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)

Healthy Volunteers Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03578146
• Other study ID #: 12-502 Module 2
• Status: Completed
• Phase: Phase 2
• Start date: December 2012
• Est. completion date: September 2015

Study information

• Verified date: February 2023
• Source: Alexion Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 48
• Est. completion date: September 2015
• Est. primary completion date: September 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 45 Years

Eligibility

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.

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

Combination Product:
• PRT064445/Rivaroxaban

• Placebo/Rivaroxaban

Drug:
• Placebo

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Portola Pharmaceuticals

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Efficacy: Percent Change From Baseline in Anti-fXa Activity at 2 Mins Following 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	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.	Baseline to 2 minutes following the end of andexanet/placebo administration
Secondary	Efficacy: Percent Change From Baseline in Unbound Rivaroaxaban Plasma Concentration at 2 Mins Following 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
Secondary	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.	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.
Secondary	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	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.
Secondary	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.	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.
Secondary	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.	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.
Secondary	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, 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.
Secondary	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.	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.