Healthy VolunteersPhase 2NCT03551730

Phase 2 Healthy Volunteer Study to Evaluate the Ability of PRT064445 to Reverse the Effects of Several Blood Thinner Drugs on Laboratory Tests (Module 3 of 4)

A Phase 2 study testing PRT064445/Enoxaparin in people with Healthy Volunteers, run by Portola Pharmaceuticals at 1 site in United States.

Completed

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

Official record

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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/Enoxaparin
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 27 participants
Where: 1 siteUnited States
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.

Trial locations and contacts

1 site in 1 country.

United States1 site

Study site
Tempe, Arizona, 85283

Other trials in United States

About this study

Official title: 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.

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/Enoxaparin, Placebo/Enoxaparin, Placebo

What participants receive

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

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

Study groups in NCT03551730
Study group	Role	What they receive
Module 3 (210 mg bolus) original	Experimental	210 mg PRT064445 given as a single IV bolus Receives: Combination Product: PRT064445/Enoxaparin; Combination Product: Placebo/Enoxaparin
Module 3 (420 mg bolus) original	Experimental	420 mg PRT064445 given as a single IV bolus Receives: Combination Product: PRT064445/Enoxaparin; Combination Product: Placebo/Enoxaparin
Module 3 (210 mg) lyophilized	Experimental	210 mg PRT064445 (lyophilized formulation) given as a single IV bolus Receives: Combination Product: PRT064445/Enoxaparin; Combination Product: Placebo/Enoxaparin
Module 3 Placebo	Placebo comparator	Placebo administered intravenously (IV) as a bolus. 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 Activity
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 (7)

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
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. Cmax 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 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.
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 posted11 Jun 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.
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: 27 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03551730
Sponsor's protocol ID: 12-502 Module 3
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

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?

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All Healthy Volunteers trials

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 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.
ClinicalTrials.gov ID: NCT03551730
Acronym / sponsor ID: 12-502 Module 3
Conditions: Healthy Volunteers
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 27 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: 11 Jun 2018 (actual)
Results: Posted 13 Aug 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: 4
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 3 (210 mg bolus) original	Experimental	Combination Product: PRT064445/Enoxaparin, Combination Product: Placebo/Enoxaparin210 mg PRT064445 given as a single IV bolus
Module 3 (420 mg bolus) original	Experimental	Combination Product: PRT064445/Enoxaparin, Combination Product: Placebo/Enoxaparin420 mg PRT064445 given as a single IV bolus
Module 3 (210 mg) lyophilized	Experimental	Combination Product: PRT064445/Enoxaparin, Combination Product: Placebo/Enoxaparin210 mg PRT064445 (lyophilized formulation) given as a single IV bolus
Module 3 Placebo	Placebo comparator	Drug: PlaceboPlacebo administered intravenously (IV) as a bolus.

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/EnoxaparinAlso: Andexanet	Combination product	Module 3 (210 mg bolus) original, Module 3 (210 mg) lyophilized, Module 3 (420 mg bolus) original
Placebo/Enoxaparin	Combination product	Module 3 (210 mg bolus) original, Module 3 (210 mg) lyophilized, Module 3 (420 mg bolus) original
Placebo	Drug	Module 3 Placebo

Primary outcome

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

7 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
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 13 Aug 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
Placebo	9	8
Module 3 (210 mg Bolus) Original	6	6
Module 3 (420 mg Bolus) Original	6	6
Module 3 (210 mg) Lyophilized	6	6

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

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

Measure	Placebo n = 8	Module 3 (210 mg Bolus) Original n = 6	Module 3 (420 mg Bolus) Original n = 6	Module 3 (210 mg) Lyophilized n = 6
Value	-3.57 (12.80)	-70.80 (6.98)	-60.83 (8.39)	-69.85 (7.46)

Placebo vs Module 3 (210 mg Bolus) Original: Least Squares Means (Difference): -0.23, p <0.0001, ANCOVA
Placebo vs Module 3 (420 mg Bolus) Original: Least Squares Means (Difference): -0.20, p <0.0001, ANCOVA
Placebo vs Module 3 (210 mg) Lyophilized: Least Squares Means (Difference): -0.23, p <0.0001, ANCOVA

Population analysed: 26 subjects who received andexanet or placebo were included in the pharmacodynamics (PD) analysis

7 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
Placebo	0 of 8 (0%)	5 of 8 (62.5%)	Not reported
Module 3 (210 mg Andexanet) Original Formulation	0 of 6 (0%)	4 of 6 (66.7%)	Not reported
Module 3 (420 mg Andexanet) Original Forumulation	0 of 6 (0%)	4 of 6 (66.7%)	Not reported
Module 3 (210 mg Andexanet ) Lyophilized	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.

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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.

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing PRT064445/Enoxaparin in people with Healthy Volunteers, run by Portola Pharmaceuticals at 1 site in United States.

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.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. 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 13 Aug 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 Activity (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 NCT03551730.

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.