Liver Disease
Conditions
Keywords
Pharmacokinetics, Protein Binding, Conivaptan, Vaprisol, Liver Disease, YM087
Brief summary
The purpose of this study is to assess the pharmacokinetics and safety of a 48-hour continuous infusion of conivaptan in subjects with severe liver impairment compared to subjects with normal liver function.
Detailed description
Subjects will be admitted to the Phase 1 unit Day -2 and will remain confined to the unit until discharge on Study Day 5 after completion of all study procedures.
Interventions
Intravenous
Sponsors
Cumberland Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
30 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
Subjects with Normal Hepatic Function: Female subject must be either: * post-menopausal prior to Screening, or * premenarchal prior to Screening, or * documented surgically sterile or post hysterectomy, or * if of childbearing potential, must have a negative pregnancy test at Screening and must be using highly effective contraception prior to Screening and throughout the study period and for 28 days after final study drug administration * Female subject must not be lactating and must not be breastfeeding at Screening or during the study period, and for 28 days after final study drug administration * Female subject must not donate ova starting at Screening or during the study period, and for 28 days after final study drug administration * Male subject must: * be using highly effective contraception consisting of two forms of birth control (one of which must be a barrier method) starting at Screening and continue throughout the study period, and for 28 days after final study drug administration * not donate sperm starting at Screening and throughout the study period, and for at least 28 days after final study drug administration * Subject weighs at least 45 kg and has a body mass index between 18 and 40 kg/m2 inclusive * The subject must have clinical laboratory test results within normal range, including liver function tests (LFTs) * The subject must have had a normal 12-lead electrocardiogram (ECG) Hepatic Impaired Subjects: * Female subject must be either: * post-menopausal prior to Screening, or * premenarchal prior to Screening, or * documented surgically sterile or post hysterectomy, or * if of childbearing potential, must have a negative pregnancy test at Screening and must be using highly effective contraception prior to Screening and throughout the study period and for 28 days after final study drug administration * Female subject must not be lactating and must not be breastfeeding at Screening or during the study period, and for 28 days after final study drug administration * Female subject must not donate ova starting at Screening or during the study period, and for 28 days after final study drug administration * Male subject must: * be using highly effective contraception consisting of two forms of birth control (one of which must be a barrier method) starting at Screening and continue throughout the study period, and for 28 days after final study drug administration * not donate sperm starting at Screening and throughout the study period, and for at least 28 days after final study drug administration * Subject meets criteria for severe hepatic impairment defined by Child-Pugh method * Subject weighs at least 45 kg and has a body mass index between 18 and 40 kg/m2 inclusive * The subject must have clinical laboratory test results within therapeutic range except for hepatic disease * The subject must have had a normal 12-lead electrocardiogram (ECG)
Exclusion criteria
Subjects with Normal Hepatic Function: * Subject has a history of a clinically significant illness, and associated clinical symptoms, medical condition, or laboratory abnormality within past 3 months that would preclude participation in the study * Subject has evidence of biliary obstruction or other causes of hepatic impairment * Subject is known to have hepatitis or is a carrier of hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, or is known to be HIV positive or has HIV antibodies * Subject has an impaired ability to sense thirst * Subject has serum sodium less than 115mEg/L or greater than 140 mEg/L * Subject has either a systolic blood pressure (BP) of greater than 140 mmHg or a diastolic BP of less than 56 mmHg * Subject has taken any prescription or over-the-counter medications except for contraceptives, hormone replacement therapy and occasional acetaminophen, or alternative and complementary medicines within past 14 days * Subject has a history of carcinoma, except for basal cell or cutaneous squamous cell carcinoma within past 5 years * Subject drinks greater than 14 units of alcohol per week (Note: one unit = 12 ounces of beer, 4 ounces of wine, or 1 ounce of spirits) * Subject has a history of substance abuse within past 6 months prior to Screening Visit or the subject tests positive at Screening or clinic admission for alcohol or drugs of abuse * Subject is currently participating in another clinical trial or has received an investigational medication within past 30 days * Subject is known to have hypersensitivity to conivaptan or its derivatives * Subject has had a blood transfusion or donated/lost more than 550ml of blood within past 8 weeks * Subject is incapable of being compliant with the protocol Subjects with Hepatic Impairment: * Subject has a history of a clinically significant illness, and associated clinical symptoms, medical condition, or laboratory abnormality within past 3 months that would preclude participation in the study. Subjects with controlled hypertension may be allowed * Subject has a condition associated with hepatic disease including; biliary obstruction, or other cause of hepatic impairment not related to parenchymal disorder and/or disease of the liver, fluctuating or rapidly deteriorating hepatic function, biliary liver cirrhosis, history or presence of hepatic encephalopathy greater than Grade 1 within past 3 months or unstable encephalopathy prior to Screening, tense ascites, esophageal/gastric variceal bleeding with past 6 months, server portal hypertension, surgical portal systemic shunt or peritoneal venous shunt, thrombocyte level below 50,000 x 10\^9/L and prothrombin time (PT) above 18 seconds * Subject is hypovolemic or has evidence of orthostatic hypotension * Subject has an impaired ability to sense thirst * Subject has serum sodium less than 115mEg/L or greater than 140 mEg/L * Subject has either a systolic blood pressure (BP) of greater than 140 mmHg or a diastolic BP of less than 56 mmHg * Subject is known to be HIV positive or has HIV antibodies * Subject has had a change in dose regimen of medication needed for their underlying medical condition with the past four weeks * Subject is currently taking a prohibited medication * Subject drinks greater than 14 units of alcohol per week (Note: one unit equals 12 ounces of beer, 4 ounces of wine, or 1 ounce of spirits) * Subject has a history of substance abuse within past 6 months prior to Screening Visit or the subject tests positive at Screening or clinic admission for alcohol or drugs of abuse * Subject is currently participating in another clinical trial or has received an investigational medication with past 30 days * Subject has had a blood transfusion or donated/lost more than 550ml of blood within past 8 weeks * Subject is known to have hypersensitivity of conivaptan or its derivatives * Subject is incapable of being compliant with the protocol
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Assess the effect of severe hepatic impairment on the plasma drug concentration of conivaptan through analysis of blood samples | 5 days |
Countries
United States
Outcome results
None listed