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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Horizon Pharma Ireland, Ltd., Dublin Ireland
ClinicalTrials.gov Identifier:
NCT00999167
First received: October 8, 2009
Last updated: August 27, 2015
Last verified: August 2015
Results First Received: July 1, 2015  
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
Conditions: Cirrhosis
Hepatic Encephalopathy
Interventions: Drug: HPN-100
Drug: Placebo

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Part A enrollment: 01 December 2009 to 24 February 2010 Part B enrollment: 01 June 2010 to 31 October 2011

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
The study consisted of Part A, an open-label, dose-escalation lead-in to assess HPN-100 safety and PK, followed by Part B, a randomized, placebo controlled study to assess safety and efficacy of HPN-100.

Reporting Groups
  Description
HPN-100 6 mL and 9 mL Subjects 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 a satisfactory safety assessment of the subject, the dose will be escalated to 9 mL BID for an additional 3 weeks.
HPN-100 6 mL Subjects will receive 6 mL BID HPN-100 for 16 weeks (Part B)
Placebo Subjects will receive 6 mL BID placebo for 16 weeks (Part B)

Participant Flow for 2 periods

Period 1:   Part A: Open Label Safety run-in
    HPN-100 6 mL and 9 mL     HPN-100 6 mL     Placebo  
STARTED     15     0     0  
Received 9 mL BID     15     0     0  
COMPLETED     8     0     0  
NOT COMPLETED     7     0     0  
Met protocol defined stopping rule                 4                 0                 0  
Adverse Event                 3                 0                 0  

Period 2:   Part B: Randomized, Placebo Controlled
    HPN-100 6 mL and 9 mL     HPN-100 6 mL     Placebo  
STARTED     0     90 [1]   88  
COMPLETED     0     55     67  
NOT COMPLETED     0     35     21  
Met protocol defined stopping rule                 0                 19                 16  
Withdrawal by Subject                 0                 7                 4  
Adverse Event                 0                 6                 1  
Noncompliance                 0                 1                 0  
Physician Decision                 0                 1                 0  
Physician stopped drug                 0                 1                 0  
[1] 4 subjects who participated in Part A enrolled in Part B and remainder were newly enrolled



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Only the baseline characteristics of the subjects enrolled in Part B are presented.

Reporting Groups
  Description
HPN-100 6 mL BID
Placebo 6 mL BID
Total Total of all reporting groups

Baseline Measures
    HPN-100     Placebo     Total  
Number of Participants  
[units: participants]
  90     88     178  
Age  
[units: participants]
     
<=18 years     0     0     0  
Between 18 and 65 years     85     78     163  
>=65 years     5     10     15  
Age  
[units: years]
Mean (Standard Deviation)
  53.8  (8.94)     55.4  (8.85)     54.6  (8.85)  
Gender  
[units: participants]
     
Female     45     29     74  
Male     45     59     104  
Region of Enrollment  
[units: participants]
     
United States     44     44     88  
Russian Federation     26     24     50  
Ukraine     20     20     40  



  Outcome Measures
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1.  Primary:   Part A: The Rate of AEs and Tolerability of HPN-100   [ Time Frame: Part A: 28 days ]

2.  Primary:   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 B: 112 Days ]

3.  Secondary:   Total Number of HE Events   [ Time Frame: 112 Days ]

4.  Secondary:   Time to Meeting the Primary Endpoint   [ Time Frame: 112 Days ]

5.  Secondary:   Change From Baseline in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Score   [ Time Frame: Day 56, Final Visit (D112) ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Julia Egofske
Organization: Horizon Therapeutics, Inc.
phone: 224-383-3078
e-mail: jegofske@horizonpharma.com


Publications of Results:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Horizon Pharma Ireland, Ltd., Dublin Ireland
ClinicalTrials.gov Identifier: NCT00999167     History of Changes
Other Study ID Numbers: HPN-100-008
Study First Received: October 8, 2009
Results First Received: July 1, 2015
Last Updated: August 27, 2015
Health Authority: United States: Food and Drug Administration