BleedingPhase 2NCT03330457
A Healthy Volunteer PK/PD, Safety and Tolerability Study of Andexanet After Betrixaban Dosing
A Phase 2 study testing Andexanet alfa (bolus), Betrixaban 80 mg PO QD and Andexanet alfa (infusion IV) in people with Bleeding, run by Portola Pharmaceuticals at 1 site in United States.
Trial summary
This is a randomized, double-blind, single center study in healthy volunteers dosed to steady state with betrixaban, designed to (1) Determine an andexanet dosing regimen required to reverse anticoagulant activity of betrixaban in healthy subjects, (2) Assess the safety and tolerability of andexanet vs. Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Bleeding
- What is being tested?
- Andexanet alfa (bolus), Betrixaban 80 mg PO QD and Andexanet alfa (infusion IV)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- 6 Aug 2015to 22 Feb 2016
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- The subject is a healthy man or woman between the ages of 18 and 45 years old, inclusive, who agrees to comply with the contraception and reproduction restrictions of the study:
- Men must be using two acceptable methods of contraception, at least one of which must be a barrier method (e.g., spermicidal gel plus condom) for the entire duration of the study and for at least three months following last study drug administration, and refrain from attempting to father a child or donating sperm in the three (3) months following the last study drug administration. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
- OR Men who report surgical sterilization (e.g., bilateral vasectomy) must have had the procedure at least six (6) months prior to initial dosing. Surgical sterilization procedures should be supported with clinical documentation and noted in the Relevant Medical History/Current Medical Conditions section of the Case report forms (CRFs).
- Women of childbearing potential must be using two medically acceptable methods of contraception, at least one of which must be a barrier method, (e.g., intra-uterine device plus condom, spermicidal gel plus condom, diaphragm plus condom, etc.), from the time of screening and for the duration of the study, through at least three months following last study drug administration. NOTE: Oral contraceptive use is not permitted due to their increased risk of thromboembolism. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
- OR Postmenopausal women must have had no regular menstrual bleeding for at least one (1) year prior to initial dosing. Menopause will be confirmed by an elevated plasma Follicle-stimulating hormone (FSH) level > 40mIU/mL at screening for women not in receipt of hormone replacement therapy (HRT); OR Women who report surgical sterilization (i.e., hysterectomy and/or bilateral oophorectomy) must have had the procedure at least six (6) months prior to initial dosing. Surgical sterilization procedures should be supported with clinical documentation and noted in the Relevant Medical History/Current Medical Conditions section of the CRF.
- AND All women must have a documented negative pregnancy test result at screening and at baseline.
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- The subject has clinically unremarkable medical history, physical examination, ECG, and vital signs, as determined by the Investigator. Laboratory values must also be clinically unremarkable as determined by the Investigator, with the exception of the following labs which must be strictly within the normal range:
- Coagulation labs - PT, aPTT, ACT;
- Hematology lab - Hematocrit/Hemoglobin;
- Liver function labs - Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) (may be below lower limit of normal [LLN], but not above upper limit of normal [ULN]).
- The subject has a body mass index 19 to 30 kg/m2, inclusive, and weighs at least 60 kg.
- The subject agrees to abstain from alcohol consumption for 48 hours prior to dosing and for the duration of the in-house study period.
- The subject smokes <4 cigarettes/day (or equivalent: ≤0.5 can of chewing tobacco/week, 1 cigar/day) and agrees to abstain from smoking while domiciled.
- The subject is able to read and give written informed consent and has signed a consent form approved by the Investigator's Institutional Review Board (IRB) or Ethics Committee (EC).
Who cannot join
- The subject has a known history (including family history) of, symptoms of, or risk factors for bleeding (e.g., prior gastrointestinal bleeding, known berry aneurysm/ vascular malformation) or a stool specimen within 6 months of randomization that is positive for occult blood.
- The subject has an absolute/relative contraindication to anticoagulation.
- The subject has a history (including family history) of or risk factors for a hypercoagulable or thrombotic condition (e.g., deep vein thrombosis/pulmonary embolism, Factor V Leiden carrier).
- The subject has a history of any clinically significant (as determined by the Investigator) cardiac, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, renal, or other major disease or condition which is known to make the subject susceptible to volume overload.
- The subject has taken any prescription drugs (including oral contraceptives/HRT) or illicit drugs in the 30 days prior to randomization. The subject is also excluded if he/she has taken over the counter drugs, including dietary supplements and herbal products, in the 2 weeks prior to randomization. Furthermore, the subject agrees not to take any such drugs throughout the study (if it becomes medically necessary to do so, the Investigator and Portola Medical Monitor must be informed immediately).
- The subject has a history of major surgery, severe trauma or bone fracture within 3 months prior to dosing; or planned surgery within 1 month after dosing.
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- The subject has a history of blood donation of more than 500 mL within 3 months prior to dosing.
- The subject has participated in an investigational drug study within 30 days or 5 half-lives of the investigational compound, whichever is greater, of Day -1.
- The subject has a positive screen for drugs of abuse at Day -1.
- The subject has a medical or surgical condition which may impair drug absorption.
- The subject is allergic to any of the vehicle ingredients: tris, arginine, hydrochloric acid, sucrose and polysorbate 80.
- Subject is breastfeeding.
- The subject has any condition which could interfere with or for which the treatment might interfere with the conduct of the study, or which would, in the opinion of the Investigator increase the risk of the subject's participation in the study. This would include, but is not limited to alcoholism, drug dependency or abuse, psychiatric disease, epilepsy or any unexplained blackouts.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomized, Double-blind, Placebo-Controlled Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Intravenously Administered Andexanet After Dosing to Steady-State With Oral Betrixaban in Healthy Subjects
This is a randomized, double-blind, single center study in healthy volunteers dosed to steady state with betrixaban, designed to (1) Determine an andexanet dosing regimen required to reverse anticoagulant activity of betrixaban in healthy subjects, (2) Assess the safety and tolerability of andexanet vs. placebo (3) Determine the PK properties of andexanet and betrixaban (4) Determine the PD properties of betrixaban before, during, and after receiving andexanet or placebo and (5) Investigate the immunogenicity of andexanet in the presence of betrixaban.
- Conditions
- Bleeding
- Being tested
- Andexanet alfa (bolus), Betrixaban 80 mg PO QD, Andexanet alfa (infusion IV)
- Medical subject headings
- Hemorrhage
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Andexanet alfa (bolus)Biological
fXa inhibitor antidote
Betrixaban 80 mg PO QDDrug
fXa inhibitor
Andexanet alfa (infusion IV)Biological
fXa inhibitor antidote
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 Bertrixaban/Andexanet | Experimental | 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 Receives: Biological: Andexanet alfa (bolus); Drug: Betrixaban 80 mg PO QD |
| Cohort 1 Bertrixaban/Placebo | Experimental | 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 Receives: Biological: Andexanet alfa (bolus); Drug: Betrixaban 80 mg PO QD; Biological: Andexanet alfa (infusion IV) |
| Cohort 2 Bertrixaban/Andexanet | Experimental | 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 Receives: Biological: Andexanet alfa (bolus); Drug: Betrixaban 80 mg PO QD; Biological: Andexanet alfa (infusion IV) |
| Cohort 2 Bertrixaban/Placebo | Experimental | 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 Receives: Biological: Andexanet alfa (bolus); Drug: Betrixaban 80 mg PO QD; Biological: Andexanet alfa (infusion IV) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Anti-Fxa Activity From Baseline to End of Bolus
Change in Anti-Fxa Activity from baseline to end of bolus
Measured: Baseline to end of bolus, approximately 2.5 hours
Secondary outcomes (1)
Change in Thrombin Generation From Baseline to End of Bolus
Change in Thrombin Generation from baseline to end of bolus
Measured: Baseline to end of bolus, approximately 2.5 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Nov 2017
- Study start6 Aug 2015
- Primary completion22 Feb 2016
- Study completion22 Feb 2016
Why it stopped: Ended prematurely
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for BleedingStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Portola Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03330457
- Sponsor's protocol ID
- 15-507
- Status last verified
- Aug 2023
- First submitted
- 27 Sep 2017
- Last updated
- 8 Aug 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-blind, Placebo-Controlled Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Intravenously Administered Andexanet After Dosing to Steady-State With Oral Betrixaban in Healthy Subjects
- ClinicalTrials.gov ID
- NCT03330457
- Acronym / sponsor ID
- 15-507
- Conditions
- Bleeding
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Ended prematurely
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Portola PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 6 Aug 2015 (actual)
- Primary completion
- 22 Feb 2016 (actual)
- Study completion
- 22 Feb 2016 (actual)
- First posted
- 6 Nov 2017 (actual)
- Results
- Posted 19 Aug 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a randomized, double-blind, single center study in healthy volunteers dosed to steady state with betrixaban, designed to (1) Determine an andexanet dosing regimen required to reverse anticoagulant activity of betrixaban in healthy subjects, (2) Assess the safety and tolerability of andexanet vs. placebo (3) Determine the PK properties of andexanet and betrixaban (4) Determine the PD properties of betrixaban before, during, and after receiving andexanet or placebo and (5) Investigate the immunogenicity of andexanet in the presence of betrixaban.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 Bertrixaban/Andexanet | Experimental | Biological: Andexanet alfa (bolus), Drug: Betrixaban 80 mg PO QDAndexanet 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 | Experimental | Biological: Andexanet alfa (bolus), Drug: Betrixaban 80 mg PO QD, Biological: Andexanet alfa (infusion IV)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 | Experimental | Biological: Andexanet alfa (bolus), Drug: Betrixaban 80 mg PO QD, Biological: Andexanet alfa (infusion IV)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 | Experimental | Biological: Andexanet alfa (bolus), Drug: Betrixaban 80 mg PO QD, Biological: Andexanet alfa (infusion IV)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 |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (14 listed)
- The subject is a healthy man or woman between the ages of 18 and 45 years old, inclusive, who agrees to comply with the contraception and reproduction restrictions of the study:
- Men must be using two acceptable methods of contraception, at least one of which must be a barrier method (e.g., spermicidal gel plus condom) for the entire duration of the study and for at least three months following last study drug administration, and refrain from attempting to father a child or donating sperm in the three (3) months following the last study drug administration. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
- OR Men who report surgical sterilization (e.g., bilateral vasectomy) must have had the procedure at least six (6) months prior to initial dosing. Surgical sterilization procedures should be supported with clinical documentation and noted in the Relevant Medical History/Current Medical Conditions section of the Case report forms (CRFs).
- Women of childbearing potential must be using two medically acceptable methods of contraception, at least one of which must be a barrier method, (e.g., intra-uterine device plus condom, spermicidal gel plus condom, diaphragm plus condom, etc.), from the time of screening and for the duration of the study, through at least three months following last study drug administration. NOTE: Oral contraceptive use is not permitted due to their increased risk of thromboembolism. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
- OR Postmenopausal women must have had no regular menstrual bleeding for at least one (1) year prior to initial dosing. Menopause will be confirmed by an elevated plasma Follicle-stimulating hormone (FSH) level > 40mIU/mL at screening for women not in receipt of hormone replacement therapy (HRT); OR Women who report surgical sterilization (i.e., hysterectomy and/or bilateral oophorectomy) must have had the procedure at least six (6) months prior to initial dosing. Surgical sterilization procedures should be supported with clinical documentation and noted in the Relevant Medical History/Current Medical Conditions section of the CRF.
Key exclusion criteria (13 listed)
- The subject has a known history (including family history) of, symptoms of, or risk factors for bleeding (e.g., prior gastrointestinal bleeding, known berry aneurysm/ vascular malformation) or a stool specimen within 6 months of randomization that is positive for occult blood.
- The subject has an absolute/relative contraindication to anticoagulation.
- The subject has a history (including family history) of or risk factors for a hypercoagulable or thrombotic condition (e.g., deep vein thrombosis/pulmonary embolism, Factor V Leiden carrier).
- The subject has a history of any clinically significant (as determined by the Investigator) cardiac, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, renal, or other major disease or condition which is known to make the subject susceptible to volume overload.
- The subject has taken any prescription drugs (including oral contraceptives/HRT) or illicit drugs in the 30 days prior to randomization. The subject is also excluded if he/she has taken over the counter drugs, including dietary supplements and herbal products, in the 2 weeks prior to randomization. Furthermore, the subject agrees not to take any such drugs throughout the study (if it becomes medically necessary to do so, the Investigator and Portola Medical Monitor must be informed immediately).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Andexanet alfa (bolus)fXa inhibitor antidote | Biological | Cohort 1 Bertrixaban/Andexanet, Cohort 1 Bertrixaban/Placebo, Cohort 2 Bertrixaban/Andexanet, Cohort 2 Bertrixaban/Placebo |
| Betrixaban 80 mg PO QDfXa inhibitor | Drug | Cohort 1 Bertrixaban/Andexanet, Cohort 1 Bertrixaban/Placebo, Cohort 2 Bertrixaban/Andexanet, Cohort 2 Bertrixaban/Placebo |
| Andexanet alfa (infusion IV)fXa inhibitor antidote | Biological | Cohort 1 Bertrixaban/Placebo, Cohort 2 Bertrixaban/Andexanet, Cohort 2 Bertrixaban/Placebo |
Primary outcome
Change in Anti-Fxa Activity From Baseline to End of Bolus
Time frame: Baseline to end of bolus, approximately 2.5 hours
Change in Anti-Fxa Activity from baseline to end of bolus
1 secondary outcome
Change in Thrombin Generation From Baseline to End of Bolus
Time frame: Baseline to end of bolus, approximately 2.5 hours
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Aug 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Andexanet alfa (bolus), Betrixaban 80 mg PO QD and Andexanet alfa (infusion IV) in people with Bleeding, run by Portola Pharmaceuticals at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 8 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Aug 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Anti-Fxa Activity From Baseline to End of Bolus (time frame: Baseline to end of bolus, approximately 2.5 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Aug 2023.