Trial Outcomes & Findings for Dose-Escalation Safety Study of HPN-100 to Treat Urea Cycle Disorders (NCT NCT00551200)
NCT ID: NCT00551200
Last Updated: 2024-07-10
Results Overview
Data were collected at pre-first dose and at 30 minutes and 1, 2, 4, 5, 6, 8, 10, 12, and 24 hours post first dose.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
14 participants
Primary outcome timeframe
At steady state (1 week) on each medication (Buphenyl® alone, HPN-100 alone), and at steady state (1 week) after each dose escalation
Results posted on
2024-07-10
Participant Flow
Participant milestones
| Measure |
Buphenyl to HPN-100
HPN-100 : Subjects took prescribed dose of Buphenyl® TID (not to exceed 20g/day) at least two weeks prior to enrollment. Subjects took prescribed dose of Buphenyl® TID for first week of study, and then switched over to HPN-100 TID during a dose-escalation phase. The dose of HPN-100 was increased and the dose of Buphenyl® was decreased each week by 50 mg/kg until entire daily dose of phenylbutyrate was HPN-100. Target HPN-100 dose contained the same amount of phenylbutyrate as the subject's prescribed daily dose of Buphenyl®. Subject took HPN-100 alone for one week and then switched back to previous dose of Buphenyl for the last week of the study.
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|---|---|
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Overall Study
STARTED
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14
|
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Overall Study
COMPLETED
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10
|
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Overall Study
NOT COMPLETED
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4
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Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Dose-Escalation Safety Study of HPN-100 to Treat Urea Cycle Disorders
Baseline characteristics by cohort
| Measure |
Buphenyl to HPN-100
n=14 Participants
HPN-100 : Subjects will be taking prescribed dose of Buphenyl® TID (not to exceed 20g/day) at least two weeks prior to enrollment. Subjects will take prescribed dose of Buphenyl® TID for first week of study, and then switch over to HPN-100 TID during a dose-escalation phase. The dose of HPN-100 will be increased and the dose of Buphenyl® will be decreased each week by 50 mg/kg until entire daily dose of phenylbutyrate is HPN-100. Target HPN-100 dose will contain the same amount of phenylbutyrate as the subject's prescribed daily dose of Buphenyl®. Subject will take HPN-100 alone for one week and then switch back to previous dose of Buphenyl for the last week of the study.
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|---|---|
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Age, Categorical
<=18 years
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0 Participants
n=5 Participants
|
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Age, Categorical
Between 18 and 65 years
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13 Participants
n=5 Participants
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Age, Categorical
>=65 years
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1 Participants
n=5 Participants
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Age, Continuous
|
35.7 years
STANDARD_DEVIATION 16.3 • n=5 Participants
|
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Sex: Female, Male
Female
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9 Participants
n=5 Participants
|
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Sex: Female, Male
Male
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5 Participants
n=5 Participants
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Region of Enrollment
United States
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14 participants
n=5 Participants
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PRIMARY outcome
Timeframe: At steady state (1 week) on each medication (Buphenyl® alone, HPN-100 alone), and at steady state (1 week) after each dose escalationData were collected at pre-first dose and at 30 minutes and 1, 2, 4, 5, 6, 8, 10, 12, and 24 hours post first dose.
Outcome measures
| Measure |
NaPBA Steady State
n=10 concentration of ammonia
Subjects were on NaPBA TID treatment for at least 2 weeks prior to enrollment, and were thus expected to be at steady-state levels prior to enrollment. After enrollment, subjects received 1 week of NaPBA treatment before switching over to HPN-100 dose escalation phase.
|
HPN-100 Steady State
n=10 concentration of ammonia
After dose escalation to full dose of HPN-100 was completed, subjects received only HPN-100 for 1 week (and achieved steady state) prior to switching back to their original NaPBA treatment.
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|---|---|---|
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Venous Ammonia Levels at the Peak and Mean TNUAC Time-normalized Area Under the Curve)
in peak
|
79.1 μmol/L
Standard Deviation 40.1
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56.3 μmol/L
Standard Deviation 27.9
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Venous Ammonia Levels at the Peak and Mean TNUAC Time-normalized Area Under the Curve)
in TNAUC (time-normalized area under the curve)
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38.4 μmol/L
Standard Deviation 19.6
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26.5 μmol/L
Standard Deviation 10.7
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PRIMARY outcome
Timeframe: during the period on 100% Buphenyl (up to 4 weeks) or HPN-100 (up to 10 weeks)Outcome measures
| Measure |
NaPBA Steady State
n=14 Participants
Subjects were on NaPBA TID treatment for at least 2 weeks prior to enrollment, and were thus expected to be at steady-state levels prior to enrollment. After enrollment, subjects received 1 week of NaPBA treatment before switching over to HPN-100 dose escalation phase.
|
HPN-100 Steady State
n=10 Participants
After dose escalation to full dose of HPN-100 was completed, subjects received only HPN-100 for 1 week (and achieved steady state) prior to switching back to their original NaPBA treatment.
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|---|---|---|
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Number of Subjects Experienced Adverse Events
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7 participants
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5 participants
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PRIMARY outcome
Timeframe: during the period subjects on 100% Buphenyl (up to 4 weeks) or HPN-100 (up to 10 weeks)Outcome measures
| Measure |
NaPBA Steady State
n=14 Participants
Subjects were on NaPBA TID treatment for at least 2 weeks prior to enrollment, and were thus expected to be at steady-state levels prior to enrollment. After enrollment, subjects received 1 week of NaPBA treatment before switching over to HPN-100 dose escalation phase.
|
HPN-100 Steady State
n=10 Participants
After dose escalation to full dose of HPN-100 was completed, subjects received only HPN-100 for 1 week (and achieved steady state) prior to switching back to their original NaPBA treatment.
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|---|---|---|
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Number of Subjects Experienced Serious Adverse Events
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1 participants
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0 participants
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SECONDARY outcome
Timeframe: At steady state (1 week) on each medication (Buphenyl® alone, HPN-100 alone)measured AUC0-24 (Area under the curve from time 0 (pre-dose) to 24 hours) for each metabolite in plasma. Data were collected at 30 minutes and 1, 2, 4, 5, 6, 8, 10, 12, and 24 hours post-first dose.
Outcome measures
| Measure |
NaPBA Steady State
n=86 plasma
Subjects were on NaPBA TID treatment for at least 2 weeks prior to enrollment, and were thus expected to be at steady-state levels prior to enrollment. After enrollment, subjects received 1 week of NaPBA treatment before switching over to HPN-100 dose escalation phase.
|
HPN-100 Steady State
n=82 plasma
After dose escalation to full dose of HPN-100 was completed, subjects received only HPN-100 for 1 week (and achieved steady state) prior to switching back to their original NaPBA treatment.
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|---|---|---|
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Pharmacokinetics (Plasma and Urine PK Parameters of Study Drugs and Their Metabolites)
AUC0-24 PBA (phenylbutyrate) in plasma
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740 μg*h/mL
Standard Deviation 363
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540 μg*h/mL
Standard Deviation 325
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Pharmacokinetics (Plasma and Urine PK Parameters of Study Drugs and Their Metabolites)
AUC0-24 PAA (phenylacetate) in plasma
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596 μg*h/mL
Standard Deviation 738
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575 μg*h/mL
Standard Deviation 970
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Pharmacokinetics (Plasma and Urine PK Parameters of Study Drugs and Their Metabolites)
AUC0-24 PAGN (phenylacetylglutamine) in plasma
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1133 μg*h/mL
Standard Deviation 352
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1098 μg*h/mL
Standard Deviation 485
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SECONDARY outcome
Timeframe: End of StudyOutcome measures
| Measure |
NaPBA Steady State
n=10 Participants
Subjects were on NaPBA TID treatment for at least 2 weeks prior to enrollment, and were thus expected to be at steady-state levels prior to enrollment. After enrollment, subjects received 1 week of NaPBA treatment before switching over to HPN-100 dose escalation phase.
|
HPN-100 Steady State
After dose escalation to full dose of HPN-100 was completed, subjects received only HPN-100 for 1 week (and achieved steady state) prior to switching back to their original NaPBA treatment.
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Drug Preference for HPN-100 or Buphenyl® (as Assessed by Global Preference Question)
prefer Buphenyl
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1 participants
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—
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Drug Preference for HPN-100 or Buphenyl® (as Assessed by Global Preference Question)
prefer HPN-100
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9 participants
|
—
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Adverse Events
Buphenyl
Serious events: 1 serious events
Other events: 7 other events
Deaths: 0 deaths
HPN-100
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Buphenyl
n=14 participants at risk
HPN-100 : Subjects will be taking prescribed dose of Buphenyl® TID (not to exceed 20g/day) at least two weeks prior to enrollment. Subjects will take prescribed dose of Buphenyl® TID for first week of study, and then switch over to HPN-100 TID during a dose-escalation phase. The dose of HPN-100 will be increased and the dose of Buphenyl® will be decreased each week by 50 mg/kg until entire daily dose of phenylbutyrate is HPN-100. Target HPN-100 dose will contain the same amount of phenylbutyrate as the subject's prescribed daily dose of Buphenyl®. Subject will take HPN-100 alone for one week and then switch back to previous dose of Buphenyl for the last week of the study.
|
HPN-100
n=10 participants at risk
HPN-100 : Subjects will be taking prescribed dose of Buphenyl® TID (not to exceed 20g/day) at least two weeks prior to enrollment. Subjects will take prescribed dose of Buphenyl® TID for first week of study, and then switch over to HPN-100 TID during a dose-escalation phase. The dose of HPN-100 will be increased and the dose of Buphenyl® will be decreased each week by 50 mg/kg until entire daily dose of phenylbutyrate is HPN-100. Target HPN-100 dose will contain the same amount of phenylbutyrate as the subject's prescribed daily dose of Buphenyl®. Subject will take HPN-100 alone for one week and then switch back to previous dose of Buphenyl for the last week of the study.
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|---|---|---|
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Metabolism and nutrition disorders
Hyperammonaemia
|
7.1%
1/14 • Number of events 1
The occurrence of adverse events was assessed by investigator assessment, clinical laboratory measurements, ECG, vitals signs measurements and symptom survey.
|
0.00%
0/10
The occurrence of adverse events was assessed by investigator assessment, clinical laboratory measurements, ECG, vitals signs measurements and symptom survey.
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Other adverse events
| Measure |
Buphenyl
n=14 participants at risk
HPN-100 : Subjects will be taking prescribed dose of Buphenyl® TID (not to exceed 20g/day) at least two weeks prior to enrollment. Subjects will take prescribed dose of Buphenyl® TID for first week of study, and then switch over to HPN-100 TID during a dose-escalation phase. The dose of HPN-100 will be increased and the dose of Buphenyl® will be decreased each week by 50 mg/kg until entire daily dose of phenylbutyrate is HPN-100. Target HPN-100 dose will contain the same amount of phenylbutyrate as the subject's prescribed daily dose of Buphenyl®. Subject will take HPN-100 alone for one week and then switch back to previous dose of Buphenyl for the last week of the study.
|
HPN-100
n=10 participants at risk
HPN-100 : Subjects will be taking prescribed dose of Buphenyl® TID (not to exceed 20g/day) at least two weeks prior to enrollment. Subjects will take prescribed dose of Buphenyl® TID for first week of study, and then switch over to HPN-100 TID during a dose-escalation phase. The dose of HPN-100 will be increased and the dose of Buphenyl® will be decreased each week by 50 mg/kg until entire daily dose of phenylbutyrate is HPN-100. Target HPN-100 dose will contain the same amount of phenylbutyrate as the subject's prescribed daily dose of Buphenyl®. Subject will take HPN-100 alone for one week and then switch back to previous dose of Buphenyl for the last week of the study.
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|---|---|---|
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Gastrointestinal disorders
Nausea
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14.3%
2/14
The occurrence of adverse events was assessed by investigator assessment, clinical laboratory measurements, ECG, vitals signs measurements and symptom survey.
|
0.00%
0/10
The occurrence of adverse events was assessed by investigator assessment, clinical laboratory measurements, ECG, vitals signs measurements and symptom survey.
|
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Gastrointestinal disorders
Dyspepsia
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7.1%
1/14
The occurrence of adverse events was assessed by investigator assessment, clinical laboratory measurements, ECG, vitals signs measurements and symptom survey.
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0.00%
0/10
The occurrence of adverse events was assessed by investigator assessment, clinical laboratory measurements, ECG, vitals signs measurements and symptom survey.
|
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Gastrointestinal disorders
Abdominal Pain
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14.3%
2/14
The occurrence of adverse events was assessed by investigator assessment, clinical laboratory measurements, ECG, vitals signs measurements and symptom survey.
|
0.00%
0/10
The occurrence of adverse events was assessed by investigator assessment, clinical laboratory measurements, ECG, vitals signs measurements and symptom survey.
|
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Gastrointestinal disorders
Gastrooesophageal Reflux Disease
|
7.1%
1/14
The occurrence of adverse events was assessed by investigator assessment, clinical laboratory measurements, ECG, vitals signs measurements and symptom survey.
|
0.00%
0/10
The occurrence of adverse events was assessed by investigator assessment, clinical laboratory measurements, ECG, vitals signs measurements and symptom survey.
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Metabolism and nutrition disorders
Increased Appetite
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7.1%
1/14
The occurrence of adverse events was assessed by investigator assessment, clinical laboratory measurements, ECG, vitals signs measurements and symptom survey.
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30.0%
3/10
The occurrence of adverse events was assessed by investigator assessment, clinical laboratory measurements, ECG, vitals signs measurements and symptom survey.
|
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Metabolism and nutrition disorders
Hyperammonaemia
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7.1%
1/14
The occurrence of adverse events was assessed by investigator assessment, clinical laboratory measurements, ECG, vitals signs measurements and symptom survey.
|
0.00%
0/10
The occurrence of adverse events was assessed by investigator assessment, clinical laboratory measurements, ECG, vitals signs measurements and symptom survey.
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngolaryngeal Pain
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0.00%
0/14
The occurrence of adverse events was assessed by investigator assessment, clinical laboratory measurements, ECG, vitals signs measurements and symptom survey.
|
20.0%
2/10
The occurrence of adverse events was assessed by investigator assessment, clinical laboratory measurements, ECG, vitals signs measurements and symptom survey.
|
|
Skin and subcutaneous tissue disorders
Skin Odour Abnormal
|
7.1%
1/14
The occurrence of adverse events was assessed by investigator assessment, clinical laboratory measurements, ECG, vitals signs measurements and symptom survey.
|
0.00%
0/10
The occurrence of adverse events was assessed by investigator assessment, clinical laboratory measurements, ECG, vitals signs measurements and symptom survey.
|
Additional Information
Sr. Vice President and Chief Medical Officer, Bruce F. Scharschmidt
Hyperion Therapeutics
Phone: (650) 745-7851
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60