A Study to Assess the Effect of Severe Hepatic Impairment on the Pharmacokinetics of Intravenous Conivaptan
- Registration Number
- NCT01370148
- Lead Sponsor
- Cumberland Pharmaceuticals
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 17
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)
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Subjects with severe hepatic impairment conivaptan hydrochloride - Subjects with normal hepatic function conivaptan hydrochloride -
- Primary Outcome Measures
Name Time Method Assess the effect of severe hepatic impairment on the plasma drug concentration of conivaptan through analysis of blood samples 5 days
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (3)
Advanced Clinical Research Institute
🇺🇸Anaheim, California, United States
DaVita Clinical Research
🇺🇸Lakewood, Colorado, United States
Orlando Clinical Research
🇺🇸Orlando, Florida, United States