NCT01966419

Brief Summary

The purpose of this study is to determine whether ornithine phenylacetate can speed recovery from an acute hepatic encephalopathy episode requiring hospitalization in cirrhotic patients.

Trial Health

98
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Strong global presence with extensive site network
Enrollment
231

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started Jan 2014

Typical duration for phase_2

Geographic Reach
15 countries

127 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

October 11, 2013

Completed
10 days until next milestone

First Posted

Study publicly available on registry

October 21, 2013

Completed
3 months until next milestone

Study Start

First participant enrolled

January 7, 2014

Completed
3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 29, 2016

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 29, 2016

Completed
4.7 years until next milestone

Results Posted

Study results publicly available

September 16, 2021

Completed
Last Updated

September 16, 2021

Status Verified

August 1, 2021

Enrollment Period

3 years

First QC Date

October 11, 2013

Results QC Date

July 22, 2021

Last Update Submit

August 19, 2021

Conditions

Keywords

hepatic encephalopathyhyperammonemiacirrhosisornithine phenylacetateOCR-002

Outcome Measures

Primary Outcomes (1)

  • Percentage of Participants in Each HE Stage

    To support the primary endpoint of confirmed clinical response, the investigator rated participants on a 4-point staging scale, where higher scores are worse. The stages are described as: Stage 0/1 = Participant has no tremor of the hand when the wrist is extended (asterixis) and no confusion, even about where they are (disorientation) Stage 2 = Participant has tremor of the hand when the wrist is extended (asterixis) and is confused, not knowing where they are (disorientation) Stage 3 = Participant is tired, falling asleep, answers questions but is confused, and doesn't know where they are (Stupor, arousable but falls asleep, responsive to verbal stimuli, Obvious confusion, Gross disorientation) Stage 4 = Participant is unconscious (in a coma)

    Baseline to End of Study (through 3 hours post end-of-infusion)

Study Arms (2)

Ornithine phenylacetate

ACTIVE COMPARATOR

Participants receive ornithine phenylacetate for up to 5 days via continuous IV infusion in addition to standard of care (SOC)

Drug: ornithine phenylacetate

Placebo

PLACEBO COMPARATOR

Participants receive matching placebo up to 5 days via continuous IV infusion in addition to SOC

Drug: placebo intravenous infusion

Interventions

Ornithine phenylacetate for continuous IV infusion at dose levels predicated on level of hepatic decompensation

Also known as: OCR-002
Ornithine phenylacetate

Placebo for continuous IV infusion that is visually identical to the experimental product

Also known as: Matching Placebo
Placebo

Eligibility Criteria

Age18 Years - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Hospitalized with an acute episode of hepatic encephalopathy as complication of cirrhosis
  • Elevated venous ammonia

You may not qualify if:

  • Renal failure with serum creatinine \> 3 mg/dL or need for dialysis
  • Molecular Adsorbent Recirculation System utilized
  • Pregnancy or breastfeeding

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (131)

Unknown Facility

Phoenix, Arizona, 85006, United States

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Phoenix, Arizona, 85054, United States

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Little Rock, Arkansas, 72205, United States

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Coronado, California, 92118, United States

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Los Angeles, California, 90033, United States

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Los Angeles, California, 90048, United States

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San Francisco, California, 94115, United States

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San Francisco, California, 94143, United States

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New Haven, Connecticut, 06504, United States

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Miami, Florida, 33136, United States

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Atlanta, Georgia, 30309, United States

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Atlanta, Georgia, 30322, United States

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Chicago, Illinois, 60611, United States

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Chicago, Illinois, 60612, United States

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Chicago, Illinois, 60637, United States

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Glenview, Illinois, 60026, United States

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Iowa City, Iowa, 52242, United States

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Iowa City, Iowa, 52246, United States

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New Orleans, Louisiana, 70112, United States

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New Orleans, Louisiana, 70121, United States

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Baltimore, Maryland, 21201, United States

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Baltimore, Maryland, 21287, United States

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Bethesda, Maryland, 20814, United States

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Boston, Massachusetts, 02114, United States

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Boston, Massachusetts, 02215, United States

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Minneapolis, Minnesota, 55455, United States

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Jackson, Mississippi, 39216, United States

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Columbia, Missouri, 65212, United States

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Newark, New Jersey, 07103, United States

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Buffalo, New York, 14215, United States

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New York, New York, 10029, United States

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New York, New York, 10032, United States

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Chapel Hill, North Carolina, 27514, United States

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Columbus, Ohio, 43210, United States

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Philadelphia, Pennsylvania, 19104, United States

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Philadelphia, Pennsylvania, 19107, United States

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Philadelphia, Pennsylvania, 19141, United States

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Pittsburgh, Pennsylvania, 15213, United States

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Charleston, South Carolina, 29425, United States

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Nashville, Tennessee, 37232, United States

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Dallas, Texas, 75203, United States

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Dallas, Texas, 75235, United States

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Dallas, Texas, 75246, United States

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Dallas, Texas, 75390, United States

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Houston, Texas, 77030, United States

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Richmond, Virginia, 23249, United States

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Seattle, Washington, 98104, United States

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Seattle, Washington, 98195, United States

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Milwaukee, Wisconsin, 53226, United States

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Kingswood, New South Wales, 2747, Australia

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Adelaide, South Australia, 5000, Australia

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Bedford Park, South Australia, 5042, Australia

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Melbourne, Victoria, 3004, Australia

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Melbourne, 3065, Australia

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Parkville, 3050, Australia

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Graz, 8036, Austria

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Vienna, 1090, Austria

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Vienna, 1160, Austria

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Brussels, 1020, Belgium

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Brussels, 1070, Belgium

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Brussels, 1200, Belgium

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Ghent, 9000, Belgium

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Leuven, 3000, Belgium

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Sofia, 1431, Bulgaria

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Sofia, 1606, Bulgaria

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Brno, 625 00, Czechia

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Prague, 14021, Czechia

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Ústí nad Labem, 401 13, Czechia

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Aarhus, 8000, Denmark

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Copenhagen, 2100, Denmark

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Esbjerg, 6700, Denmark

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Hvidovre, 2650, Denmark

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Tartu, 51014, Estonia

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Bordeaux, 33000, France

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Grenoble, 38043, France

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La Roche, 85925, France

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Lille, 59037, France

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Lyon, 69317, France

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Nice, 06200, France

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Paris, 75651, France

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Pessac, 33604, France

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Toulouse, 31053, France

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Villejuif, 94800, France

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Hanover, Niedersachesen, D-30625, Germany

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Bonn, 53127, Germany

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Freiburg im Breisgau, 79106, Germany

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Halle, 06120, Germany

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Hamburg, 20246, Germany

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Heidelberg, 69120, Germany

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Leipzig, 04103, Germany

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Mainz, 55131, Germany

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Debrecen, 4031, Hungary

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Gyula, 5700, Hungary

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Kaposvár, 7400, Hungary

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Pécs, 7624, Hungary

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Haifa, 3109601, Israel

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Haifa, 3436212, Israel

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Jerusalem, 9112001, Israel

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Petah Tikva, 49372, Israel

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Ramat Gan, 49372, Israel

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Safed, 13100, Israel

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Tel Aviv, 64239, Israel

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Bergamo, 24127, Italy

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Bologna, 40138, Italy

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Florence, 50134, Italy

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Milan, 20122, Italy

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Palermo, 90141, Italy

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Roma, 00161, Italy

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Rozzano, 20089, Italy

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San Giovanni Rotondo, 71013, Italy

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Leiden, 2333 ZA, Netherlands

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Maastricht, 6229 HX, Netherlands

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Auckland, 1142, New Zealand

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Moscow, 111123, Russia

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Moscow, 117198, Russia

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Moscow, 119992, Russia

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Moscow, 129090, Russia

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Samara, 443011, Russia

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A Coruña, 15706, Spain

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Barcelona, 08035, Spain

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Barcelona, 08036, Spain

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Barcelona, 08041, Spain

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Girona, 17007, Spain

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Madrid, 28007, Spain

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Madrid, 28034, Spain

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Madrid, 28222, Spain

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Málaga, 29010, Spain

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Pontevedra, 36071, Spain

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Santander, 39008, Spain

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Seville, 41014, Spain

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Valencia, 46026, Spain

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Related Publications (3)

  • Safadi R, Rahimi RS, Thabut D, Bajaj JS, Ram Bhamidimarri K, Pyrsopoulos N, Potthoff A, Bukofzer S, Wang L, Jamil K, Devarakonda KR. Pharmacokinetics/pharmacodynamics of L-ornithine phenylacetate in overt hepatic encephalopathy and the effect of plasma ammonia concentration reduction on clinical outcomes. Clin Transl Sci. 2022 Jun;15(6):1449-1459. doi: 10.1111/cts.13257. Epub 2022 Mar 3.

  • Wang X, Vilchez RA. Population Pharmacokinetic Analysis to Assist Dose Selection of the L-Ornithine Salt of Phenylacetic Acid. Clin Pharmacokinet. 2022 Apr;61(4):515-526. doi: 10.1007/s40262-021-01075-1. Epub 2021 Nov 17.

  • Rahimi RS, Safadi R, Thabut D, Bhamidimarri KR, Pyrsopoulos N, Potthoff A, Bukofzer S, Bajaj JS. Efficacy and Safety of Ornithine Phenylacetate for Treating Overt Hepatic Encephalopathy in a Randomized Trial. Clin Gastroenterol Hepatol. 2021 Dec;19(12):2626-2635.e7. doi: 10.1016/j.cgh.2020.10.019. Epub 2020 Oct 16.

MeSH Terms

Conditions

Hepatic EncephalopathyHyperammonemiaFibrosis

Interventions

ornithine phenylacetate

Condition Hierarchy (Ancestors)

Liver FailureHepatic InsufficiencyLiver DiseasesDigestive System DiseasesBrain Diseases, MetabolicBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesMetabolic DiseasesNutritional and Metabolic DiseasesPathologic ProcessesPathological Conditions, Signs and Symptoms

Results Point of Contact

Title
Medical Information Call Center
Organization
Mallinckrodt

Study Officials

  • Clinical Team Leader

    Ocera Therapeutics, Inc.

    STUDY CHAIR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Masking Details
While the study was double-blind (participant and investigator blinded), the care provider and outcomes assessor were also blinded.
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 11, 2013

First Posted

October 21, 2013

Study Start

January 7, 2014

Primary Completion

December 29, 2016

Study Completion

December 29, 2016

Last Updated

September 16, 2021

Results First Posted

September 16, 2021

Record last verified: 2021-08

Data Sharing

IPD Sharing
Will not share

Discussion of statistical endpoints and analysis are included in manuscripts. Summary aggregate (basic) results (including adverse events information) and the study protocol are made available on clinicaltrials.gov (NCT01966419) when required by regulation. Individual de-identified patient data will not be disclosed. Requests for additional information should be directed to the company at medinfo@mnk.com.

Locations