A Phase 1 Study of LJPC-501 in Patients With Hepatorenal Syndrome

Hepatorenal syndrome (HRS) is a life-threatening condition marked by rapid decline in kidney function in patients with liver cirrhosis or fulminant liver failure. Vasodilation in the gastrointestinal region is largely thought to contribute to the disease. LJPC-501 is a vasoconstrictor that may restore proper circulation and kidney function in patients with HRS.

Study Overview

• Status: Terminated
• Conditions: Hepatorenal Syndrome Type I and Type II
• Intervention / Treatment: Drug: LJPC-501

Detailed Description

Vasoconstrictors are considered a promising approach to treat HRS due to the significant vasodilation of the splanchnic circulation that contributes to systemic arterial underfilling and leads to functional decline of the kidney in these patients. Vasoconstrictors currently in use are associated with reduced organ perfusion and have marginal effect on sodium excretion. The vasoconstrictor angiotensin II has been shown to produce significant sodium excretion and urine output in patients with cirrhosis and ascites, supporting its potential utility in the treatment of HRS.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75246
      • Annette C. & Harold C. Simmons Transplant Institute @ Baylor University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients with HRS, as defined by the International Ascites Club [1]:

   • Cirrhosis with ascites
   • Serum creatinine > 1.5 mg/dL
   • No improvement of serum creatinine (decrease to a level of ≤ 1.5 mg/dL) after at least 2 days with diuretic withdrawal and volume expansion with albumin
   • Absence of shock
   • No current or recent treatment with nephrotoxic drugs
   • Absence of parenchymal kidney disease, as indicated by proteinuria > 500 mg/day, microhematuria (> 50 red blood cells per high power field) and/or abnormal renal ultrasonography

   Or patients with HRS due to acute alcoholic hepatitis

2. Patient is able to undergo a reliable neurologic exam, as determined by the investigator
3. Patient or legal surrogate is willing and able to provide written informed consent
4. Patient is willing and able to comply with all protocol requirements

Exclusion Criteria:

1. Evidence of shock
2. Current or recent treatment with nephrotoxic drugs
3. Use of midodrine, octreotide, or other vasopressors within 48 hours of screening
4. Current treatment with dialysis
5. Serum creatinine > 7 mg/dL
6. Active cardiovascular disease within 3 months of screening
7. History of transient ischemic attacks or prior stroke
8. History of organ transplant
9. Ongoing infection requiring intravenous administration of antibiotics (patients with documented infections considered by the Investigator to be controlled within 48 hours of screening may be permitted in the study upon consultation with the Sponsor's Medical Monitor)
10. Participation in a clinical trial within 30 days of screening
11. Patient unlikely to survive more than 72 hours in the opinion of the investigator
12. Patient is pregnant or planning to become pregnant during 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: LJPC-501; LJPC-501, continuous infusion

Drug: LJPC-501; Patients will receive LJPC-501 at titrated doses, with a starting range from 1 to 100 ng/kg/min, by continuous infusion on Days 1 through 5. In Group 1, drug doses will be titrated to 5, 15, and 25 ng/kg/min, after which doses will be titrated in multiples of 25 ng/kg/min. In Groups 2-5, drug doses will be titrated by 25 ng/kg/min. Dose titrations will occur every 2 hours until a MAP of 110 mmHg is reached, maximum urine output is achieved, or a dose of 250 ng/kg/min is achieved. Dosing will then continue at the maximum dose achieved through Day 5.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Adverse events through 5 days of treatment	5 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Maximum Tolerated Dose	5 days
Effects on serum creatinine through 5 days of treatment	5 days
Effects on ascites through 5 days of treatment	5 days
Effects on urine output through 5 days of treatment	5 days
Effects on sodium excretion through 5 days of treatment	5 days

Other Outcome Measures

Outcome Measure	Time Frame
Change in biomarkers of disease activity from baseline on Day 5	baseline and Day 5

Collaborators and Investigators

• Sponsor: La Jolla Pharmaceutical Company
• Investigators: Study Director: George Tidmarsh, MD, PhD

Study record dates

Study Major Dates

• Study Start: March 1, 2014
• Primary Completion (Actual): November 1, 2015
• Study Completion (Actual): December 1, 2015

Study Registration Dates

• First Submitted: July 17, 2013
• First Submitted That Met QC Criteria: July 23, 2013
• First Posted (Estimate): July 24, 2013

Study Record Updates

• Last Update Posted (Estimate): March 3, 2016
• Last Update Submitted That Met QC Criteria: March 1, 2016
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Keywords: hepatorenal syndrome
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Kidney Diseases; Urologic Diseases; Disease; Liver Diseases; Syndrome; Hepatorenal Syndrome; Vasoconstrictor Agents; Angiotensin II; Giapreza
• Other Study ID Numbers: LJPC-501-CS-5001