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Citation
Lee, William (2021). Safety Study of Ornithine Phenylacetate to Treat Patients With Acute Liver Failure/Severe Acute Liver Injury (STOP-ALF) (Version 1) [Dataset] NIDDK Central Repository. https://doi.org/10.58020/axdh-3c73
Data Availability Statement
Data from Safety Study of Ornithine Phenylacetate to Treat Patients With Acute Liver Failure/Severe Acute Liver Injury (STOP-ALF) [(Version 1) https://doi.org/10.58020/axdh-3c73] reported here are available for request at the NIDDK Central Repository (NIDDK-CR) website, Resources for Research (R4R), https://repository.niddk.nih.gov/.
Acknowledgement Statement
The STOP-ALF study was conducted by the study investigators and supported by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). The resources from the STOP-ALF (https://doi.org/10.58020/axdh-3c73) study reported here were supplied by NIDDK Central Repository (NIDDK-CR) and are available for request at https://repository.niddk.nih.gov. This manuscript was not prepared under the auspices of the STOP-ALF study and does not necessarily reflect the opinions or views of the STOP-ALF study, NIDDK-CR, or NIDDK.
Data Package Version
Version 1 (Updated on: Feb 24, 2021)
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  • Data Available for Request
  • Specimens Not Available
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General Description

There is strong experimental and clinical rationale for the use of ammonia-lowering therapies in ALF. Ammonia is normally produced in the gut and transformed by the liver into urea. As the liver fails, ammonia increases in the systemic circulation and enters into the brain. The result of a rapid rise in ammonia or related compounds in the cerebral circulation is hepatic encephalopathy (HE), a reversible neuropsychiatric condition that ranges in severity from mild impairment in attention, to delirium, the development of cerebral edema, coma and death. This is a Phase 2a, multi-center, open-label study, conducted in two cohorts in patients diagnosed with acute liver failure/acute liver injury (ALF/ALI) who meet inclusion/exclusion criteria.

This study is designed to provide data on OCR-002 with regards to the effect on circulating ammonia levels in patients with acute liver failure with and without impaired renal function at different doses after single and continuous infusion safety and dose tolerability as well as providing data on the metabolites, glutamine and phenylacetylglutamine in this patient population.

It is anticipated that this early efficacy, safety, tolerability, Pharmacokinetic/Pharmacodynamic (PK/PD) and dose-ranging study will lead to a Phase 3 development program for the use of OCR-002 in the treatment of hyperammonemia due to ALF. No clinical outcome measures will be formally studied because of the small sample size.

Objectives

The primary objective of the study was to evaluate the safety and tolerability of ascending doses of OPA in patients with ALF and severe ALI with and without renal impairment. Secondary objectives included the evaluation of the PK and pharmacodynamic profile of OPA in patients with ALI/ALF. Exploratory objectives included the evaluation of the effects of OPA on serum ammonia.

Outcome

Forty-seven patients with ALI/ALF were enrolled into the study, 36 of whom were predefined as evaluable (OPA infusion 72 hours) for measurement of ammonia-lowering efficacy (Table 1). The normal renal function cohort (serum creatinine level at screening of 1.5 mg/dL [n 5 30]) differed significantly from the impaired renal function cohort (creatinine level >1.5 mg/dL [n 5 17]) by percent female sex (80 versus 41%, respectively), the proportion with acetaminophen overdose as the etiology (83 versus 41%), and by definition, median serum creatinine (0.7 versus 2.5 mg/dL) and percent on continuous renal replacement therapy (CRRT; 3.3 versus 59%, respectively).

Research Area

Liver Disease

Study Type

Interventional

Study Start Date

2012-06

Study End Date

2017-02

Condition

Acute Liver Failure

Keywords

Pharmacokinetic/Pharmacodynamic, Phenylacetate, Hepatitis B, Autoimmune Hepatitis, Ornithine, Hepatic Encephalopathy, Renal Function Cohort, Acute Liver Failure, Acute Liver Injury, Acetaminophen Toxicity, Drug-Induced Liver Injury, Ammonia-Lowering Therapies

NIDDK Division

Division of Digestive Diseases and Nutrition

47
Participants

Target Population
Adults

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Permitted Use(s) of the Resources
  • Use is allowed only for the specified disease(s), disorder(s), condition(s), or research area(s): Acute Liver Failure ; Related Diseases
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Datasets (21)
Datasets Table
Dataset Name
Description
# of Records
# of Variables
File Format(s)
End of Study Dataset
Captures end of study data including date and reason for ending the study47sas7bdat (128 KB); csv (1.56 KB)
Ammonia Collection Log Dataset
Captures data including date/time/type/location of blood draw and ammonia levels reported in the Ammonia Collection Log627sas7bdat (128 KB); csv (22.83 KB)
Study Drug Monitoring Log Dataset
Captures study drug monitoring data1316sas7bdat (128 KB); csv (26.77 KB)
West Haven Scale for Hepatic Encephalopathy Dataset
Captures data from the West Haven Scale for Hepatic Encephalopathy, including sedation status and scale grade412sas7bdat (128 KB); csv (15.71 KB)
Glasgow Coma Scale Dataset
Captures data from the Glasgow Coma Scale, including sedation status, coma grade, eye opening, verbal and motor response 460sas7bdat (192 KB); csv (20.47 KB)
Day 30 Ammonia Dataset
Captures data at the Day 30 visit including date/time/type/location of blood draw and ammonia levels reported in the Ammonia Collection Log15sas7bdat (128 KB); csv (751 B)
Adverse Events Dataset
Captures adverse event data, including type, intubation status, relationship to study drug, severity, outcome, and date of resolution118sas7bdat (128 KB); csv (9.91 KB)
Electrocardiogram Dataset
Captures electrocardiogram data including date/time of scan, average QTc, and arrhythmia325sas7bdat (128 KB); csv (14.47 KB)
Pharmacokinetic Dataset
Pharmacokinetic data was read at a central laboratory and steady state values were calculated by a central reader46csv (3.14 KB); sas7bdat (128 KB)
End of Treatment Dataset
Captures end of treatment data, including status of treatment and reasons for premature study infusion termination47sas7bdat (128 KB); csv (1.53 KB)
Physical Exam Dataset
Captures physical exam data, including any abnormal findings460sas7bdat (192 KB); csv (18.55 KB)
Registry Dataset
Captures registry data, including etiology and indication of liver injury or liver failure, which are derived from the ALFSG registry database47sas7bdat (128 KB); csv (603 B)
Demographics Dataset
Captures demographic data47sas7bdat (128 KB); csv (1.76 KB)
Neurological Exam Dataset
Captures neurological data, including asterixis, pupillary, patellar, and biceps reflexes, babinski, and posturing408sas7bdat (192 KB); csv (18.07 KB)
Vital Signs Dataset
Captures vital signs data460sas7bdat (192 KB); csv (24.75 KB)
Urinalysis Dataset
Captures urinalysis results data207sas7bdat (128 KB); csv (9.74 KB)
The Orientation Log (O-Log) Dataset
Captures responses from the Orientation Log questions such as what city the participant is in and what year it is314sas7bdat (128 KB); csv (14.4 KB)
Medical History Dataset
Captures medical history data, including hospitalization and specific symptoms or signs47sas7bdat (128 KB); csv (4.88 KB)
Study Drug Infusion Log Dataset
Captures study drug infusion data including infusion site, start/stop time, highest MAP, lowest MAP, highest ICP, and lowest ICP109sas7bdat (128 KB); csv (3.94 KB)
Labs Dataset
Captures results from laboratory tests423sas7bdat (256 KB); csv (61.54 KB)
Eligibility Dataset
Captures eligibility data, including venous ammonia, creatinine, mean arterial pressure, medical history including chronic liver disease, and demographic information47sas7bdat (128 KB); csv (5.1 KB)