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

NCT01906307 | Terminated Phase 1

• 1 other identifier: LJPC-501-CS-5001
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

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.

Conditions

Hepatorenal Syndrome Type I and Type II

Keywords

hepatorenal syndrome

Outcome Measures

Primary Outcomes (1)

• Adverse events through 5 days of treatment

  5 days

Secondary Outcomes (5)

• 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 Outcomes (1)

• Change in biomarkers of disease activity from baseline on Day 5

  baseline and Day 5

Study Arms (1)

LJPC-501

EXPERIMENTAL

LJPC-501, continuous infusion

Drug: LJPC-501

Interventions

LJPC-501 DRUG

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.

LJPC-501

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• La Jolla Pharmaceutical Company: lead

Study Sites (1)

Annette C. & Harold C. Simmons Transplant Institute @ Baylor University Medical Center

Dallas, Texas, 75246, United States

Location

MeSH Terms

Conditions

Hepatorenal Syndrome

Interventions

Angiotensin I

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Angiotensins; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Autacoids; Inflammation Mediators; Biological Factors

Study Officials

• George Tidmarsh, MD, PhD

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 17, 2013
• First Posted: July 24, 2013
• Study Start: March 1, 2014
• Primary Completion: November 1, 2015
• Study Completion: December 1, 2015
• Last Updated: March 3, 2016

Record last verified: 2016-03

Locations

US (1)