A Study of Terlipressin in Patients With Hepatorenal Syndrome Type 1

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

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

Conditions
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Hepatorenal Syndrome Type 1

Intervention / Treatment
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* Drug: Terlipressin


Participation Criteria
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Eligibility Criteria
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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] Chronic or acute liver disease with advanced hepatic failure and portal hypertension. Low glomerular filtration rate (SCr >1.5 mg/dL or 24h Ccr <40 mL/min) Absence of shock, ongoing bacterial infection, current or recent (within 2 weeks) treatment with nephrotoxic drug 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. 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

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 79 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Terlipressin<br> | Drug: Terlipressin<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in SCr value from baseline to end of treatment |  | 16 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events and its severity |  | Up to 84 days | 
| Laboratory test values |  | Up to 84 days | 
| Vital signs |  | 16 days | 
| ECG |  | Day 1,4,7,10,13,16 | 
| The percentage of patients with Hepatorenal syndrome reversal (SCr value <=1.5 mg/dL) |  | 16 days | 
| The percentage of patients showing 20% or more reduction in SCr value from the baseline |  | 16 days | 
| 24h Ccr, urine volume, urea nitrogen (BUN), urinary sodium excretions |  | 16 days | 
| Mean arterial blood pressure, serum Na, serum K, plasma renin activity, aldosterone, norepinephrine, antidiuretic hormone (ADH), atrial natriuresis peptide (ANP) |  | 16 days | 
| Overall survival |  | Up to 84 days | 
| Pharmacokinetics - assessment of blood concentration |  | Blood PK sample collection: pre-dose, 5, 15, 30, 60, 90, 120, 150, 180, 240, and 360 minutes post-dose |