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)

NCT03578146 | Completed Phase 2 Results DMC

• 1 other identifier: 12-502 Module 2
• Study Type: interventional
• Target: 48
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Healthy Volunteers

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (8)

• Efficacy: Percent Change From Baseline in Thrombin Generation at 2 Mins Following Andexanet/Placebo Administration

  Baseline to 2 minutes following the end of andexanet/placebo administration

• Efficacy: Percent Change From Baseline in Unbound Rivaroaxaban Plasma Concentration at 2 Mins Following Andexanet/Placebo Administration

  Baseline to 2 minutes following the end of andexanet/placebo administration

• Andexanet Maximum Observed Plasma Concentration (Cmax)

  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 Area Under the Drug Concentration-time Curve From Time 0 Extrapolated to Infinity (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.

• Andexanet Time of Maximum Observed Plasma Concentration (Tmax)

  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.

Study Arms (6)

Module 2 (210 mg)

EXPERIMENTAL

210 mg andexanet IV bolus administered over 7 minutes (\~30 mg/min)

Combination Product: PRT064445/Rivaroxaban; Combination Product: Placebo/Rivaroxaban

Module 2 (420 mg)

EXPERIMENTAL

420 mg andexanet IV bolus administered over 14 minutes (\~30 mg/min)

Combination Product: PRT064445/Rivaroxaban; Combination Product: Placebo/Rivaroxaban

Module 2 (600 mg)

EXPERIMENTAL

600 mg andexanet IV bolus administered over 20 minutes (\~30 mg/min)

Combination Product: PRT064445/Rivaroxaban; Combination Product: Placebo/Rivaroxaban

Module 2 (720 mg bolus + 240 mg infusion)

EXPERIMENTAL

720 mg IV bolus administered over 24 minutes \[\~30 mg/min\] followed by 240 mg continuous IV infusion \[4 mg/min over 60 min)

Combination Product: PRT064445/Rivaroxaban; Combination Product: Placebo/Rivaroxaban

Module 2 (800 mg bolus + 960 mg infusion)

EXPERIMENTAL

800 mg IV bolus administered over 26.7 minutes \[\~30 mg/min\] followed by 960 mg continuous IV infusion \[8 mg/min over 120 min\]

Combination Product: PRT064445/Rivaroxaban; Combination Product: Placebo/Rivaroxaban

Module 2 Placebo

EXPERIMENTAL

Placebo administered intravenously (IV) as a bolus or a bolus followed by continuous fusion.

Drug: Placebo

Interventions

PRT064445/Rivaroxaban COMBINATION_PRODUCT

Also known as: Andexanet

Module 2 (210 mg); Module 2 (420 mg); Module 2 (600 mg); Module 2 (720 mg bolus + 240 mg infusion); Module 2 (800 mg bolus + 960 mg infusion)

Placebo/Rivaroxaban COMBINATION_PRODUCT

Module 2 (210 mg); Module 2 (420 mg); Module 2 (600 mg); Module 2 (720 mg bolus + 240 mg infusion); Module 2 (800 mg bolus + 960 mg infusion)

Placebo DRUG

Module 2 Placebo

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy men or women between the ages of 18 and 45 years old

You may not qualify if:

• 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.

Sponsors & Collaborators

• Portola Pharmaceuticals: lead

Related Publications (1)

• Lu G, Conley PB, Leeds JM, Karbarz MJ, Levy GG, Mathur VS, Castillo J, Crowther M, Curnutte JT. A phase 2 PK/PD study of andexanet alfa for reversal of rivaroxaban and edoxaban anticoagulation in healthy volunteers. Blood Adv. 2020 Feb 25;4(4):728-739. doi: 10.1182/bloodadvances.2019000885.

  PMID: 32092140 DERIVED

MeSH Terms

Interventions

PRT064445; Rivaroxaban

Intervention Hierarchy (Ancestors)

Thiophenes; Sulfur Compounds; Organic Chemicals; Morpholines; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Head of Clinical Development
• Organization: Portola Pharmaceuticals, Inc.

650-246-7000

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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)

Study Record Dates

• First Submitted: May 15, 2018
• First Posted: July 6, 2018
• Study Start: December 1, 2012
• Primary Completion: September 1, 2015
• Study Completion: September 1, 2015
• Last Updated: February 22, 2023
• Results First Posted: September 5, 2018

Record last verified: 2023-02