Trial Outcomes & Findings for Study of the Safety and Tolerability of HPN-100 Compared to Sodium Phenylbutyrate in Children With Urea Cycle Disorders (NCT NCT00947544)
NCT ID: NCT00947544
Last Updated: 2024-07-11
Results Overview
To evaluate the safety and PK characteristics of HPN-100 compared with sodium phenylbutyrate (NaPBA) in pediatric patients with urea cycle disorders (UCDs)
COMPLETED
PHASE2
17 participants
1 week on each treatment for a total of 2 week.
2024-07-11
Participant Flow
Participant milestones
| Measure |
Swich Over and Safety Extension
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.
|
Safety Extension Only
Participants entered the safety extension part of the study only, and received open-label HPN-100 for up to 12 months.
|
|---|---|---|
|
Switch-Over Period (2 Weeks)
COMPLETED
|
11
|
0
|
|
Switch-Over Period (2 Weeks)
STARTED
|
11
|
0
|
|
Switch-Over Period (2 Weeks)
NOT COMPLETED
|
0
|
0
|
|
Safety-Extension Period (12 Months)
STARTED
|
11
|
6
|
|
Safety-Extension Period (12 Months)
COMPLETED
|
10
|
6
|
|
Safety-Extension Period (12 Months)
NOT COMPLETED
|
1
|
0
|
Reasons for withdrawal
| Measure |
Swich Over and Safety Extension
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.
|
Safety Extension Only
Participants entered the safety extension part of the study only, and received open-label HPN-100 for up to 12 months.
|
|---|---|---|
|
Safety-Extension Period (12 Months)
Withdrawal by Subject
|
1
|
0
|
Baseline Characteristics
Study of the Safety and Tolerability of HPN-100 Compared to Sodium Phenylbutyrate in Children With Urea Cycle Disorders
Baseline characteristics by cohort
| Measure |
Participants in SO and SE
n=17 Participants
Patients who completed switch over study and enrolled safety extension study
|
|---|---|
|
Age, Categorical
<=18 years
|
17 Participants
n=99 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
0 Participants
n=99 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=99 Participants
|
|
Age, Continuous
|
10 years
STANDARD_DEVIATION 3.482 • n=99 Participants
|
|
Sex: Female, Male
Female
|
14 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=99 Participants
|
|
Region of Enrollment
United States
|
16 participants
n=99 Participants
|
|
Region of Enrollment
Canada
|
1 participants
n=99 Participants
|
PRIMARY outcome
Timeframe: 1 week on each treatment for a total of 2 week.To evaluate the safety and PK characteristics of HPN-100 compared with sodium phenylbutyrate (NaPBA) in pediatric patients with urea cycle disorders (UCDs)
Outcome measures
| Measure |
HPN-100
n=11 Participants
HPN-100: Patients treated with HPN-100
|
NaPBA
n=11 Participants
NaPBA: Patients treated with NaPBA
|
|---|---|---|
|
Rate of Adverse Events During the Switchover Part of the Study Rate of Adverse Events (Number of Participants Showing Adverse Events)
|
4 participants
|
2 participants
|
SECONDARY outcome
Timeframe: 1 yearNumber of Subjects with at Least One Hyperammonemic Crisis. Hyperammonemic crisis is defined as follows: • Clinical symptoms associated with ammonia of ≥ 100 µmol/L
Outcome measures
| Measure |
HPN-100
n=17 Participants
HPN-100: Patients treated with HPN-100
|
NaPBA
n=17 Participants
NaPBA: Patients treated with NaPBA
|
|---|---|---|
|
Number and Causes of Hyperammonemic Events (Safety Extension)
Number of subjects with at least 1 HAC
|
5 participants
|
3 participants
|
|
Number and Causes of Hyperammonemic Events (Safety Extension)
Number of Crises
|
8 participants
|
3 participants
|
SECONDARY outcome
Timeframe: Day 7 (NaPBA) and Day 14 (HPN-100)To evaluate control of blood ammonia by HPN-100 compared with NaPBA in pediatric patients with UCDs.
Outcome measures
| Measure |
HPN-100
n=11 Participants
HPN-100: Patients treated with HPN-100
|
NaPBA
n=11 Participants
NaPBA: Patients treated with NaPBA
|
|---|---|---|
|
Blood Ammonia Control
|
603.83 μmol∙h/L
Standard Deviation 187.92
|
814.62 μmol∙h/L
Standard Deviation 322.36
|
SECONDARY outcome
Timeframe: Day 7 (NaPBA) and Day 14 (HPN-100)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).
Outcome measures
| Measure |
HPN-100
n=11 Participants
HPN-100: Patients treated with HPN-100
|
NaPBA
n=11 Participants
NaPBA: Patients treated with NaPBA
|
|---|---|---|
|
NH3 Cmax on NaPBA vs. HPN-100 on the Last Day of Treatment With Each Drug
|
47.77 μmol/L
Standard Deviation 12.8
|
55.66 μmol/L
Standard Deviation 21.61
|
SECONDARY outcome
Timeframe: Day 7 (NaPBA) and Day 14 (HPN-100)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).
Outcome measures
| Measure |
HPN-100
n=11 Participants
HPN-100: Patients treated with HPN-100
|
NaPBA
n=11 Participants
NaPBA: Patients treated with NaPBA
|
|---|---|---|
|
Average Ammonia Values on NaPBA vs. HPN-100 on the Last Day of Treatment With Each Drug (Switch Over)
|
28.68 µmol/L
Standard Deviation 14.867
|
37.75 µmol/L
Standard Deviation 20.310
|
SECONDARY outcome
Timeframe: Day 7 (NaPBA) and Day 14 (HPN-100)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).
Outcome measures
| Measure |
HPN-100
n=76 number of blood sample
HPN-100: Patients treated with HPN-100
|
NaPBA
n=76 number of blood sample
NaPBA: Patients treated with NaPBA
|
|---|---|---|
|
Rate (Percentage) of Ammonia Values Above Upper Limit of Normal (ULN) on NaPBA vs. HPN-100
|
18.4 percentage of sample
|
31.6 percentage of sample
|
SECONDARY outcome
Timeframe: Day 7 (NaPBA) and Day 14 (HPN-100)Urinary PAGN (phenylacetylglutamine) 24-hour excretion. Urine was collect during 0-12 hrs and 12-24 hrs.
Outcome measures
| Measure |
HPN-100
n=11 Participants
HPN-100: Patients treated with HPN-100
|
NaPBA
n=11 Participants
NaPBA: Patients treated with NaPBA
|
|---|---|---|
|
Urinary PAGN 24-hour Excretion Values on NaPBA vs. HPN-100 (Switch Over)
|
12501037 μg
Standard Deviation 56.9
|
12512426 μg
Standard Deviation 51.3
|
SECONDARY outcome
Timeframe: Day 7 (NaPBA) and Day 14 (HPN-100)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).
Outcome measures
| Measure |
HPN-100
n=11 Participants
HPN-100: Patients treated with HPN-100
|
NaPBA
n=11 Participants
NaPBA: Patients treated with NaPBA
|
|---|---|---|
|
Plasma PAA (Phenylacetate) AUC0-24 Values on NaPBA vs. HPN-100 on on the Last Day of Treatment With Each Drug
|
964 μg•h/mL AUC 0-24
Standard Deviation 63.6
|
773 μg•h/mL AUC 0-24
Standard Deviation 73.3
|
SECONDARY outcome
Timeframe: Day 7 (NaPBA) and Day 14 (HPN-100)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).
Outcome measures
| Measure |
HPN-100
n=11 Participants
HPN-100: Patients treated with HPN-100
|
NaPBA
n=11 Participants
NaPBA: Patients treated with NaPBA
|
|---|---|---|
|
Plasma PBA (Phenylbutyrate) AUC0-24 Values on NaPBA vs. HPN-100 on on the Last Day of Treatment With Each Drug
|
631 µg*h/ml AUC 0-24
Standard Deviation 44.9
|
236 µg*h/ml AUC 0-24
Standard Deviation 105.2
|
SECONDARY outcome
Timeframe: Day 7 (NaPBA) and Day 14 (HPN-100)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).
Outcome measures
| Measure |
HPN-100
n=11 Participants
HPN-100: Patients treated with HPN-100
|
NaPBA
n=11 Participants
NaPBA: Patients treated with NaPBA
|
|---|---|---|
|
Plasma PAGN AUC0-24 Values on NaPBA vs. HPN-100 on on the Last Day of Treatment With Each Drug
|
1378 μg*h/mL AUC 0-24
Standard Deviation 40.2
|
1015 μg*h/mL AUC 0-24
Standard Deviation 44.7
|
SECONDARY outcome
Timeframe: 1 yearPopulation: Patients who completed SF-15 at baseline and Month 12 both time in the safety extension period.
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.
Outcome measures
| Measure |
HPN-100
n=30 total score from SF-15 report
HPN-100: Patients treated with HPN-100
|
NaPBA
NaPBA: Patients treated with NaPBA
|
|---|---|---|
|
Quality of Life Assessed by the SF-15 Questionnaire
|
4.0 score on a scale
Standard Deviation 10.67
|
—
|
Adverse Events
HPN-100
Serious adverse events
| Measure |
HPN-100
n=17 participants at risk
HPN-100: Patient treated with HPN-100
|
|---|---|
|
Metabolism and nutrition disorders
hyperammonemia
|
11.8%
2/17 • Safety Extension period only (from Day 15 to 1 year)
|
|
Gastrointestinal disorders
gastroenteritis
|
5.9%
1/17 • Safety Extension period only (from Day 15 to 1 year)
|
|
Psychiatric disorders
Aggression
|
5.9%
1/17 • Safety Extension period only (from Day 15 to 1 year)
|
Other adverse events
| Measure |
HPN-100
n=17 participants at risk
HPN-100: Patient treated with HPN-100
|
|---|---|
|
Gastrointestinal disorders
Abdominal pain upper
|
17.6%
3/17 • Safety Extension period only (from Day 15 to 1 year)
|
|
Gastrointestinal disorders
Vomiting
|
23.5%
4/17 • Safety Extension period only (from Day 15 to 1 year)
|
|
Infections and infestations
Upper respiratory tract infection
|
23.5%
4/17 • Safety Extension period only (from Day 15 to 1 year)
|
|
General disorders
Pyrexia
|
11.8%
2/17 • Safety Extension period only (from Day 15 to 1 year)
|
|
Infections and infestations
Nasopharyngitis
|
11.8%
2/17 • Safety Extension period only (from Day 15 to 1 year)
|
|
Infections and infestations
Sinusitis
|
11.8%
2/17 • Safety Extension period only (from Day 15 to 1 year)
|
|
Investigations
ALT increased
|
11.8%
2/17 • Safety Extension period only (from Day 15 to 1 year)
|
|
Investigations
Anion gap increased
|
11.8%
2/17 • Safety Extension period only (from Day 15 to 1 year)
|
|
Investigations
AST increased
|
11.8%
2/17 • Safety Extension period only (from Day 15 to 1 year)
|
|
Metabolism and nutrition disorders
Decreased appetite
|
11.8%
2/17 • Safety Extension period only (from Day 15 to 1 year)
|
|
Metabolism and nutrition disorders
Hyperammonemia
|
17.6%
3/17 • Safety Extension period only (from Day 15 to 1 year)
|
|
Nervous system disorders
Headache
|
11.8%
2/17 • Safety Extension period only (from Day 15 to 1 year)
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
11.8%
2/17 • Safety Extension period only (from Day 15 to 1 year)
|
|
Skin and subcutaneous tissue disorders
Skin odour abnormal
|
11.8%
2/17 • Safety Extension period only (from Day 15 to 1 year)
|
Additional Information
Craig James-Associate Director, Clinical Operations
Hyperion Therapeutics
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60