Trial Outcomes & Findings for Efficacy and Safety of HPN-100 for the Treatment of Adults With Urea Cycle Disorders (NCT NCT00992459)
NCT ID: NCT00992459
Last Updated: 2024-07-09
Results Overview
Blood samples were collected at pre-dose, 2, 4, 8, 12, 16, 20 and 24 hours after first dose on days 14 and 28. Arm A day 14 and Arm B day 28 data were combined as a NaPBA treatment Arm. Arm B day 14 and Arm A day 28 data were combined as a HPN-100 treatment Arm.
COMPLETED
PHASE3
46 participants
pre-dose, 2, 4, 8, 12, 16, 20 and 24 hours after first dose on days 14 and 28
2024-07-09
Participant Flow
Forty six subjects were screened and randomized at the participating sites between October 2009 to August 2010.
There were no screen failures.
Participant milestones
| Measure |
Arm A
Subjects in Arm A were assigned to receive NaPBA + HPN 100 placebo for 2 weeks All patients in Arm A received HPN100 placebo (+ concomitant active NaPBA)
|
Arm B
Subjects in Arm B were assigned to receive HPN-100 + NaPBA placebo for 2 weeks All patients in Arm B received NaPBA placebo (+ concomitant active HPN 100)
|
|---|---|---|
|
Overall Study
STARTED
|
22
|
24
|
|
Overall Study
COMPLETED
|
21
|
23
|
|
Overall Study
NOT COMPLETED
|
1
|
1
|
Reasons for withdrawal
| Measure |
Arm A
Subjects in Arm A were assigned to receive NaPBA + HPN 100 placebo for 2 weeks All patients in Arm A received HPN100 placebo (+ concomitant active NaPBA)
|
Arm B
Subjects in Arm B were assigned to receive HPN-100 + NaPBA placebo for 2 weeks All patients in Arm B received NaPBA placebo (+ concomitant active HPN 100)
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
0
|
1
|
|
Overall Study
Adverse Event
|
1
|
0
|
Baseline Characteristics
Efficacy and Safety of HPN-100 for the Treatment of Adults With Urea Cycle Disorders
Baseline characteristics by cohort
| Measure |
Treatment Arm A
n=22 Participants
Patients randomized to receive NaPBA + HPN 100 placebo for 2 weeks (Treatment Period 1) followed by HPN-100 + NaPBA placebo for 2 weeks (Treatment Period 2)
|
Treatment Arm B
n=24 Participants
Patients randomized to receive HPN-100 + NaPBA placebo for 2 weeks (Treatment Period 1) followed by NaPBA + HPN-100 placebo for 2 weeks (Treatment Period 2)
|
Total
n=46 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
22 Participants
n=5 Participants
|
24 Participants
n=7 Participants
|
46 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
15 Participants
n=5 Participants
|
17 Participants
n=7 Participants
|
32 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
7 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
14 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: pre-dose, 2, 4, 8, 12, 16, 20 and 24 hours after first dose on days 14 and 28Population: Intent-to-Treat (ITT) (N = 45): Patients receiving any amount of NaPBA or HPN-100 comprise the ITT population. ITT population was to be used for the primary analysis of this endpoint. One subject who withdrew from study after receiving one dose of NaPBA yielding N=44
Blood samples were collected at pre-dose, 2, 4, 8, 12, 16, 20 and 24 hours after first dose on days 14 and 28. Arm A day 14 and Arm B day 28 data were combined as a NaPBA treatment Arm. Arm B day 14 and Arm A day 28 data were combined as a HPN-100 treatment Arm.
Outcome measures
| Measure |
NaPBA
n=44 Participants
Patients treated with NaPBA
|
HPN-100
n=44 Participants
Patients treated with HPN-100
|
|---|---|---|
|
The Primary Endpoint Was the 24-hour Area Under the Curve for Blood Ammonia (NH324-hour AUC) on Days 14 and 28.
|
976.6 μmol∙h/L
Standard Deviation 865.9
|
865.35 μmol∙h/L
Standard Deviation 660.53
|
SECONDARY outcome
Timeframe: 28 DaysPopulation: Intent-to-Treat (ITT) (N = 45): Patients receiving any amount of NaPBA or HPN-100 comprise the ITT population. ITT population was to be used for the primary analysis of this secondary endpoint. One subject who withdrew from study after receiving one dose of NaPBA yielding N=44
The correlation between 24-hour urinary phenylacetylglutamine (PAGN) excretion (U-PAGN24-hour Excr) and venous ammonia AUC0-24 was summarized and the correlation was tested using the Spearman rank-order correlation.
Outcome measures
| Measure |
NaPBA
n=44 Participants
Patients treated with NaPBA
|
HPN-100
n=44 Participants
Patients treated with HPN-100
|
|---|---|---|
|
Correlation Between Urinary Phenylacetylglutamine (PAGN) Excretion Over 24 Hours (U-PAGN24-hour Excr) and Venous Ammonia - Area Under the Concentration-time Curve From Time 0 (Predose) to 24 Hours (AUC0-24)
|
0.437 correlation coefficient
|
0.219 correlation coefficient
|
SECONDARY outcome
Timeframe: pre-dose, 2, 4, 8, 12, 16, 20 and 24 hours after first dose on days 14 and 28Population: Intent-to-Treat (ITT) (N = 45): Patients receiving any amount of NaPBA or HPN-100 comprise the ITT population. ITT population was to be used for the primary analysis of this endpoint. One subject who withdrew from study after receiving one dose of NaPBA yielding N=44
Blood samples were collected at pre-dose, 2, 4, 8, 12, 16, 20 and 24 hours after first dose on days 14 and 28.
Outcome measures
| Measure |
NaPBA
n=44 Participants
Patients treated with NaPBA
|
HPN-100
n=44 Participants
Patients treated with HPN-100
|
|---|---|---|
|
Maximum Ammonia Values Observed on NaPBA Versus HPN-100
|
70.83 µmol/L
Standard Deviation 66.705
|
60.94 µmol/L
Standard Deviation 46.213
|
SECONDARY outcome
Timeframe: on Day 14 and Day 28Population: Intent-to-Treat (ITT) (N = 45): Patients receiving any amount of NaPBA or HPN-100 comprise the ITT population. ITT population was to be used for the primary analysis of this secondary endpoint. One subject who withdrew from study after receiving one dose of NaPBA yielding N=44
NaPBA treated arm: total 345 blood samples were collected. HPN-100 treated arm: 343 blood samples were collected.
Outcome measures
| Measure |
NaPBA
n=345 blood samples
Patients treated with NaPBA
|
HPN-100
n=343 blood samples
Patients treated with HPN-100
|
|---|---|---|
|
Rate (Percentage) of Ammonia Values Above Upper Limit of Normal (ULN) on NaPBA Versus HPN-100
|
125 samples
|
122 samples
|
SECONDARY outcome
Timeframe: 29 DaysPopulation: Safety population: (N=45 for NaPBA; N = 44 for HPN): Patients receiving any amount of NaPBA or HPN-100 comprise the Safety population. Safety population was to be used for safety analysis performed.
Severity of symptomatic hyperammonemic crises was measured by peak ammonia level (µmol/L) when it is \>= 100 µmol/L.
Outcome measures
| Measure |
NaPBA
n=45 Participants
Patients treated with NaPBA
|
HPN-100
n=44 Participants
Patients treated with HPN-100
|
|---|---|---|
|
Number and Severity of Symptomatic Hyperammonemic Crises
|
1 events
|
0 events
|
SECONDARY outcome
Timeframe: 29 DaysPopulation: Safety population: (N=45 for NaPBA; N = 44 for HPN): Patients receiving any amount of NaPBA or HPN-100 comprise the Safety population. Safety population was to be used for safety analysis performed.
Outcome measures
| Measure |
NaPBA
n=45 Participants
Patients treated with NaPBA
|
HPN-100
n=44 Participants
Patients treated with HPN-100
|
|---|---|---|
|
Rate of Adverse Events in Each Treatment Group
|
23 participants
|
27 participants
|
SECONDARY outcome
Timeframe: pre-dose, 2, 4, 8, 12, 16, 20 and 24 hours after first dose on days 14 and 28Population: Intent-to-Treat (ITT) (N = 45): Patients receiving any amount of NaPBA or HPN-100 comprise the ITT population. ITT population was to be used for the primary analysis of this secondary endpoint. One subject who withdrew from study after receiving one dose of NaPBA yielding N=44
Blood samples were collected at pre-dose, 2, 4, 8, 12, 16, 20 and 24 hours after first dose on days 14 and 28.
Outcome measures
| Measure |
NaPBA
n=44 Participants
Patients treated with NaPBA
|
HPN-100
n=44 Participants
Patients treated with HPN-100
|
|---|---|---|
|
Cmax for PAA of NaPBA and HPN-100 in Plasma
|
52.2 μg/mL
Standard Deviation 41.86
|
38.5 μg/mL
Standard Deviation 39.5
|
SECONDARY outcome
Timeframe: pre-dose, 2, 4, 8, 12, 16, 20 and 24 hours after first dose on days 14 and 28Population: Intent-to-Treat (ITT) (N = 45): Patients receiving any amount of NaPBA or HPN-100 comprise the ITT population. ITT population was to be used for the primary analysis of this secondary endpoint. One subject who withdrew from study after receiving one dose of NaPBA yielding N=44
Blood samples were collected at pre-dose, 2, 4, 8, 12, 16, 20 and 24 hours after first dose on days 14 and 28.
Outcome measures
| Measure |
NaPBA
n=44 Participants
Patients treated with NaPBA
|
HPN-100
n=44 Participants
Patients treated with HPN-100
|
|---|---|---|
|
Cmax for PBA of NaPBA and HPN-100 in Plasma
|
80.9 μg/mL
Standard Deviation 52.5
|
51.9 μg/mL
Standard Deviation 34.87
|
SECONDARY outcome
Timeframe: pre-dose, 2, 4, 8, 12, 16, 20 and 24 hours after first dose on days 14 and 28Population: Intent-to-Treat (ITT) (N = 45): Patients receiving any amount of NaPBA or HPN-100 comprise the ITT population. ITT population was to be used for the primary analysis of this secondary endpoint. One subject who withdrew from study after receiving one dose of NaPBA yielding N=44
Blood samples were collected at pre-dose, 2, 4, 8, 12, 16, 20 and 24 hours after first dose on days 14 and 28.
Outcome measures
| Measure |
NaPBA
n=44 Participants
Patients treated with NaPBA
|
HPN-100
n=44 Participants
Patients treated with HPN-100
|
|---|---|---|
|
Cmax PAGN of NaPBA and HPN-100 in Plasma
|
78.6 μg/mL
Standard Deviation 43.86
|
86.8 μg/mL
Standard Deviation 44.7
|
SECONDARY outcome
Timeframe: 24 hours on Day 14 of each treatmentsPopulation: Intent-to-Treat (ITT) (N = 45): Patients receiving any amount of NaPBA or HPN-100 comprise the ITT population. ITT population was to be used for the primary analysis of this secondary endpoint. One subject who withdrew from study after receiving one dose of NaPBA yielding N=44
Outcome measures
| Measure |
NaPBA
n=44 Participants
Patients treated with NaPBA
|
HPN-100
n=44 Participants
Patients treated with HPN-100
|
|---|---|---|
|
U-PAGN24-hour Excr of NaPBA and HPN-100
|
13627515 μg
Standard Deviation 7086307.8
|
13502745 μg
Standard Deviation 7088941.1
|
Adverse Events
NaPBA
HPN-100
Serious adverse events
| Measure |
NaPBA
n=45 participants at risk
Patients received NaPBA
|
HPN-100
n=44 participants at risk
Patients received HPN-100
|
|---|---|---|
|
Infections and infestations
Gastroenteritis
|
0.00%
0/45 • 29 days
|
2.3%
1/44 • 29 days
|
|
Metabolism and nutrition disorders
Hyperammonaemia
|
2.2%
1/45 • 29 days
|
0.00%
0/44 • 29 days
|
Other adverse events
| Measure |
NaPBA
n=45 participants at risk
Patients received NaPBA
|
HPN-100
n=44 participants at risk
Patients received HPN-100
|
|---|---|---|
|
Gastrointestinal disorders
Abdominal discomfort
|
6.7%
3/45 • 29 days
|
0.00%
0/44 • 29 days
|
|
General disorders
Oral discomfort
|
4.4%
2/45 • 29 days
|
0.00%
0/44 • 29 days
|
|
Gastrointestinal disorders
abdominal pain
|
4.4%
2/45 • 29 days
|
6.8%
3/44 • 29 days
|
|
Metabolism and nutrition disorders
decreased appetite
|
4.4%
2/45 • 29 days
|
6.8%
3/44 • 29 days
|
|
Gastrointestinal disorders
diarrhea
|
6.7%
3/45 • 29 days
|
15.9%
7/44 • 29 days
|
|
General disorders
dyspepsia
|
6.7%
3/45 • 29 days
|
4.5%
2/44 • 29 days
|
|
General disorders
fatigue
|
2.2%
1/45 • 29 days
|
6.8%
3/44 • 29 days
|
|
Gastrointestinal disorders
flatulence
|
2.2%
1/45 • 29 days
|
13.6%
6/44 • 29 days
|
|
General disorders
food aversion
|
4.4%
2/45 • 29 days
|
2.3%
1/44 • 29 days
|
|
Nervous system disorders
headache
|
8.9%
4/45 • 29 days
|
13.6%
6/44 • 29 days
|
|
Metabolism and nutrition disorders
increased appetite
|
4.4%
2/45 • 29 days
|
0.00%
0/44 • 29 days
|
|
Gastrointestinal disorders
nausea
|
6.7%
3/45 • 29 days
|
2.3%
1/44 • 29 days
|
|
Gastrointestinal disorders
vomiting
|
4.4%
2/45 • 29 days
|
6.8%
3/44 • 29 days
|
|
Nervous system disorders
dizziness
|
8.9%
4/45 • 29 days
|
0.00%
0/44 • 29 days
|
|
Investigations
ammonia increased
|
2.2%
1/45 • 29 days
|
4.5%
2/44 • 29 days
|
|
Skin and subcutaneous tissue disorders
dermatitis contact
|
0.00%
0/45 • 29 days
|
4.5%
2/44 • 29 days
|
Additional Information
Bruce Scharschmidt, MD, SVP, Chief MedicaL & Development Officer
Hyperion Therapeutics
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60