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 2 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: NCT03578146
Recruitment Status : Completed
First Posted : July 6, 2018
Results First Posted : September 5, 2018
Last Update Posted : October 2, 2018
Sponsor:
Information provided by (Responsible Party):
Portola Pharmaceuticals

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Healthy Volunteers
Interventions Combination Product: PRT064445/Rivaroxaban
Combination Product: Placebo/Rivaroxaban
Drug: Placebo
Enrollment 48
Recruitment Details Subject recruitment occurred at investigative site in the US between March 2013 through April 2014
Pre-assignment Details Rivaroxaban was administered orally at 20 mg once daily for 6 days to steady-state in an open label fashion. Subjects were then randomized to receive study treatment (andexanet or placebo) intravenously at different doses/dose regimens on Day 6, all bolus doses administered such that they ended at 3 hours after the last dose of rivaroxaban.
Arm/Group Title Module 2 Placebo 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)
Hide Arm/Group Description Placebo administered intravenously (IV) as a bolus or a bolus followed by continuous infusion 210 mg andexanet IV bolus administered over 7 minutes (~30 mg/min) 420 mg andexanet IV bolus administered over 14 minutes (~30 mg/min) 600 mg andexanet IV bolus administered over 20 minutes (~30 mg/min) 720 mg IV bolus administered over 24 minutes [~30 mg/min] followed by 240 mg continuous IV infusion [4 mg/min over 60 min) 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]
Period Title: Overall Study
Started 16 6 6 6 6 8
Completed 15 5 5 6 6 5
Not Completed 1 1 1 0 0 3
Reason Not Completed
Did Not Receive Treatment             1             0             0             0             0             2
Lost to Follow-up             0             1             1             0             0             1
Arm/Group Title Module 2 Placebo 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) Total
Hide Arm/Group Description Placebo administered intravenously (IV) as a bolus or a bolus followed by continuous infusion 210 mg andexanet IV bolus administered over 7 minutes (~30 mg/min) 420 mg andexanet IV bolus administered over 14 minutes (~30 mg/min) 600 mg andexanet IV bolus administered over 20 minutes (~30 mg/min) 720 mg IV bolus administered over 24 minutes [~30 mg/min] followed by 240 mg continuous IV infusion [4 mg/min over 60 min) 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] Total of all reporting groups
Overall Number of Baseline Participants 16 6 6 6 6 8 48
Hide Baseline Analysis Population Description
48 subjects were enrolled in this study. Three subjects received rivaroxaban but were discontinued prior to receiving andexanet/placebo due to problems with the infusion pumps observed in prior subjects in the cohort and these subjects were replaced.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 16 participants 6 participants 6 participants 6 participants 6 participants 8 participants 48 participants
38.2  (6.69) 35.7  (3.33) 35.7  (9.07) 34.2  (7.25) 35.2  (5.04) 32.9  (8.10) 35.8  (6.79)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 16 participants 6 participants 6 participants 6 participants 6 participants 8 participants 48 participants
Female
3
  18.8%
0
   0.0%
1
  16.7%
4
  66.7%
0
   0.0%
1
  12.5%
9
  18.8%
Male
13
  81.3%
6
 100.0%
5
  83.3%
2
  33.3%
6
 100.0%
7
  87.5%
39
  81.3%
1.Primary Outcome
Title Efficacy: Percent Change From Baseline in Anti-fXa Activity at 2 Mins Following Andexanet/Placebo Administration
Hide Description 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)
Time Frame Baseline to 2 minutes following the end of andexanet/placebo administration
Hide Outcome Measure Data
Hide Analysis Population Description
45 subjects who received andexanet or placebo were included in the pharmacodynamics (PD) analysis
Arm/Group Title Module 2 Placebo 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)
Hide Arm/Group Description:
Placebo administered intravenously (IV) as a bolus or a bolus followed by continuous infusion
210 mg andexanet IV bolus administered over 7 minutes (~30 mg/min)
420 mg andexanet IV bolus administered over 14 minutes (~30 mg/min)
600 mg andexanet IV bolus administered over 20 minutes (~30 mg/min)
720 mg IV bolus administered over 24 minutes [~30 mg/min] followed by 240 mg continuous IV infusion [4 mg/min over 60 min)
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]
Overall Number of Participants Analyzed 15 6 6 6 6 6
Mean (Standard Deviation)
Unit of Measure: Percent change in anti-fXa activity
22.37  (42.247) -18.09  (23.922) -50.59  (22.056) -75.26  (19.072) -88.91  (6.098) -92.72  (3.084)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Module 2 Placebo, Module 2 (210 mg)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0121
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Means (Difference)
Estimated Value -73.14
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Module 2 Placebo, Module 2 (420 mg)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Means (Difference)
Estimated Value -153.99
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Module 2 Placebo, Module 2 (600 mg)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Means (Difference)
Estimated Value -189.57
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Module 2 Placebo, Module 2 (720 mg Bolus + 240 mg Infusion)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Means (Difference)
Estimated Value -239.3
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Module 2 Placebo, Module 2 (800 mg Bolus + 960 mg Infusion)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Means (Difference)
Estimated Value -231.12
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Efficacy: Percent Change From Baseline in Thrombin Generation at 2 Mins Following Andexanet/Placebo Administration
Hide Description 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.
Time Frame Baseline to 2 minutes following the end of andexanet/placebo administration
Hide Outcome Measure Data
Hide Analysis Population Description
45 subjects who received andexanet or placebo were included in the PD analysis
Arm/Group Title Module 2 Placebo 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)
Hide Arm/Group Description:
Placebo administered intravenously (IV) as a bolus or a bolus followed by continuous infusion
210 mg andexanet IV bolus administered over 7 minutes (~30 mg/min)
420 mg andexanet IV bolus administered over 14 minutes (~30 mg/min)
600 mg andexanet IV bolus administered over 20 minutes (~30 mg/min)
720 mg IV bolus administered over 24 minutes [~30 mg/min] followed by 240 mg continuous IV infusion [4 mg/min over 60 min)
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]
Overall Number of Participants Analyzed 15 6 6 6 6 6
Mean (Standard Deviation)
Unit of Measure: Percent change in thrombin generation
14.00  (29.267) 107.47  (48.977) 167.67  (36.568) 246.02  (135.387) 513.85  (285.992) 559.14  (288.258)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Module 2 Placebo, Module 2 (210 mg)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Means (Difference)
Estimated Value 52837.94
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Module 2 Placebo, Module 2 (420 mg)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Means (Difference)
Estimated Value 110388.3
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Module 2 Placebo, Module 2 (600 mg)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Means (Difference)
Estimated Value 163880.7
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Module 2 Placebo, Module 2 (720 mg Bolus + 240 mg Infusion)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Means (Difference)
Estimated Value 263236.5
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Module 2 Placebo, Module 2 (800 mg Bolus + 960 mg Infusion)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Means (Difference)
Estimated Value 270297.2
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Efficacy: Percent Change From Baseline in Unbound Rivaroaxaban Plasma Concentration at 2 Mins Following Andexanet/Placebo Administration
Hide Description 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.
Time Frame Baseline to 2 minutes following the end of andexanet/placebo administration
Hide Outcome Measure Data
Hide Analysis Population Description
45 subjects who received rivaroxaban were included in the rivaroxaban pharmacokinetics (PK) analysis
Arm/Group Title Module 2 Placebo 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)
Hide Arm/Group Description:
Placebo administered intravenously (IV) as a bolus or a bolus followed by continuous infusion
210 mg andexanet IV bolus administered over 7 minutes (~30 mg/min)
420 mg andexanet IV bolus administered over 14 minutes (~30 mg/min)
600 mg andexanet IV bolus administered over 20 minutes (~30 mg/min)
720 mg IV bolus administered over 24 minutes [~30 mg/min] followed by 240 mg continuous IV infusion [4 mg/min over 60 min)
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]
Overall Number of Participants Analyzed 15 6 6 6 6 6
Mean (Standard Deviation)
Unit of Measure: Percent change in unbound apixaban conc.
-11  (11) 34  (22) 52  (18) 75  (16) 67  (24) 80  (12)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Module 2 Placebo, Module 2 (210 mg)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Means (Difference)
Estimated Value -9.91
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Module 2 Placebo, Module 2 (420 mg)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Means (Difference)
Estimated Value -15.06
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Module 2 Placebo, Module 2 (600 mg)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Means (Difference)
Estimated Value -17.53
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Module 2 Placebo, Module 2 (720 mg Bolus + 240 mg Infusion)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Means (Difference)
Estimated Value -17.05
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Module 2 Placebo, Module 2 (800 mg Bolus + 960 mg Infusion)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Means (Difference)
Estimated Value -19.33
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Andexanet Maximum Observed Plasma Concentration (Cmax)
Hide Description Plasma concentrations of andexanet was determined using a validated method that involved analysis of citrated human plasma by an electrochemiluminescent assay.
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.
Hide Outcome Measure Data
Hide Analysis Population Description
30 subjects who received andexanet were included in the andexanet PK analysis
Arm/Group Title Module 2 Placebo 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)
Hide Arm/Group Description:
Placebo administered intravenously (IV) as a bolus or a bolus followed by continuous infusion
210 mg andexanet IV bolus administered over 7 minutes (~30 mg/min)
420 mg andexanet IV bolus administered over 14 minutes (~30 mg/min)
600 mg andexanet IV bolus administered over 20 minutes (~30 mg/min)
720 mg IV bolus administered over 24 minutes [~30 mg/min] followed by 240 mg continuous IV infusion [4 mg/min over 60 min)
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]
Overall Number of Participants Analyzed 15 6 6 6 6 6
Mean (Standard Deviation)
Unit of Measure: ng/mL
NA [1]   (NA) 50400  (12100) 105000  (28500) 110000  (7070) 123000  (28900) 161000  (40400)
[1]
Andexanet was not administered (placebo group)
5.Secondary Outcome
Title Andexanet Area Under the Drug Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC0-inf )
Hide Description 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
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.
Hide Outcome Measure Data
Hide Analysis Population Description
30 subjects who received andexanet were included in the andexanet PK analysis
Arm/Group Title Module 2 Placebo 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)
Hide Arm/Group Description:
Placebo administered intravenously (IV) as a bolus or a bolus followed by continuous infusion
210 mg andexanet IV bolus administered over 7 minutes (~30 mg/min)
420 mg andexanet IV bolus administered over 14 minutes (~30 mg/min)
600 mg andexanet IV bolus administered over 20 minutes (~30 mg/min)
720 mg IV bolus administered over 24 minutes [~30 mg/min] followed by 240 mg continuous IV infusion [4 mg/min over 60 min)
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]
Overall Number of Participants Analyzed 15 6 6 6 6 6
Mean (Standard Deviation)
Unit of Measure: ng*hr/mL
NA [1]   (NA) 51400  (7520) 111000  (35900) 133000  (11500) 216000  (41300) 429000  (85300)
[1]
Andexanet was not administered (placebo group)
6.Secondary Outcome
Title Andexanet Time of Maximum Observed Plasma Concentration (Tmax)
Hide Description 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.
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.
Hide Outcome Measure Data
Hide Analysis Population Description
30 subjects who received andexanet were included in the andexanet PK analysis
Arm/Group Title Module 2 Placebo 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)
Hide Arm/Group Description:
Placebo administered intravenously (IV) as a bolus or a bolus followed by continuous infusion
210 mg andexanet IV bolus administered over 7 minutes (~30 mg/min)
420 mg andexanet IV bolus administered over 14 minutes (~30 mg/min)
600 mg andexanet IV bolus administered over 20 minutes (~30 mg/min)
720 mg IV bolus administered over 24 minutes [~30 mg/min] followed by 240 mg continuous IV infusion [4 mg/min over 60 min)
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]
Overall Number of Participants Analyzed 15 6 6 6 6 6
Median (Full Range)
Unit of Measure: hr
NA [1] 
(NA to NA)
0.17
(0.16 to 0.41)
0.36
(0.29 to 0.52)
0.51
(0.39 to 0.83)
0.56
(0.44 to 0.70)
0.52
(0.49 to 0.73)
[1]
Andexanet was not administered (placebo group)
7.Secondary Outcome
Title Andexanet Apparent Terminal Elimination Half-life (t1/2)
Hide Description 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.
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.
Hide Outcome Measure Data
Hide Analysis Population Description
30 subjects who received andexanet were included in the andexanet PK analysis
Arm/Group Title Module 2 Placebo 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)
Hide Arm/Group Description:
Placebo administered intravenously (IV) as a bolus or a bolus followed by continuous infusion
210 mg andexanet IV bolus administered over 7 minutes (~30 mg/min)
420 mg andexanet IV bolus administered over 14 minutes (~30 mg/min)
600 mg andexanet IV bolus administered over 20 minutes (~30 mg/min)
720 mg IV bolus administered over 24 minutes [~30 mg/min] followed by 240 mg continuous IV infusion [4 mg/min over 60 min)
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]
Overall Number of Participants Analyzed 15 6 6 6 6 6
Mean (Standard Deviation)
Unit of Measure: hr
NA [1]   (NA) 4.97  (0.74) 3.91  (0.43) 4.54  (1.65) 6.47  (3.59) 4.45  (0.58)
[1]
Andexanet was not administered (placebo group)
8.Secondary Outcome
Title Andexanet Total Systemic Clearance (CL)
Hide Description 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
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.
Hide Outcome Measure Data
Hide Analysis Population Description
30 subjects who received andexanet were included in the andexanet PK analysis
Arm/Group Title Module 2 Placebo 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)
Hide Arm/Group Description:
Placebo administered intravenously (IV) as a bolus or a bolus followed by continuous infusion
210 mg andexanet IV bolus administered over 7 minutes (~30 mg/min)
420 mg andexanet IV bolus administered over 14 minutes (~30 mg/min)
600 mg andexanet IV bolus administered over 20 minutes (~30 mg/min)
720 mg IV bolus administered over 24 minutes [~30 mg/min] followed by 240 mg continuous IV infusion [4 mg/min over 60 min)
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]
Overall Number of Participants Analyzed 15 6 6 6 6 6
Mean (Standard Deviation)
Unit of Measure: L/hr
NA [1]   (NA) 4.15  (0.556) 4.18  (1.51) 4.53  (0.399) 4.58  (0.837) 4.23  (0.808)
[1]
Andexanet was not administered (placebo group)
9.Secondary Outcome
Title Andexanet Total Volume of Distribution (Vss)
Hide Description 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.
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.
Hide Outcome Measure Data
Hide Analysis Population Description
30 subjects who received andexanet were included in the andexanet PK analysis
Arm/Group Title Module 2 Placebo 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)
Hide Arm/Group Description:
Placebo administered intravenously (IV) as a bolus or a bolus followed by continuous infusion
210 mg andexanet IV bolus administered over 7 minutes (~30 mg/min)
420 mg andexanet IV bolus administered over 14 minutes (~30 mg/min)
600 mg andexanet IV bolus administered over 20 minutes (~30 mg/min)
720 mg IV bolus administered over 24 minutes [~30 mg/min] followed by 240 mg continuous IV infusion [4 mg/min over 60 min)
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]
Overall Number of Participants Analyzed 15 6 6 6 6 6
Mean (Standard Deviation)
Unit of Measure: L
NA [1]   (NA) 5.23  (1.09) 4.65  (1.69) 5.39  (0.546) 4.17  (0.797) 3.34  (1.20)
[1]
Andexanet was not administered (placebo group)
Time Frame ~7 weeks
Adverse Event Reporting Description Only subjects who received at least one dose of study drug were included in the safety analysis.
 
Arm/Group Title Module 2 Placebo 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)
Hide Arm/Group Description Placebo administered intravenously (IV) as a bolus or a bolus followed by continuous infusion 210 mg andexanet IV bolus administered over 7 minutes (~30 mg/min) 420 mg andexanet IV bolus administered over 14 minutes (~30 mg/min) 600 mg andexanet IV bolus administered over 20 minutes (~30 mg/min) 720 mg IV bolus administered over 24 minutes [~30 mg/min] followed by 240 mg continuous IV infusion [4 mg/min over 60 min) 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]
All-Cause Mortality
Module 2 Placebo 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)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Module 2 Placebo 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)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/15 (0.00%)   0/6 (0.00%)   0/6 (0.00%)   0/6 (0.00%)   0/6 (0.00%)   0/6 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 3%
Module 2 Placebo 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)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   12/15 (80.00%)   4/6 (66.67%)   3/6 (50.00%)   5/6 (83.33%)   5/6 (83.33%)   5/6 (83.33%) 
Blood and lymphatic system disorders             
Anaemia  1  1/15 (6.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%) 
Gastrointestinal disorders             
Abdominal pain upper  1  1/15 (6.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%) 
Abdominal tenderness  1  0/15 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%) 
Constipation  1  1/15 (6.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%) 
Diarrhoea  1  0/15 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%) 
Dry mouth  1  0/15 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%) 
Nausea  1  1/15 (6.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%) 
Toothache  1  0/15 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%) 
General disorders             
Catheter site haemorrhage  1  0/15 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%) 
Catheter site phlebitis  1  0/15 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%) 
Fatigue  1  0/15 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%) 
Feeling cold  1  1/15 (6.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%) 
Feeling hot  1  0/15 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%) 
Oedema peripheral  1  0/15 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%) 
Tenderness  1  1/15 (6.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%) 
Vessel puncture site haematoma  1  1/15 (6.67%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%) 
Vessel puncture site pain  1  1/15 (6.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%) 
Vessel puncture site reaction  1  0/15 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  1/6 (16.67%)  0/6 (0.00%) 
Vessel puncture site swelling  1  1/15 (6.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%) 
Infections and infestations             
Respiratory tract infection  1  0/15 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%) 
Upper respiratory tract infection  1  0/15 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%) 
Viral infection  1  0/15 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%) 
Injury, poisoning and procedural complications             
Infusion-related reaction  1  1/15 (6.67%)  1/6 (16.67%)  2/6 (33.33%)  2/6 (33.33%)  3/6 (50.00%)  2/6 (33.33%) 
Post procedural haematoma  1  3/15 (20.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  2/6 (33.33%)  0/6 (0.00%) 
Post procedural swelling  1  0/15 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%) 
Procedural site reaction  1  2/15 (13.33%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%) 
Thermal burn  1  0/15 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%) 
Wound dehiscence  1  0/15 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%) 
Investigations             
Blood creatine phosphokinase increased  1  1/15 (6.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%) 
Musculoskeletal and connective tissue disorders             
Musculoskeletal chest pain  1  0/15 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%) 
Pain in extremity  1  0/15 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%) 
Nervous system disorders             
Dizziness  1  1/15 (6.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%) 
Dizziness postural  1  2/15 (13.33%)  0/6 (0.00%)  1/6 (16.67%)  2/6 (33.33%)  1/6 (16.67%)  0/6 (0.00%) 
Headache  1  3/15 (20.00%)  0/6 (0.00%)  1/6 (16.67%)  2/6 (33.33%)  0/6 (0.00%)  2/6 (33.33%) 
Paraesthesia  1  1/15 (6.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%) 
Somnolence  1  0/15 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%) 
Tunnel vision  1  0/15 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%) 
Psychiatric disorders             
Anxiety  1  1/15 (6.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%) 
Reproductive system and breast disorders             
Menorrhagia  1  1/15 (6.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%) 
Respiratory, thoracic and mediastinal disorders             
Haemoptysis  1  0/15 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%) 
Oropharyngeal pain  1  1/15 (6.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%) 
Skin and subcutaneous tissue disorders             
Dermatitis contact  1  3/15 (20.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%) 
Ecchymosis  1  1/15 (6.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%) 
Hyperhidrosis  1  1/15 (6.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%) 
Ingrowing nail  1  1/15 (6.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%) 
Papule  1  1/15 (6.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%) 
Pruritus  1  1/15 (6.67%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%) 
Pruritus generalised  1  0/15 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%)  0/6 (0.00%) 
Rash papular  1  0/15 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  0/6 (0.00%)  1/6 (16.67%)  0/6 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (15.0)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Conducted in healthy volunteers at Clinical Research Organization.
Results Point of Contact
Name/Title: Head of Clinical Development
Organization: Portola Pharmaceuticals, Inc.
Phone: 650-246-7000
Responsible Party: Portola Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03578146     History of Changes
Other Study ID Numbers: 12-502 Module 2
First Submitted: May 15, 2018
First Posted: July 6, 2018
Results First Submitted: July 10, 2018
Results First Posted: September 5, 2018
Last Update Posted: October 2, 2018