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Hepatic ImpairmentPhase 1NCT03397888

The Effect o f Hepatic Impairment on the Pharmacokinetics and Pharmacodynamics of Betrixiban, an Oral FXa Antagonist

A Phase 1 study testing Betrixaban in people with Hepatic Impairment, run by Portola Pharmaceuticals at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

Single center, prospective open label PK and PD study of betrixaban in subjects with mild and moderate hepatic impairment vs healthy volunteers. Read more about this study

Who is it for?
Ages 18 to 70 yearsHealthy volunteers can take part
Conditions the study is for
Hepatic Impairment
What is being tested?
Betrixaban
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
32 participants
Where
1 siteUnited States
Study dates
16 Nov 2017to 16 Jan 2018
Phase
Phase 1
Are there results?
None posted in the registry

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 70 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • Cohorts 1 \& 2: Man or a woman 18 to 70 with stable chronic hepatic impairment disease due to cirrhosis confirmed by biopsy, ultrasound, CT or MRI (Cohort 1 - Mild impairment, Child-Pugh Category A; Cohort 2 - Moderate Impairment, Child-Pugh Category B). Cohort 3: essentially healthy man or woman without liver disease whose sex, age and weight match patients in Cohorts 1 \& 2 in order to result in similar average demographics.
  • Body Mass Index between 18 and 35 kg*m-2 and weighs at least 50 kg.
  • Contraception. Men must agree to acceptable methods of contraception. Women of child-bearing potential must agree to two acceptable forms of contraception. Post-menopausal women must have had no regular menstrual bleeding for at least one year prior to initial dosing and confirmed by an elevated plasma Follicle-stimulating hormone level test at screening for women not in receipt of hormone replacement therapy (HRT). Women who report surgical sterilization must have had the procedure at least six months prior to dosing, supported by clinical documentation.
  • The subject has clinical unremarkable medical history, physical examination, ECG, laboratory values and vital signs, as determined by the investigator. Subjects in Cohorts 1 \& 2 may have: abnormal liver function tests, INR up to 2.2, PT up to 6 seconds over control, aPPT up to 45 seconds and platelets down to 45,000/uL.
  • The subject smokes <12 cigarettes per day or equivalent and agrees to no or reduced tobacco products while domiciled.
  • The subject is able to read and give written informed consent and signed the IRB approved consent form.
  • The subject has adequate venous access for blood sampling.

Who cannot join

  • The subject has a history, symptoms of, or risk factors for bleeding or a stool specimen within 6 months of dosing positive for occult blood.
  • The subject has an absolute/relative contraindication to anticoagulation due to: history of intracranial bleeding, severe active bleeding, recent brain, eye, or spinal cord surgery or major surgery within 6 months of dosing.
  • The subject has a history of or risk factors for a hypercoagulable or thrombotic condition.
  • The subject has a history of any clinically significant cardiac, endocrinologic, hematologic, hepatic (except for Cohorts 1 \& 2), immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, renal or other major disease other than the underlying disease in Cohorts 1 \& 2.
  • The subject has a calculated creatinine clearance of <60mL/min as determined by Cockcroft-Gault method.
  • Concomitant medication use:
Show all 18Show fewer
  • For all subjects, illicit drugs, oral contraceptives, and hormone replacement therapy are excluded within 30 days prior to Day -1.
  • For all subjects, over the counter drugs, including dietary supplements and herbal products are excluded within 14 days prior to Day -1.
  • Subjects enrolled in Cohort 3 will be excluded if the subject has taken any prescription drugs in the 30 days prior to dosing. Furthermore, the subject will be excluded if he/she does not agree to refrain from concomitant drugs throughout the study unless medically necessary as determined by the Investigator.
  • Subjects enrolled in Cohort 1 and 2 may continue taking stable preexisting medications throughout the study with the exception of strong P-gp inhibitors. Strong P-gp inhibitors include but are not limited to: amiodarone, azithromycin, clarithromycin, erythromycin, ketoconazole, and verapamil. Prescribed stable acetaminophen use up to 2,000 mg per day is allowable. Any acetaminophen use with alcohol within 48 hours of dosing is prohibited. Furthermore, the subject will be excluded if he/she does not agree to refrain from additional concomitant drugs throughout the study unless medically necessary as determined by the Investigator.
  • The subject has a history of severe trauma or bone fracture within 6 months prior to dosing; or planned surgery within 1 month after dosing.
  • The subject has a history of blood donation of more than 500mL within 3 months prior to dosing.
  • The subject has received an investigational drug product within 30 days or 5 half-lives of the investigational compound, whichever is greater, from Day -1.
  • The subject has positive screen for drugs of abuse at Day -1.
  • The subject does not agree to withhold from alcohol consumption from 48 hours prior to dosing through discharge.
  • The subject has a medical or surgical condition which may impair drug absorption.
  • The subject is pregnant or breastfeeding.
  • The subject has any condition which could interfere with or for which the treatment might interfere with the conduct of the study, or would, in the opinion of the Investigator, increase the risk of the subject's participation in the study.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Clinical Pharmacology of Miami

    Hialeah, Florida, 33014

Other trials in United States

About this study

Single center, prospective open label PK and PD study of betrixaban in subjects with mild and moderate hepatic impairment vs healthy volunteers.

Being tested
Betrixaban

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BetrixabanDrug

    80 mg capsule

Study groups in NCT03397888
Study groupRoleWhat they receive
Cohort 1ExperimentalMild Impairment, Child-Pugh Category A
Receives: Drug: Betrixaban
Cohort 2ExperimentalModerate Impairment, Child-Pugh Category B
Receives: Drug: Betrixaban
Cohort 3ExperimentalEssentially Healthy man or woman without liver disease matched to Cohorts 1 \& 2 for age, sex and weight.
Receives: Drug: Betrixaban

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. PK - Plasma half-life (t1/2)

    Plasma half-life (t1/2), distribution half-life and terminal half-life.

    Measured: Day 1 through Day 6

  2. PK - Tmax

    Time to maximum observed plasma concentration (Tmax).

    Measured: Day 1 through Day 6

  3. PK - Cmax

    Maximum observed plasma concentration (Cmax)

    Measured: Day 1 through Day 6

  4. PK - AUC (0-last)

    Area under the plasma concentration-time curve from 0 to last measurable concentration (AUC (0-last)).

    Measured: Day 1 through Day 6

  5. PK - (AUC(0-∞)).

    Total area under the plasma concentration-time curve from time 0 to infinity (AUC(0-∞)).

    Measured: Day 1 through Day 6

  6. PK - Volume of distribution

    Apparent volume of distribution (Vd/F).

    Measured: Day 1 through Day 6

  7. PK - Total clearance

    Apparent total clearance (CL/F).

    Measured: Day 1 through Day 6

Secondary outcomes (75)

  1. Safety - Treatment Emergent AEs

    Safety evaluation will study the adverse event (AE) profile

    Measured: Day -1 through up to Day 21

  2. Safety - Demographics

    Safety will be evaluated by assessment of Demographics

    Measured: Day -30 through Day -2 (Screening)

  3. Safety - Vital Signs Temperature

    Safety will be evaluated by assessment of Temperature - Celsius

    Measured: Day -30 through up to Day 21

  4. Safety - Vital Signs Respiratory Rate

    Safety will be evaluated by assessment of Respiratory Rate - Breaths per Minute

    Measured: Day -30 through up to Day 21

  5. Safety - Vital Signs Heart Rate

    Safety will be evaluated by assessment of Heart Rate - Beats per Minute

    Measured: Day -30 through up to Day 21

  6. Safety - Vital Signs Blood Pressure

    Safety will be evaluated by assessment of Blood Pressure - mmHg

    Measured: Day -30 through up to Day 21

  7. Safety - 12 Lead ECG - PR

    Safety will be evaluated by assessment of 12 ECG - PR (ms)

    Measured: Day -30 through up to Day 21

  8. Safety - 12 Lead ECG - RR

    Safety will be evaluated by assessment of 12 ECG - RR (ms)

    Measured: Day -30 through up to Day 21

  9. Safety - 12 Lead ECG - WRS

    Safety will be evaluated by assessment of 12 ECG - WRS (ms)

    Measured: Day -30 through up to Day 21

  10. Safety - 12 Lead ECG - QT

    Safety will be evaluated by assessment of 12 ECG - QT (ms)

    Measured: Day -30 through up to Day 21

  11. Safety - 12 Lead ECG - QTcF

    Safety will be evaluated by assessment of 12 ECG - QTcF (ms)

    Measured: Day -30 through up to Day 21

  12. Safety - 12 Lead ECG - QTcB

    Safety will be evaluated by assessment of 12 ECG - QTcB (ms)

    Measured: Day -30 through up to Day 21

  13. Safety - Physical Exam - Height

    Safety will be evaluated by assessment Physical Exam - Height (centimeters)

    Measured: Day -30 through up to Day 21

  14. Safety - Physical Exam - Weight

    Safety will be evaluated by assessment Physical Exam - Weight (kilogram)

    Measured: Day -30 through up to Day 21

  15. Safety - Lab - Hematology - hemoglobin

    Safety will be evaluated by analyzing Hematology - hemoglobin (g/dL)

    Measured: Day -30 through up to Day 21

  16. Safety - Lab - Hematology - hematocrit

    Safety will be evaluated by analyzing Hematology - hematocrit (%)

    Measured: Day -30 through up to Day 21

  17. Safety - Lab - Hematology - white blood cell [WBC]

    Safety will be evaluated by analyzing Hematology - WBC (K/UL)

    Measured: Day -30 through up to Day 21

  18. Safety - Lab - Hematology - Platelet Count

    Safety will be evaluated by analyzing Platelet Count (Plt/mL)

    Measured: Day -30 through up to Day 21

  19. Safety - Lab - Hematology - Absolute Neutrophil Count

    Safety will be evaluated by analyzing Absolute Neutrophil Count (K/UL)

    Measured: Day -30 through up to Day 21

  20. Safety - Lab - Hematology - Absolute Basophils

    Safety will be evaluated by analyzing Absolute Basophils (K/UL)

    Measured: Day -30 through up to Day 21

  21. Safety - Lab - Hematology - Eosinophil's

    Safety will be evaluated by analyzing Eosinophil's (K/UL)

    Measured: Day -30 through up to Day 21

  22. Safety - Lab - Hematology - Lymphocytes

    Safety will be evaluated by analyzing Lymphocytes (K/UL)

    Measured: Day -30 through up to Day 21

  23. Safety - Lab - Hematology - Mean Corpuscular Hemoglobin

    Safety will be evaluated by analyzing Mean Corpuscular Hemoglobin (PG)

    Measured: Day -30 through up to Day 21

  24. Safety - Lab - Hematology - Mean Corpuscular Hemoglobin Concentration

    Safety will be evaluated by analyzing Mean Corpuscular Hemoglobin Concentration (g/dL)

    Measured: Day -30 through up to Day 21

  25. Safety - Lab - Hematology - Mean Corpuscular Hemoglobin Volume

    Safety will be evaluated by analyzing Mean Corpuscular Hemoglobin Volume (FL)

    Measured: Day -30 through up to Day 21

  26. Safety - Lab - Hematology - Monocytes

    Safety will be evaluated by analyzing Monocytes (K/UL)

    Measured: Day -30 through up to Day 21

  27. Safety - Lab - Hematology - Neutrophils

    Safety will be evaluated by analyzing Neutrophils (K/UL)

    Measured: Day -30 through up to Day 21

  28. Safety - Lab - Hematology - Red Blood Cell Count

    Safety will be evaluated by analyzing Red Blood Cell Count (MIL/UL)

    Measured: Day -30 through up to Day 21

  29. Safety - Lab - Hematology - Red Cell Distribution Width

    Safety will be evaluated by analyzing Red Cell Distribution Width (%)

    Measured: Day -30 through up to Day 21

  30. Safety - Lab - Hematology - Reticulocyte

    Safety will be evaluated by analyzing Reticulocyte (K/UL)

    Measured: Day -30 through up to Day 21

  31. Safety- Lab - Coagulation - PT

    Safety will be evaluated by analyzing Coagulation - PT (seconds)

    Measured: Day -30 through up to Day 21

  32. Safety- Lab - Coagulation - INR

    Safety will be evaluated by analyzing Coagulation - INR (no unit)

    Measured: Day -30 through up to Day 21

  33. Safety- Lab - Coagulation - aPTT

    Safety will be evaluated by analyzing Coagulation - aPTT (seconds)

    Measured: Day -30 through up to Day 21

  34. Safety- Lab - Coagulation - Factor V Leiden

    Safety will be evaluated by analyzing Coagulation - Factor V Leiden (positive/negative)

    Measured: Day -30 through up to Day 21

  35. Safety - Lab - Serum Chemistry - Sodium

    Safety will be evaluated by analyzing Serum Chemistry - Sodium (mEq/L)

    Measured: Day -30 through up to Day 21

  36. Safety - Lab - Serum Chemistry - Potassium

    Safety will be evaluated by analyzing Serum Chemistry - Potassium (mEq/L)

    Measured: Day -30 through up to Day 21

  37. Safety - Lab - Serum Chemistry - Chloride

    Safety will be evaluated by analyzing Serum Chemistry - Chloride (mEq/L)

    Measured: Day -30 through up to Day 21

  38. Safety - Lab - Serum Chemistry - Carbon Dioxide

    Safety will be evaluated by analyzing Serum Chemistry - Carbon Dioxide (mEq/L)

    Measured: Day -30 through up to Day 21

  39. Safety - Lab - Serum Chemistry - Glucose

    Safety will be evaluated by analyzing Serum Chemistry - Glucose (mg/dL)

    Measured: Day -30 through up to Day 21

  40. Safety - Lab - Serum Chemistry - Blood Urea Nitrogen

    Safety will be evaluated by analyzing Serum Chemistry - Blood Urea Nitrogen (mg/dL)

    Measured: Day -30 through up to Day 21

  41. Safety - Lab - Serum Chemistry - Creatinine

    Safety will be evaluated by analyzing Serum Chemistry - Creatinine (mg/dL)

    Measured: Day -30 through up to Day 21

  42. Safety - Lab - Serum Chemistry - AST

    Safety will be evaluated by analyzing Serum Chemistry - AST (U/L)

    Measured: Day -30 through up to Day 21

  43. Safety - Lab - Serum Chemistry - ALT

    Safety will be evaluated by analyzing Serum Chemistry - ALT (U/L)

    Measured: Day -30 through up to Day 21

  44. Safety - Lab - Serum Chemistry - GGT

    Safety will be evaluated by analyzing Serum Chemistry - GGT (U/L)

    Measured: Day -30 through up to Day 21

  45. Safety - Lab - Serum Chemistry - Total Protein

    Safety will be evaluated by analyzing Serum Chemistry - Total Protein (g/dL)

    Measured: Day -30 through up to Day 21

  46. Safety - Lab - Serum Chemistry - Albumin

    Safety will be evaluated by analyzing Serum Chemistry - Albumin(g/dL)

    Measured: Day -30 through up to Day 21

  47. Safety - Lab - Serum Chemistry - Alkaline Phosphatase

    Safety will be evaluated by analyzing Serum Chemistry - Alkaline Phosphatase (U/L)

    Measured: Day -30 through up to Day 21

  48. Safety - Lab - Serum Chemistry - Calcium

    Safety will be evaluated by analyzing Serum Chemistry - Calcium (mg/dL)

    Measured: Day -30 through up to Day 21

  49. Safety - Lab - Serum Chemistry - Phosphorus

    Safety will be evaluated by analyzing Serum Chemistry - Phosphorus (mg/dL)

    Measured: Day -30 through up to Day 21

  50. Safety - Lab - Serum Chemistry - Total Bilirubin

    Safety will be evaluated by analyzing Serum Chemistry - Total Bilirubin (mg/dL)

    Measured: Day -30 through up to Day 21

  51. Safety - Lab - Serum Chemistry - Fractionated Bilirubin

    Safety will be evaluated by analyzing Serum Chemistry - Fractionated Bilirubin(mg/dL)

    Measured: Day -30 through up to Day 21

  52. Safety - Lab - Serum Chemistry - Uric Acid

    Safety will be evaluated by analyzing Serum Chemistry - Uric Acid (mg/dL)

    Measured: Day -30 through up to Day 21

  53. Safety - Lab - Serum Chemistry - LDH

    Safety will be evaluated by analyzing Serum Chemistry LDH (U/L)

    Measured: Day -30 through up to Day 21

  54. Safety - Lab - Urine toxicology Panel - Amphetamines

    Safety will be evaluated by analyzing Urine toxicology Panel - Amphetamines (NG/ML)

    Measured: Day -30 through Day -1

  55. Safety - Lab - Urine toxicology Panel - Barbiturates

    Safety will be evaluated by analyzing Urine toxicology Panel - Barbiturates (NG/ML)

    Measured: Day -30 through Day -1

  56. Safety - Lab - Urine toxicology Panel - Cannabinoids

    Safety will be evaluated by analyzing Urine toxicology Panel - Cannabinoids (NG/ML)

    Measured: Day -30 through Day -1

  57. Safety - Lab - Urine toxicology Panel - Cocaine

    Safety will be evaluated by analyzing Urine toxicology Panel - Cocaine (NG/ML)

    Measured: Day -30 through Day -1

  58. Safety - Lab - Urine toxicology Panel - Ethanol

    Safety will be evaluated by analyzing Urine toxicology Panel - Ethanol (MG/DL)

    Measured: Day -30 through Day -1

  59. Safety - Lab - Urine toxicology Panel - Opiates

    Safety will be evaluated by analyzing Urine toxicology Panel - Opiates (NG/ML)

    Measured: Day -30 through Day -1

  60. Safety - Lab - Urinalysis - Specific Gravity

    Safety will be evaluated by analyzing Urinalysis - Specific Gravity (no unit)

    Measured: Day -30 through up to Day 21

  61. Safety - Lab - Urinalysis - pH

    Safety will be evaluated by analyzing Urinalysis - pH (no unit)

    Measured: Day -30 through up to Day 21

  62. Safety - Lab - Urinalysis - Glucose

    Safety will be evaluated by analyzing Urinalysis - Glucose (no unit)

    Measured: Day -30 through up to Day 21

  63. Safety - Lab - Urinalysis - Protein

    Safety will be evaluated by analyzing Urinalysis - Protein (no unit)

    Measured: Day -30 through up to Day 21

  64. Safety - Lab - Urinalysis - Hemoglobin

    Safety will be evaluated by analyzing Urinalysis - Hemoglobin (no unit)

    Measured: Day -30 through up to Day 21

  65. Safety - Lab - Urinalysis - Leukocyte esterase

    Safety will be evaluated by analyzing Urinalysis - Leukocyte esterase (no unit)

    Measured: Day -30 through up to Day 21

  66. Safety - Lab - Urinalysis - Nitrate

    Safety will be evaluated by analyzing Urinalysis - Nitrate (no unit)

    Measured: Day -30 through up to Day 21

  67. Safety - Urine Occult Blood Testing

    Safety will be evaluated by assessment of Urine Occult Blood Testing (positive/negative)

    Measured: Day -30 through Day -2 (screening)

  68. Safety - Fecal Occult Blood Testing

    Safety will be evaluated by assessment of Fecal Occult Blood Testing (positive/negative)

    Measured: Day -30 through Day -2 (screening)

  69. Safety - Lab - Blood Virology - HIV I

    Safety will be evaluated by analyzing Blood Virology - HIV I (positive/negative)

    Measured: Day-30 through Day -2 (Screening)

  70. Safety - Lab - Blood Virology - HIV II

    Safety will be evaluated by analyzing Blood Virology - HIV II (positive/negative)

    Measured: Day-30 through Day -2 (Screening)

  71. Safety - Lab - Blood Virology - Hepatitis B

    Safety will be evaluated by analyzing Blood Virology - Hepatitis B (positive/negative)

    Measured: Day-30 through Day -2 (Screening)

  72. Safety - Lab - Blood Virology - Hepatitis C

    Safety will be evaluated by analyzing Blood Virology - Hepatitis C (positive/negative)

    Measured: Day-30 through Day -2 (Screening)

  73. Safety - Lab - Serum Pregnancy

    Safety will be evaluated by analyzing Serum Pregnancy

    Measured: Day -30 through up to Day 21

  74. PD - Anti-Factor Xa Concentration

    Anti-fXa will be analyzed for changes/percent changes from baseline over time.

    Measured: Day 1 through Day 6

  75. PD - Thrombin Concentrations

    Thrombin will be analyzed for changes/percent changes from baseline over time.

    Measured: Day 1 through Day 6

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Jan 2018
  2. Study start16 Nov 2017
  3. Primary completion16 Jan 2018
  4. Study completion16 Jan 2018

Resources

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 1
Primary purpose
Prevention
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
32 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03397888
Sponsor's protocol ID
17-022
Status last verified
Feb 2023
First submitted
7 Dec 2017
Last updated
21 Feb 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Betrixaban in people with Hepatic Impairment, 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 7 inclusion and 18 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: finished, as of the sponsor's last update on 21 Feb 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

PK - Plasma half-life (t1/2) (time frame: Day 1 through Day 6). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03397888.

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 21 Feb 2023.

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