A Study of Terlipressin in Patients With Hepatorenal Syndrome Type 1 (HRS)

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.

Study Overview

• Status: Completed
• Conditions: Hepatorenal Syndrome Type 1
• Intervention / Treatment: Drug: Terlipressin

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Japan
  • Kansai, Japan
    • Investigational Site
  • Kanto, Japan
    • Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 79 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Terlipressin	Drug: Terlipressin

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Ferring Pharmaceuticals

Publications and helpful links

General Publications

• Narahara Y, Kanazawa H, Sakamoto C, Maruyama H, Yokosuka O, Mochida S, Uemura M, Fukui H, Sumino Y, Matsuzaki Y, Masaki N, Kokubu S, Okita K. The efficacy and safety of terlipressin and albumin in patients with type 1 hepatorenal syndrome: a multicenter, open-label, explorative study. J Gastroenterol. 2012 Mar;47(3):313-20. doi: 10.1007/s00535-011-0485-8. Epub 2011 Oct 25.

Study record dates

Study Major Dates

• Study Start: November 1, 2007
• Primary Completion (Actual): March 1, 2009
• Study Completion (Actual): December 1, 2009

Study Registration Dates

• First Submitted: June 10, 2011
• First Submitted That Met QC Criteria: June 14, 2011
• First Posted (Estimate): June 15, 2011

Study Record Updates

• Last Update Posted (Estimate): February 14, 2012
• Last Update Submitted That Met QC Criteria: February 13, 2012
• Last Verified: February 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Kidney Diseases; Urologic Diseases; Disease; Liver Diseases; Syndrome; Hepatorenal Syndrome; Antihypertensive Agents; Vasoconstrictor Agents; Terlipressin
• Other Study ID Numbers: FE999908 CS01