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

Liver Disease Clinical Trial

Official title:

A Phase 1, Open-Label Study to Assess the Effect of Severe Hepatic Impairment on the Pharmacokinetics of Intravenous Conivaptan

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01370148
• Other study ID #: 087-CL-099
• Status: Completed
• Phase: Phase 1
• First received: June 8, 2011
• Last updated: April 30, 2014
• Start date: April 2011
• Est. completion date: February 2014

Study information

• Verified date: April 2014
• Source: Cumberland Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 17
• Est. completion date: February 2014
• Est. primary completion date: February 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 30 Years to 75 Years

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Liver Disease
• Liver Diseases

Intervention

Drug:
• conivaptan hydrochloride
Intravenous

Locations

Country	Name	City	State
United States	Advanced Clinical Research Institute	Anaheim	California
United States	DaVita Clinical Research	Lakewood	Colorado
United States	Orlando Clinical Research	Orlando	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Cumberland Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Assess the effect of severe hepatic impairment on the plasma drug concentration of conivaptan through analysis of blood samples		5 days	Yes