A Study of Glyceryl Tri-(4-phenylbutyrate) Administered Orally as a Single Dose, and Twice Daily for Seven Consecutive Days to Subjects With Hepatic Impairment With Cirrhosis and to a Control Group

Fecha de inicio: 1 de septiembre de 2006

Inclusion Criteria: Subjects were required to fulfill the following criteria in order to participate in the study: Screening: * Males or females aged ≥ 18 years of age * Able to provide written informed consent before any study-related procedures, and ability, in the opinion of the Investigator, to comply with all the requirements of the study * Classification to one of the following: * current diagnosis of hepatic impairment with cirrhosis * healthy subject * Subjects with hepatic impairment with cirrhosis were classifiable to one of the following groups: * Child-Pugh score A * Child-Pugh score B * Child-Pugh score C * Subjects with hepatic impairment with cirrhosis who were on a therapeutic regimen of lactulose must have been on a stable dose for ≥ 30 days prior to screening * If female, a negative pregnancy test at screening and pre-dose on day 0, or a documented sterilization procedure; a female of child-bearing potential must have been using a medically approved birth control method and must have agreed to use the same method of contraception during the full course of the study (on pre-dose day 0 as well as at screening) * Weight within the range of 60-100 kg (at screening and pre-dose on day 0) * Willing to stop taking any medication that the Sponsor and the Investigator felt was not appropriate for use during the study, beginning 2 days before dosing and throughout the study Exclusion Criteria: Subjects who fulfilled any of the following criteria were excluded from the study: Screening: * Clinically significant history or evidence of cardiovascular, respiratory, renal, gastrointestinal, endocrine, neurological, immunological, or psychiatric disorder(s), as determined by the Investigator * Serum sodium \< 120 mEq/L * Serum creatinine ≥ 1.5 upper limit of normal * Potassium ≤ 3.5 mEq/L * Other laboratory values outside the normal range which were determined to be clinically significant by the Investigator * Significant illness within the last 14 days * Oral temperature \> 38.5°C or \< 36°C and/or a suspected site of active infection * Inflammatory bowel disease or malabsorption defined with steatorrhea * Active gastrointestinal bleeding, defined as melena, hematochezia, or hematemesis requiring hospitalization within the last 30 days * Use of probenecid, valproate, or corticosteroids within the last 24 hours * Use of any medication, other than those approved by the Sponsor and Investigator, in the last 48 hours * History of seizures within the last 72 hours * Positive drugs of abuse urine test * Positive alcohol breath test * Donation or loss of blood (500 mL or more) within the last 30 days * Donation or loss of plasma within the last 7 days * History of acquired immunodeficiency syndrome (AIDS) or determined human immunodeficiency virus (HIV) positive * Hepatitis B or C (HBV; HCV) positive (healthy volunteers only) * Use of any investigational drug within the last 30 days * Known hypersensitivity to sodium phenylbutyrate or similar drugs * Emergency hospitalization within the last 90 days * Intake of alcohol in the last 7 days Pre-dose (days 0 and 7): * Significant illness or emergency hospitalization since the last study visit * Oral temperature \> 38.5°C or \< 36°C and/or a suspected site of active infection * Use of probenecid, valproate, or corticosteroids within the last 24 hours * Use of any non-approved medication (by the Sponsor/Investigator) within the 48 hours before dosing * History of seizures within the last 72 hours * Positive drugs of abuse urine test * Positive alcohol breath test * Donation or loss of blood (500 mL or more) or plasma since the last study visit * Use of any investigational drug since the last study visit * Intake of alcohol in the last 7 days