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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hyperion Therapeutics, Inc.
ClinicalTrials.gov Identifier:
NCT00999167
First received: October 8, 2009
Last updated: April 30, 2012
Last verified: January 2012
  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:


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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

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Sponsors and Collaborators
Hyperion Therapeutics, Inc.
  More Information

No publications provided by Hyperion Therapeutics, Inc.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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:
Brain Diseases
Hepatic Encephalopathy
Liver Cirrhosis
Brain Diseases, Metabolic
Central Nervous System Diseases
Digestive System Diseases
Hepatic Insufficiency
Liver Diseases
Liver Failure
Metabolic Diseases
Nervous System Diseases

ClinicalTrials.gov processed this record on October 20, 2014