The Effect o f Hepatic Impairment on the Pharmacokinetics... | NCT03397888

NCT03397888

Protocol Section

Identification Module

Results Section

No data available

No data is available for this block.

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Status Module

Label	Type	Description	Intervention Names
Cohort 1	Experimental	Mild Impairment, Child-Pugh Category A	Drug: Betrixaban
Cohort 2	Experimental	Moderate Impairment, Child-Pugh Category B	Drug: Betrixaban
Cohort 3	Experimental	Essentially Healthy man or woman without liver disease matched to Cohorts 1 & 2 for age, sex and weight.	Drug: Betrixaban

Name	Type	Description	Arm Group Labels	Other Names
Betrixaban	Drug	80 mg capsule	Cohort 1 Cohort 2 Cohort 3

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
PK - Plasma half-life (t1/2)	Plasma half-life (t1/2), distribution half-life and terminal half-life.	Day 1 through Day 6
PK - Tmax	Time to maximum observed plasma concentration (Tmax).	Day 1 through Day 6
PK - Cmax	Maximum observed plasma concentration (Cmax)	Day 1 through Day 6
PK - AUC (0-last)	Area under the plasma concentration-time curve from 0 to last measurable concentration (AUC (0-last)).	Day 1 through Day 6
PK - (AUC(0-∞)).	Total area under the plasma concentration-time curve from time 0 to infinity (AUC(0-∞)).	Day 1 through Day 6
PK - Volume of distribution	Apparent volume of distribution (Vd/F).	Day 1 through Day 6
PK - Total clearance	Apparent total clearance (CL/F).	Day 1 through Day 6

Secondary Outcomes

Measure	Description	Time Frame
Safety - Treatment Emergent AEs	Safety evaluation will study the adverse event (AE) profile	Day -1 through up to Day 21
Safety - Demographics	Safety will be evaluated by assessment of Demographics

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

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.

Exclusion Criteria:

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:
1. For all subjects, illicit drugs, oral contraceptives, and hormone replacement therapy are excluded within 30 days prior to Day -1.
2. For all subjects, over the counter drugs, including dietary supplements and herbal products are excluded within 14 days prior to Day -1.
3. 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.
4. 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.