ClinicalTrials.gov
ClinicalTrials.gov Menu

Study of the Safety and Tolerability of HPN-100 Compared to Sodium Phenylbutyrate in Children With Urea Cycle Disorders

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00947544
Recruitment Status : Completed
First Posted : July 28, 2009
Results First Posted : December 25, 2013
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
Interventions Drug: HPN-100
Drug: NaPBA
Enrollment 17
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Swich Over and Safety Extension Safety Extension Only
Hide Arm/Group Description NaPBA was dosed three times daily (TID) with during the first week and the same PBA mole-equivalent dose of HPN-100 during the second week. If there were safety concerns regarding a single-step transition from NaPBA to HPN-100, at the investigator's discretion, the transition could occur in 2 steps such that in the second week, subjects might receive 50% of the PBA equivalent dose as NaPBA and 50% as HPN-100 before receiving 100% of Serial blood samples were collected for PK and blood ammonia assessments after each drug reached steady state, which was achieved approximately 4 days after initiation of 100% NaPBA or HPN100 treatment. After the switch over, participants entered the safety extension part of the study and continued receiving open-label HPN-100 for up to 12 months. Participants entered the safety extension part of the study only, and received open-label HPN-100 for up to 12 months.
Period Title: Switch-Over Period (2 Weeks)
Started 11 0
Completed 11 0
Not Completed 0 0
Period Title: Safety-Extension Period (12 Months)
Started 11 6 [1]
Completed 10 6
Not Completed 1 0
Reason Not Completed
Withdrawal by Subject             1             0
[1]
New participants were enrolled due to DSMB approval.
Arm/Group Title Participants in SO and SE
Hide Arm/Group Description Patients who completed switch over study and enrolled safety extension study
Overall Number of Baseline Participants 17
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 17 participants
<=18 years
17
 100.0%
Between 18 and 65 years
0
   0.0%
>=65 years
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 17 participants
10  (3.482)
Gender  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 17 participants
Female
14
  82.4%
Male
3
  17.6%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 17 participants
United States 16
Canada 1
1.Primary Outcome
Title Rate of Adverse Events During the Switchover Part of the Study Rate of Adverse Events (Number of Participants Showing Adverse Events)
Hide Description To evaluate the safety and PK characteristics of HPN-100 compared with sodium phenylbutyrate (NaPBA) in pediatric patients with urea cycle disorders (UCDs)
Time Frame 1 week on each treatment for a total of 2 week.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title HPN-100 NaPBA
Hide Arm/Group Description:
HPN-100: Patients treated with HPN-100
NaPBA: Patients treated with NaPBA
Overall Number of Participants Analyzed 11 11
Measure Type: Number
Unit of Measure: participants
4 2
2.Secondary Outcome
Title Number and Causes of Hyperammonemic Events (Safety Extension)
Hide Description

Number of Subjects with at Least One Hyperammonemic Crisis.

Hyperammonemic crisis is defined as follows:

• Clinical symptoms associated with ammonia of ≥ 100 µmol/L

Time Frame 1 year
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Pre-Enrollment (NaPBA) Safety Extension (HPN-100)
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 17 17
Measure Type: Number
Unit of Measure: participants
Number of subjects with at least 1 HAC 5 3
Number of Crises 8 3
3.Secondary Outcome
Title Blood Ammonia Control
Hide Description To evaluate control of blood ammonia by HPN-100 compared with NaPBA in pediatric patients with UCDs.
Time Frame Day 7 (NaPBA) and Day 14 (HPN-100)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title HPN-100 NaPBA
Hide Arm/Group Description:
Patients treated with HPN-100
Patients treated with NaPBA
Overall Number of Participants Analyzed 11 11
Mean (Standard Deviation)
Unit of Measure: μmol∙h/L
603.83  (187.92) 814.62  (322.36)
4.Secondary Outcome
Title NH3 Cmax on NaPBA vs. HPN-100 on the Last Day of Treatment With Each Drug
Hide Description blood samples were collected at pre-dose, 4, 8, 12, 16, 20, and 24 hour post dose on both Day 7 (NaPBA) and Day 14 (HPN-100).
Time Frame Day 7 (NaPBA) and Day 14 (HPN-100)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title HPN-100 NaPBA
Hide Arm/Group Description:
Patients treated with HPN-100
Patients treated with NaPBA
Overall Number of Participants Analyzed 11 11
Mean (Standard Deviation)
Unit of Measure: μmol/L
47.77  (12.8) 55.66  (21.61)
5.Secondary Outcome
Title Average Ammonia Values on NaPBA vs. HPN-100 on the Last Day of Treatment With Each Drug (Switch Over)
Hide Description blood samples were collected at pre-dose, 4, 8, 12, 16, 20, and 24 hour post dose on both Day 7 (NaPBA) and Day 14 (HPN-100).
Time Frame Day 7 (NaPBA) and Day 14 (HPN-100)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title HPN-100 NaPBA
Hide Arm/Group Description:
Patients treated with HPN-100
Patients treated with NaPBA
Overall Number of Participants Analyzed 11 11
Mean (Standard Deviation)
Unit of Measure: µmol/L
28.68  (14.867) 37.75  (20.310)
6.Secondary Outcome
Title Rate (Percentage) of Ammonia Values Above Upper Limit of Normal (ULN) on NaPBA vs. HPN-100
Hide Description blood samples were collected at pre-dose, 4, 8, 12, 16, 20, and 24 hour post dose on both Day 7 (NaPBA) and Day 14 (HPN-100).
Time Frame Day 7 (NaPBA) and Day 14 (HPN-100)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title HPN-100 NaPBA
Hide Arm/Group Description:
Patients treated with HPN-100
Patients treated with NaPBA
Overall Number of Participants Analyzed 11 11
Overall Number of Units Analyzed
Type of Units Analyzed: Number of blood sample
76 76
Measure Type: Number
Unit of Measure: percentage of sample
18.4 31.6
7.Secondary Outcome
Title Urinary PAGN 24-hour Excretion Values on NaPBA vs. HPN-100 (Switch Over)
Hide Description Urinary PAGN (phenylacetylglutamine) 24-hour excretion. Urine was collect during 0-12 hrs and 12-24 hrs.
Time Frame Day 7 (NaPBA) and Day 14 (HPN-100)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title HPN-100 NaPBA
Hide Arm/Group Description:
Patients treated with HPN-100
Patients treated with NaPBA
Overall Number of Participants Analyzed 11 11
Mean (Standard Deviation)
Unit of Measure: μg
12501037  (56.9) 12512426  (51.3)
8.Secondary Outcome
Title Plasma PAA (Phenylacetate) AUC0-24 Values on NaPBA vs. HPN-100 on on the Last Day of Treatment With Each Drug
Hide Description blood samples were collected at pre-dose, 4, 8, 12, 16, 20, and 24 hour post dose on both Day 7 (NaPBA) and Day 14 (HPN-100).
Time Frame Day 7 (NaPBA) and Day 14 (HPN-100)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title HPN-100 NaPBA
Hide Arm/Group Description:
Patients treated with HPN-100
Patients treated with NaPBA
Overall Number of Participants Analyzed 11 11
Mean (Standard Deviation)
Unit of Measure: μg•h/mL AUC 0-24
964  (63.6) 773  (73.3)
9.Secondary Outcome
Title Plasma PBA (Phenylbutyrate) AUC0-24 Values on NaPBA vs. HPN-100 on on the Last Day of Treatment With Each Drug
Hide Description blood samples were collected at pre-dose, 4, 8, 12, 16, 20, and 24 hour post dose on both Day 7 (NaPBA) and Day 14 (HPN-100).
Time Frame Day 7 (NaPBA) and Day 14 (HPN-100)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title HPN-100 NaPBA
Hide Arm/Group Description:
Patients treated with HPN-100
Patients treated with NaPBA
Overall Number of Participants Analyzed 11 11
Mean (Standard Deviation)
Unit of Measure: µg*h/ml AUC 0-24
631  (44.9) 236  (105.2)
10.Secondary Outcome
Title Plasma PAGN AUC0-24 Values on NaPBA vs. HPN-100 on on the Last Day of Treatment With Each Drug
Hide Description blood samples were collected at pre-dose, 4, 8, 12, 16, 20, and 24 hour post dose on both Day 7 (NaPBA) and Day 14 (HPN-100).
Time Frame Day 7 (NaPBA) and Day 14 (HPN-100)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title HPN-100 NaPBA
Hide Arm/Group Description:
Patients treated with HPN-100
Patients treated with NaPBA
Overall Number of Participants Analyzed 11 11
Mean (Standard Deviation)
Unit of Measure: μg*h/mL AUC 0-24
1378  (40.2) 1015  (44.7)
11.Secondary Outcome
Title Quality of Life Assessed by the SF-15 Questionnaire
Hide Description

change from baseline to Month 12.

The SF 15 questionnaire consists of 15 questions that assess the following:

  • Physical functioning (5 questions)
  • Emotional functioning (4 questions)
  • Social functioning (3 questions)
  • School functioning (3 questions) Items were scored on a 5-point Likert scale from 0 (never) to 4 (almost always) or a 3-point scale (0 [not at all], 2 [sometimes], or 4 [a lot] for the young child self-report). Items were reverse-scored and linearly transformed to a 0–100 scale as follows: 0=100, 1=75, 2=50, 3=25, and 4=0. Total score was 0-100 scale (averaged from each functional areas). In the 0-100 scale, 0 is the worst score and 100 is best score.

Improved quality of life was shown by increased total score from baseline to Month 12.

Time Frame 1 year
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Patients who completed SF-15 at baseline and Month 12 both time in the safety extension period.
Arm/Group Title HPN-100
Hide Arm/Group Description:
Patients treated with HPN-100 who completed SF-15 at baseline and Month 12
Overall Number of Participants Analyzed 15
Overall Number of Units Analyzed
Type of Units Analyzed: Total score from SF-15 report
30
Mean (Standard Deviation)
Unit of Measure: score on a scale
4.0  (10.67)
Time Frame Safety Extension period only (from Day 15 to 1 year)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title HPN-100
Hide Arm/Group Description HPN-100: Patient treated with HPN-100
All-Cause Mortality
HPN-100
Affected / at Risk (%)
Total   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
HPN-100
Affected / at Risk (%)
Total   3/17 (17.65%) 
Gastrointestinal disorders   
gastroenteritis  1  1/17 (5.88%) 
Metabolism and nutrition disorders   
hyperammonemia  1  2/17 (11.76%) 
Psychiatric disorders   
Aggression  1  1/17 (5.88%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE (3.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
HPN-100
Affected / at Risk (%)
Total   4/17 (23.53%) 
Gastrointestinal disorders   
Abdominal pain upper  1  3/17 (17.65%) 
Vomiting  1  4/17 (23.53%) 
General disorders   
Pyrexia  1  2/17 (11.76%) 
Infections and infestations   
Upper respiratory tract infection  1  4/17 (23.53%) 
Nasopharyngitis  1  2/17 (11.76%) 
Sinusitis  1  2/17 (11.76%) 
Investigations   
ALT increased  1  2/17 (11.76%) 
Anion gap increased  1  2/17 (11.76%) 
AST increased  1  2/17 (11.76%) 
Metabolism and nutrition disorders   
Decreased appetite  1  2/17 (11.76%) 
Hyperammonemia  1  3/17 (17.65%) 
Nervous system disorders   
Headache  1  2/17 (11.76%) 
Respiratory, thoracic and mediastinal disorders   
Cough  1  2/17 (11.76%) 
Skin and subcutaneous tissue disorders   
Skin odour abnormal  1  2/17 (11.76%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE (3.0)
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.
Results Point of Contact
Name/Title: Craig James-Associate Director, Clinical Operations
Organization: Hyperion Therapeutics
Phone: 650-745-7840
Responsible Party: Horizon Pharma Ireland, Ltd., Dublin Ireland
ClinicalTrials.gov Identifier: NCT00947544     History of Changes
Other Study ID Numbers: HPN-100-005
First Submitted: July 24, 2009
First Posted: July 28, 2009
Results First Submitted: April 30, 2013
Results First Posted: December 25, 2013
Last Update Posted: January 16, 2017