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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Cumberland Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01370148
First received: June 8, 2011
Last updated: April 30, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Liver Disease
Drug: conivaptan hydrochloride
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Official Title: A Phase 1, Open-Label Study to Assess the Effect of Severe Hepatic Impairment on the Pharmacokinetics of Intravenous Conivaptan

Resource links provided by NLM:


Further study details as provided by Cumberland Pharmaceuticals:

Primary Outcome Measures:
  • Assess the effect of severe hepatic impairment on the plasma drug concentration of conivaptan through analysis of blood samples [ Time Frame: 5 days ] [ Designated as safety issue: Yes ]

Enrollment: 17
Study Start Date: April 2011
Study Completion Date: February 2014
Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Subjects with severe hepatic impairment Drug: conivaptan hydrochloride
Intravenous
Other Names:
  • Vaprisol
  • YM087
Active Comparator: Subjects with normal hepatic function Drug: conivaptan hydrochloride
Intravenous
Other Names:
  • Vaprisol
  • YM087

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.

  Eligibility

Ages Eligible for Study:   30 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01370148

Locations
United States, California
Advanced Clinical Research Institute
Anaheim, California, United States, 92801
United States, Colorado
DaVita Clinical Research
Lakewood, Colorado, United States, 80228
United States, Florida
Orlando Clinical Research
Orlando, Florida, United States, 32809
Sponsors and Collaborators
Cumberland Pharmaceuticals
Investigators
Study Director: Art Wheeler, MD Cumberland Pharmaceuticals Inc.
  More Information

No publications provided

Responsible Party: Cumberland Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01370148     History of Changes
Other Study ID Numbers: 087-CL-099
Study First Received: June 8, 2011
Last Updated: April 30, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Cumberland Pharmaceuticals:
Pharmacokinetics
Protein Binding
Conivaptan
Vaprisol
Liver Disease
YM087

Additional relevant MeSH terms:
Liver Diseases
Digestive System Diseases

ClinicalTrials.gov processed this record on July 23, 2014