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

NCT ID: NCT00999167

Last Updated: 2024-07-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 189 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-12-31
• Study Completion Date: 2012-04-30

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).

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.

Study acquired from Horizon in 2024.

Conditions

Cirrhosis; Hepatic Encephalopathy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

HPN-100

Group Type: EXPERIMENTAL

HPN-100

Intervention Type: DRUG

Part B: 6 mL BID for 16 weeks.

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Part B: same as experimental arm

Interventions

HPN-100

Part B: 6 mL BID for 16 weeks.

Intervention Type: DRUG

Placebo

Part B: same as experimental arm

Intervention Type: DRUG

Other Intervention Names

GT4P

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Amgen

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

MD

Role: STUDY_DIRECTOR

Amgen

Locations

Stanford University Medical Center, Division of Gastroenterology and Hepatology

Palo Alto, California, United States

Georgetown University Hospital

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

University of Miami / Center for Liver Diseases

Miami, Florida, United States

Tampa General Hospital

Tampa, Florida, United States

The University of Chicago Medical Center

Chicago, Illinois, United States

Indiana University

Indianapolis, Indiana, United States

University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States

University of Kansas Medical Center

Kansas City, Kansas, United States

Tulane University Health Science Center

New Orleans, Louisiana, United States

University of Maryland

Baltimore, Maryland, United States

Henry Ford Hospital / Department of Gastroenterology

Detroit, Michigan, United States

University of Nebraska Medical Center

Omaha, Nebraska, United States

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, United States

Concorde Medical Group PLLC

New York, New York, United States

NYU Medical Center

New York, New York, United States

Mount Sinai Medical Center

New York, New York, United States

Columbia University Medical Center / Center for Liver Disease and Transplantation

New York, New York, United States

University of Rochester Medical Center

Rochester, New York, United States

New York Medical College / Westchester Medical Center

Valhalla, New York, United States

University of Cincinnati / Division of Digestive Diseases

Cincinnati, Ohio, United States

Cleveland Clinic

Cleveland, Ohio, United States

University of Pennsylvania

Philadelphia, Pennsylvania, United States

The Digestive Disease Center at Vanderbilt

Nashville, Tennessee, United States

Methodist Dallas Medical Center

Dallas, Texas, United States

UT Southwestern Medical Center

Dallas, Texas, United States

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

Houston, Texas, United States

University of Virginia Health System

Charlottesville, Virginia, United States

University of Wisconsin Hospital & Clinics

Madison, Wisconsin, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 23847109 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 24144944 (View on PubMed)

Other Identifiers

HPN-100-008

Identifier Type: -

Identifier Source: org_study_id