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

NCT ID: NCT01370148

Last Updated: 2014-05-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 17 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-04-30
• Study Completion Date: 2014-02-28

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.

Conditions

Liver Disease

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Blinding Strategy: NONE

Study Groups

Subjects with severe hepatic impairment

Group Type: EXPERIMENTAL

conivaptan hydrochloride

Intervention Type: DRUG

Intravenous

Subjects with normal hepatic function

Group Type: ACTIVE_COMPARATOR

conivaptan hydrochloride

Intervention Type: DRUG

Intravenous

Interventions

conivaptan hydrochloride

Intravenous

Intervention Type: DRUG

Other Intervention Names

Vaprisol; YM087

Eligibility Criteria

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

• Minimum Eligible Age: 30 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Cumberland Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Art Wheeler, MD

Role: STUDY_DIRECTOR

Cumberland Pharmaceuticals, Inc.

Locations

Advanced Clinical Research Institute

Anaheim, California, United States

DaVita Clinical Research

Lakewood, Colorado, United States

Orlando Clinical Research

Orlando, Florida, United States

Countries

United States

Other Identifiers

087-CL-099

Identifier Type: -

Identifier Source: org_study_id