A Study of Safety and Efficacy of HPN-100 in Subjects With Cirrhosis and Episodic Hepatic Encephalopathy

NCT00999167 | Completed Phase 2 Results DMC

• 1 other identifier: HPN-100-008
• Study Type: interventional
• Target: 189
• Locations: 1 country
• Sites: 28

Brief Summary

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).

Conditions

Cirrhosis; Hepatic Encephalopathy

Keywords

Cirrhosis; Episodic Hepatic Encephalopathy; HE; HPN-100; GT4P; glycerol phenylbutyrate

Outcome Measures

Primary Outcomes (2)

• Part A: The Rate of AEs and Tolerability of HPN-100

  Part A: The rate of AEs and tolerability of 6 mL and 9 mL doses of HPN-100 were considered the primary safety endpoints for Part A. Safety assessments included adverse events, laboratory tests (including ammonia, hematology, coagulation, liver function and serum chemistry parameters), vital signs, physical and neurological examinations, and electrocardiograms.

  Part A: 28 days

• 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

  An HE event was defined as occurrences of either a West Haven (WH) Grade ≥2 or a WH Grade 1 and asterixis grade increase of 1 (if baseline WH = 0). The WH criteria are widely used for rating the severity of HE and are summarized below: Grade 1: trivial lack of awareness, euphoria or anxiety, shortened attention span, impaired performance of addition Grade 2: lethargy or apathy, minimal disorientation for time or place, subtle personality change, inappropriate behavior, impaired performance of subtraction Grade 3: somnolence to semi-stupor but responsive to verbal stimuli, confusion, gross disorientation Grade 4: coma (unresponsive to verbal or noxious stimuli) Asterixis was assessed after arm and forearm extension along with wrist dorsiflexion for 30 seconds and assigned a grade according to the following criteria: Grade 1: rare flaps Grade 2: occasional irregular flaps Grade 3: frequent flaps Grade 4: continuous flaps

  Part B: 112 Days

Secondary Outcomes (3)

• Total Number of HE Events

  112 Days

• Time to Meeting the Primary Endpoint

  112 Days

• Change From Baseline in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Score

  Day 56, Final Visit (D112)

Study Arms (2)

HPN-100

EXPERIMENTAL

Drug: HPN-100

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

HPN-100 DRUG

Part B: 6 mL BID for 16 weeks.

Also known as: GT4P

HPN-100

Placebo DRUG

Part B: same as experimental arm

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Amgen: lead

Study Sites (28)

Stanford University Medical Center, Division of Gastroenterology and Hepatology

Palo Alto, California, 94304, United States

Location

Georgetown University Hospital

Washington D.C., District of Columbia, 20007, United States

Location

University of Miami / Center for Liver Diseases

Miami, Florida, 33136, United States

Location

Tampa General Hospital

Tampa, Florida, 33606, United States

Location

The University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

Indiana University

Indianapolis, Indiana, 46202, United States

Location

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

Tulane University Health Science Center

New Orleans, Louisiana, 70112, United States

Location

University of Maryland

Baltimore, Maryland, 21201, United States

Location

Henry Ford Hospital / Department of Gastroenterology

Detroit, Michigan, 48202, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

Location

Concorde Medical Group PLLC

New York, New York, 10016, United States

Location

NYU Medical Center

New York, New York, 10016, United States

Location

Mount Sinai Medical Center

New York, New York, 10029, United States

Location

Columbia University Medical Center / Center for Liver Disease and Transplantation

New York, New York, 10032, United States

Location

University of Rochester Medical Center

Rochester, New York, 14642, United States

Location

New York Medical College / Westchester Medical Center

Valhalla, New York, 10595, United States

Location

University of Cincinnati / Division of Digestive Diseases

Cincinnati, Ohio, 45267, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

The Digestive Disease Center at Vanderbilt

Nashville, Tennessee, 37232, United States

Location

Methodist Dallas Medical Center

Dallas, Texas, 75203, United States

Location

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Baylor College of Medicine-St. Luke's Episcopal Hospital

Houston, Texas, 77030, United States

Location

University of Virginia Health System

Charlottesville, Virginia, 22908, United States

Location

University of Wisconsin Hospital & Clinics

Madison, Wisconsin, 53792, United States

Location

Related Publications (2)

• Rockey DC, Vierling JM, Mantry P, Ghabril M, Brown RS Jr, Alexeeva O, Zupanets IA, Grinevich V, Baranovsky A, Dudar L, Fadieienko G, Kharchenko N, Klaryts'ka I, Morozov V, Grewal P, McCashland T, Reddy KG, Reddy KR, Syplyviy V, Bass NM, Dickinson K, Norris C, Coakley D, Mokhtarani M, Scharschmidt BF; HALT-HE Study Group. Randomized, double-blind, controlled study of glycerol phenylbutyrate in hepatic encephalopathy. Hepatology. 2014 Mar;59(3):1073-83. doi: 10.1002/hep.26611.

  PMID: 23847109 RESULT

• Mokhtarani M, Diaz GA, Rhead W, Berry SA, Lichter-Konecki U, Feigenbaum A, Schulze A, Longo N, Bartley J, Berquist W, Gallagher R, Smith W, McCandless SE, Harding C, Rockey DC, Vierling JM, Mantry P, Ghabril M, Brown RS Jr, Dickinson K, Moors T, Norris C, Coakley D, Milikien DA, Nagamani SC, Lemons C, Lee B, Scharschmidt BF. Elevated phenylacetic acid levels do not correlate with adverse events in patients with urea cycle disorders or hepatic encephalopathy and can be predicted based on the plasma PAA to PAGN ratio. Mol Genet Metab. 2013 Dec;110(4):446-53. doi: 10.1016/j.ymgme.2013.09.017. Epub 2013 Oct 8.

  PMID: 24144944 DERIVED

MeSH Terms

Conditions

Fibrosis; Hepatic Encephalopathy

Interventions

glycerol phenylbutyrate

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Liver Failure; Hepatic Insufficiency; Liver Diseases; Digestive System Diseases; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: Julia Egofske
• Organization: Horizon Therapeutics, Inc.

clinicaltrials@horizonpharma.com

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 8, 2009
• First Posted: October 21, 2009
• Study Start: December 1, 2009
• Primary Completion: April 1, 2012
• Study Completion: April 1, 2012
• Last Updated: July 10, 2024
• Results First Posted: September 30, 2015

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.

Locations

US (28)