A Study to Assess the Effect of Severe Hepatic Impairment on the Pharmacokinetics of Intravenous Conivaptan

Cumberland Pharmaceuticals

Status and phase

Completed

Phase 1

Conditions

Liver Disease

Treatments

Drug: conivaptan hydrochloride

Study type

Interventional

Funder types

Industry

Identifiers

NCT01370148

087-CL-099

Details and patient eligibility

About

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.

Full 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.

Enrollment

17 patients

Sex

All

Ages

30 to 75 years old

Volunteers

Accepts Healthy Volunteers

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