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

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.

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