NCT01758432

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
54

participants targeted

Target at P25-P50 for phase_2 healthy-volunteers

Timeline
Completed

Started Dec 2012

Typical duration for phase_2 healthy-volunteers

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

December 1, 2012

Completed
17 days until next milestone

First Submitted

Initial submission to the registry

December 18, 2012

Completed
14 days until next milestone

First Posted

Study publicly available on registry

January 1, 2013

Completed
2.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 1, 2015

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

September 1, 2015

Completed
2.9 years until next milestone

Results Posted

Study results publicly available

August 10, 2018

Completed
Last Updated

August 7, 2023

Status Verified

August 1, 2023

Enrollment Period

2.8 years

First QC Date

December 18, 2012

Results QC Date

May 30, 2018

Last Update Submit

August 3, 2023

Conditions

Healthy Volunteers

Keywords

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 Apixaban 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 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.

  • Andexanet Total Volume of Distribution (Vss)

    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.

  • +3 more secondary outcomes

Study Arms (7)

Module 1 (90 mg bolus)

EXPERIMENTAL

90 mg PRT064445 given as a single IV

Combination Product: PRT064445/ApixabanCombination Product: Placebo/Apixaban

Module 1 (210 mg bolus)

EXPERIMENTAL

210 mg PRT064445 given as a single IV bolus

Combination Product: PRT064445/ApixabanCombination Product: Placebo/Apixaban

Module 1 (420 mg bolus)

EXPERIMENTAL

420 mg PRT064445 given as a single IV bolus

Combination Product: PRT064445/ApixabanCombination Product: Placebo/Apixaban

Module 1 (420 mg bolus + 180 mg infusion) 4 mg/min

EXPERIMENTAL

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/ApixabanCombination Product: Placebo/Apixaban

Module 1 (420 mg bolus + 180 mg bolus) 30mg/min

EXPERIMENTAL

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/ApixabanCombination Product: Placebo/Apixaban

Module 1 (420 mg bolus + 480 mg infusion) 4mg/min

EXPERIMENTAL

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/ApixabanCombination Product: Placebo/Apixaban

Module 1 Placebo

PLACEBO COMPARATOR

Placebo administered intravenously (IV) as a bolus, two bolus doses or a bolus followed by continuous infusion.

Drug: Placebo

Interventions

PRT064445/ApixabanCOMBINATION_PRODUCT
Also known as: Andexanet
Module 1 (210 mg bolus)Module 1 (420 mg bolus + 180 mg bolus) 30mg/minModule 1 (420 mg bolus + 180 mg infusion) 4 mg/minModule 1 (420 mg bolus + 480 mg infusion) 4mg/minModule 1 (420 mg bolus)Module 1 (90 mg bolus)
Placebo/ApixabanCOMBINATION_PRODUCT
Module 1 (210 mg bolus)Module 1 (420 mg bolus + 180 mg bolus) 30mg/minModule 1 (420 mg bolus + 180 mg infusion) 4 mg/minModule 1 (420 mg bolus + 480 mg infusion) 4mg/minModule 1 (420 mg bolus)Module 1 (90 mg bolus)
PlaceboDRUG
Module 1 Placebo

Eligibility Criteria

Age18 Years - 45 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Unknown Facility

Tempe, Arizona, 85283, United States

Location

Related Publications (1)

  • Siegal D, Lu G, Leeds JM, Karbarz M, Castillo J, Mathur V, Hutchaleelaha A, Sinha U, Kitt M, McClure M, Hollenbach SJ, Curnutte JT, Conley PB, Crowther M. Safety, pharmacokinetics, and reversal of apixaban anticoagulation with andexanet alfa. Blood Adv. 2017 Sep 22;1(21):1827-1838. doi: 10.1182/bloodadvances.2017007112. eCollection 2017 Sep 26.

    PMID: 29296829DERIVED

MeSH Terms

Interventions

PRT064445apixaban

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
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 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)
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

December 18, 2012

First Posted

January 1, 2013

Study Start

December 1, 2012

Primary Completion

September 1, 2015

Study Completion

September 1, 2015

Last Updated

August 7, 2023

Results First Posted

August 10, 2018

Record last verified: 2023-08

Locations

US(1)