Trial Outcomes & Findings for A Healthy Volunteer PK/PD, Safety and Tolerability Study of Andexanet After Betrixaban Dosing (NCT NCT03330457)
NCT ID: NCT03330457
Last Updated: 2023-08-08
Results Overview
Change in Anti-Fxa Activity from baseline to end of bolus
Recruitment status
TERMINATED
Study phase
PHASE2
Target enrollment
18 participants
Primary outcome timeframe
Baseline to end of bolus, approximately 2.5 hours
Results posted on
2023-08-08
Participant Flow
healthy subjects
18 subjects met the inclusion/exclusion criteria; 18 subjects were randomized to two cohorts (6 andexanet and 3 placebo each cohort)
Participant milestones
| Measure |
Cohort 1 Bertrixaban/Andexanet
Andexanet 800 mg, administered as a slow IV bolus after having been dosed to steady-state with betrixaban 80 mg PO once daily (QD) for 7 days
|
Cohort 1 Bertrixaban/Placebo
Placebo, administered as a slow IV bolus after having been dosed to steady-state with betrixaban 80 mg PO once daily (QD) for 7 days
|
Cohort 2 Bertrixaban/Andexanet
Andexanet 800 mg administered as a slow IV bolus at a target rate of approximately 30 mg/min followed by a continuous infusion of up to 8 mg/min for 120 min (960 mg) starting 4 h after the last dose of betrixaban
|
Cohort 2 Bertrixaban/Placebo
Placebo administered as a slow IV bolus at a target rate of approximately 30 mg/min followed by a continuous infusion of up to 8 mg/min for 120 min (960 mg) starting 4 h after the last dose of betrixaban
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
6
|
3
|
6
|
3
|
|
Overall Study
COMPLETED
|
6
|
3
|
6
|
3
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Race and Ethnicity were not collected from any participant.
Baseline characteristics by cohort
| Measure |
Cohort 1 Bertrixaban/Andexanet
n=6 Participants
Andexanet 800 mg, administered as a slow IV bolus after having been dosed to steady-state with betrixaban 80 mg PO once daily (QD) for 7 days
|
Cohort 1 Bertrixaban/Placebo
n=3 Participants
Placebo, administered as a slow IV bolus after having been dosed to steady-state with betrixaban 80 mg PO once daily (QD) for 7 days
|
Cohort 2 Bertrixaban/Andexanet
n=6 Participants
Andexanet 800 mg administered as a slow IV bolus at a target rate of approximately 30 mg/min followed by a continuous infusion of up to 8 mg/min for 120 min (960 mg) starting 4 h after the last dose of betrixaban
|
Cohort 2 Bertrixaban/Placebo
n=3 Participants
Placebo administered as a slow IV bolus at a target rate of approximately 30 mg/min followed by a continuous infusion of up to 8 mg/min for 120 min (960 mg) starting 4 h after the last dose of betrixaban
|
Total
n=18 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
39.5 years
n=6 Participants
|
42.0 years
n=3 Participants
|
31.0 years
n=6 Participants
|
41.0 years
n=3 Participants
|
34.5 years
n=18 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=6 Participants
|
1 Participants
n=3 Participants
|
2 Participants
n=6 Participants
|
2 Participants
n=3 Participants
|
9 Participants
n=18 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=6 Participants
|
2 Participants
n=3 Participants
|
4 Participants
n=6 Participants
|
1 Participants
n=3 Participants
|
9 Participants
n=18 Participants
|
|
Race and Ethnicity Not Collected
|
—
|
—
|
—
|
—
|
0 Participants
Race and Ethnicity were not collected from any participant.
|
PRIMARY outcome
Timeframe: Baseline to end of bolus, approximately 2.5 hoursPopulation: The PD analysis populations will consist of all subjects who have received the requisite treatments and have data at any required time points.
Change in Anti-Fxa Activity from baseline to end of bolus
Outcome measures
| Measure |
Cohort 1 Bertrixaban/Andexanet
n=6 Participants
Andexanet 800 mg, administered as a slow IV bolus after having been dosed to steady-state with betrixaban 80 mg PO once daily (QD) for 7 days
|
Cohort 1 Bertrixaban/Placebo
n=3 Participants
Placebo, administered as a slow IV bolus after having been dosed to steady-state with betrixaban 80 mg PO once daily (QD) for 7 days
|
Cohort 2 Bertrixaban/Andexanet
n=6 Participants
Andexanet 800 mg administered as a slow IV bolus at a target rate of approximately 30 mg/min followed by a continuous infusion of up to 8 mg/min for 120 min (960 mg) starting 4 h after the last dose of betrixaban
|
Cohort 2 Bertrixaban/Placebo
n=3 Participants
Placebo administered as a slow IV bolus at a target rate of approximately 30 mg/min followed by a continuous infusion of up to 8 mg/min for 120 min (960 mg) starting 4 h after the last dose of betrixaban
|
|---|---|---|---|---|
|
Change in Anti-Fxa Activity From Baseline to End of Bolus
|
-23.45 ug/L
Standard Deviation 7.453
|
-1.67 ug/L
Standard Deviation 10.090
|
-26.17 ug/L
Standard Deviation 16.661
|
-2.17 ug/L
Standard Deviation 4.065
|
SECONDARY outcome
Timeframe: Baseline to end of bolus, approximately 2.5 hoursPopulation: The PD analysis populations will consist of all subjects who have received the requisite treatments and have data at any required time points.
Change in Thrombin Generation from baseline to end of bolus
Outcome measures
| Measure |
Cohort 1 Bertrixaban/Andexanet
n=6 Participants
Andexanet 800 mg, administered as a slow IV bolus after having been dosed to steady-state with betrixaban 80 mg PO once daily (QD) for 7 days
|
Cohort 1 Bertrixaban/Placebo
n=3 Participants
Placebo, administered as a slow IV bolus after having been dosed to steady-state with betrixaban 80 mg PO once daily (QD) for 7 days
|
Cohort 2 Bertrixaban/Andexanet
n=6 Participants
Andexanet 800 mg administered as a slow IV bolus at a target rate of approximately 30 mg/min followed by a continuous infusion of up to 8 mg/min for 120 min (960 mg) starting 4 h after the last dose of betrixaban
|
Cohort 2 Bertrixaban/Placebo
n=3 Participants
Placebo administered as a slow IV bolus at a target rate of approximately 30 mg/min followed by a continuous infusion of up to 8 mg/min for 120 min (960 mg) starting 4 h after the last dose of betrixaban
|
|---|---|---|---|---|
|
Change in Thrombin Generation From Baseline to End of Bolus
|
129984.5 RFU
Standard Deviation 39858.49
|
28646.7 RFU
Standard Deviation 43991.66
|
116834.7 RFU
Standard Deviation 49006.72
|
15998.7 RFU
Standard Deviation 18081.07
|
Adverse Events
Cohort 1 Bertrixaban/Andexanet
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Cohort 1 Bertrixaban/Placebo
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Cohort 2 Bertrixaban/Andexanet
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Cohort 2 Bertrixaban/Placebo
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Cohort 1 Bertrixaban/Andexanet
n=6 participants at risk
Andexanet 800 mg, administered as a slow IV bolus after having been dosed to steady-state with betrixaban 80 mg PO once daily (QD) for 7 days
|
Cohort 1 Bertrixaban/Placebo
n=3 participants at risk
Placebo, administered as a slow IV bolus after having been dosed to steady-state with betrixaban 80 mg PO once daily (QD) for 7 days
|
Cohort 2 Bertrixaban/Andexanet
n=6 participants at risk
Andexanet 800 mg administered as a slow IV bolus at a target rate of approximately 30 mg/min followed by a continuous infusion of up to 8 mg/min for 120 min (960 mg) starting 4 h after the last dose of betrixaban
|
Cohort 2 Bertrixaban/Placebo
n=3 participants at risk
Placebo administered as a slow IV bolus at a target rate of approximately 30 mg/min followed by a continuous infusion of up to 8 mg/min for 120 min (960 mg) starting 4 h after the last dose of betrixaban
|
|---|---|---|---|---|
|
Gastrointestinal disorders
Toothache
|
0.00%
0/6 • Study day 1 to 48(+3)
AEs, both serious and non-serious, occurring between signing informed consent and through the Termination Visit will be recorded on the eCRFs. All AEs/SAEs should be monitored until they are resolved, are not expected to improve further, or are determined to be due to a stable or chronic condition or intercurrent illness. Any AE/SAE that occurs with an onset date \> 30 days after study completion and that the Investigator considers to be related to study medication, must be reported to Portola.
|
0.00%
0/3 • Study day 1 to 48(+3)
AEs, both serious and non-serious, occurring between signing informed consent and through the Termination Visit will be recorded on the eCRFs. All AEs/SAEs should be monitored until they are resolved, are not expected to improve further, or are determined to be due to a stable or chronic condition or intercurrent illness. Any AE/SAE that occurs with an onset date \> 30 days after study completion and that the Investigator considers to be related to study medication, must be reported to Portola.
|
16.7%
1/6 • Study day 1 to 48(+3)
AEs, both serious and non-serious, occurring between signing informed consent and through the Termination Visit will be recorded on the eCRFs. All AEs/SAEs should be monitored until they are resolved, are not expected to improve further, or are determined to be due to a stable or chronic condition or intercurrent illness. Any AE/SAE that occurs with an onset date \> 30 days after study completion and that the Investigator considers to be related to study medication, must be reported to Portola.
|
0.00%
0/3 • Study day 1 to 48(+3)
AEs, both serious and non-serious, occurring between signing informed consent and through the Termination Visit will be recorded on the eCRFs. All AEs/SAEs should be monitored until they are resolved, are not expected to improve further, or are determined to be due to a stable or chronic condition or intercurrent illness. Any AE/SAE that occurs with an onset date \> 30 days after study completion and that the Investigator considers to be related to study medication, must be reported to Portola.
|
|
General disorders
Vessel Puncture Site Haemorrhage
|
16.7%
1/6 • Study day 1 to 48(+3)
AEs, both serious and non-serious, occurring between signing informed consent and through the Termination Visit will be recorded on the eCRFs. All AEs/SAEs should be monitored until they are resolved, are not expected to improve further, or are determined to be due to a stable or chronic condition or intercurrent illness. Any AE/SAE that occurs with an onset date \> 30 days after study completion and that the Investigator considers to be related to study medication, must be reported to Portola.
|
0.00%
0/3 • Study day 1 to 48(+3)
AEs, both serious and non-serious, occurring between signing informed consent and through the Termination Visit will be recorded on the eCRFs. All AEs/SAEs should be monitored until they are resolved, are not expected to improve further, or are determined to be due to a stable or chronic condition or intercurrent illness. Any AE/SAE that occurs with an onset date \> 30 days after study completion and that the Investigator considers to be related to study medication, must be reported to Portola.
|
0.00%
0/6 • Study day 1 to 48(+3)
AEs, both serious and non-serious, occurring between signing informed consent and through the Termination Visit will be recorded on the eCRFs. All AEs/SAEs should be monitored until they are resolved, are not expected to improve further, or are determined to be due to a stable or chronic condition or intercurrent illness. Any AE/SAE that occurs with an onset date \> 30 days after study completion and that the Investigator considers to be related to study medication, must be reported to Portola.
|
0.00%
0/3 • Study day 1 to 48(+3)
AEs, both serious and non-serious, occurring between signing informed consent and through the Termination Visit will be recorded on the eCRFs. All AEs/SAEs should be monitored until they are resolved, are not expected to improve further, or are determined to be due to a stable or chronic condition or intercurrent illness. Any AE/SAE that occurs with an onset date \> 30 days after study completion and that the Investigator considers to be related to study medication, must be reported to Portola.
|
|
Injury, poisoning and procedural complications
Infusion Related Reaction
|
0.00%
0/6 • Study day 1 to 48(+3)
AEs, both serious and non-serious, occurring between signing informed consent and through the Termination Visit will be recorded on the eCRFs. All AEs/SAEs should be monitored until they are resolved, are not expected to improve further, or are determined to be due to a stable or chronic condition or intercurrent illness. Any AE/SAE that occurs with an onset date \> 30 days after study completion and that the Investigator considers to be related to study medication, must be reported to Portola.
|
0.00%
0/3 • Study day 1 to 48(+3)
AEs, both serious and non-serious, occurring between signing informed consent and through the Termination Visit will be recorded on the eCRFs. All AEs/SAEs should be monitored until they are resolved, are not expected to improve further, or are determined to be due to a stable or chronic condition or intercurrent illness. Any AE/SAE that occurs with an onset date \> 30 days after study completion and that the Investigator considers to be related to study medication, must be reported to Portola.
|
16.7%
1/6 • Study day 1 to 48(+3)
AEs, both serious and non-serious, occurring between signing informed consent and through the Termination Visit will be recorded on the eCRFs. All AEs/SAEs should be monitored until they are resolved, are not expected to improve further, or are determined to be due to a stable or chronic condition or intercurrent illness. Any AE/SAE that occurs with an onset date \> 30 days after study completion and that the Investigator considers to be related to study medication, must be reported to Portola.
|
0.00%
0/3 • Study day 1 to 48(+3)
AEs, both serious and non-serious, occurring between signing informed consent and through the Termination Visit will be recorded on the eCRFs. All AEs/SAEs should be monitored until they are resolved, are not expected to improve further, or are determined to be due to a stable or chronic condition or intercurrent illness. Any AE/SAE that occurs with an onset date \> 30 days after study completion and that the Investigator considers to be related to study medication, must be reported to Portola.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place