Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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

Tracking Information
First Submitted Date  ICMJE May 15, 2018
First Posted Date  ICMJE June 11, 2018
Results First Submitted Date  ICMJE June 8, 2018
Results First Posted Date  ICMJE August 13, 2018
Last Update Posted Date September 26, 2018
Study Start Date  ICMJE December 2012
Actual Primary Completion Date September 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 12, 2018)
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)
Original Primary Outcome Measures  ICMJE
 (submitted: June 7, 2018)
Efficacy: Reversal of anticoagulant effect as measured by reductions in anti-fXa activity [ Time Frame: From the time immediately prior to andexanet/placebo administration to 14.5 hours after 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)
Change History Complete list of historical versions of study NCT03551730 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 12, 2018)
  • 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.
  • 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.
  • 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
  • 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.
  • 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.
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: June 7, 2018)
  • Efficacy: Reversal of anticoagulant effect as measured by increases in thrombin generation [ Time Frame: From the time immediately prior to andexanet/placebo administration to 14.5 hours after 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.
  • Andexanet Cmax [ Time Frame: From the time immediately prior to andexanet/placebo administration to 14.5 hours after andexanet/placebo administration ]
    Plasma concentrations of andexanet was determined using a validated method that involved analysis of citrated human plasma by an electrochemiluminescent assay. Maximum observed plasma concentration was taken directly from the raw data.
  • Andexanet AUC0-inf [ Time Frame: From the time immediately prior to andexanet/placebo administration to 14.5 hours after andexanet/placebo administration ]
    Plasma concentrations of andexanet was determined using a validated method that involved analysis of citrated human plasma by an electrochemiluminescent assay. Area under the drug concentration-time curve from time 0 extrapolated to infinity (AUC0-inf) was calculated using a non-compartmental approach
  • Andexanet tmax [ Time Frame: From the time immediately prior to andexanet/placebo administration to 14.5 hours after andexanet/placebo administration ]
    Plasma concentrations of andexanet was determined using a validated method that involved analysis of citrated human plasma by an electrochemiluminescent assay. Time of the maximum observed plasma concentration was taken directly from the raw data.
  • Andexanet t1/2 [ Time Frame: From the time immediately prior to andexanet/placebo administration to 14.5 hours after andexanet/placebo administration ]
    Plasma concentrations of andexanet was determined using a validated method that involved analysis of citrated human plasma by an electrochemiluminescent assay. Apparent terminal elimination half-life (t1/2) determined by linear regression of the log concentration on the terminal portion of the plasma concentration-time curve.
  • Andexanet CL [ Time Frame: From the time immediately prior to andexanet/placebo administration to 14.5 hours after andexanet/placebo administration ]
    Plasma concentrations of andexanet was determined using a validated method that involved analysis of citrated human plasma by an electrochemiluminescent assay. Total systemic clearance (CL) was calculated using a non-compartmental approach.
  • Andexanet Vss [ Time Frame: From the time immediately prior to andexanet/placebo administration to 14.5 hours after andexanet/placebo administration ]
    Plasma concentrations of andexanet was determined using a validated method that involved analysis of citrated human plasma by an electrochemiluminescent assay. Total volume of distribution (Vss) was calculated using a non-compartmental approach.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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)
Official Title  ICMJE 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.
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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE 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
Condition  ICMJE Healthy Volunteers
Intervention  ICMJE
  • Combination Product: PRT064445/Enoxaparin
    Other Name: Andexanet
  • Combination Product: Placebo/Enoxaparin
  • Drug: Placebo
Study Arms  ICMJE
  • Experimental: Module 3 (210 mg bolus) original
    210 mg PRT064445 given as a single IV bolus
    Interventions:
    • Combination Product: PRT064445/Enoxaparin
    • Combination Product: Placebo/Enoxaparin
  • Experimental: Module 3 (420 mg bolus) original
    420 mg PRT064445 given as a single IV bolus
    Interventions:
    • Combination Product: PRT064445/Enoxaparin
    • Combination Product: Placebo/Enoxaparin
  • Experimental: Module 3 (210 mg) lyophilized
    210 mg PRT064445 (lyophilized formulation) given as a single IV bolus
    Interventions:
    • Combination Product: PRT064445/Enoxaparin
    • Combination Product: Placebo/Enoxaparin
  • Placebo Comparator: Module 3 Placebo
    Placebo administered intravenously (IV) as a bolus.
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: August 24, 2018)
27
Original Actual Enrollment  ICMJE
 (submitted: June 7, 2018)
54
Actual Study Completion Date  ICMJE September 2015
Actual Primary Completion Date September 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 45 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03551730
Other Study ID Numbers  ICMJE 12-502 Module 3
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Portola Pharmaceuticals
Study Sponsor  ICMJE Portola Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Portola Pharmaceuticals
Verification Date September 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP