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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 3 of 4)

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ClinicalTrials.gov Identifier: NCT03551730
Recruitment Status : Completed
First Posted : June 11, 2018
Results First Posted : August 13, 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/Enoxaparin Combination Product: Placebo/Enoxaparin Drug: Placebo Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 27 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 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 (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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.
Study Start Date : December 2012
Actual Primary Completion Date : September 2015
Actual Study Completion Date : September 2015

Arm Intervention/treatment
Experimental: Module 3 (210 mg bolus) original
210 mg PRT064445 given as a single IV bolus
Combination Product: PRT064445/Enoxaparin
Other Name: Andexanet

Combination Product: Placebo/Enoxaparin
Experimental: Module 3 (420 mg bolus) original
420 mg PRT064445 given as a single IV bolus
Combination Product: PRT064445/Enoxaparin
Other Name: Andexanet

Combination Product: Placebo/Enoxaparin
Experimental: Module 3 (210 mg) lyophilized
210 mg PRT064445 (lyophilized formulation) given as a single IV bolus
Combination Product: PRT064445/Enoxaparin
Other Name: Andexanet

Combination Product: Placebo/Enoxaparin
Placebo Comparator: Module 3 Placebo
Placebo administered intravenously (IV) as a bolus.
Drug: Placebo



Primary Outcome Measures :
  1. 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)


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. 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.

  3. 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

  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 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.

  6. 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.

  7. 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.



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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): NCT03551730


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

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Responsible Party: Portola Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03551730     History of Changes
Other Study ID Numbers: 12-502 Module 3
First Posted: June 11, 2018    Key Record Dates
Results First Posted: August 13, 2018
Last Update Posted: September 26, 2018
Last Verified: September 2015