A Study of Terlipressin in Patients With Hepatorenal Syndrome Type 1

An Exploratory Study of FE999908 in Patients With Hepatorenal Syndrome Type 1

This is an open-label, multi-center study, investigating the efficacy and safety of terlipressin in Japanese patients with hepatorenal syndrome type 1.

Inclusion Criteria:

- Patients who were diagnosed with HRS type 1 according to the diagnostic criteria of HRS and whose serum creatinine value (SCr) doubled at 2.5 mg/dL or greater within 2 weeks or whose 24h creatinine clearance (Ccr) decreased by half at less than 20 mL/min.

Patients should meet all the following 5 criteria:

[Modified International Ascites Club's Diagnostic criteria of HRS]

1. Chronic or acute liver disease with advanced hepatic failure and portal hypertension.

2. Low glomerular filtration rate (SCr >1.5 mg/dL or 24h Ccr <40 mL/min)

3. Absence of shock, ongoing bacterial infection, current or recent (within 2 weeks) treatment with nephrotoxic drug

4. No sustained improvement in renal function (decrease in SCr to 1.5 mg/dL or less or increase in 24h Ccr to 40 mL/min or more) following diuretic withdrawal and expansion of plasma volume with 1,500 mL/24h of isotonic saline for 24 to 48h.

5. Protein urea <500 mg/dL, and no ultrasonographic evidence of obstructive uropathy or parenchymal renal disease

   • Age; 20 to 79 years

Exclusion Criteria:

• Cr value ≥5 mg/dL
• Child-Pugh Score ≥14
• Fulminant hepatitis
• Septic shock
• Hepatocellular carcinoma that does not meet the Milan Criteria
• Acute renal failure caused by contrast medium
• Chronic renal failure
• Bradycardia (heart rate <50/min)
• Hyponatraemia (serum Na <120 mEq/L)
• Ischemic heart diseases (angina pectoris, myocardial infarction), heart failure or clinically relevant arrhythmia
• Poor-controlled hypertension
• Arteriosclerosis obliterans or peripheral vascular disorder
• Cerebrovascular disorder
• Respiratory diseases such as chronic obstructive pulmonary disease
• Pregnant or possibly pregnant women and patients who or whose partner desire -pregnancy during the study period
• Patients considered by the investigator or sub-investigator as unsuitable to participate in the study