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Study of the Safety, Pharmacokinetics and Efficacy of HPN-100, in Pediatric Subjects With Urea Cycle Disorders (UCDs)

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ClinicalTrials.gov Identifier: NCT01347073
Recruitment Status : Completed
First Posted : May 4, 2011
Results First Posted : May 28, 2015
Last Update Posted : January 16, 2017
Sponsor:
Information provided by (Responsible Party):
Horizon Pharma Ireland, Ltd., Dublin Ireland

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Urea Cycle Disorders
Intervention Drug: HPN-100
Enrollment 23

Recruitment Details

Study Locations: Houston, TX; Minneapolis, MN; Washington, DC; New York, NY; Cleveland, OH; Portland, ME; Portland, OR

Study Initiation Date: September 9, 2011 Study Completion Date: April 4, 2013

Pre-assignment Details This is an open-label, fixed-sequence NaPBA to HPN-100 switchover study with no control group.
Arm/Group Title HPN-100
Hide Arm/Group Description The first part of this open-label study consisted of a switch-over period during which patients were switched from the current medication (NaPBA) to HPN-100. The second part of this open-label study consisted of a 12-month long-term treatment phase with HPN-100. All participants in the switch-over were enrolled into the long-term treatment phase.
Period Title: Overall Study
Started 23
Completed 21
Not Completed 2
Reason Not Completed
Adverse Event             1
Liver Transplant             1
Arm/Group Title HPN-100
Hide Arm/Group Description The first part of this open-label study consisted of a switch-over period during which patients were switched from the current medication (NaPBA) to HPN-100. The second part of this open-label study consisted of a 12-month long-term treatment phase with HPN-100. All participants in the switch-over were enrolled into the long-term treatment phase.
Overall Number of Baseline Participants 23
Hide Baseline Analysis Population Description
Analyses were based on the safety population, defined as all patients who received any amount of study medication.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 23 participants
<=18 years
23
 100.0%
Between 18 and 65 years
0
   0.0%
>=65 years
0
   0.0%
Gender  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 23 participants
Female
12
  52.2%
Male
11
  47.8%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 23 participants
23
1.Primary Outcome
Title Adverse Events
Hide Description Rate of adverse events during the Switch-Over portion of the Protocol
Time Frame 2 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All patients who received any amount of study medication were included in this population, which is the primary population for all baseline, accountability, demographic and safety analyses.
Arm/Group Title NaPBA HPN-100
Hide Arm/Group Description:
Switch Over Arm
Switch Over and Long Term Treatment Arm
Overall Number of Participants Analyzed 15 15
Measure Type: Number
Unit of Measure: participants
0 6
2.Primary Outcome
Title Adverse Events
Hide Description Rate of adverse events during the Safety Extension portion of the protocol ( please note: HPN-100 treatment only during Safety Extension )
Time Frame 12 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All patients that entered the Safety Extension were included in the analysis of adverse events
Arm/Group Title HPN-100
Hide Arm/Group Description:
Long Term Treatment
Overall Number of Participants Analyzed 23
Measure Type: Number
Unit of Measure: participants
23
3.Secondary Outcome
Title Blood Ammonia
Hide Description 24-hour ammonia AUC of blood ammonia levels on Days 1 (NaPBA) and 10 (HPN-100) were compared. Ammonia was assessed at Hour 0 (pre-first dose, fasted), Hour 8 (~2-4 hours after lunch or the second main meal and dose of NaPBA), Hour 12 (~4 hours after the last main meal) and 24 hours post-first dose (pre-first dose on following day, fasted).
Time Frame 2 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All patients who received any amount of both study medications (NaPBA and HPN-100) were included in this population, which is the primary population for analysis of efficacy and pharmacokinetic parameters.
Arm/Group Title NaPBA HPN-100
Hide Arm/Group Description:
Switch Over
Switch Over and Long Term Treatment
Overall Number of Participants Analyzed 15 15
Mean (Standard Deviation)
Unit of Measure: umol/L*hours
914.43  (630.21) 647.63  (379.94)
4.Secondary Outcome
Title Frequency of Ammonia Levels Greater Than the Upper Limit of Normal (ULN) on HPN-100 Compared With NaPBA
Hide Description Ammonia values were converted to SI units (umol/L) and normalized to a standard ULN of 35 umol/L prior to analysis
Time Frame 2 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All patients who received any amount of both study medications (NaPBA and HPN-100) were included in this population, which is the primary population for analysis of efficacy and pharmacokinetic parameters.
Arm/Group Title NaPBA HPN-100
Hide Arm/Group Description:
Switch Over
Switch Over and Long Term Treatment
Overall Number of Participants Analyzed 15 15
Overall Number of Units Analyzed
Type of Units Analyzed: Ammonia Values
58 53
Measure Type: Number
Unit of Measure: Ammonia Values > ULN
22 8
5.Secondary Outcome
Title Hyperammonemic Crisis
Hide Description Rate of HAC during pre-enrollment on NaPBA compared to HAC during HPN-100 treatment
Time Frame 1 year
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Pre-enrollment Long-term Phase
Hide Arm/Group Description:
12-months preceding the study
The second part of this open-label study consisted of a 12-month long-term treatment phase with HPN-100. All participants in the switch-over were enrolled into the long-term treatment phase.
Overall Number of Participants Analyzed 23 23
Measure Type: Number
Unit of Measure: number of crises
29 12
Time Frame Approximately 1 year, 7 months (from study initiation date to 30 days after study completion date)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title HPN-100
Hide Arm/Group Description The first part of this open-label study consisted of a switch-over period during which patients were switched from the current medication (NaPBA) to HPN-100. The second part of this open-label study consisted of a 12-month long-term treatment phase with HPN-100. All participants in the switch-over were enrolled into the long-term treatment phase.
All-Cause Mortality
HPN-100
Affected / at Risk (%)
Total   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
HPN-100
Affected / at Risk (%)
Total   11/23 (47.83%) 
Gastrointestinal disorders   
Vomiting  1  2/23 (8.70%) 
Gastroenteritis  1  1/23 (4.35%) 
Injury, poisoning and procedural complications   
Chemical Burn  1  1/23 (4.35%) 
Metabolism and nutrition disorders   
Hyperammonemia  1  7/23 (30.43%) 
Hypophagia  1  2/23 (8.70%) 
Nervous system disorders   
Convulsion  1  2/23 (8.70%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 12.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
HPN-100
Affected / at Risk (%)
Total   23/23 (100.00%) 
Blood and lymphatic system disorders   
Lymphadenopathy  1  2/23 (8.70%) 
Neutropenia  1  2/23 (8.70%) 
Gastrointestinal disorders   
Diarrhea  1  6/23 (26.09%) 
Gastroesophageal reflux disease  1  2/23 (8.70%) 
Vomiting  1  12/23 (52.17%) 
General disorders   
Pyrexia  1  9/23 (39.13%) 
Infections and infestations   
Ear infection  1  2/23 (8.70%) 
Gastroenteritis  1  4/23 (17.39%) 
Otitis media  1  3/23 (13.04%) 
Upper respiratory tract infection  1  14/23 (60.87%) 
Investigations   
Alanine aminotransferase increased  1  2/23 (8.70%) 
Aspartate aminotransferase increased  1  2/23 (8.70%) 
Blood alkaline phosphatase increased  1  2/23 (8.70%) 
Blood bicarbonate decreased  1  2/23 (8.70%) 
Metabolism and nutrition disorders   
Decreased appetite  1  3/23 (13.04%) 
Hyperammonemia  1  7/23 (30.43%) 
Hypophagia  1  2/23 (8.70%) 
Nervous system disorders   
Convulsion  1  2/23 (8.70%) 
Hyporeflexia  1  2/23 (8.70%) 
Lethargy  1  2/23 (8.70%) 
Respiratory, thoracic and mediastinal disorders   
Cough  1  6/23 (26.09%) 
Nasal congestion  1  3/23 (13.04%) 
Rhinorrhea  1  4/23 (17.39%) 
Skin and subcutaneous tissue disorders   
Rash papular  1  3/23 (13.04%) 
Skin odor abnormal  1  2/23 (8.70%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 12.1
The protocol was designed to capture information important for evaluating safety, pharmacokinetics, and efficacy while recognizing sampling limitations in young children and current standard of care.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT 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.
Results Point of Contact
Name/Title: Craig James R.N. Associate Dir. UCD Clinical Operations
Organization: Hyperion Therapeutics, Inc.
Phone: (650) 745- 7480
Responsible Party: Horizon Pharma Ireland, Ltd., Dublin Ireland
ClinicalTrials.gov Identifier: NCT01347073     History of Changes
Other Study ID Numbers: HPN-100-012
First Submitted: April 29, 2011
First Posted: May 4, 2011
Results First Submitted: April 3, 2015
Results First Posted: May 28, 2015
Last Update Posted: January 16, 2017