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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

October 8, 2009
April 30, 2012
October 2009
April 2012   (final data collection date for primary outcome measure)
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 ]
  • Efficacy Endpoint (Part B):proportion of subjects who exhibit an HE episode, defined as either of the following during the treatment phase:WH Grade greater than or =2; WH grade and asterixis grade increase of 1 each, if baseline WH = 0
  • Safety Endpoint (Part A: )The rate of AEs and tolerability of 6mL and 9mL doses of HPN-100.
Complete list of historical versions of study NCT00999167 on ClinicalTrials.gov Archive Site
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 ]
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
Not Provided
Not Provided
 
A Study of the Safety and Efficacy of HPN-100 for Maintaining Remission in Subjects With Cirrhosis and Episodic Hepatic Encephalopathy (HALT-HE)
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

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).

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
  • Cirrhosis
  • Hepatic Encephalopathy
  • Drug: HPN-100 (formerly known as GT4P)
    Part B: 6 mL BID for 16 weeks.
    Other Name: HPN-100
  • Drug: Placebo
    Part B: same as experimental arm
  • Experimental: HPN-100
    Intervention: Drug: HPN-100 (formerly known as GT4P)
  • Placebo Comparator: Placebo
    Intervention: Drug: Placebo

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
193
April 2012
April 2012   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00999167
HPN-100-008
Yes
Hyperion Therapeutics, Inc.
Hyperion Therapeutics, Inc.
Not Provided
Not Provided
Hyperion Therapeutics, Inc.
January 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP