Back to resultsA Phase 1 Study of LJPC-501 in Patients With Hepatorenal Syndrome
Primary Purpose
Hepatorenal Syndrome Type I and Type II
Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
LJPC-501
Sponsored by
About this trial
This is an interventional treatment trial for Hepatorenal Syndrome Type I and Type II focused on measuring hepatorenal syndrome
Eligibility Criteria
Inclusion Criteria:
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
- Patient is able to undergo a reliable neurologic exam, as determined by the investigator
- Patient or legal surrogate is willing and able to provide written informed consent
- Patient is willing and able to comply with all protocol requirements
Exclusion Criteria:
- Evidence of shock
- Current or recent treatment with nephrotoxic drugs
- Use of midodrine, octreotide, or other vasopressors within 48 hours of screening
- Current treatment with dialysis
- Serum creatinine > 7 mg/dL
- Active cardiovascular disease within 3 months of screening
- History of transient ischemic attacks or prior stroke
- History of organ transplant
- 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)
- Participation in a clinical trial within 30 days of screening
- Patient unlikely to survive more than 72 hours in the opinion of the investigator
- Patient is pregnant or planning to become pregnant during study
Sites / Locations
- Annette C. & Harold C. Simmons Transplant Institute @ Baylor University Medical Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
LJPC-501
Arm Description
LJPC-501, continuous infusion
Outcomes
Primary Outcome Measures
Adverse events through 5 days of treatment
Secondary Outcome Measures
Maximum Tolerated Dose
Effects on serum creatinine through 5 days of treatment
Effects on ascites through 5 days of treatment
Effects on urine output through 5 days of treatment
Effects on sodium excretion through 5 days of treatment
Full Information
NCT ID
NCT01906307
First Posted
July 17, 2013
Last Updated
March 1, 2016
Sponsor
La Jolla Pharmaceutical Company
1. Study Identification
Unique Protocol Identification Number
NCT01906307
Brief Title
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
2. Study Status
Record Verification Date
March 2016
Overall Recruitment Status
Terminated
Why Stopped
Corporate decision
Study Start Date
March 2014 (undefined)
Primary Completion Date
November 2015 (Actual)
Study Completion Date
December 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
La Jolla Pharmaceutical Company
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatorenal Syndrome Type I and Type II
Keywords
hepatorenal syndrome
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
6 (Actual)
8. Arms, Groups, and Interventions
Arm Title
LJPC-501
Arm Type
Experimental
Arm Description
LJPC-501, continuous infusion
Intervention Type
Drug
Intervention Name(s)
LJPC-501
Intervention Description
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.
Primary Outcome Measure Information:
Title
Adverse events through 5 days of treatment
Time Frame
5 days
Secondary Outcome Measure Information:
Title
Maximum Tolerated Dose
Time Frame
5 days
Title
Effects on serum creatinine through 5 days of treatment
Time Frame
5 days
Title
Effects on ascites through 5 days of treatment
Time Frame
5 days
Title
Effects on urine output through 5 days of treatment
Time Frame
5 days
Title
Effects on sodium excretion through 5 days of treatment
Time Frame
5 days
Other Pre-specified Outcome Measures:
Title
Change in biomarkers of disease activity from baseline on Day 5
Time Frame
baseline and Day 5
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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
Patient is able to undergo a reliable neurologic exam, as determined by the investigator
Patient or legal surrogate is willing and able to provide written informed consent
Patient is willing and able to comply with all protocol requirements
Exclusion Criteria:
Evidence of shock
Current or recent treatment with nephrotoxic drugs
Use of midodrine, octreotide, or other vasopressors within 48 hours of screening
Current treatment with dialysis
Serum creatinine > 7 mg/dL
Active cardiovascular disease within 3 months of screening
History of transient ischemic attacks or prior stroke
History of organ transplant
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)
Participation in a clinical trial within 30 days of screening
Patient unlikely to survive more than 72 hours in the opinion of the investigator
Patient is pregnant or planning to become pregnant during study
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
George Tidmarsh, MD, PhD
Official's Role
Study Director
Facility Information:
Facility Name
Annette C. & Harold C. Simmons Transplant Institute @ Baylor University Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75246
Country
United States
12. IPD Sharing Statement
Learn more about this trial
A Phase 1 Study of LJPC-501 in Patients With Hepatorenal Syndrome
We'll reach out to this number within 24 hrs