Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Andexanet alfa · 1 trial · 1 indication
To determine the pharmacodynamic (PD) effect of andexanet doses by assessing reversal of rivaroxaban or apixaban anticoagulation measured by chromogenic enzymatic anti-FXa activity assays.
To determine the PD effect of andexanet doses by assessing reversal of rivaroxaban or apixaban anticoagulation measured by chromogenic enzymatic anti-FXa activity assays.
To determine the PD effect of andexanet doses by assessing reversal of rivaroxaban or apixaban anticoagulation measured as thrombin generation potential (including Endogenous Thrombin Potential \[ETP\]).
To determine the PD effect of andexanet doses by assessing reversal of rivaroxaban or apixaban anticoagulation measured as thrombin generation potential (including ETP).
To determine the PD effect of andexanet doses by assessing reversal of rivaroxaban or apixaban anticoagulation measured as thrombin generation potential (including ETP).
To determine the PD effect of andexanet doses by assessing reversal of rivaroxaban or apixaban anticoagulation measured as time to onset of coagulation.
To determine the PD effect of andexanet doses by assessing reversal of rivaroxaban or apixaban anticoagulation measured as time to onset of coagulation.
To determine the PD effect of andexanet doses by assessing reversal of rivaroxaban or apixaban anticoagulation measured as time to onset of coagulation.
To determine anticoagulation by enoxaparin at different time points after andexanet treatment measured by chromogenic enzymatic anti-FXa activity assays.
To determine anticoagulation by enoxaparin at different time points after andexanet treatment measured as thrombin generation potential (including ETP).
| Arm | Type | Description |
|---|---|---|
| Module 1: Rivaroxaban + Andexanet (dose A) | EXPERIMENTAL | Participants will receive once daily dose of 20 mg rivaroxaban from Day -3 to Day -1 to achieve steady state plasma levels. On Day 1, approximately 3 hours before andexanet (dose A) dosing, the participants will receive an additional dose of rivaroxaban. Participants will be further allocated to groups to receive doses of enoxaparin at different time points after the end of andexanet bolus. |
| Module 1: Rivaroxaban + Andexanet (dose B) | EXPERIMENTAL | Participants will receive once daily dose of 20 mg rivaroxaban from Day -3 to Day -1 to achieve steady state plasma levels. On Day 1, approximately 3 hours before andexanet (dose B) dosing, the participants will receive an additional dose of rivaroxaban. |
| Module 1: Rivaroxaban + Andexanet (dose C) | EXPERIMENTAL | Participants will receive once daily dose of 20 mg rivaroxaban from Day -3 to Day -1 to achieve steady state plasma levels. On Day 1, approximately 3 hours before andexanet (dose C) dosing, the participants will receive an additional dose of rivaroxaban. |
| Module 1: Rivaroxaban + Placebo | EXPERIMENTAL | Participants will receive once daily dose of 20 mg rivaroxaban from Day -3 to Day -1 to achieve steady state plasma levels. On Day 1, approximately 3 hours before placebo (equivalent to dose B of andexanet) dosing, the participants will receive an additional dose of rivaroxaban. Participants will be further allocated to groups to receive doses of enoxaparin at different time points after placebo administration. |
| Module 2: Apixaban + Andexanet (dose B) | EXPERIMENTAL | Participants will receive twice daily dose of 5 mg apixaban from Day -3 to Day -1 to achieve steady state plasma levels. On Day 1, approximately 3 hours before andexanet (dose B) dosing, the participants will receive an additional dose of apixaban. Participants will be further allocated to groups to receive doses of enoxaparin at different time points after the end of andexanet bolus. |
| Module 2: Apixaban + Andexanet (dose C) | EXPERIMENTAL | Participants will receive twice daily dose of 5 mg apixaban from Day -3 to Day -1 to achieve steady state plasma levels. On Day 1, approximately 3 hours before andexanet (dose C) dosing, the participants will receive an additional dose of apixaban. |
| Module 2: Apixaban + Andexanet (dose D) | EXPERIMENTAL | Participants will receive twice daily dose of 5 mg apixaban from Day -3 to Day -1 to achieve steady state plasma levels. On Day 1, approximately 3 hours before andexanet (dose D) dosing, the participants will receive an additional dose of apixaban. |
| Module 2: Apixaban + Placebo | EXPERIMENTAL | Participants will receive twice daily dose of 5 mg apixaban from Day -3 to Day -1 to achieve steady state plasma levels. On Day 1, approximately 3 hours before placebo (equivalent to dose B of andexanet) dosing, the participants will receive an additional dose of apixaban. Participants will be further allocated to groups to receive doses of enoxaparin at different time points after placebo administration. |
| Module 3: Rivaroxaban + Andexanet (Dose A) | EXPERIMENTAL | Participants will receive once daily dose of 20 mg rivaroxaban from Day -3 to Day -1 to achieve steady state plasma levels. On Day 1, approximately 3 hours before andexanet (dose A) dosing, the participants will receive an additional dose of rivaroxaban. |
| Module 3: Apixaban + Andexanet (Dose B) | EXPERIMENTAL | Participants will receive twice daily dose of 5 mg apixaban from Day -3 to Day -1 to achieve steady state plasma levels. On Day 1, approximately 3 hours before andexanet (dose B) dosing, the participants will receive an additional dose of apixaban. |
| Module 3: Rivaroxaban + Placebo | EXPERIMENTAL | Participants will receive once daily dose of 20 mg rivaroxaban from Day -3 to Day -1 to achieve steady state plasma levels. On Day 1, approximately 3 hours before placebo (equivalent to dose A of andexanet) dosing, the participants will receive an additional dose of rivaroxaban. |
| Module 3: Apixaban + Placebo | EXPERIMENTAL | Participants will receive twice daily dose of 5 mg apixaban from Day -3 to Day -1 to achieve steady state plasma levels. On Day 1, approximately 3 hours before placebo (equivalent to dose B of andexanet) dosing, the participants will receive an additional dose of apixaban. |
| Module 4: Placebo + Andexanet (dose C) | EXPERIMENTAL | Participants will receive daily dose of one placebo tablet from Day -3 to Day -1. On Day 1, approximately 3 hours before andexanet (dose C) dosing, the participants will receive an additional placebo tablet. |
| Module 4: Placebo + Andexanet (dose B) | EXPERIMENTAL | Participants will receive daily dose of one placebo tablet from Day -3 to Day -1. On Day 1, approximately 3 hours before andexanet (dose B) dosing, the participants will receive an additional placebo tablet. Participants will be further allocated to groups to receive doses of enoxaparin at different time points after the end of andexanet bolus. |
| Name | Type | Description |
|---|---|---|
| Andexanet alfa | DRUG | Andexanet alfa will be administered as an intravenous bolus followed by an infusion, however, in Module 3, only a bolus will be given. |
| Rivaroxaban | DRUG | Rivaroxaban will be administered as an oral tablet. |
| Apixaban | DRUG | Apixaban will be administered as an oral tablet. |
| Enoxaparin | DRUG | Enoxaparin will be administered as a subcutaneous injection. |
| Placebo | OTHER | Placebo will replace andexanet and be given as an IV bolus plus infusion in Modules 1 and 2; in Module 3, placebo will be IV bolus only. In Module 4, an oral placebo tablet will replace rivaroxaban and apixaban. |
Main Inclusion Criteria: * All females must have a negative pregnancy test at the Screening Visit. * Females of childbearing potential must not be lactating and if heterosexually active must agree to use an approved method of highly effective contraception. * Sexually active fertile male participan...
Andexanet alfa is an investigational small molecule developed by AstraZeneca PLC (ticker AZN). It is a TFPI inhibitor that has been studied in a Phase 1 clinical trial in healthy participants. The program's specific therapeutic indications have not been disclosed.
Andexanet alfa targets TFPI, or tissue factor pathway inhibitor. It is classified as a TFPI inhibitor. By inhibiting TFPI, the drug is designed to modulate the tissue factor pathway involved in blood coagulation. This mechanism was evaluated in a Phase 1 study in healthy volunteers.
Andexanet alfa is developed by AstraZeneca PLC, which trades under the ticker AZN. AstraZeneca is the sponsor of the clinical program for this TFPI inhibitor. The drug remains investigational and has not been approved for commercial use.
Andexanet alfa is in Phase 1 clinical development. One Phase 1 trial has been completed, and no active trials are currently listed. The completed study enrolled 191 healthy participants. The drug is investigational and is not approved for any indication.
Andexanet alfa has been studied in one completed Phase 1 trial, NCT07312851, titled A Study to Investigate Andexanet Dosing and the Interaction Between Andexanet and Subsequent Enoxaparin in Healthy Participants. It enrolled 191 healthy volunteers across Germany and the United Kingdom and used a controlled, randomized design.