Clinical trial NCT01906307: A Phase 1 Study of LJPC-501 in Patients With Hepatorenal Syndrome
Official title: A Phase 1 Study of LJPC-501 in Patients With Hepatorenal Syndrome
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Hepatorenal Syndrome Type I and Type II
Keywords: hepatorenal syndrome
Lead sponsor: La Jolla Pharmaceutical Company
Sponsor class: INDUSTRY
First posted: 2013-07-24
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Adverse events through 5 days of treatment
timeFrame: 5 days
Secondary outcomes:
measure: Maximum Tolerated Dose
timeFrame: 5 days
measure: Effects on serum creatinine through 5 days of treatment
timeFrame: 5 days
measure: Effects on ascites through 5 days of treatment
timeFrame: 5 days
measure: Effects on urine output through 5 days of treatment
timeFrame: 5 days
measure: Effects on sodium excretion through 5 days of treatment
timeFrame: 5 days
Other outcomes:
measure: Change in biomarkers of disease activity from baseline on Day 5
timeFrame: baseline and Day 5
Locations:
city: Dallas
country: United States
facility: Annette C. & Harold C. Simmons Transplant Institute @ Baylor University Medical Center
state: Texas
Study officials:
name: George Tidmarsh, MD, PhD
role: STUDY_DIRECTOR
References: