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To Evaluate the Safety of Long-term Use of HPN-100 in the Management of Urea Cycle Disorders (UCDs)

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ClinicalTrials.gov Identifier: NCT01257737
Recruitment Status : Completed
First Posted : December 10, 2010
Results First Posted : May 4, 2018
Last Update Posted : May 4, 2018
Sponsor:
Information provided by (Responsible Party):
Horizon Pharma Ireland, Ltd., Dublin Ireland ( Horizon Therapeutics, LLC )

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 88

Recruitment Details  
Pre-assignment Details  
Arm/Group Title HPN-100- Pediatric HPN-100 - Adult
Hide Arm/Group Description Pediatric participants (age 1-17) continued HPN-100 treatment after completion of HPN-100-005SE, HPN-100-007, or HPN-100-012SE. Adult participants (age 19-61) continued HPN-100 treatment after completion of HPN-100-005SE, HPN-100-007, or HPN-100-012SE.
Period Title: Overall Study
Started 45 43
Completed 43 39
Not Completed 2 4
Reason Not Completed
Lost to Follow-up             1             2
Liver transplant             1             0
Relocation out of the country             0             1
Withdrew from study             0             1
Arm/Group Title HPN-100- Pediatric HPN-100 - Adult Total
Hide Arm/Group Description Pediatric participants (age 1-17) continued HPN-100 treatment after completion of HPN-100-005SE, HPN-100-007, or HPN-100-012SE. Adult participants (age 19-61) continued HPN-100 treatment after completion of HPN-100-005SE, HPN-100-007, or HPN-100-012SE. Total of all reporting groups
Overall Number of Baseline Participants 45 43 88
Hide Baseline Analysis Population Description
Safety Population: All participants who received any amount of study medication
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 45 participants 43 participants 88 participants
7.3  (4.33) 33.3  (11.90) 20.0  (15.76)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 45 participants 43 participants 88 participants
Female
32
  71.1%
26
  60.5%
58
  65.9%
Male
13
  28.9%
17
  39.5%
30
  34.1%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 45 participants 43 participants 88 participants
American Indian or Alaska Native
1
   2.2%
1
   2.3%
2
   2.3%
Asian
2
   4.4%
2
   4.7%
4
   4.5%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
3
   6.7%
2
   4.7%
5
   5.7%
White
38
  84.4%
36
  83.7%
74
  84.1%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
1
   2.2%
2
   4.7%
3
   3.4%
Urea Cycle Disorder Diagnosis  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 45 participants 43 participants 88 participants
Argininosuccinate synthetase (ASS) deficiency
7
  15.6%
2
   4.7%
9
  10.2%
Ornithine transcarbamylase (OTC) deficiency
26
  57.8%
35
  81.4%
61
  69.3%
Arginase (ARG) deficiency
1
   2.2%
1
   2.3%
2
   2.3%
Argininosuccinate lyase (ASL) deficiency
11
  24.4%
2
   4.7%
13
  14.8%
Hyperornithinemia-hyperammonemia-homocitrullinuria
0
   0.0%
3
   7.0%
3
   3.4%
1.Primary Outcome
Title Number of Participants With at Least One Adverse Event
Hide Description Safety was assessed by the incidence of treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events (SAEs). An AE/adverse experience was any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which did not necessarily have a causal relationship with this treatment. For additional information regarding adverse events, please see the safety section of the record.
Time Frame From the time of informed consent until 7 days after the last dose of study drug, up to 66 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety Population: All participants who received any amount of study medication
Arm/Group Title HPN-100- Pediatric HPN-100 - Adult
Hide Arm/Group Description:
Pediatric participants (age 1-17) continued HPN-100 treatment after completion of HPN-100-005SE, HPN-100-007, or HPN-100-012SE.
Adult participants (age 19-61) continued HPN-100 treatment after completion of HPN-100-005SE, HPN-100-007, or HPN-100-012SE.
Overall Number of Participants Analyzed 45 43
Measure Type: Count of Participants
Unit of Measure: Participants
34 40
2.Secondary Outcome
Title Mean Normalized Blood Ammonia Levels
Hide Description Blood samples were collected for the assessment of plasma ammonia concentrations at baseline, at least every 6 months, at all unscheduled visits, and at the end of study participation. Ammonia level data were obtained from different local laboratories and each laboratory may have used a slightly different normal reference range. Therefore, the ammonia level data were normalized to a standard laboratory reference range before performing any analysis of ammonia data.
Time Frame From baseline through the end of the study, up to 66 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants with available data
Arm/Group Title HPN-100- Pediatric HPN-100 - Adult
Hide Arm/Group Description:
Pediatric participants (age 1-17) continued HPN-100 treatment after completion of HPN-100-005SE, HPN-100-007, or HPN-100-012SE.
Adult participants (age 19-61) continued HPN-100 treatment after completion of HPN-100-005SE, HPN-100-007, or HPN-100-012SE.
Overall Number of Participants Analyzed 44 43
Mean (Standard Deviation)
Unit of Measure: μmol/L
Baseline Number Analyzed 44 participants 43 participants
19.445  (16.4478) 26.005  (23.4156)
Month 6 Number Analyzed 25 participants 38 participants
18.437  (14.7127) 24.235  (18.2070)
Month 12 Number Analyzed 23 participants 38 participants
18.236  (13.7955) 27.843  (20.3701)
Month 18 Number Analyzed 23 participants 39 participants
25.145  (26.2123) 31.378  (26.1624)
Month 24 Number Analyzed 11 participants 13 participants
15.428  (11.8506) 26.044  (12.5713)
Month 30 Number Analyzed 2 participants 4 participants
19.139  (15.1512) 31.140  (21.6156)
Month 36 Number Analyzed 1 participants 4 participants
9.265 39.890  (31.2392)
Month 42 Number Analyzed 1 participants 4 participants
10.294 21.360  (9.1448)
Month 48 Number Analyzed 1 participants 4 participants
53.529 15.956  (7.9071)
Month 54 Number Analyzed 1 participants 4 participants
42.206 45.810  (25.5722)
Month 60 Number Analyzed 1 participants 4 participants
42.21 50.175  (52.9026)
Month 66 Number Analyzed 1 participants 1 participants
9.26 9.26
End of Study Number Analyzed 39 participants 33 participants
20.412  (14.4513) 32.340  (31.2273)
3.Secondary Outcome
Title Number of Hyperammonemic Crises
Hide Description An hyperammonemic crisis (HAC) was defined as clinical symptoms associated with a venous ammonia concentration of ≥100 μmol/L.
Time Frame From the time of informed consent until 7 days after the last dose of study drug, up to 66 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety Population: All participants who received any amount of study medication
Arm/Group Title HPN-100- Pediatric HPN-100 - Adult
Hide Arm/Group Description:
Pediatric participants (age 1-17) continued HPN-100 treatment after completion of HPN-100-005SE, HPN-100-007, or HPN-100-012SE.
Adult participants (age 19-61) continued HPN-100 treatment after completion of HPN-100-005SE, HPN-100-007, or HPN-100-012SE.
Overall Number of Participants Analyzed 45 43
Measure Type: Number
Unit of Measure: Number of crises
22 22
4.Secondary Outcome
Title Causes of Hyperammonemic Crises
Hide Description An hyperammonemic crisis (HAC) was defined as clinical symptoms associated with a venous ammonia concentration of ≥100 μmol/L. Peak observed ammonia concentrations during an HAC, precipitating factors, and symptoms recorded as suggestive to hyperammonemia were documented. There can be multiple contributing factors to an hyperammonemic crisis; in some cases several causes were identified.
Time Frame From the time of informed consent until 7 days after the last dose of study drug, up to 66 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants who experienced hyperammonemic crises
Arm/Group Title HPN-100- Pediatric HPN-100 - Adult
Hide Arm/Group Description:
Pediatric participants (age 1-17) continued HPN-100 treatment after completion of HPN-100-005SE, HPN-100-007, or HPN-100-012SE.
Adult participants (age 19-61) continued HPN-100 treatment after completion of HPN-100-005SE, HPN-100-007, or HPN-100-012SE.
Overall Number of Participants Analyzed 11 10
Overall Number of Units Analyzed
Type of Units Analyzed: Hyperammonemic crises
22 22
Measure Type: Number
Unit of Measure: Number of crises
Change in Diet 0 4
Non-compliance with urea cycle disorder medication 1 0
Infection 6 0
Intercurrent illness 6 4
Non-compliance with study drug 2 4
Unknown 4 4
Other 5 9
None 1 4
5.Secondary Outcome
Title Mean Wechsler Abbreviated Scale of Intelligence (WASI) Scores
Hide Description The Wechsler Abbreviated Scale of Intelligence (WASI) was administered to adults and pediatric participants who were at least 6 years of age. It was used to estimate general intellectual ability (IQ) based on the vocabulary and matrix reasoning subtests. The vocabulary subtest included 4 images and 38 verbal items. In the matrix reasoning subtest, the participant viewed 35 incomplete grid patterns and was asked to complete the pattern using responses from 5 possible choices. The number of correct responses for each of the subtests was converted to a T-score using the WASI assessment manual; T-scores are standard scores with a mean of 50 and a standard deviation (SD) of 10. Raw scores for the 2 subtests were summed, and converted to a standard score (mean of 100 with SD of 15) for the general IQ score for adults and to a T-score for children in accordance with the WASI manual. Higher scores indicate a higher level of intelligence.
Time Frame Baseline, Month 12, Month 24, Month 36, Month 48, and study exit visit (up to 66 months)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants ≥ 6 years of age with available data; data were not analyzed for the 5 ongoing participants in Canada after the cutoff for the clinical study report (29 Oct 2015).
Arm/Group Title HPN-100- Pediatric HPN-100 - Adult
Hide Arm/Group Description:
Pediatric participants (age 1-17) continued HPN-100 treatment after completion of HPN-100-005SE, HPN-100-007, or HPN-100-012SE.
Adult participants (age 19-61) continued HPN-100 treatment after completion of HPN-100-005SE, HPN-100-007, or HPN-100-012SE.
Overall Number of Participants Analyzed 28 41
Mean (Standard Deviation)
Unit of Measure: T-score
Vocabulary T Score- Baseline Number Analyzed 28 participants 41 participants
46.5  (13.53) 45.2  (14.43)
Vocabulary T Score- Month 12 Number Analyzed 24 participants 35 participants
48.9  (11.66) 44.2  (15.59)
Vocabulary T Score- Month 24 Number Analyzed 9 participants 12 participants
44.9  (12.48) 45.2  (13.99)
Vocabulary T Score- Month 36 Number Analyzed 1 participants 2 participants
20.0 36.5  (23.33)
Vocabulary T Score- Month 48 Number Analyzed 1 participants 1 participants
20.0 20.0
Vocabulary T Score- Study Exit Number Analyzed 24 participants 36 participants
47.8  (11.42) 44.3  (15.87)
Matrix Reasoning T Score- Baseline Number Analyzed 27 participants 41 participants
46.8  (10.37) 45.5  (15.24)
Matrix Reasoning T Score- Month 12 Number Analyzed 24 participants 35 participants
48.8  (12.91) 46.5  (15.88)
Matrix Reasoning T Score- Month 24 Number Analyzed 9 participants 12 participants
50.0  (14.82) 48.0  (16.75)
Matrix Reasoning T Score- Month 36 Number Analyzed 1 participants 2 participants
20.0 44.5  (24.75)
Matrix Reasoning T Score- Month 48 Number Analyzed 1 participants 1 participants
20.0 25.0
Matrix Reasoning T Score- Study Exit Number Analyzed 24 participants 36 participants
49.2  (12.53) 46.1  (16.07)
Est. Full Scale IQ T Score- Baseline Number Analyzed 27 participants 0 participants
95.6  (17.07)
Est. Full Scale IQ T Score- Month 12 Number Analyzed 22 participants 0 participants
99.5  (18.72)
Est. Full Scale IQ T Score- Month 24 Number Analyzed 8 participants 0 participants
97.5  (21.58)
Est. Full Scale IQ T Score- Month 36 Number Analyzed 1 participants 0 participants
55
Est. Full Scale IQ T Score- Study Exit Number Analyzed 22 participants 0 participants
99.5  (18.18)
Est. Full Scale IQ Standard Score- Baseline Number Analyzed 0 participants 41 participants
95.1  (20.85)
Est. Full Scale IQ Standard Score- Month 12 Number Analyzed 2 participants 35 participants
92.0  (8.49) 93.9  (22.61)
Est. Full Scale IQ Standard Score- Month 24 Number Analyzed 1 participants 12 participants
97.0 94.7  (24.03)
Est. Full Scale IQ Standard Score- Month 36 Number Analyzed 0 participants 2 participants
85.5  (33.23)
Est. Full Scale IQ Standard Score- Month 48 Number Analyzed 1 participants 1 participants
51.0 55.0
Est. Full Scale IQ Standard Score- Study Exit Number Analyzed 4 participants 36 participants
85.5  (24.69) 93.5  (23.24)
6.Secondary Outcome
Title Mean Child Behavior Checklist (CBCL) Problems Scores
Hide Description The Child Behavior Checklist (CBCL) is a widely-used method of identifying problem behavior. Two versions of the CBCL were used in this study; the assessment for children 6-18 years of age was used for participants ≥6 years of age, and the assessment for children 1.5-5 years of age was used for those who were at least 5 years old but <6 years of age. Parents/caregivers answered questions (120 and 100 questions, respectively, for the older and younger populations) using a 3-point Likert scale (0= not true; 1= somewhat or sometimes true; 2 =very true or often true). Using a computer program, responses to similar questions were grouped together into 20 domains (e.g., activities, social, school, etc.), and domain response scores were converted to T-scores and percentiles. A mean score of 50 is average, with a standard deviation of 10 points. Higher scores indicate greater problems. The total problems score is the sum of all of the problem items.
Time Frame Baseline, Month 12, Month 24, and study exit visit (up to 66 months)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants 5-18 years of age with available data; data were not analyzed for the 1 ongoing pediatric participant in Canada after the cutoff for the clinical study report (29 Oct 2015).
Arm/Group Title HPN-100- Pediatric
Hide Arm/Group Description:
Pediatric participants (age 1-17) continued HPN-100 treatment after completion of HPN-100-005SE, HPN-100-007, or HPN-100-012SE.
Overall Number of Participants Analyzed 31
Mean (Standard Deviation)
Unit of Measure: T-Score
Internalizing Problems T Score- Baseline Number Analyzed 31 participants
53.4  (14.01)
Internalizing Problems T Score- Month 12 Number Analyzed 21 participants
52.5  (13.88)
Internalizing Problems T Score- Month 24 Number Analyzed 6 participants
55.5  (11.61)
Internalizing Problems T Score- Study Exit Number Analyzed 21 participants
52.5  (13.22)
Externalizing Problems T Score- Baseline Number Analyzed 31 participants
53.5  (13.19)
Externalizing Problems T Score- Month 12 Number Analyzed 21 participants
52.1  (10.51)
Externalizing Problems T Score- Month 24 Number Analyzed 6 participants
54.8  (9.68)
Externalizing Problems T Score- Study Exit Number Analyzed 21 participants
53.0  (10.30)
Affective Problems T Score- Baseline Number Analyzed 30 participants
59.2  (9.73)
Affective Problems T Score- Month 12 Number Analyzed 21 participants
57.5  (9.09)
Affective Problems T Score- Month 24 Number Analyzed 6 participants
59.3  (8.38)
Affective Problems T Score- Study Exit Number Analyzed 21 participants
57.7  (9.13)
Somatic Problems T Score- Baseline Number Analyzed 28 participants
55.6  (9.28)
Somatic Problems T Score- Month 12 Number Analyzed 21 participants
54.3  (5.40)
Somatic Problems T Score- Month 24 Number Analyzed 6 participants
54.8  (5.67)
Somatic Problems T Score- Study Exit Number Analyzed 20 participants
54.0  (5.25)
Attention-Def. Hyp. Problems T Score- Baseline Number Analyzed 29 participants
60.3  (7.88)
Attention-Def. Hyp. Problems T Score- Month 12 Number Analyzed 21 participants
60.5  (7.96)
Attention-Def. Hyp. Problems T Score- Month 24 Number Analyzed 6 participants
67.2  (9.87)
Attention-Def. Hyp. Problems T Score- Study Exit Number Analyzed 21 participants
61.1  (8.60)
Oppositional Defiant Problems T Score- Baseline Number Analyzed 30 participants
57.1  (7.52)
Oppositional Defiant Problems T Score- Month 12 Number Analyzed 21 participants
55.8  (8.61)
Oppositional Defiant Problems T Score- Month 24 Number Analyzed 6 participants
56.3  (7.31)
Oppositional Defiant Problems T Score- Study Exit Number Analyzed 21 participants
56.3  (8.60)
Conduct Problems T Score- Baseline Number Analyzed 28 participants
56.4  (8.42)
Conduct Problems T Score- Month 12 Number Analyzed 21 participants
54.7  (8.79)
Conduct Problems T Score- Month 24 Number Analyzed 6 participants
55.7  (5.68)
Conduct Problems T Score- Study Exit Number Analyzed 20 participants
55.5  (8.23)
Total Problems T Score- Baseline Number Analyzed 31 participants
56.2  (12.00)
Total Problems T Score- Month 12 Number Analyzed 21 participants
55.5  (10.20)
Total Problems T Score- Month 24 Number Analyzed 6 participants
58.8  (6.85)
Total Problems T Score- Study Exit Number Analyzed 21 participants
56.1  (9.99)
7.Secondary Outcome
Title Mean Behavior Rating Inventory of Executive Function (BRIEF) Scores
Hide Description The Behavior Rating Inventory of Executive Function (BRIEF) is designed to assess executive functioning in children and adolescents ages 5 to 18 years of age. Parents/caregivers answered 86 questions on a 3-point scale (never, sometimes, often). Similar questions were grouped together into 8 scales; these scales were summed to produce 2 index measures and a global executive composite score. Raw scores for the indices/scales and composite score were converted to T-scores with corresponding 90% confidence intervals using computer software. Higher T-scores indicate a higher level of dysfunction.
Time Frame Baseline, Month 12, Month 24, and study exit visit (up to 66 months)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants 5-18 years of age with available data; data were not analyzed for the 1 ongoing pediatric participant in Canada after the cutoff for the clinical study report (29 Oct 2015).
Arm/Group Title HPN-100- Pediatric
Hide Arm/Group Description:
Pediatric participants (age 1-17) continued HPN-100 treatment after completion of HPN-100-005SE, HPN-100-007, or HPN-100-012SE.
Overall Number of Participants Analyzed 30
Mean (Standard Deviation)
Unit of Measure: T-Score
Behavioral Regulation Index T Score- Baseline Number Analyzed 30 participants
54.0  (9.58)
Behavioral Regulation Index T Score- Month 12 Number Analyzed 21 participants
56.8  (10.96)
Behavioral Regulation Index T Score- Month 24 Number Analyzed 7 participants
57.3  (8.54)
Behavioral Regulation Index T Score- Study Exit Number Analyzed 22 participants
56.1  (9.92)
Metacognition Index T Score- Baseline Number Analyzed 30 participants
57.7  (9.41)
Metacognition Index T Score- Month 12 Number Analyzed 21 participants
59.0  (10.80)
Metacognition Index T Score- Month 24 Number Analyzed 7 participants
61.3  (13.17)
Metacognition Index T Score- Study Exit Number Analyzed 22 participants
59.2  (10.20)
Global Executive Composite T Score- Baseline Number Analyzed 30 participants
56.7  (8.95)
Global Executive Composite T Score- Month 12 Number Analyzed 21 participants
58.7  (10.18)
Global Executive Composite T Score- Month 24 Number Analyzed 7 participants
60.6  (11.33)
Global Executive Composite T Score- Study Exit Number Analyzed 22 participants
58.6  (9.52)
8.Secondary Outcome
Title Mean California Verbal Learning Test Scores: List A Total 1-5 T-Scores
Hide Description The California Verbal Learning Test – Second Edition (CVLT-II) assesses recall and recognition of word lists over several immediate- and delayed-memory trials. In the learning phase, adult participants were presented a list of 16 words (List A; 4 words each in 4 categories [e.g., fruit, toys, etc.]) for 5 trials, but words from the same category were never presented consecutively. An interference list (List B) of 16 different words was then presented for 1 trial. Short-and long-delay recalls for List A, yes/no recognition trials of List A, and a forced-choice recognition trial of List A was also administered. The total score for the 5 immediate-recall trials was converted to a T-score. Lower T-scores reflect worse performance.
Time Frame Baseline, Month 12, Month 24, Month 36, Month 48, and study exit visit (up to 66 months)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Adult participants (age 19-61) with available data; data were not analyzed for the 4 ongoing adult participants in Canada after the cutoff for the clinical study report (29 Oct 2015).
Arm/Group Title HPN-100 - Adult
Hide Arm/Group Description:
Adult participants (age 19-61) continued HPN-100 treatment after completion of HPN-100-005SE, HPN-100-007, or HPN-100-012SE.
Overall Number of Participants Analyzed 40
Mean (Standard Deviation)
Unit of Measure: T-Score
List A Total 1-5 T-Score- Baseline Number Analyzed 40 participants
45.3  (13.80)
List A Total 1-5 T-Score- Month 12 Number Analyzed 35 participants
45.4  (14.83)
List A Total 1-5 T-Score- Month 24 Number Analyzed 12 participants
48.3  (17.67)
List A Total 1-5 T-Score- Month 36 Number Analyzed 2 participants
30.0  (22.63)
List A Total 1-5 T-Score- Month 48 Number Analyzed 1 participants
19.0
List A Total 1-5 T-Score- Study Exit Number Analyzed 36 participants
46.3  (14.81)
9.Secondary Outcome
Title Mean California Verbal Learning Test Scores: Short and Long Delay Free Recall, Short and Long Delay Cued Recall, CVLT-II-Learning Slope, and Total Word Recognition Discrimination
Hide Description The California Verbal Learning Test – Second Edition (CVLT-II) assesses recall and recognition of word lists over several immediate- and delayed-memory trials. In the learning phase, adult participants were presented a list of 16 words (List A; 4 words each in 4 categories [e.g., fruit, toys, etc.]) for 5 trials, but words from the same category were never presented consecutively. An interference list (List B) of 16 different words was then presented for 1 trial. Short-and long-delay recalls for List A, yes/no recognition trials of List A, and a forced-choice recognition trial of List A was also administered. The scores for the learning slope, the short- and long-delay scores and total word recognition discrimination scores were converted to Z-scores by computer software. The CVLT-II Z-score has a mean of 0 and a standard deviation of 1. Negative scores indicate below-average performance.
Time Frame Baseline, Month 12, Month 24, Month 36, Month 48, and study exit visit (up to 66 months)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Adult participants (age 19-61) with available data; data were not analyzed for the 4 ongoing adult participants in Canada after the cutoff for the clinical study report (29 Oct 2015).
Arm/Group Title HPN-100 - Adult
Hide Arm/Group Description:
Adult participants (age 19-61) continued HPN-100 treatment after completion of HPN-100-005SE, HPN-100-007, or HPN-100-012SE.
Overall Number of Participants Analyzed 40
Mean (Standard Deviation)
Unit of Measure: Z-Score
Short Delay Free Recall Z Score- Baseline Number Analyzed 39 participants
-0.6  (1.72)
Short Delay Free Recall Z Score- Month 12 Number Analyzed 35 participants
-0.4  (1.50)
Short Delay Free Recall Z Score- Month 24 Number Analyzed 12 participants
-0.6  (1.82)
Short Delay Free Recall Z Score- Month 36 Number Analyzed 2 participants
-2.0  (2.83)
Short Delay Free Recall Z Score- Month 48 Number Analyzed 1 participants
-3.5
Short Delay Free Recall Z Score- Study Exit Number Analyzed 36 participants
-0.4  (1.47)
Short Delay Cued Recall Z Score- Baseline Number Analyzed 39 participants
-0.6  (1.50)
Short Delay Cued Recall Z Score- Month 12 Number Analyzed 35 participants
-0.4  (1.35)
Short Delay Cued Recall Z Score- Month 24 Number Analyzed 12 participants
-0.2  (1.35)
Short Delay Cued Recall Z Score- Month 36 Number Analyzed 2 participants
-1.8  (2.47)
Short Delay Cued Recall Z Score- Month 48 Number Analyzed 1 participants
-4.0
Short Delay Cued Recall Z Score- Study Exit Number Analyzed 36 participants
-0.3  (1.37)
Long Delay Free Recall Z Score- Baseline Number Analyzed 40 participants
-0.8  (1.72)
Long Delay Free Recall Z Score- Month 12 Number Analyzed 35 participants
-0.7  (1.61)
Long Delay Free Recall Z Score- Month 24 Number Analyzed 12 participants
-0.5  (2.12)
Long Delay Free Recall Z Score- Month 36 Number Analyzed 2 participants
-1.8  (3.18)
Long Delay Free Recall Z Score- Month 48 Number Analyzed 1 participants
-3.5
Long Delay Free Recall Z Score- Study Exit Number Analyzed 36 participants
-0.5  (1.75)
Long Delay Cued Recall Z Score- Baseline Number Analyzed 40 participants
-0.5  (1.50)
Long Delay Cued Recall Z Score- Month 12 Number Analyzed 35 participants
-0.6  (1.62)
Long Delay Cued Recall Z Score- Month 24 Number Analyzed 12 participants
-0.3  (1.75)
Long Delay Cued Recall Z Score- Month 36 Number Analyzed 2 participants
-1.8  (2.47)
Long Delay Cued Recall Z Score- Month 48 Number Analyzed 1 participants
-4.0
Long Delay Cued Recall Z Score- Study Exit Number Analyzed 36 participants
-0.4  (1.69)
CVLT-II-Learning Slope Z Score- Baseline Number Analyzed 39 participants
-0.7  (1.15)
CVLT-II-Learning Slope Z Score- Month 12 Number Analyzed 35 participants
-0.5  (1.51)
CVLT-II-Learning Slope Z Score- Month 24 Number Analyzed 12 participants
-0.8  (1.34)
CVLT-II-Learning Slope Z Score- Month 36 Number Analyzed 2 participants
-1.5  (1.41)
CVLT-II-Learning Slope Z Score- Month 48 Number Analyzed 1 participants
-2.5
CVLT-II-Learning Slope Z Score- Study Exit Number Analyzed 36 participants
-0.8  (1.36)
Total Recognition Discrim. Z Score- Baseline Number Analyzed 39 participants
-0.6  (1.48)
Total Recognition Discrim. Z Score- Month 12 Number Analyzed 35 participants
-0.6  (1.39)
Total Recognition Discrim. Z Score- Month 24 Number Analyzed 12 participants
-0.4  (2.00)
Total Recognition Discrim. Z Score- Month 36 Number Analyzed 2 participants
-3.0  (2.12)
Total Recognition Discrim. Z Score- Month 48 Number Analyzed 1 participants
-5.0
Total Recognition Discrim. Z Score- Study Exit Number Analyzed 36 participants
-0.6  (1.53)
Time Frame From the time of informed consent until 7 days after the last dose of study drug, up to 66 months
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title HPN-100- Pediatric HPN-100 - Adult
Hide Arm/Group Description Pediatric participants (age 1-17) continued HPN-100 treatment after completion of HPN-100-005SE, HPN-100-007, or HPN-100-012SE. Adult participants (age 19-61) continued HPN-100 treatment after completion of HPN-100-005SE, HPN-100-007, or HPN-100-012SE.
All-Cause Mortality
HPN-100- Pediatric HPN-100 - Adult
Affected / at Risk (%) Affected / at Risk (%)
Total   0/45 (0.00%)   0/43 (0.00%) 
Show Serious Adverse Events Hide Serious Adverse Events
HPN-100- Pediatric HPN-100 - Adult
Affected / at Risk (%) Affected / at Risk (%)
Total   12/45 (26.67%)   19/43 (44.19%) 
Gastrointestinal disorders     
Abdominal pain  1  0/45 (0.00%)  3/43 (6.98%) 
Abdominal pain lower  1  0/45 (0.00%)  1/43 (2.33%) 
Pancreatitis  1  0/45 (0.00%)  1/43 (2.33%) 
Vomiting  1  0/45 (0.00%)  1/43 (2.33%) 
Hepatobiliary disorders     
Biliary dyskinesia  1  0/45 (0.00%)  1/43 (2.33%) 
Infections and infestations     
Gastroenteritis  1  1/45 (2.22%)  0/43 (0.00%) 
Influenza  1  1/45 (2.22%)  0/43 (0.00%) 
Localised infection  1  0/45 (0.00%)  1/43 (2.33%) 
Mastoiditis  1  0/45 (0.00%)  1/43 (2.33%) 
Perirectal abscess  1  0/45 (0.00%)  1/43 (2.33%) 
Pharyngitis  1  0/45 (0.00%)  1/43 (2.33%) 
Injury, poisoning and procedural complications     
Femur fracture  1  0/45 (0.00%)  1/43 (2.33%) 
Procedural pain  1  0/45 (0.00%)  1/43 (2.33%) 
Spinal compression fracture  1  0/45 (0.00%)  1/43 (2.33%) 
Investigations     
Ammonia increased  1  0/45 (0.00%)  1/43 (2.33%) 
Metabolism and nutrition disorders     
Dehydration  1  2/45 (4.44%)  0/43 (0.00%) 
Hyperammonaemia  1  10/45 (22.22%)  12/43 (27.91%) 
Hypokalaemia  1  1/45 (2.22%)  0/43 (0.00%) 
Hyponatraemia  1  0/45 (0.00%)  1/43 (2.33%) 
Musculoskeletal and connective tissue disorders     
Back pain  1  0/45 (0.00%)  1/43 (2.33%) 
Nervous system disorders     
Convulsion  1  0/45 (0.00%)  1/43 (2.33%) 
Psychiatric disorders     
Psychological factor affecting medical condition  1  0/45 (0.00%)  1/43 (2.33%) 
Respiratory, thoracic and mediastinal disorders     
Bronchitis chronic  1  0/45 (0.00%)  1/43 (2.33%) 
Bronchospasm  1  0/45 (0.00%)  1/43 (2.33%) 
Hypocapnia  1  0/45 (0.00%)  1/43 (2.33%) 
Pneumothorax  1  0/45 (0.00%)  1/43 (2.33%) 
1
Term from vocabulary, MedDRA 12.1
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
HPN-100- Pediatric HPN-100 - Adult
Affected / at Risk (%) Affected / at Risk (%)
Total   26/45 (57.78%)   27/43 (62.79%) 
Gastrointestinal disorders     
Diarrhoea  1  3/45 (6.67%)  7/43 (16.28%) 
Nausea  1  2/45 (4.44%)  4/43 (9.30%) 
Vomiting  1  6/45 (13.33%)  5/43 (11.63%) 
General disorders     
Pain  1  1/45 (2.22%)  3/43 (6.98%) 
Pyrexia  1  3/45 (6.67%)  2/43 (4.65%) 
Infections and infestations     
Bronchitis  1  1/45 (2.22%)  5/43 (11.63%) 
Ear infection  1  3/45 (6.67%)  0/43 (0.00%) 
Sinusitis  1  1/45 (2.22%)  4/43 (9.30%) 
Upper respiratory tract infection  1  7/45 (15.56%)  8/43 (18.60%) 
Investigations     
Amino acid level decreased  1  3/45 (6.67%)  0/43 (0.00%) 
Amino acid level increased  1  3/45 (6.67%)  1/43 (2.33%) 
Ammonia increased  1  4/45 (8.89%)  6/43 (13.95%) 
Metabolism and nutrition disorders     
Dehydration  1  1/45 (2.22%)  3/43 (6.98%) 
Nervous system disorders     
Convulsion  1  0/45 (0.00%)  4/43 (9.30%) 
Dizziness  1  1/45 (2.22%)  4/43 (9.30%) 
Headache  1  6/45 (13.33%)  3/43 (6.98%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  3/45 (6.67%)  3/43 (6.98%) 
Oropharyngeal pain  1  2/45 (4.44%)  3/43 (6.98%) 
1
Term from vocabulary, MedDRA 12.1
Indicates events were collected by systematic assessment
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.
Horizon requests that any Investigator/institution that plans on presenting or publishing results provide written notification of their request a minimum of 60 days prior to presentation or publication. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsors’ Intellectual Property rights.
Results Point of Contact
Name/Title: Colleen Canavan, Director
Organization: Horizon Therapeutics, LLC
Phone: 1-224-383-3000
Responsible Party: Horizon Pharma Ireland, Ltd., Dublin Ireland ( Horizon Therapeutics, LLC )
ClinicalTrials.gov Identifier: NCT01257737     History of Changes
Other Study ID Numbers: HPN-100-011
First Submitted: December 2, 2010
First Posted: December 10, 2010
Results First Submitted: February 16, 2018
Results First Posted: May 4, 2018
Last Update Posted: May 4, 2018