Trial Outcomes & Findings for Study of the Safety, Pharmacokinetics and Efficacy of HPN-100, in Pediatric Subjects With Urea Cycle Disorders (UCDs) (NCT NCT01347073)
NCT ID: NCT01347073
Last Updated: 2024-07-11
Results Overview
Rate of adverse events during the Switch-Over portion of the Protocol
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
23 participants
Primary outcome timeframe
2 weeks
Results posted on
2024-07-11
Participant Flow
Study Locations: Houston, TX; Minneapolis, MN; Washington, DC; New York, NY; Cleveland, OH; Portland, ME; Portland, OR Study Initiation Date: September 9, 2011 Study Completion Date: April 4, 2013
This is an open-label, fixed-sequence NaPBA to HPN-100 switchover study with no control group.
Participant milestones
| Measure |
HPN-100
The first part of this open-label study consisted of a switch-over period during which patients were switched from the current medication (NaPBA) to HPN-100. The second part of this open-label study consisted of a 12-month long-term treatment phase with HPN-100. All participants in the switch-over were enrolled into the long-term treatment phase.
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|---|---|
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Overall Study
STARTED
|
23
|
|
Overall Study
COMPLETED
|
21
|
|
Overall Study
NOT COMPLETED
|
2
|
Reasons for withdrawal
| Measure |
HPN-100
The first part of this open-label study consisted of a switch-over period during which patients were switched from the current medication (NaPBA) to HPN-100. The second part of this open-label study consisted of a 12-month long-term treatment phase with HPN-100. All participants in the switch-over were enrolled into the long-term treatment phase.
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|---|---|
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Overall Study
Adverse Event
|
1
|
|
Overall Study
Liver Transplant
|
1
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Baseline Characteristics
Study of the Safety, Pharmacokinetics and Efficacy of HPN-100, in Pediatric Subjects With Urea Cycle Disorders (UCDs)
Baseline characteristics by cohort
| Measure |
HPN-100
n=23 Participants
The first part of this open-label study consisted of a switch-over period during which patients were switched from the current medication (NaPBA) to HPN-100. The second part of this open-label study consisted of a 12-month long-term treatment phase with HPN-100. All participants in the switch-over were enrolled into the long-term treatment phase.
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|---|---|
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Age, Categorical
<=18 years
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23 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
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0 Participants
n=5 Participants
|
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Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
12 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
11 Participants
n=5 Participants
|
|
Region of Enrollment
United States
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23 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 2 weeksPopulation: All patients who received any amount of study medication were included in this population, which is the primary population for all baseline, accountability, demographic and safety analyses.
Rate of adverse events during the Switch-Over portion of the Protocol
Outcome measures
| Measure |
NaPBA
n=15 Participants
Switch Over Arm
|
HPN-100
n=15 Participants
Switch Over and Long Term Treatment Arm
|
|---|---|---|
|
Adverse Events
|
0 participants
|
6 participants
|
PRIMARY outcome
Timeframe: 12 monthsPopulation: All patients that entered the Safety Extension were included in the analysis of adverse events
Rate of adverse events during the Safety Extension portion of the protocol ( please note: HPN-100 treatment only during Safety Extension )
Outcome measures
| Measure |
NaPBA
n=23 Participants
Switch Over Arm
|
HPN-100
Switch Over and Long Term Treatment Arm
|
|---|---|---|
|
Adverse Events
|
23 participants
|
—
|
SECONDARY outcome
Timeframe: 2 weeksPopulation: All patients who received any amount of both study medications (NaPBA and HPN-100) were included in this population, which is the primary population for analysis of efficacy and pharmacokinetic parameters.
24-hour ammonia AUC of blood ammonia levels on Days 1 (NaPBA) and 10 (HPN-100) were compared. Ammonia was assessed at Hour 0 (pre-first dose, fasted), Hour 8 (\~2-4 hours after lunch or the second main meal and dose of NaPBA), Hour 12 (\~4 hours after the last main meal) and 24 hours post-first dose (pre-first dose on following day, fasted).
Outcome measures
| Measure |
NaPBA
n=15 Participants
Switch Over Arm
|
HPN-100
n=15 Participants
Switch Over and Long Term Treatment Arm
|
|---|---|---|
|
Blood Ammonia
|
914.43 umol/L*hours
Standard Deviation 630.21
|
647.63 umol/L*hours
Standard Deviation 379.94
|
SECONDARY outcome
Timeframe: 2 weeksPopulation: All patients who received any amount of both study medications (NaPBA and HPN-100) were included in this population, which is the primary population for analysis of efficacy and pharmacokinetic parameters.
Ammonia values were converted to SI units (umol/L) and normalized to a standard ULN of 35 umol/L prior to analysis
Outcome measures
| Measure |
NaPBA
n=58 Ammonia Values
Switch Over Arm
|
HPN-100
n=53 Ammonia Values
Switch Over and Long Term Treatment Arm
|
|---|---|---|
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Frequency of Ammonia Levels Greater Than the Upper Limit of Normal (ULN) on HPN-100 Compared With NaPBA
|
22 Ammonia Values > ULN
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8 Ammonia Values > ULN
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SECONDARY outcome
Timeframe: 1 yearRate of HAC during pre-enrollment on NaPBA compared to HAC during HPN-100 treatment
Outcome measures
| Measure |
NaPBA
n=23 Participants
Switch Over Arm
|
HPN-100
n=23 Participants
Switch Over and Long Term Treatment Arm
|
|---|---|---|
|
Hyperammonemic Crisis
|
29 number of crises
|
12 number of crises
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Adverse Events
HPN-100
Serious events: 11 serious events
Other events: 23 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
HPN-100
n=23 participants at risk
The first part of this open-label study consisted of a switch-over period during which patients were switched from the current medication (NaPBA) to HPN-100. The second part of this open-label study consisted of a 12-month long-term treatment phase with HPN-100. All participants in the switch-over were enrolled into the long-term treatment phase.
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|---|---|
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Metabolism and nutrition disorders
Hyperammonemia
|
30.4%
7/23 • Approximately 1 year, 7 months (from study initiation date to 30 days after study completion date)
|
|
Gastrointestinal disorders
Vomiting
|
8.7%
2/23 • Approximately 1 year, 7 months (from study initiation date to 30 days after study completion date)
|
|
Nervous system disorders
Convulsion
|
8.7%
2/23 • Approximately 1 year, 7 months (from study initiation date to 30 days after study completion date)
|
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Gastrointestinal disorders
Gastroenteritis
|
4.3%
1/23 • Approximately 1 year, 7 months (from study initiation date to 30 days after study completion date)
|
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Injury, poisoning and procedural complications
Chemical Burn
|
4.3%
1/23 • Approximately 1 year, 7 months (from study initiation date to 30 days after study completion date)
|
|
Metabolism and nutrition disorders
Hypophagia
|
8.7%
2/23 • Approximately 1 year, 7 months (from study initiation date to 30 days after study completion date)
|
Other adverse events
| Measure |
HPN-100
n=23 participants at risk
The first part of this open-label study consisted of a switch-over period during which patients were switched from the current medication (NaPBA) to HPN-100. The second part of this open-label study consisted of a 12-month long-term treatment phase with HPN-100. All participants in the switch-over were enrolled into the long-term treatment phase.
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|---|---|
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Blood and lymphatic system disorders
Lymphadenopathy
|
8.7%
2/23 • Approximately 1 year, 7 months (from study initiation date to 30 days after study completion date)
|
|
Blood and lymphatic system disorders
Neutropenia
|
8.7%
2/23 • Approximately 1 year, 7 months (from study initiation date to 30 days after study completion date)
|
|
Gastrointestinal disorders
Diarrhea
|
26.1%
6/23 • Approximately 1 year, 7 months (from study initiation date to 30 days after study completion date)
|
|
Gastrointestinal disorders
Gastroesophageal reflux disease
|
8.7%
2/23 • Approximately 1 year, 7 months (from study initiation date to 30 days after study completion date)
|
|
Gastrointestinal disorders
Vomiting
|
52.2%
12/23 • Approximately 1 year, 7 months (from study initiation date to 30 days after study completion date)
|
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General disorders
Pyrexia
|
39.1%
9/23 • Approximately 1 year, 7 months (from study initiation date to 30 days after study completion date)
|
|
Infections and infestations
Ear infection
|
8.7%
2/23 • Approximately 1 year, 7 months (from study initiation date to 30 days after study completion date)
|
|
Infections and infestations
Gastroenteritis
|
17.4%
4/23 • Approximately 1 year, 7 months (from study initiation date to 30 days after study completion date)
|
|
Infections and infestations
Otitis media
|
13.0%
3/23 • Approximately 1 year, 7 months (from study initiation date to 30 days after study completion date)
|
|
Infections and infestations
Upper respiratory tract infection
|
60.9%
14/23 • Approximately 1 year, 7 months (from study initiation date to 30 days after study completion date)
|
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Investigations
Alanine aminotransferase increased
|
8.7%
2/23 • Approximately 1 year, 7 months (from study initiation date to 30 days after study completion date)
|
|
Investigations
Aspartate aminotransferase increased
|
8.7%
2/23 • Approximately 1 year, 7 months (from study initiation date to 30 days after study completion date)
|
|
Investigations
Blood alkaline phosphatase increased
|
8.7%
2/23 • Approximately 1 year, 7 months (from study initiation date to 30 days after study completion date)
|
|
Investigations
Blood bicarbonate decreased
|
8.7%
2/23 • Approximately 1 year, 7 months (from study initiation date to 30 days after study completion date)
|
|
Metabolism and nutrition disorders
Decreased appetite
|
13.0%
3/23 • Approximately 1 year, 7 months (from study initiation date to 30 days after study completion date)
|
|
Metabolism and nutrition disorders
Hyperammonemia
|
30.4%
7/23 • Approximately 1 year, 7 months (from study initiation date to 30 days after study completion date)
|
|
Metabolism and nutrition disorders
Hypophagia
|
8.7%
2/23 • Approximately 1 year, 7 months (from study initiation date to 30 days after study completion date)
|
|
Nervous system disorders
Convulsion
|
8.7%
2/23 • Approximately 1 year, 7 months (from study initiation date to 30 days after study completion date)
|
|
Nervous system disorders
Hyporeflexia
|
8.7%
2/23 • Approximately 1 year, 7 months (from study initiation date to 30 days after study completion date)
|
|
Nervous system disorders
Lethargy
|
8.7%
2/23 • Approximately 1 year, 7 months (from study initiation date to 30 days after study completion date)
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
26.1%
6/23 • Approximately 1 year, 7 months (from study initiation date to 30 days after study completion date)
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
13.0%
3/23 • Approximately 1 year, 7 months (from study initiation date to 30 days after study completion date)
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhea
|
17.4%
4/23 • Approximately 1 year, 7 months (from study initiation date to 30 days after study completion date)
|
|
Skin and subcutaneous tissue disorders
Rash papular
|
13.0%
3/23 • Approximately 1 year, 7 months (from study initiation date to 30 days after study completion date)
|
|
Skin and subcutaneous tissue disorders
Skin odor abnormal
|
8.7%
2/23 • Approximately 1 year, 7 months (from study initiation date to 30 days after study completion date)
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Additional Information
Craig James R.N. Associate Dir. UCD Clinical Operations
Hyperion Therapeutics, Inc.
Phone: (650) 745- 7480
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place