A Study of the Safety and Efficacy of HPN-100 for Maintaining Remission in Subjects With Cirrhosis and Episodic Hepatic Encephalopathy (HALT-HE) - Full Text View

Purpose

This is a phase 2 study of HPN-100 in subjects with hepatic encephalopathy (HE) consisting of an open label safety lead-in (Part A), followed by randomized, double-blind, placebo-controlled treatment (Part B).

Condition	Intervention	Phase
Cirrhosis Hepatic Encephalopathy	Drug: HPN-100 (formerly known as GT4P) Drug: Placebo	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study of the Safety and Efficacy of HPN-100 for Maintaining Remission in Subjects With Cirrhosis and Episodic Hepatic Encephalopathy

Resource links provided by NLM:

Genetics Home Reference related topics: North American Indian childhood cirrhosis

MedlinePlus related topics: Cirrhosis

Drug Information available for: Glycerol phenylbutyrate

U.S. FDA Resources

Further study details as provided by Hyperion Therapeutics, Inc.:

Primary Outcome Measures:

Part A: The rate of AEs and tolerability of HPN-100. Part B: proportion of subjects who exhibit an HE episode, defined as either of the following during the treatment phase: WH ≥2; WH grade and asterixis grade increase of 1 each, if baseline WH = 0 [ Time Frame: Part A: 28 days, Part B: 112 Days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Secondary efficacy endpoints include the following: (1) Change from baseline in RBANS score, (2) Total HE episodes in the placebo and active arms, (3) Time to meeting the primary endpoint. [ Time Frame: 112 Days ] [ Designated as safety issue: No ]

Enrollment:	193
Study Start Date:	October 2009
Study Completion Date:	April 2012
Primary Completion Date:	April 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: HPN-100	Drug: HPN-100 (formerly known as GT4P) Part B: 6 mL BID for 16 weeks. Other Name: HPN-100
Placebo Comparator: Placebo	Drug: Placebo Part B: same as experimental arm

Detailed Description:

Part A: Open-label, dose-escalation lead-in to assess HPN-100 safety and PK Approximately 10 subjects with HE and cirrhosis classified as Child Pugh B or C will undergo a one-step dose escalation over 4 weeks. Subjects will initially receive 6 mL HPN-100 BID for 1 week. On Day 7 and following satisfactory safety assessment of the subject, the dose will be escalated to 9 mL BID for an additional 3 weeks.

In addition to a safety assessment, subjects will undergo 12-hour PK assessments on Days 7 and 28, with sampling at the following time points (relative to the first dose): 0 (pre-first daily dose of HPN-100), 2, 4, 8 (approximately 2 hours before the second daily dose of HPN 100), and 12 hours post-first dose (approximately 2 hours after the second daily dose of HPN-100). Additional PK samples will be collected on Days 8, 15, and 21 (at pre-first dose and 4 hours post-first dose).

The DSMB will review all safety information, including laboratory values, to determine if Part B may be initiated.

Subjects enrolled in Part A may be eligible for Part B as long as they meet the eligibility criteria.

Part B: Randomized, double-blind assessment of HPN-100 in HE subjects Subjects who meet all entry criteria and are judged to be compliant with their prescribed SOC will be eligible for randomization to receive either HPN-100 or matching placebo for 16 weeks. Efficacy will be assessed by the proportion of subjects experiencing episodes of HE, as well as by other outcome measures, including daily home assessments.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Subjects aged 18 and over
Clinical diagnosis of cirrhosis of any cause
Potential to benefit from HE treatment
History of greater than or equal to 2 documented episodes of WH Grade 2 or more HE within the past 6 months, at least one of which occurred within the preceding 3 months
No change in other HE-specific medications within 1 week before randomization
Able to give informed consent and comply with study activities
Availability of at least one designated family member or caregiver who is capable of and willing to assume responsibility for facilitating subject compliance with study procedures
All females of childbearing age and all sexually active males must agree to use an acceptable method of contraception throughout the study.

Exclusion Criteria:

Use of any investigational drug within 30 days
Use of prohibited medications
Uncontrolled infection
Active GI bleeding or a history of GI bleeding requiring blood transfusion (> 2 units) within 3 months
Transjugular intrahepatic portosystemic shunt (TIPS) placement or revision within the past 90 days
Recreational drug use or alcohol consumption for subjects with a history of alcohol or drug abuse within 6 months
Lactating and/or pregnant females
Active malignancy
Clinically significant bowel disease, including obstruction, inflammatory bowel disease, or malabsorption
Expected to undergo transplantation within 6 months
Model for end-stage liver disease (MELD) score of > 25

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00999167

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Locations

United States, California
Stanford University Medical Center, Division of Gastroenterology and Hepatology
Palo Alto, California, United States, 94304
United States, District of Columbia
Georgetown University Hospital
Washington, District of Columbia, United States, 20007
United States, Florida
University of Miami / Center for Liver Diseases
Miami, Florida, United States, 33136
Tampa General Hospital
Tampa, Florida, United States, 33606
United States, Illinois
The University of Chicago Medical Center
Chicago, Illinois, United States, 60637
United States, Indiana
Indiana University
Indianapolis, Indiana, United States, 46202
United States, Iowa
University of Iowa Hospitals and Clinics
Iowa City, Iowa, United States, 52242
United States, Kansas
University of Kansas Medical Center
Kansas City, Kansas, United States, 66160
United States, Louisiana
Tulane University Health Science Center
New Orleans, Louisiana, United States, 70112
United States, Maryland
University of Maryland
Baltimore, Maryland, United States, 21201
United States, Michigan
Henry Ford Hospital / Department of Gastroenterology
Detroit, Michigan, United States, 48202
United States, Nebraska
University of Nebraska Medical Center
Omaha, Nebraska, United States, 68198
United States, New Hampshire
Dartmouth Hitchcock Medical Center
Lebanon, New Hampshire, United States, 03756
United States, New York
Columbia University Medical Center / Center for Liver Disease and Transplantation
New York, New York, United States, 10032
Mount Sinai Medical Center
New York, New York, United States, 10029
NYU Medical Center
New York, New York, United States, 10016
Concorde Medical Group PLLC
New York, New York, United States, 10016
University of Rochester Medical Center
Rochester, New York, United States, 14642
New York Medical College / Westchester Medical Center
Valhalla, New York, United States, 10595
United States, Ohio
University of Cincinnati / Division of Digestive Diseases
Cincinnati, Ohio, United States, 45267
Cleveland Clinic
Cleveland, Ohio, United States, 44195
United States, Pennsylvania
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
United States, Tennessee
The Digestive Disease Center at Vanderbilt
Nashville, Tennessee, United States, 37232
United States, Texas
Methodist Dallas Medical Center
Dallas, Texas, United States, 75203
UT Southwestern Medical Center
Dallas, Texas, United States, 75390
Baylor College of Medicine-St. Luke's Episcopal Hospital
Houston, Texas, United States, 77030
United States, Virginia
University of Virginia Health System
Charlottesville, Virginia, United States, 22908
United States, Wisconsin
University of Wisconsin Hospital & Clinics
Madison, Wisconsin, United States, 53792

Sponsors and Collaborators

Hyperion Therapeutics, Inc.

More Information

No publications provided

Responsible Party:	Hyperion Therapeutics, Inc.
ClinicalTrials.gov Identifier:	NCT00999167 History of Changes
Other Study ID Numbers:	HPN-100-008
Study First Received:	October 8, 2009
Last Updated:	April 30, 2012
Health Authority:	United States: Food and Drug Administration

Keywords provided by Hyperion Therapeutics, Inc.:

Cirrhosis
Episodic Hepatic Encephalopathy
HE

HPN-100
GT4P
glycerol phenylbutyrate

Additional relevant MeSH terms:

Hepatic Encephalopathy
Liver Cirrhosis
Fibrosis
Brain Damage, Chronic
Delirium
Encephalitis
Neurotoxicity Syndromes
Liver Failure
Hepatic Insufficiency
Liver Diseases
Digestive System Diseases
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases

Nervous System Diseases
Metabolic Diseases
Pathologic Processes
Confusion
Neurobehavioral Manifestations
Neurologic Manifestations
Signs and Symptoms
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Central Nervous System Viral Diseases
Virus Diseases
Central Nervous System Infections
Poisoning
Substance-Related Disorders

ClinicalTrials.gov processed this record on June 18, 2013