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Phase 2 Healthy Volunteer Study to Evaluate the Ability of PRT064445 to Reverse the Effects of Several Blood Thinner Drugs on Laboratory Tests (Module 1 of 4)

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ClinicalTrials.gov Identifier: NCT01758432
Recruitment Status : Completed
First Posted : January 1, 2013
Results First Posted : August 10, 2018
Last Update Posted : September 26, 2018
Sponsor:
Information provided by (Responsible Party):
Portola Pharmaceuticals

Brief 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.

Condition or disease Intervention/treatment Phase
Healthy Volunteers Combination Product: PRT064445/Apixaban Combination Product: Placebo/Apixaban Drug: Placebo Phase 2

Detailed Description:
A randomized, double-blind, vehicle-controlled 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

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 54 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention 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 7cohorts 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 (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind, Vehicle-Controlled 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
Study Start Date : December 2012
Actual Primary Completion Date : September 2015
Actual Study Completion Date : September 2015

Resource links provided by the National Library of Medicine

Drug Information available for: Apixaban

Arm Intervention/treatment
Experimental: Module 1 (90 mg bolus)
90 mg PRT064445 given as a single IV
Combination Product: PRT064445/Apixaban
Other Name: Andexanet

Combination Product: Placebo/Apixaban
Experimental: Module 1 (210 mg bolus)
210 mg PRT064445 given as a single IV bolus
Combination Product: PRT064445/Apixaban
Other Name: Andexanet

Combination Product: Placebo/Apixaban
Experimental: Module 1 (420 mg bolus)
420 mg PRT064445 given as a single IV bolus
Combination Product: PRT064445/Apixaban
Other Name: Andexanet

Combination Product: Placebo/Apixaban
Experimental: Module 1 (420 mg bolus + 180 mg infusion) 4 mg/min
600 mg PRT064445 given as follows: 420 mg IV over ~14 minutes (~30 mg/min), followed by a continuous infusion of 180 mg (4 mg/min over 45 minutes)
Combination Product: PRT064445/Apixaban
Other Name: Andexanet

Combination Product: Placebo/Apixaban
Experimental: Module 1 (420 mg bolus + 180 mg bolus) 30mg/min
600 mg PRT064445 given as follows: up to 420 mg IV over ~14 minutes (~30 mg/min), followed by a second bolus of 180 mg IV over ~6 minutes (~30 mg/min), 45 minutes after completion of the bolus
Combination Product: PRT064445/Apixaban
Other Name: Andexanet

Combination Product: Placebo/Apixaban
Experimental: Module 1 (420 mg bolus + 480 mg infusion) 4mg/min
900 mg PRT064445 given as follows: 420 mg IV, followed by a continuous infusion of 480 mg (4 mg/min over 120 minutes
Combination Product: PRT064445/Apixaban
Other Name: Andexanet

Combination Product: Placebo/Apixaban
Placebo Comparator: Module 1 Placebo
Placebo administered intravenously (IV) as a bolus, two bolus doses or a bolus followed by continuous infusion.
Drug: Placebo



Primary Outcome Measures :
  1. 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)


Secondary Outcome Measures :
  1. 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.

  2. Efficacy: Percent Change From Baseline in Unbound Apixaban Plasma Concentration at 2 Mins Following Andexanet/Placebo Administration [ Time Frame: Baseline to 2 minutes following the end of andexanet/placebo administration ]
    Unbound apixaban concentrations was measured immediately prior to (Baseline) and at 2 mins following andexanet/placebo administration. Unbound plasma concentrations for apixaban were determined by a rapid equilibrium dialysis method followed by Liquid Chromatography-Mass Spectometry assay.

  3. 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. Cmax was taken directly from the raw data.

  4. 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.

  5. 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.

  6. 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

  7. 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

  8. 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 electro chemiluminescent assay. t1/2 was determined by linear regression of the log concentration on the terminal portion of the plasma concentration-time curve.



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Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01758432


Locations
United States, Arizona
Tempe, Arizona, United States, 85283
Sponsors and Collaborators
Portola Pharmaceuticals

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Portola Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01758432     History of Changes
Other Study ID Numbers: 12-502 Module 1
First Posted: January 1, 2013    Key Record Dates
Results First Posted: August 10, 2018
Last Update Posted: September 26, 2018
Last Verified: September 2015

Keywords provided by Portola Pharmaceuticals:
Healthy volunteers

Additional relevant MeSH terms:
Apixaban
Factor Xa Inhibitors
Antithrombins
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anticoagulants