, 5.5, 6.5, 7.5, 8.5 and 14.5 hours postdose.
Andexanet Area Under the Drug Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC0-inf )
Plasma concentrations of andexanet was determined using a validated method that involved analysis of citrated human plasma by an electrochemiluminescent assay. AUC0-inf was calculated using a non-compartmental approach
Measured: Blood was collected at predose, 0.033, 0.2, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4.5, 5.5, 6.5, 7.5, 8.5 and 14.5 hours postdose.
Andexanet Time of Maximum Observed Plasma Concentration (Tmax)
Plasma concentrations of andexanet was determined using a validated method that involved analysis of citrated human plasma by an electrochemiluminescent assay. Tmax was taken directly from the raw data.
Measured: Blood was collected at predose, 0.033, 0.2, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4.5, 5.5, 6.5, 7.5, 8.5 and 14.5 hours postdose.
Andexanet Apparent Terminal Elimination Half-life (t1/2)
Plasma concentrations of andexanet was determined using a validated method that involved analysis of citrated human plasma by an electrochemiluminescent assay. t1/2 was determined by linear regression of the log concentration on the terminal portion of the plasma concentration-time curve.
Measured: Blood was collected at predose, 0.033, 0.2, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4.5, 5.5, 6.5, 7.5, 8.5 and 14.5 hours postdose.
Andexanet Total Systemic Clearance (CL)
Plasma concentrations of andexanet was determined using a validated method that involved analysis of citrated human plasma by an electrochemiluminescent assay. CL was calculated using a non-compartmental approach, calculated as Dose/AUC0-inf
Measured: Blood was collected at predose, 0.033, 0.2, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4.5, 5.5, 6.5, 7.5, 8.5 and 14.5 hours postdose.
Andexanet Total Volume of Distribution (Vss)
Plasma concentrations of andexanet was determined using a validated method that involved analysis of citrated human plasma by an electrochemiluminescent assay. Vss was calculated using a non-compartmental approach.
Measured: Blood was collected at predose, 0.033, 0.2, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4.5, 5.5, 6.5, 7.5, 8.5 and 14.5 hours postdose.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Dec 2012Sep 2015

First posted6 Jul 2018
Study startDec 2012
Primary completionSep 2015
Study completionSep 2015

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Healthy VolunteersStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Model description: This study has four modules with a total of 21 cohorts, each module was reported and submitted separately. Module 1, NCT01758432 (54 subjects with 7 cohorts including placebo); Module 2, NCT03578146 (48 subjects with 6 cohorts including placebo); Module 3, NCT03551730 (27 subjects with 4 cohorts including placebo); Module 4, NCT03551743 (28 subjects with 4 cohorts including placebo)
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 48 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03578146
Sponsor's protocol ID: 12-502 Module 2
Status last verified: Feb 2023
First submitted: 15 May 2018
Last updated: 22 Feb 2023
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

Lu G, Conley PB, Leeds JM, Karbarz MJ, Levy GG, Mathur VS, Castillo J, Crowther M, Curnutte JT. A phase 2 PK/PD study of andexanet alfa for reversal of rivaroxaban and edoxaban anticoagulation in healthy volunteers. Blood Adv. 2020 Feb 25;4(4):728-739. doi: 10.1182/bloodadvances.2019000885.
PubMed 32092140

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

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Study at a glance

From the registry record, last updated by the sponsor on 22 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomized, Double-Blind, Vehicle-Controlled Multiple Dose Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Intravenously Administered PRT064445 After Dosing to Steady State With One of Four Direct/Indirect fXa Inhibitors in Healthy Volunteers
ClinicalTrials.gov ID: NCT03578146
Acronym / sponsor ID: 12-502 Module 2
Conditions: Healthy Volunteers
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 48 participants (actual)
Lead sponsor: Portola PharmaceuticalsIndustry (pharma, biotech, devices)
Study start: Dec 2012
Primary completion: Sep 2015 (actual)
Study completion: Sep 2015 (actual)
First posted: 6 Jul 2018 (actual)
Results: Posted 5 Sep 2018

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 6
Model description: This study has four modules with a total of 21 cohorts, each module was reported and submitted separately. Module 1, NCT01758432 (54 subjects with 7 cohorts including placebo); Module 2, NCT03578146 (48 subjects with 6 cohorts including placebo); Module 3, NCT03551730 (27 subjects with 4 cohorts including placebo); Module 4, NCT03551743 (28 subjects with 4 cohorts including placebo)

Arm	Type	Receives
Module 2 (210 mg)	Experimental	Combination Product: PRT064445/Rivaroxaban, Combination Product: Placebo/Rivaroxaban210 mg andexanet IV bolus administered over 7 minutes (~30 mg/min)
Module 2 (420 mg)	Experimental	Combination Product: PRT064445/Rivaroxaban, Combination Product: Placebo/Rivaroxaban420 mg andexanet IV bolus administered over 14 minutes (~30 mg/min)
Module 2 (600 mg)	Experimental	Combination Product: PRT064445/Rivaroxaban, Combination Product: Placebo/Rivaroxaban600 mg andexanet IV bolus administered over 20 minutes (~30 mg/min)
Module 2 (720 mg bolus + 240 mg infusion)	Experimental	Combination Product: PRT064445/Rivaroxaban, Combination Product: Placebo/Rivaroxaban720 mg IV bolus administered over 24 minutes [~30 mg/min] followed by 240 mg continuous IV infusion [4 mg/min over 60 min)
Module 2 (800 mg bolus + 960 mg infusion)	Experimental	Combination Product: PRT064445/Rivaroxaban, Combination Product: Placebo/Rivaroxaban800 mg IV bolus administered over 26.7 minutes [~30 mg/min] followed by 960 mg continuous IV infusion [8 mg/min over 120 min]
Module 2 Placebo	Experimental	Drug: PlaceboPlacebo administered intravenously (IV) as a bolus or a bolus followed by continuous fusion.

Who may qualify

Ages: 18 to 45 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (1 listed)

Healthy men or women between the ages of 18 and 45 years old

Key exclusion criteria (4 listed)

History (including family history) or symptoms of, or risk factors for bleeding
History (including family history) of or risk factors for a hypercoagulable or thrombotic condition
Absolute/relative contraindication to anticoagulation or treatment with specific anticoagulants
History of major surgery, severe trauma or bone fracture within 3 months prior to dosing; or planned surgery within 1 month after dosing.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
PRT064445/RivaroxabanAlso: Andexanet	Combination product	Module 2 (210 mg), Module 2 (420 mg), Module 2 (600 mg), Module 2 (720 mg bolus + 240 mg infusion), Module 2 (800 mg bolus + 960 mg infusion)
Placebo/Rivaroxaban	Combination product	Module 2 (210 mg), Module 2 (420 mg), Module 2 (600 mg), Module 2 (720 mg bolus + 240 mg infusion), Module 2 (800 mg bolus + 960 mg infusion)
Placebo	Drug	Module 2 Placebo

Primary outcome

Efficacy: Percent Change From Baseline in Anti-fXa Activity at 2 Mins Following Andexanet/Placebo Administration
Time frame: Baseline to 2 minutes following the end of andexanet/placebo administration
Anti-fXa activity was measured immediately prior to (Baseline) and at 2 mins following andexanet/placebo administration. Anti-fXa activity was measured using a commercial kit (Coamatic Heparin-82 33 9363, DiaPharma)

8 secondary outcomes

Efficacy: Percent Change From Baseline in Thrombin Generation at 2 Mins Following Andexanet/Placebo Administration
Time frame: Baseline to 2 minutes following the end of andexanet/placebo administration
Efficacy: Percent Change From Baseline in Unbound Rivaroaxaban Plasma Concentration at 2 Mins Following Andexanet/Placebo Administration
Time frame: Baseline to 2 minutes following the end of andexanet/placebo administration
Andexanet Maximum Observed Plasma Concentration (Cmax)
Time frame: Blood was collected at predose, 0.033, 0.2, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4.5, 5.5, 6.5, 7.5, 8.5 and 14.5 hours postdose.
Andexanet Area Under the Drug Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC0-inf )
Time frame: Blood was collected at predose, 0.033, 0.2, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4.5, 5.5, 6.5, 7.5, 8.5 and 14.5 hours postdose.
Andexanet Time of Maximum Observed Plasma Concentration (Tmax)
Time frame: Blood was collected at predose, 0.033, 0.2, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4.5, 5.5, 6.5, 7.5, 8.5 and 14.5 hours postdose.
Andexanet Apparent Terminal Elimination Half-life (t1/2)
Time frame: Blood was collected at predose, 0.033, 0.2, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4.5, 5.5, 6.5, 7.5, 8.5 and 14.5 hours postdose.
Andexanet Total Systemic Clearance (CL)
Time frame: Blood was collected at predose, 0.033, 0.2, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4.5, 5.5, 6.5, 7.5, 8.5 and 14.5 hours postdose.
Andexanet Total Volume of Distribution (Vss)
Time frame: Blood was collected at predose, 0.033, 0.2, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4.5, 5.5, 6.5, 7.5, 8.5 and 14.5 hours postdose.

Results and safety

Results posted to the registry on 5 Sep 2018, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Module 2 Placebo	16	15
Module 2 (210 mg)	6	5
Module 2 (420 mg)	6	5
Module 2 (600 mg)	6	6
Module 2 (720 mg Bolus + 240 mg Infusion)	6	6
Module 2 (800 mg Bolus + 960 mg Infusion)	8	5

Primary outcome: Efficacy: Percent Change From Baseline in Anti-fXa Activity at 2 Mins Following Andexanet/Placebo Administration

Time frame: Baseline to 2 minutes following the end of andexanet/placebo administration. Mean (Standard Deviation). Unit: Percent change in anti-fXa activity

Measure	Module 2 Placebo n = 15	Module 2 (210 mg) n = 6	Module 2 (420 mg) n = 6	Module 2 (600 mg) n = 6	Module 2 (720 mg Bolus + 240 mg Infusion) n = 6	Module 2 (800 mg Bolus + 960 mg Infusion) n = 6
Value	22.37 (42.247)	-18.09 (23.922)	-50.59 (22.056)	-75.26 (19.072)	-88.91 (6.098)	-92.72 (3.084)

Module 2 Placebo vs Module 2 (210 mg): Least Squares Means (Difference): -73.14, p = 0.0121, ANCOVA
Module 2 Placebo vs Module 2 (420 mg): Least Squares Means (Difference): -153.99, p <0.0001, ANCOVA
Module 2 Placebo vs Module 2 (600 mg): Least Squares Means (Difference): -189.57, p <0.0001, ANCOVA

Population analysed: 45 subjects who received andexanet or placebo were included in the pharmacodynamics (PD) analysis

8 secondary outcomes are reported in the full results.

Adverse events

Time frame: ~7 weeks. Other adverse events reported at 3% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Module 2 Placebo	0 of 15 (0%)	12 of 15 (80%)	Not reported
Module 2 (210 mg)	0 of 6 (0%)	4 of 6 (66.7%)	Not reported
Module 2 (420 mg)	0 of 6 (0%)	3 of 6 (50%)	Not reported
Module 2 (600 mg)	0 of 6 (0%)	5 of 6 (83.3%)	Not reported
Module 2 (720 mg Bolus + 240 mg Infusion)	0 of 6 (0%)	5 of 6 (83.3%)	Not reported
Module 2 (800 mg Bolus + 960 mg Infusion)	0 of 6 (0%)	5 of 6 (83.3%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 22 Feb 2023.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 32092140Lu G, Conley PB, Leeds JM, Karbarz MJ, Levy GG, Mathur VS, Castillo J, Crowther M, Curnutte JT. A phase 2 PK/PD study of andexanet alfa for reversal of rivaroxaban and edoxaban anticoagulation in healthy volunteers. Blood Adv. 2020 Feb 25;4(4):728-739. doi: 10.1182/bloodadvances.2019000885.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing PRT064445/Rivaroxaban in people with Healthy Volunteers, run by Portola Pharmaceuticals.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 1 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 5 Sep 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Efficacy: Percent Change From Baseline in Anti-fXa Activity at 2 Mins Following Andexanet/Placebo Administration (time frame: Baseline to 2 minutes following the end of andexanet/placebo administration). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03578146, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Feb 2023.