Trial Outcomes & Findings for To Evaluate the Safety of Long-term Use of HPN-100 in the Management of Urea Cycle Disorders (UCDs) (NCT NCT01257737)
NCT ID: NCT01257737
Last Updated: 2024-08-22
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
88 participants
Primary outcome timeframe
From the time of informed consent until 7 days after the last dose of study drug, up to 66 months
Results posted on
2024-08-22
Participant Flow
Participant milestones
| Measure |
HPN-100- Pediatric
Pediatric participants (age 1-17) continued HPN-100 treatment after completion of HPN-100-005SE, HPN-100-007, or HPN-100-012SE.
|
HPN-100 - Adult
Adult participants (age 19-61) continued HPN-100 treatment after completion of HPN-100-005SE, HPN-100-007, or HPN-100-012SE.
|
|---|---|---|
|
Overall Study
STARTED
|
45
|
43
|
|
Overall Study
COMPLETED
|
43
|
39
|
|
Overall Study
NOT COMPLETED
|
2
|
4
|
Reasons for withdrawal
| Measure |
HPN-100- Pediatric
Pediatric participants (age 1-17) continued HPN-100 treatment after completion of HPN-100-005SE, HPN-100-007, or HPN-100-012SE.
|
HPN-100 - Adult
Adult participants (age 19-61) continued HPN-100 treatment after completion of HPN-100-005SE, HPN-100-007, or HPN-100-012SE.
|
|---|---|---|
|
Overall Study
Lost to Follow-up
|
1
|
2
|
|
Overall Study
Liver transplant
|
1
|
0
|
|
Overall Study
Relocation out of the country
|
0
|
1
|
|
Overall Study
Withdrew from study
|
0
|
1
|
Baseline Characteristics
To Evaluate the Safety of Long-term Use of HPN-100 in the Management of Urea Cycle Disorders (UCDs)
Baseline characteristics by cohort
| Measure |
HPN-100- Pediatric
n=45 Participants
Pediatric participants (age 1-17) continued HPN-100 treatment after completion of HPN-100-005SE, HPN-100-007, or HPN-100-012SE.
|
HPN-100 - Adult
n=43 Participants
Adult participants (age 19-61) continued HPN-100 treatment after completion of HPN-100-005SE, HPN-100-007, or HPN-100-012SE.
|
Total
n=88 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
7.3 years
STANDARD_DEVIATION 4.33 • n=5 Participants
|
33.3 years
STANDARD_DEVIATION 11.90 • n=7 Participants
|
20.0 years
STANDARD_DEVIATION 15.76 • n=5 Participants
|
|
Sex: Female, Male
Female
|
32 Participants
n=5 Participants
|
26 Participants
n=7 Participants
|
58 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
13 Participants
n=5 Participants
|
17 Participants
n=7 Participants
|
30 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
38 Participants
n=5 Participants
|
36 Participants
n=7 Participants
|
74 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Urea Cycle Disorder Diagnosis
Argininosuccinate synthetase (ASS) deficiency
|
7 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
|
Urea Cycle Disorder Diagnosis
Ornithine transcarbamylase (OTC) deficiency
|
26 Participants
n=5 Participants
|
35 Participants
n=7 Participants
|
61 Participants
n=5 Participants
|
|
Urea Cycle Disorder Diagnosis
Arginase (ARG) deficiency
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Urea Cycle Disorder Diagnosis
Argininosuccinate lyase (ASL) deficiency
|
11 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
|
Urea Cycle Disorder Diagnosis
Hyperornithinemia-hyperammonemia-homocitrullinuria
|
0 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: From the time of informed consent until 7 days after the last dose of study drug, up to 66 monthsPopulation: Safety Population: All participants who received any amount of study medication
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.
Outcome measures
| Measure |
HPN-100- Pediatric
n=45 Participants
Pediatric participants (age 1-17) continued HPN-100 treatment after completion of HPN-100-005SE, HPN-100-007, or HPN-100-012SE.
|
HPN-100 - Adult
n=43 Participants
Adult participants (age 19-61) continued HPN-100 treatment after completion of HPN-100-005SE, HPN-100-007, or HPN-100-012SE.
|
|---|---|---|
|
Number of Participants With at Least One Adverse Event
|
34 Participants
|
40 Participants
|
SECONDARY outcome
Timeframe: From baseline through the end of the study, up to 66 monthsPopulation: Participants with available data
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.
Outcome measures
| Measure |
HPN-100- Pediatric
n=44 Participants
Pediatric participants (age 1-17) continued HPN-100 treatment after completion of HPN-100-005SE, HPN-100-007, or HPN-100-012SE.
|
HPN-100 - Adult
n=43 Participants
Adult participants (age 19-61) continued HPN-100 treatment after completion of HPN-100-005SE, HPN-100-007, or HPN-100-012SE.
|
|---|---|---|
|
Mean Normalized Blood Ammonia Levels
Baseline
|
19.445 μmol/L
Standard Deviation 16.4478
|
26.005 μmol/L
Standard Deviation 23.4156
|
|
Mean Normalized Blood Ammonia Levels
Month 66
|
9.26 μmol/L
|
9.26 μmol/L
|
|
Mean Normalized Blood Ammonia Levels
Month 6
|
18.437 μmol/L
Standard Deviation 14.7127
|
24.235 μmol/L
Standard Deviation 18.2070
|
|
Mean Normalized Blood Ammonia Levels
Month 12
|
18.236 μmol/L
Standard Deviation 13.7955
|
27.843 μmol/L
Standard Deviation 20.3701
|
|
Mean Normalized Blood Ammonia Levels
Month 18
|
25.145 μmol/L
Standard Deviation 26.2123
|
31.378 μmol/L
Standard Deviation 26.1624
|
|
Mean Normalized Blood Ammonia Levels
Month 24
|
15.428 μmol/L
Standard Deviation 11.8506
|
26.044 μmol/L
Standard Deviation 12.5713
|
|
Mean Normalized Blood Ammonia Levels
Month 30
|
19.139 μmol/L
Standard Deviation 15.1512
|
31.140 μmol/L
Standard Deviation 21.6156
|
|
Mean Normalized Blood Ammonia Levels
Month 36
|
9.265 μmol/L
|
39.890 μmol/L
Standard Deviation 31.2392
|
|
Mean Normalized Blood Ammonia Levels
Month 42
|
10.294 μmol/L
|
21.360 μmol/L
Standard Deviation 9.1448
|
|
Mean Normalized Blood Ammonia Levels
Month 48
|
53.529 μmol/L
|
15.956 μmol/L
Standard Deviation 7.9071
|
|
Mean Normalized Blood Ammonia Levels
Month 54
|
42.206 μmol/L
|
45.810 μmol/L
Standard Deviation 25.5722
|
|
Mean Normalized Blood Ammonia Levels
Month 60
|
42.21 μmol/L
|
50.175 μmol/L
Standard Deviation 52.9026
|
|
Mean Normalized Blood Ammonia Levels
End of Study
|
20.412 μmol/L
Standard Deviation 14.4513
|
32.340 μmol/L
Standard Deviation 31.2273
|
SECONDARY outcome
Timeframe: From the time of informed consent until 7 days after the last dose of study drug, up to 66 monthsPopulation: Safety Population: All participants who received any amount of study medication
An hyperammonemic crisis (HAC) was defined as clinical symptoms associated with a venous ammonia concentration of ≥100 μmol/L.
Outcome measures
| Measure |
HPN-100- Pediatric
n=45 Participants
Pediatric participants (age 1-17) continued HPN-100 treatment after completion of HPN-100-005SE, HPN-100-007, or HPN-100-012SE.
|
HPN-100 - Adult
n=43 Participants
Adult participants (age 19-61) continued HPN-100 treatment after completion of HPN-100-005SE, HPN-100-007, or HPN-100-012SE.
|
|---|---|---|
|
Number of Hyperammonemic Crises
|
22 Number of crises
|
22 Number of crises
|
SECONDARY outcome
Timeframe: From the time of informed consent until 7 days after the last dose of study drug, up to 66 monthsPopulation: Participants who experienced hyperammonemic crises
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.
Outcome measures
| Measure |
HPN-100- Pediatric
n=22 Hyperammonemic crises
Pediatric participants (age 1-17) continued HPN-100 treatment after completion of HPN-100-005SE, HPN-100-007, or HPN-100-012SE.
|
HPN-100 - Adult
n=22 Hyperammonemic crises
Adult participants (age 19-61) continued HPN-100 treatment after completion of HPN-100-005SE, HPN-100-007, or HPN-100-012SE.
|
|---|---|---|
|
Causes of Hyperammonemic Crises
Intercurrent illness
|
6 Number of crises
|
4 Number of crises
|
|
Causes of Hyperammonemic Crises
Change in Diet
|
0 Number of crises
|
4 Number of crises
|
|
Causes of Hyperammonemic Crises
Non-compliance with urea cycle disorder medication
|
1 Number of crises
|
0 Number of crises
|
|
Causes of Hyperammonemic Crises
Infection
|
6 Number of crises
|
0 Number of crises
|
|
Causes of Hyperammonemic Crises
Non-compliance with study drug
|
2 Number of crises
|
4 Number of crises
|
|
Causes of Hyperammonemic Crises
Unknown
|
4 Number of crises
|
4 Number of crises
|
|
Causes of Hyperammonemic Crises
Other
|
5 Number of crises
|
9 Number of crises
|
|
Causes of Hyperammonemic Crises
None
|
1 Number of crises
|
4 Number of crises
|
SECONDARY outcome
Timeframe: Baseline, Month 12, Month 24, Month 36, Month 48, and study exit visit (up to 66 months)Population: 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).
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.
Outcome measures
| Measure |
HPN-100- Pediatric
n=28 Participants
Pediatric participants (age 1-17) continued HPN-100 treatment after completion of HPN-100-005SE, HPN-100-007, or HPN-100-012SE.
|
HPN-100 - Adult
n=41 Participants
Adult participants (age 19-61) continued HPN-100 treatment after completion of HPN-100-005SE, HPN-100-007, or HPN-100-012SE.
|
|---|---|---|
|
Mean Wechsler Abbreviated Scale of Intelligence (WASI) Scores
Vocabulary T Score- Baseline
|
46.5 T-score
Standard Deviation 13.53
|
45.2 T-score
Standard Deviation 14.43
|
|
Mean Wechsler Abbreviated Scale of Intelligence (WASI) Scores
Vocabulary T Score- Month 12
|
48.9 T-score
Standard Deviation 11.66
|
44.2 T-score
Standard Deviation 15.59
|
|
Mean Wechsler Abbreviated Scale of Intelligence (WASI) Scores
Vocabulary T Score- Month 24
|
44.9 T-score
Standard Deviation 12.48
|
45.2 T-score
Standard Deviation 13.99
|
|
Mean Wechsler Abbreviated Scale of Intelligence (WASI) Scores
Vocabulary T Score- Month 36
|
20.0 T-score
|
36.5 T-score
Standard Deviation 23.33
|
|
Mean Wechsler Abbreviated Scale of Intelligence (WASI) Scores
Vocabulary T Score- Month 48
|
20.0 T-score
|
20.0 T-score
|
|
Mean Wechsler Abbreviated Scale of Intelligence (WASI) Scores
Vocabulary T Score- Study Exit
|
47.8 T-score
Standard Deviation 11.42
|
44.3 T-score
Standard Deviation 15.87
|
|
Mean Wechsler Abbreviated Scale of Intelligence (WASI) Scores
Matrix Reasoning T Score- Baseline
|
46.8 T-score
Standard Deviation 10.37
|
45.5 T-score
Standard Deviation 15.24
|
|
Mean Wechsler Abbreviated Scale of Intelligence (WASI) Scores
Matrix Reasoning T Score- Month 12
|
48.8 T-score
Standard Deviation 12.91
|
46.5 T-score
Standard Deviation 15.88
|
|
Mean Wechsler Abbreviated Scale of Intelligence (WASI) Scores
Matrix Reasoning T Score- Month 24
|
50.0 T-score
Standard Deviation 14.82
|
48.0 T-score
Standard Deviation 16.75
|
|
Mean Wechsler Abbreviated Scale of Intelligence (WASI) Scores
Matrix Reasoning T Score- Month 36
|
20.0 T-score
|
44.5 T-score
Standard Deviation 24.75
|
|
Mean Wechsler Abbreviated Scale of Intelligence (WASI) Scores
Matrix Reasoning T Score- Month 48
|
20.0 T-score
|
25.0 T-score
|
|
Mean Wechsler Abbreviated Scale of Intelligence (WASI) Scores
Matrix Reasoning T Score- Study Exit
|
49.2 T-score
Standard Deviation 12.53
|
46.1 T-score
Standard Deviation 16.07
|
|
Mean Wechsler Abbreviated Scale of Intelligence (WASI) Scores
Est. Full Scale IQ T Score- Baseline
|
95.6 T-score
Standard Deviation 17.07
|
—
|
|
Mean Wechsler Abbreviated Scale of Intelligence (WASI) Scores
Est. Full Scale IQ T Score- Month 12
|
99.5 T-score
Standard Deviation 18.72
|
—
|
|
Mean Wechsler Abbreviated Scale of Intelligence (WASI) Scores
Est. Full Scale IQ T Score- Month 24
|
97.5 T-score
Standard Deviation 21.58
|
—
|
|
Mean Wechsler Abbreviated Scale of Intelligence (WASI) Scores
Est. Full Scale IQ T Score- Month 36
|
55 T-score
|
—
|
|
Mean Wechsler Abbreviated Scale of Intelligence (WASI) Scores
Est. Full Scale IQ T Score- Study Exit
|
99.5 T-score
Standard Deviation 18.18
|
—
|
|
Mean Wechsler Abbreviated Scale of Intelligence (WASI) Scores
Est. Full Scale IQ Standard Score- Baseline
|
—
|
95.1 T-score
Standard Deviation 20.85
|
|
Mean Wechsler Abbreviated Scale of Intelligence (WASI) Scores
Est. Full Scale IQ Standard Score- Month 12
|
92.0 T-score
Standard Deviation 8.49
|
93.9 T-score
Standard Deviation 22.61
|
|
Mean Wechsler Abbreviated Scale of Intelligence (WASI) Scores
Est. Full Scale IQ Standard Score- Month 24
|
97.0 T-score
|
94.7 T-score
Standard Deviation 24.03
|
|
Mean Wechsler Abbreviated Scale of Intelligence (WASI) Scores
Est. Full Scale IQ Standard Score- Month 36
|
—
|
85.5 T-score
Standard Deviation 33.23
|
|
Mean Wechsler Abbreviated Scale of Intelligence (WASI) Scores
Est. Full Scale IQ Standard Score- Month 48
|
51.0 T-score
|
55.0 T-score
|
|
Mean Wechsler Abbreviated Scale of Intelligence (WASI) Scores
Est. Full Scale IQ Standard Score- Study Exit
|
85.5 T-score
Standard Deviation 24.69
|
93.5 T-score
Standard Deviation 23.24
|
SECONDARY outcome
Timeframe: Baseline, Month 12, Month 24, and study exit visit (up to 66 months)Population: 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).
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.
Outcome measures
| Measure |
HPN-100- Pediatric
n=31 Participants
Pediatric participants (age 1-17) continued HPN-100 treatment after completion of HPN-100-005SE, HPN-100-007, or HPN-100-012SE.
|
HPN-100 - Adult
Adult participants (age 19-61) continued HPN-100 treatment after completion of HPN-100-005SE, HPN-100-007, or HPN-100-012SE.
|
|---|---|---|
|
Mean Child Behavior Checklist (CBCL) Problems Scores
Externalizing Problems T Score- Study Exit
|
53.0 T-Score
Standard Deviation 10.30
|
—
|
|
Mean Child Behavior Checklist (CBCL) Problems Scores
Affective Problems T Score- Baseline
|
59.2 T-Score
Standard Deviation 9.73
|
—
|
|
Mean Child Behavior Checklist (CBCL) Problems Scores
Affective Problems T Score- Month 12
|
57.5 T-Score
Standard Deviation 9.09
|
—
|
|
Mean Child Behavior Checklist (CBCL) Problems Scores
Affective Problems T Score- Month 24
|
59.3 T-Score
Standard Deviation 8.38
|
—
|
|
Mean Child Behavior Checklist (CBCL) Problems Scores
Affective Problems T Score- Study Exit
|
57.7 T-Score
Standard Deviation 9.13
|
—
|
|
Mean Child Behavior Checklist (CBCL) Problems Scores
Somatic Problems T Score- Baseline
|
55.6 T-Score
Standard Deviation 9.28
|
—
|
|
Mean Child Behavior Checklist (CBCL) Problems Scores
Somatic Problems T Score- Month 12
|
54.3 T-Score
Standard Deviation 5.40
|
—
|
|
Mean Child Behavior Checklist (CBCL) Problems Scores
Somatic Problems T Score- Month 24
|
54.8 T-Score
Standard Deviation 5.67
|
—
|
|
Mean Child Behavior Checklist (CBCL) Problems Scores
Somatic Problems T Score- Study Exit
|
54.0 T-Score
Standard Deviation 5.25
|
—
|
|
Mean Child Behavior Checklist (CBCL) Problems Scores
Attention-Def. Hyp. Problems T Score- Baseline
|
60.3 T-Score
Standard Deviation 7.88
|
—
|
|
Mean Child Behavior Checklist (CBCL) Problems Scores
Attention-Def. Hyp. Problems T Score- Month 12
|
60.5 T-Score
Standard Deviation 7.96
|
—
|
|
Mean Child Behavior Checklist (CBCL) Problems Scores
Attention-Def. Hyp. Problems T Score- Month 24
|
67.2 T-Score
Standard Deviation 9.87
|
—
|
|
Mean Child Behavior Checklist (CBCL) Problems Scores
Attention-Def. Hyp. Problems T Score- Study Exit
|
61.1 T-Score
Standard Deviation 8.60
|
—
|
|
Mean Child Behavior Checklist (CBCL) Problems Scores
Oppositional Defiant Problems T Score- Baseline
|
57.1 T-Score
Standard Deviation 7.52
|
—
|
|
Mean Child Behavior Checklist (CBCL) Problems Scores
Oppositional Defiant Problems T Score- Month 12
|
55.8 T-Score
Standard Deviation 8.61
|
—
|
|
Mean Child Behavior Checklist (CBCL) Problems Scores
Oppositional Defiant Problems T Score- Month 24
|
56.3 T-Score
Standard Deviation 7.31
|
—
|
|
Mean Child Behavior Checklist (CBCL) Problems Scores
Oppositional Defiant Problems T Score- Study Exit
|
56.3 T-Score
Standard Deviation 8.60
|
—
|
|
Mean Child Behavior Checklist (CBCL) Problems Scores
Conduct Problems T Score- Baseline
|
56.4 T-Score
Standard Deviation 8.42
|
—
|
|
Mean Child Behavior Checklist (CBCL) Problems Scores
Internalizing Problems T Score- Baseline
|
53.4 T-Score
Standard Deviation 14.01
|
—
|
|
Mean Child Behavior Checklist (CBCL) Problems Scores
Internalizing Problems T Score- Month 12
|
52.5 T-Score
Standard Deviation 13.88
|
—
|
|
Mean Child Behavior Checklist (CBCL) Problems Scores
Internalizing Problems T Score- Month 24
|
55.5 T-Score
Standard Deviation 11.61
|
—
|
|
Mean Child Behavior Checklist (CBCL) Problems Scores
Internalizing Problems T Score- Study Exit
|
52.5 T-Score
Standard Deviation 13.22
|
—
|
|
Mean Child Behavior Checklist (CBCL) Problems Scores
Externalizing Problems T Score- Baseline
|
53.5 T-Score
Standard Deviation 13.19
|
—
|
|
Mean Child Behavior Checklist (CBCL) Problems Scores
Externalizing Problems T Score- Month 12
|
52.1 T-Score
Standard Deviation 10.51
|
—
|
|
Mean Child Behavior Checklist (CBCL) Problems Scores
Externalizing Problems T Score- Month 24
|
54.8 T-Score
Standard Deviation 9.68
|
—
|
|
Mean Child Behavior Checklist (CBCL) Problems Scores
Conduct Problems T Score- Month 12
|
54.7 T-Score
Standard Deviation 8.79
|
—
|
|
Mean Child Behavior Checklist (CBCL) Problems Scores
Conduct Problems T Score- Month 24
|
55.7 T-Score
Standard Deviation 5.68
|
—
|
|
Mean Child Behavior Checklist (CBCL) Problems Scores
Conduct Problems T Score- Study Exit
|
55.5 T-Score
Standard Deviation 8.23
|
—
|
|
Mean Child Behavior Checklist (CBCL) Problems Scores
Total Problems T Score- Baseline
|
56.2 T-Score
Standard Deviation 12.00
|
—
|
|
Mean Child Behavior Checklist (CBCL) Problems Scores
Total Problems T Score- Month 12
|
55.5 T-Score
Standard Deviation 10.20
|
—
|
|
Mean Child Behavior Checklist (CBCL) Problems Scores
Total Problems T Score- Month 24
|
58.8 T-Score
Standard Deviation 6.85
|
—
|
|
Mean Child Behavior Checklist (CBCL) Problems Scores
Total Problems T Score- Study Exit
|
56.1 T-Score
Standard Deviation 9.99
|
—
|
SECONDARY outcome
Timeframe: Baseline, Month 12, Month 24, and study exit visit (up to 66 months)Population: 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).
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.
Outcome measures
| Measure |
HPN-100- Pediatric
n=30 Participants
Pediatric participants (age 1-17) continued HPN-100 treatment after completion of HPN-100-005SE, HPN-100-007, or HPN-100-012SE.
|
HPN-100 - Adult
Adult participants (age 19-61) continued HPN-100 treatment after completion of HPN-100-005SE, HPN-100-007, or HPN-100-012SE.
|
|---|---|---|
|
Mean Behavior Rating Inventory of Executive Function (BRIEF) Scores
Global Executive Composite T Score- Month 24
|
60.6 T-Score
Standard Deviation 11.33
|
—
|
|
Mean Behavior Rating Inventory of Executive Function (BRIEF) Scores
Global Executive Composite T Score- Study Exit
|
58.6 T-Score
Standard Deviation 9.52
|
—
|
|
Mean Behavior Rating Inventory of Executive Function (BRIEF) Scores
Behavioral Regulation Index T Score- Baseline
|
54.0 T-Score
Standard Deviation 9.58
|
—
|
|
Mean Behavior Rating Inventory of Executive Function (BRIEF) Scores
Behavioral Regulation Index T Score- Month 12
|
56.8 T-Score
Standard Deviation 10.96
|
—
|
|
Mean Behavior Rating Inventory of Executive Function (BRIEF) Scores
Behavioral Regulation Index T Score- Month 24
|
57.3 T-Score
Standard Deviation 8.54
|
—
|
|
Mean Behavior Rating Inventory of Executive Function (BRIEF) Scores
Behavioral Regulation Index T Score- Study Exit
|
56.1 T-Score
Standard Deviation 9.92
|
—
|
|
Mean Behavior Rating Inventory of Executive Function (BRIEF) Scores
Metacognition Index T Score- Baseline
|
57.7 T-Score
Standard Deviation 9.41
|
—
|
|
Mean Behavior Rating Inventory of Executive Function (BRIEF) Scores
Metacognition Index T Score- Month 12
|
59.0 T-Score
Standard Deviation 10.80
|
—
|
|
Mean Behavior Rating Inventory of Executive Function (BRIEF) Scores
Metacognition Index T Score- Month 24
|
61.3 T-Score
Standard Deviation 13.17
|
—
|
|
Mean Behavior Rating Inventory of Executive Function (BRIEF) Scores
Metacognition Index T Score- Study Exit
|
59.2 T-Score
Standard Deviation 10.20
|
—
|
|
Mean Behavior Rating Inventory of Executive Function (BRIEF) Scores
Global Executive Composite T Score- Baseline
|
56.7 T-Score
Standard Deviation 8.95
|
—
|
|
Mean Behavior Rating Inventory of Executive Function (BRIEF) Scores
Global Executive Composite T Score- Month 12
|
58.7 T-Score
Standard Deviation 10.18
|
—
|
SECONDARY outcome
Timeframe: Baseline, Month 12, Month 24, Month 36, Month 48, and study exit visit (up to 66 months)Population: 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).
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.
Outcome measures
| Measure |
HPN-100- Pediatric
n=40 Participants
Pediatric participants (age 1-17) continued HPN-100 treatment after completion of HPN-100-005SE, HPN-100-007, or HPN-100-012SE.
|
HPN-100 - Adult
Adult participants (age 19-61) continued HPN-100 treatment after completion of HPN-100-005SE, HPN-100-007, or HPN-100-012SE.
|
|---|---|---|
|
Mean California Verbal Learning Test Scores: List A Total 1-5 T-Scores
List A Total 1-5 T-Score- Month 48
|
19.0 T-Score
|
—
|
|
Mean California Verbal Learning Test Scores: List A Total 1-5 T-Scores
List A Total 1-5 T-Score- Baseline
|
45.3 T-Score
Standard Deviation 13.80
|
—
|
|
Mean California Verbal Learning Test Scores: List A Total 1-5 T-Scores
List A Total 1-5 T-Score- Month 12
|
45.4 T-Score
Standard Deviation 14.83
|
—
|
|
Mean California Verbal Learning Test Scores: List A Total 1-5 T-Scores
List A Total 1-5 T-Score- Month 24
|
48.3 T-Score
Standard Deviation 17.67
|
—
|
|
Mean California Verbal Learning Test Scores: List A Total 1-5 T-Scores
List A Total 1-5 T-Score- Month 36
|
30.0 T-Score
Standard Deviation 22.63
|
—
|
|
Mean California Verbal Learning Test Scores: List A Total 1-5 T-Scores
List A Total 1-5 T-Score- Study Exit
|
46.3 T-Score
Standard Deviation 14.81
|
—
|
SECONDARY outcome
Timeframe: Baseline, Month 12, Month 24, Month 36, Month 48, and study exit visit (up to 66 months)Population: 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).
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.
Outcome measures
| Measure |
HPN-100- Pediatric
n=40 Participants
Pediatric participants (age 1-17) continued HPN-100 treatment after completion of HPN-100-005SE, HPN-100-007, or HPN-100-012SE.
|
HPN-100 - Adult
Adult participants (age 19-61) continued HPN-100 treatment after completion of HPN-100-005SE, HPN-100-007, or HPN-100-012SE.
|
|---|---|---|
|
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
Short Delay Free Recall Z Score- Baseline
|
-0.6 Z-Score
Standard Deviation 1.72
|
—
|
|
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
Short Delay Free Recall Z Score- Month 12
|
-0.4 Z-Score
Standard Deviation 1.50
|
—
|
|
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
Short Delay Free Recall Z Score- Month 24
|
-0.6 Z-Score
Standard Deviation 1.82
|
—
|
|
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
Short Delay Free Recall Z Score- Month 36
|
-2.0 Z-Score
Standard Deviation 2.83
|
—
|
|
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
Short Delay Free Recall Z Score- Month 48
|
-3.5 Z-Score
|
—
|
|
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
Short Delay Free Recall Z Score- Study Exit
|
-0.4 Z-Score
Standard Deviation 1.47
|
—
|
|
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
Short Delay Cued Recall Z Score- Baseline
|
-0.6 Z-Score
Standard Deviation 1.50
|
—
|
|
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
Short Delay Cued Recall Z Score- Month 12
|
-0.4 Z-Score
Standard Deviation 1.35
|
—
|
|
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
Short Delay Cued Recall Z Score- Month 24
|
-0.2 Z-Score
Standard Deviation 1.35
|
—
|
|
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
Short Delay Cued Recall Z Score- Month 36
|
-1.8 Z-Score
Standard Deviation 2.47
|
—
|
|
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
Short Delay Cued Recall Z Score- Month 48
|
-4.0 Z-Score
|
—
|
|
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
Short Delay Cued Recall Z Score- Study Exit
|
-0.3 Z-Score
Standard Deviation 1.37
|
—
|
|
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
Long Delay Free Recall Z Score- Baseline
|
-0.8 Z-Score
Standard Deviation 1.72
|
—
|
|
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
Long Delay Free Recall Z Score- Month 12
|
-0.7 Z-Score
Standard Deviation 1.61
|
—
|
|
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
Long Delay Free Recall Z Score- Month 24
|
-0.5 Z-Score
Standard Deviation 2.12
|
—
|
|
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
Long Delay Free Recall Z Score- Month 36
|
-1.8 Z-Score
Standard Deviation 3.18
|
—
|
|
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
Long Delay Free Recall Z Score- Month 48
|
-3.5 Z-Score
|
—
|
|
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
Long Delay Free Recall Z Score- Study Exit
|
-0.5 Z-Score
Standard Deviation 1.75
|
—
|
|
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
Long Delay Cued Recall Z Score- Baseline
|
-0.5 Z-Score
Standard Deviation 1.50
|
—
|
|
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
Long Delay Cued Recall Z Score- Month 12
|
-0.6 Z-Score
Standard Deviation 1.62
|
—
|
|
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
Long Delay Cued Recall Z Score- Month 24
|
-0.3 Z-Score
Standard Deviation 1.75
|
—
|
|
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
Long Delay Cued Recall Z Score- Month 36
|
-1.8 Z-Score
Standard Deviation 2.47
|
—
|
|
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
Long Delay Cued Recall Z Score- Month 48
|
-4.0 Z-Score
|
—
|
|
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
Long Delay Cued Recall Z Score- Study Exit
|
-0.4 Z-Score
Standard Deviation 1.69
|
—
|
|
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
CVLT-II-Learning Slope Z Score- Baseline
|
-0.7 Z-Score
Standard Deviation 1.15
|
—
|
|
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
CVLT-II-Learning Slope Z Score- Month 12
|
-0.5 Z-Score
Standard Deviation 1.51
|
—
|
|
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
CVLT-II-Learning Slope Z Score- Month 24
|
-0.8 Z-Score
Standard Deviation 1.34
|
—
|
|
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
CVLT-II-Learning Slope Z Score- Month 36
|
-1.5 Z-Score
Standard Deviation 1.41
|
—
|
|
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
CVLT-II-Learning Slope Z Score- Month 48
|
-2.5 Z-Score
|
—
|
|
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
CVLT-II-Learning Slope Z Score- Study Exit
|
-0.8 Z-Score
Standard Deviation 1.36
|
—
|
|
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
Total Recognition Discrim. Z Score- Baseline
|
-0.6 Z-Score
Standard Deviation 1.48
|
—
|
|
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
Total Recognition Discrim. Z Score- Month 12
|
-0.6 Z-Score
Standard Deviation 1.39
|
—
|
|
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
Total Recognition Discrim. Z Score- Month 24
|
-0.4 Z-Score
Standard Deviation 2.00
|
—
|
|
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
Total Recognition Discrim. Z Score- Month 36
|
-3.0 Z-Score
Standard Deviation 2.12
|
—
|
|
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
Total Recognition Discrim. Z Score- Month 48
|
-5.0 Z-Score
|
—
|
|
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
Total Recognition Discrim. Z Score- Study Exit
|
-0.6 Z-Score
Standard Deviation 1.53
|
—
|
Adverse Events
HPN-100- Pediatric
Serious events: 12 serious events
Other events: 26 other events
Deaths: 0 deaths
HPN-100 - Adult
Serious events: 19 serious events
Other events: 27 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
HPN-100- Pediatric
n=45 participants at risk
Pediatric participants (age 1-17) continued HPN-100 treatment after completion of HPN-100-005SE, HPN-100-007, or HPN-100-012SE.
|
HPN-100 - Adult
n=43 participants at risk
Adult participants (age 19-61) continued HPN-100 treatment after completion of HPN-100-005SE, HPN-100-007, or HPN-100-012SE.
|
|---|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/45 • From the time of informed consent until 7 days after the last dose of study drug, up to 66 months
|
7.0%
3/43 • From the time of informed consent until 7 days after the last dose of study drug, up to 66 months
|
|
Gastrointestinal disorders
Abdominal pain lower
|
0.00%
0/45 • From the time of informed consent until 7 days after the last dose of study drug, up to 66 months
|
2.3%
1/43 • From the time of informed consent until 7 days after the last dose of study drug, up to 66 months
|
|
Gastrointestinal disorders
Pancreatitis
|
0.00%
0/45 • From the time of informed consent until 7 days after the last dose of study drug, up to 66 months
|
2.3%
1/43 • From the time of informed consent until 7 days after the last dose of study drug, up to 66 months
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/45 • From the time of informed consent until 7 days after the last dose of study drug, up to 66 months
|
2.3%
1/43 • From the time of informed consent until 7 days after the last dose of study drug, up to 66 months
|
|
Hepatobiliary disorders
Biliary dyskinesia
|
0.00%
0/45 • From the time of informed consent until 7 days after the last dose of study drug, up to 66 months
|
2.3%
1/43 • From the time of informed consent until 7 days after the last dose of study drug, up to 66 months
|
|
Infections and infestations
Gastroenteritis
|
2.2%
1/45 • From the time of informed consent until 7 days after the last dose of study drug, up to 66 months
|
0.00%
0/43 • From the time of informed consent until 7 days after the last dose of study drug, up to 66 months
|
|
Infections and infestations
Influenza
|
2.2%
1/45 • From the time of informed consent until 7 days after the last dose of study drug, up to 66 months
|
0.00%
0/43 • From the time of informed consent until 7 days after the last dose of study drug, up to 66 months
|
|
Infections and infestations
Localised infection
|
0.00%
0/45 • From the time of informed consent until 7 days after the last dose of study drug, up to 66 months
|
2.3%
1/43 • From the time of informed consent until 7 days after the last dose of study drug, up to 66 months
|
|
Infections and infestations
Mastoiditis
|
0.00%
0/45 • From the time of informed consent until 7 days after the last dose of study drug, up to 66 months
|
2.3%
1/43 • From the time of informed consent until 7 days after the last dose of study drug, up to 66 months
|
|
Infections and infestations
Perirectal abscess
|
0.00%
0/45 • From the time of informed consent until 7 days after the last dose of study drug, up to 66 months
|
2.3%
1/43 • From the time of informed consent until 7 days after the last dose of study drug, up to 66 months
|
|
Infections and infestations
Pharyngitis
|
0.00%
0/45 • From the time of informed consent until 7 days after the last dose of study drug, up to 66 months
|
2.3%
1/43 • From the time of informed consent until 7 days after the last dose of study drug, up to 66 months
|
|
Injury, poisoning and procedural complications
Femur fracture
|
0.00%
0/45 • From the time of informed consent until 7 days after the last dose of study drug, up to 66 months
|
2.3%
1/43 • From the time of informed consent until 7 days after the last dose of study drug, up to 66 months
|
|
Injury, poisoning and procedural complications
Procedural pain
|
0.00%
0/45 • From the time of informed consent until 7 days after the last dose of study drug, up to 66 months
|
2.3%
1/43 • From the time of informed consent until 7 days after the last dose of study drug, up to 66 months
|
|
Injury, poisoning and procedural complications
Spinal compression fracture
|
0.00%
0/45 • From the time of informed consent until 7 days after the last dose of study drug, up to 66 months
|
2.3%
1/43 • From the time of informed consent until 7 days after the last dose of study drug, up to 66 months
|
|
Investigations
Ammonia increased
|
0.00%
0/45 • From the time of informed consent until 7 days after the last dose of study drug, up to 66 months
|
2.3%
1/43 • From the time of informed consent until 7 days after the last dose of study drug, up to 66 months
|
|
Metabolism and nutrition disorders
Dehydration
|
4.4%
2/45 • From the time of informed consent until 7 days after the last dose of study drug, up to 66 months
|
0.00%
0/43 • From the time of informed consent until 7 days after the last dose of study drug, up to 66 months
|
|
Metabolism and nutrition disorders
Hyperammonaemia
|
22.2%
10/45 • From the time of informed consent until 7 days after the last dose of study drug, up to 66 months
|
27.9%
12/43 • From the time of informed consent until 7 days after the last dose of study drug, up to 66 months
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
2.2%
1/45 • From the time of informed consent until 7 days after the last dose of study drug, up to 66 months
|
0.00%
0/43 • From the time of informed consent until 7 days after the last dose of study drug, up to 66 months
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.00%
0/45 • From the time of informed consent until 7 days after the last dose of study drug, up to 66 months
|
2.3%
1/43 • From the time of informed consent until 7 days after the last dose of study drug, up to 66 months
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/45 • From the time of informed consent until 7 days after the last dose of study drug, up to 66 months
|
2.3%
1/43 • From the time of informed consent until 7 days after the last dose of study drug, up to 66 months
|
|
Nervous system disorders
Convulsion
|
0.00%
0/45 • From the time of informed consent until 7 days after the last dose of study drug, up to 66 months
|
2.3%
1/43 • From the time of informed consent until 7 days after the last dose of study drug, up to 66 months
|
|
Psychiatric disorders
Psychological factor affecting medical condition
|
0.00%
0/45 • From the time of informed consent until 7 days after the last dose of study drug, up to 66 months
|
2.3%
1/43 • From the time of informed consent until 7 days after the last dose of study drug, up to 66 months
|
|
Respiratory, thoracic and mediastinal disorders
Bronchitis chronic
|
0.00%
0/45 • From the time of informed consent until 7 days after the last dose of study drug, up to 66 months
|
2.3%
1/43 • From the time of informed consent until 7 days after the last dose of study drug, up to 66 months
|
|
Respiratory, thoracic and mediastinal disorders
Bronchospasm
|
0.00%
0/45 • From the time of informed consent until 7 days after the last dose of study drug, up to 66 months
|
2.3%
1/43 • From the time of informed consent until 7 days after the last dose of study drug, up to 66 months
|
|
Respiratory, thoracic and mediastinal disorders
Hypocapnia
|
0.00%
0/45 • From the time of informed consent until 7 days after the last dose of study drug, up to 66 months
|
2.3%
1/43 • From the time of informed consent until 7 days after the last dose of study drug, up to 66 months
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
0.00%
0/45 • From the time of informed consent until 7 days after the last dose of study drug, up to 66 months
|
2.3%
1/43 • From the time of informed consent until 7 days after the last dose of study drug, up to 66 months
|
Other adverse events
| Measure |
HPN-100- Pediatric
n=45 participants at risk
Pediatric participants (age 1-17) continued HPN-100 treatment after completion of HPN-100-005SE, HPN-100-007, or HPN-100-012SE.
|
HPN-100 - Adult
n=43 participants at risk
Adult participants (age 19-61) continued HPN-100 treatment after completion of HPN-100-005SE, HPN-100-007, or HPN-100-012SE.
|
|---|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
6.7%
3/45 • From the time of informed consent until 7 days after the last dose of study drug, up to 66 months
|
16.3%
7/43 • From the time of informed consent until 7 days after the last dose of study drug, up to 66 months
|
|
Gastrointestinal disorders
Nausea
|
4.4%
2/45 • From the time of informed consent until 7 days after the last dose of study drug, up to 66 months
|
9.3%
4/43 • From the time of informed consent until 7 days after the last dose of study drug, up to 66 months
|
|
Gastrointestinal disorders
Vomiting
|
13.3%
6/45 • From the time of informed consent until 7 days after the last dose of study drug, up to 66 months
|
11.6%
5/43 • From the time of informed consent until 7 days after the last dose of study drug, up to 66 months
|
|
General disorders
Pain
|
2.2%
1/45 • From the time of informed consent until 7 days after the last dose of study drug, up to 66 months
|
7.0%
3/43 • From the time of informed consent until 7 days after the last dose of study drug, up to 66 months
|
|
General disorders
Pyrexia
|
6.7%
3/45 • From the time of informed consent until 7 days after the last dose of study drug, up to 66 months
|
4.7%
2/43 • From the time of informed consent until 7 days after the last dose of study drug, up to 66 months
|
|
Infections and infestations
Bronchitis
|
2.2%
1/45 • From the time of informed consent until 7 days after the last dose of study drug, up to 66 months
|
11.6%
5/43 • From the time of informed consent until 7 days after the last dose of study drug, up to 66 months
|
|
Infections and infestations
Ear infection
|
6.7%
3/45 • From the time of informed consent until 7 days after the last dose of study drug, up to 66 months
|
0.00%
0/43 • From the time of informed consent until 7 days after the last dose of study drug, up to 66 months
|
|
Infections and infestations
Sinusitis
|
2.2%
1/45 • From the time of informed consent until 7 days after the last dose of study drug, up to 66 months
|
9.3%
4/43 • From the time of informed consent until 7 days after the last dose of study drug, up to 66 months
|
|
Infections and infestations
Upper respiratory tract infection
|
15.6%
7/45 • From the time of informed consent until 7 days after the last dose of study drug, up to 66 months
|
18.6%
8/43 • From the time of informed consent until 7 days after the last dose of study drug, up to 66 months
|
|
Investigations
Amino acid level decreased
|
6.7%
3/45 • From the time of informed consent until 7 days after the last dose of study drug, up to 66 months
|
0.00%
0/43 • From the time of informed consent until 7 days after the last dose of study drug, up to 66 months
|
|
Investigations
Amino acid level increased
|
6.7%
3/45 • From the time of informed consent until 7 days after the last dose of study drug, up to 66 months
|
2.3%
1/43 • From the time of informed consent until 7 days after the last dose of study drug, up to 66 months
|
|
Investigations
Ammonia increased
|
8.9%
4/45 • From the time of informed consent until 7 days after the last dose of study drug, up to 66 months
|
14.0%
6/43 • From the time of informed consent until 7 days after the last dose of study drug, up to 66 months
|
|
Metabolism and nutrition disorders
Dehydration
|
2.2%
1/45 • From the time of informed consent until 7 days after the last dose of study drug, up to 66 months
|
7.0%
3/43 • From the time of informed consent until 7 days after the last dose of study drug, up to 66 months
|
|
Nervous system disorders
Convulsion
|
0.00%
0/45 • From the time of informed consent until 7 days after the last dose of study drug, up to 66 months
|
9.3%
4/43 • From the time of informed consent until 7 days after the last dose of study drug, up to 66 months
|
|
Nervous system disorders
Dizziness
|
2.2%
1/45 • From the time of informed consent until 7 days after the last dose of study drug, up to 66 months
|
9.3%
4/43 • From the time of informed consent until 7 days after the last dose of study drug, up to 66 months
|
|
Nervous system disorders
Headache
|
13.3%
6/45 • From the time of informed consent until 7 days after the last dose of study drug, up to 66 months
|
7.0%
3/43 • From the time of informed consent until 7 days after the last dose of study drug, up to 66 months
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
6.7%
3/45 • From the time of informed consent until 7 days after the last dose of study drug, up to 66 months
|
7.0%
3/43 • From the time of informed consent until 7 days after the last dose of study drug, up to 66 months
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
4.4%
2/45 • From the time of informed consent until 7 days after the last dose of study drug, up to 66 months
|
7.0%
3/43 • From the time of informed consent until 7 days after the last dose of study drug, up to 66 months
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER