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)
February 17, 2023 updated by: Portola Pharmaceuticals
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
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
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.
Study Type
Interventional
Enrollment (Actual)
48
Phase
- Phase 2
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 45 years (Adult)
Accepts Healthy Volunteers
Yes
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Healthy men or women between the ages of 18 and 45 years old
Exclusion Criteria:
- 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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Experimental: Module 2 (210 mg)
210 mg andexanet IV bolus administered over 7 minutes (~30 mg/min)
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Other Names:
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Experimental: Module 2 (420 mg)
420 mg andexanet IV bolus administered over 14 minutes (~30 mg/min)
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Other Names:
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Experimental: Module 2 (600 mg)
600 mg andexanet IV bolus administered over 20 minutes (~30 mg/min)
|
Other Names:
|
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Experimental: Module 2 (720 mg bolus + 240 mg infusion)
720 mg IV bolus administered over 24 minutes [~30 mg/min] followed by 240 mg continuous IV infusion [4 mg/min over 60 min)
|
Other Names:
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Experimental: Module 2 (800 mg bolus + 960 mg infusion)
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]
|
Other Names:
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Experimental: Module 2 Placebo
Placebo administered intravenously (IV) as a bolus or a bolus followed by continuous fusion.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
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)
|
Baseline to 2 minutes following the end of andexanet/placebo administration
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
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
|
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.
|
Baseline to 2 minutes following the end of andexanet/placebo administration
|
|
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.
|
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
|
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.
|
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.
|
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.
|
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.
|
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.
|
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.
|
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.
|
|
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
|
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.
|
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.
|
Plasma concentrations of andexanet was determined using a validated method that involved analysis of citrated human plasma by an electrochemiluminescent assay.
|
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.
|
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
|
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.
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
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Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
December 1, 2012
Primary Completion (Actual)
September 1, 2015
Study Completion (Actual)
September 1, 2015
Study Registration Dates
First Submitted
May 15, 2018
First Submitted That Met QC Criteria
June 22, 2018
First Posted (Actual)
July 6, 2018
Study Record Updates
Last Update Posted (Estimate)
February 22, 2023
Last Update Submitted That Met QC Criteria
February 17, 2023
Last Verified
February 1, 2023
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 12-502 Module 2
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