A Phase 2a Study to Evaluate the Safety and Tolerability of OCR-002 (ornithine phenylacetate) in the Treatment of Patients with Acute Liver Failure/Severe Acute Liver Injury (STOP-ALF)

Study ID
STU 122011-059

Cancer Related
No

Healthy Volunteers
No

Study Sites

  • Clements University Hospital
  • UT Southwestern-Clinical Translational Research Center (CTRC)
  • Zale Lipshy University Hospital
  • Parkland Health & Hospital System

Contact
Angela Bowling
214/645-3971
angela.bowling@utsouthwestern.edu

Principal Investigator
William Lee, M.D.

Summary

approximately 18 subjects will be enrolled in Group 1 (minimal renal dysfunction) and 18 subjects in Group 2 (compromised renal function) based upon the following dose schedule:

-Study patients will receive the oCR-002 at 20g/24 hours for up to 5 days (total of 5 days of treatment).

Group 1 will have up to 6 evaluable study patients at uT Southwestern
Group 2 will have up to 6 evaluable study patients at uT Southwestern

Results of blood tests and pharmacokinetic (PK - how the study drug is processed by the body) studies will be reviewed periodically by the Safety Review Committee (SRC)

Procedures and evaluations While Receiving Study Drug
at regular intervals (time points) during the treatment period you will have the following tests and procedures. The time points for the study are:
* Day 1 x 0, 6, 12, 18, and 24 hours after starting study drug
* Day 2 x 30, 36, 42, and 48 hours after starting study drug
* Day 3 x 60 and 72 hours after starting study drug
* Day 4 x96 hours after starting study drug
* Day 5 x120 hours after starting study drug (when study medication is stopped)
* Day 6 x 144 hours (or 24 hours after stopping of study drug)

Participant Eligibility

To be consided eligible to participate in this study, as subject must meet the following inclusion criteria:
1. Men and women, ages 18-65 (have not reached their 66th birthday).
2. Acute liver failure, defined as the development of coagulopathy (International normalized ratio [INR] >=1.5) with encephalopathy in a patient with no prior history of liver disease, with onset of symptoms within 28 days of the inciting event. Patients may have a history of acetaminophen overdose (defined as >4 g/day within 7 days of presentation) and/or detectable acetaminophen levels in the serum, with a pattern of liver function tests typical for acetaminophen toxicity (bilirubin <10 mg/dL and alanine aminotransferase (ALT) >=1000 IU/L), or a diagnosis of hepatitis A, hepatitis B, drug-induced liver injury, autoimmune hepatitis or indeterminate cause.
3. ALI patients may also be enrolled (those meeting the above criteria plus coagulopathy (INR >= 2.0) and no evidence of encephalopathy).
4. Written informed consent from the patient (ALI) or patient[Single Quote]s legally authorized representative or family member if he/she is considered encephalopathic (ALF).
5. Ammonia level >60 [MICRO-SYMBOL]mol/L at baseline (within 8h prior to T0/initiation of infusion).
The conversion factor/units used for ammonia in recruiting sites is [MICRO-SYMBOL]mol/L to [MICRO-SYMBOL]g/dL. To obtain this conversion, divide the ammonia level in units of umol/L by 0.587 to convert the value to ug/dL units.

Example: (30 umol/L)/0.587 = 51 ug/dL (normal reference interval: 15-56 ug/dL)

6. Serum creatinine levels as follows:
a. Cohort 1: Creatinine < 1.5 mg/dL.
b. Cohort 2 only: Creatinine >= 1.5 mg/dL and 10 mg/dL.
7. Mean arterial pressure of >65 mmHg with no use of vasopressors and in Cohort 2 patients, after correction of hypovolemia.
8. Patients enrolled in the Acute Liver Failure Study (IRB #062010-126)