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Phase 2B Efficacy/Safety of Ornithine Phenylacetate in Hospitalized Cirrhotic Patients With Hepatic Encephalopathy (STOP-HE) (STOP-HE)

Primary Purpose

Acute Episode of Overt Hepatic Encephalopathy, Hepatic Encephalopathy

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
ornithine phenylacetate
placebo intravenous infusion
Sponsored by
Ocera Therapeutics, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Episode of Overt Hepatic Encephalopathy focused on measuring hepatic encephalopathy, hyperammonemia, cirrhosis, ornithine phenylacetate, OCR-002

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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

Exclusion Criteria:

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

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Ornithine phenylacetate

Placebo

Arm Description

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

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

Outcomes

Primary Outcome Measures

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)

Secondary Outcome Measures

Full Information

First Posted
October 11, 2013
Last Updated
August 19, 2021
Sponsor
Ocera Therapeutics, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT01966419
Brief Title
Phase 2B Efficacy/Safety of Ornithine Phenylacetate in Hospitalized Cirrhotic Patients With Hepatic Encephalopathy (STOP-HE)
Acronym
STOP-HE
Official Title
Multicenter, Randomized Phase 2B Study to Evaluate the Efficacy, Safety and Tolerability of OCR-002 (Ornithine Phenylacetate) in Hospitalized Patients With Cirrhosis and Associated Hyperammonemia With an Episode of Hepatic Encephalopathy (STOP-HE Study)
Study Type
Interventional

2. Study Status

Record Verification Date
August 2021
Overall Recruitment Status
Completed
Study Start Date
January 7, 2014 (Actual)
Primary Completion Date
December 29, 2016 (Actual)
Study Completion Date
December 29, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ocera Therapeutics, Inc.

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.
Detailed Description
The primary objectives of the study were to evaluate the efficacy of OCR-002 for treatment of an acute hepatic encephalopathy (HE) episode in cirrhotic patients requiring hospitalization and the safety and tolerability of OCR-002 in hospitalized cirrhotic patients with an acute episode of HE.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Episode of Overt Hepatic Encephalopathy, Hepatic Encephalopathy
Keywords
hepatic encephalopathy, hyperammonemia, cirrhosis, ornithine phenylacetate, OCR-002

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Masking Description
While the study was double-blind (participant and investigator blinded), the care provider and outcomes assessor were also blinded.
Allocation
Randomized
Enrollment
231 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Ornithine phenylacetate
Arm Type
Active Comparator
Arm Description
Participants receive ornithine phenylacetate for up to 5 days via continuous IV infusion in addition to standard of care (SOC)
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Participants receive matching placebo up to 5 days via continuous IV infusion in addition to SOC
Intervention Type
Drug
Intervention Name(s)
ornithine phenylacetate
Other Intervention Name(s)
OCR-002
Intervention Description
Ornithine phenylacetate for continuous IV infusion at dose levels predicated on level of hepatic decompensation
Intervention Type
Drug
Intervention Name(s)
placebo intravenous infusion
Other Intervention Name(s)
Matching Placebo
Intervention Description
Placebo for continuous IV infusion that is visually identical to the experimental product
Primary Outcome Measure Information:
Title
Percentage of Participants in Each HE Stage
Description
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)
Time Frame
Baseline to End of Study (through 3 hours post end-of-infusion)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Hospitalized with an acute episode of hepatic encephalopathy as complication of cirrhosis Elevated venous ammonia Exclusion Criteria: Renal failure with serum creatinine > 3 mg/dL or need for dialysis Molecular Adsorbent Recirculation System utilized Pregnancy or breastfeeding
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Team Leader
Organizational Affiliation
Ocera Therapeutics, Inc.
Official's Role
Study Chair
Facility Information:
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85006
Country
United States
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85054
Country
United States
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72205
Country
United States
City
Coronado
State/Province
California
ZIP/Postal Code
92118
Country
United States
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
City
Los Angeles
State/Province
California
ZIP/Postal Code
90048
Country
United States
City
San Francisco
State/Province
California
ZIP/Postal Code
94115
Country
United States
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06504
Country
United States
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30309
Country
United States
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
City
Glenview
State/Province
Illinois
ZIP/Postal Code
60026
Country
United States
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52246
Country
United States
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70112
Country
United States
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70121
Country
United States
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20814
Country
United States
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
City
Jackson
State/Province
Mississippi
ZIP/Postal Code
39216
Country
United States
City
Columbia
State/Province
Missouri
ZIP/Postal Code
65212
Country
United States
City
Newark
State/Province
New Jersey
ZIP/Postal Code
07103
Country
United States
City
Buffalo
State/Province
New York
ZIP/Postal Code
14215
Country
United States
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27514
Country
United States
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19141
Country
United States
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
City
Dallas
State/Province
Texas
ZIP/Postal Code
75203
Country
United States
City
Dallas
State/Province
Texas
ZIP/Postal Code
75235
Country
United States
City
Dallas
State/Province
Texas
ZIP/Postal Code
75246
Country
United States
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23249
Country
United States
City
Seattle
State/Province
Washington
ZIP/Postal Code
98104
Country
United States
City
Seattle
State/Province
Washington
ZIP/Postal Code
98195
Country
United States
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
City
Kingswood
State/Province
New South Wales
ZIP/Postal Code
2747
Country
Australia
City
Adelaide
State/Province
South Australia
ZIP/Postal Code
5000
Country
Australia
City
Bedford Park
State/Province
South Australia
ZIP/Postal Code
5042
Country
Australia
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3004
Country
Australia
City
Melbourne
ZIP/Postal Code
3065
Country
Australia
City
Parkville
ZIP/Postal Code
3050
Country
Australia
City
Graz
ZIP/Postal Code
8036
Country
Austria
City
Vienna
ZIP/Postal Code
1090
Country
Austria
City
Wien
ZIP/Postal Code
1160
Country
Austria
City
Bruxelles
ZIP/Postal Code
1020
Country
Belgium
City
Bruxelles
ZIP/Postal Code
1070
Country
Belgium
City
Bruxelles
ZIP/Postal Code
1200
Country
Belgium
City
Gent
ZIP/Postal Code
9000
Country
Belgium
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
City
Sofia
ZIP/Postal Code
1431
Country
Bulgaria
City
Sofia
ZIP/Postal Code
1606
Country
Bulgaria
City
Brno
ZIP/Postal Code
625 00
Country
Czechia
City
Praha
ZIP/Postal Code
14021
Country
Czechia
City
Usti nad Labem
ZIP/Postal Code
401 13
Country
Czechia
City
Arhus
ZIP/Postal Code
8000
Country
Denmark
City
Copenhagen
ZIP/Postal Code
2100
Country
Denmark
City
Esbjerg
ZIP/Postal Code
6700
Country
Denmark
City
Hvidovre
ZIP/Postal Code
2650
Country
Denmark
City
Kobenhavn
ZIP/Postal Code
2100
Country
Denmark
City
Tartu
ZIP/Postal Code
51014
Country
Estonia
City
Bordeaux
ZIP/Postal Code
33000
Country
France
City
Grenoble
ZIP/Postal Code
38043
Country
France
City
La Roche
ZIP/Postal Code
85925
Country
France
City
Lille
ZIP/Postal Code
59037
Country
France
City
Lyon
ZIP/Postal Code
69317
Country
France
City
Nice
ZIP/Postal Code
06200
Country
France
City
Paris
ZIP/Postal Code
75651
Country
France
City
Pessac
ZIP/Postal Code
33604
Country
France
City
Toulouse
ZIP/Postal Code
31053
Country
France
City
Villejuif
ZIP/Postal Code
94800
Country
France
City
Hanover
State/Province
Niedersachesen
ZIP/Postal Code
D-30625
Country
Germany
City
Bonn
ZIP/Postal Code
53127
Country
Germany
City
Freiburg
ZIP/Postal Code
79106
Country
Germany
City
Halle
ZIP/Postal Code
06120
Country
Germany
City
Hamburg
ZIP/Postal Code
20246
Country
Germany
City
Heidelberg
ZIP/Postal Code
69120
Country
Germany
City
Leipzig
ZIP/Postal Code
04103
Country
Germany
City
Mainz
ZIP/Postal Code
55131
Country
Germany
City
Debrecen
ZIP/Postal Code
4031
Country
Hungary
City
Gyula
ZIP/Postal Code
5700
Country
Hungary
City
Kaposvar
ZIP/Postal Code
7400
Country
Hungary
City
Pecs
ZIP/Postal Code
7624
Country
Hungary
City
Haifa
ZIP/Postal Code
3109601
Country
Israel
City
Haifa
ZIP/Postal Code
3436212
Country
Israel
City
Jerusalem
ZIP/Postal Code
9112001
Country
Israel
City
Petah-Tikva
ZIP/Postal Code
49372
Country
Israel
City
Ramat-Gan
ZIP/Postal Code
49372
Country
Israel
City
Safed
ZIP/Postal Code
13100
Country
Israel
City
Tel Aviv
ZIP/Postal Code
64239
Country
Israel
City
Bergamo
ZIP/Postal Code
24127
Country
Italy
City
Bologna
ZIP/Postal Code
40138
Country
Italy
City
Firenze
ZIP/Postal Code
50134
Country
Italy
City
Milano
ZIP/Postal Code
20122
Country
Italy
City
Palermo
ZIP/Postal Code
90141
Country
Italy
City
Roma
ZIP/Postal Code
00161
Country
Italy
City
Rozzano
ZIP/Postal Code
20089
Country
Italy
City
San Giovanni Rotondo
ZIP/Postal Code
71013
Country
Italy
City
Leiden
ZIP/Postal Code
2333 ZA
Country
Netherlands
City
Maastricht
ZIP/Postal Code
6229 HX
Country
Netherlands
City
Auckland
ZIP/Postal Code
1142
Country
New Zealand
City
Moscow
ZIP/Postal Code
111123
Country
Russian Federation
City
Moscow
ZIP/Postal Code
117198
Country
Russian Federation
City
Moscow
ZIP/Postal Code
119992
Country
Russian Federation
City
Moscow
ZIP/Postal Code
129090
Country
Russian Federation
City
Samara
ZIP/Postal Code
443011
Country
Russian Federation
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
City
Barcelona
ZIP/Postal Code
08036
Country
Spain
City
Barcelona
ZIP/Postal Code
08041
Country
Spain
City
Girona
ZIP/Postal Code
17007
Country
Spain
City
La Coruña
ZIP/Postal Code
15706
Country
Spain
City
Madrid
ZIP/Postal Code
28007
Country
Spain
City
Madrid
ZIP/Postal Code
28034
Country
Spain
City
Madrid
ZIP/Postal Code
28222
Country
Spain
City
Malaga
ZIP/Postal Code
29010
Country
Spain
City
Pontevedra
ZIP/Postal Code
36071
Country
Spain
City
Santander
ZIP/Postal Code
39008
Country
Spain
City
Sevilla
ZIP/Postal Code
41014
Country
Spain
City
Valencia
ZIP/Postal Code
46026
Country
Spain

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
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.
Citations:
PubMed Identifier
35238476
Citation
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.
Results Reference
derived
PubMed Identifier
34786649
Citation
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.
Results Reference
derived
PubMed Identifier
33069881
Citation
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.
Results Reference
derived

Learn more about this trial

Phase 2B Efficacy/Safety of Ornithine Phenylacetate in Hospitalized Cirrhotic Patients With Hepatic Encephalopathy (STOP-HE)

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