Dose-Escalation Safety Study of HPN-100 to Treat Urea Cycle Disorders
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|ClinicalTrials.gov Identifier: NCT00551200|
Recruitment Status : Completed
First Posted : October 30, 2007
Results First Posted : May 12, 2015
Last Update Posted : January 16, 2017
|Condition or disease||Intervention/treatment||Phase|
|Urea Cycle Disorders||Drug: HPN-100 Drug: BUPHENYL®||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||14 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 2, Open-Label, Switch-Over, Dose-Escalation Study of the Safety and Tolerability of HPN-100 Compared to Buphenyl® (Sodium Phenylbutyrate) in Patients With Urea Cycle Disorders|
|Study Start Date :||October 2007|
|Actual Primary Completion Date :||July 2008|
|Actual Study Completion Date :||December 2008|
Active Comparator: BUPHENYL® to HPN-100 vs. HPN-100
Buphenyl treatment for one week was followed by dose escalation to HPN-100. Dose of Buphenyl was gradually decreased while HPN-100 dose was gradually increased until subject reached dosing of 100% HPN-100. HPN-100 at 100% of the dose was given for 1 week before subject was switched back to original Buphenyl treatment.
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.
BUPHENYL® (sodium phenylbutyrate) tablets and powder have been approved for marketing in the United States since 1996 as an adjunctive therapy in the long-term management of patients with UCDs involving deficiencies of CPS, OTC, or ASS.
- Venous Ammonia Levels at the Peak and Mean TNUAC Time-normalized Area Under the Curve) [ Time Frame: At steady state (1 week) on each medication (Buphenyl® alone, HPN-100 alone), and at steady state (1 week) after each dose escalation ]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.
- Number of Subjects Experienced Adverse Events [ Time Frame: during the period on 100% Buphenyl (up to 4 weeks) or HPN-100 (up to 10 weeks) ]
- Number of Subjects Experienced Serious Adverse Events [ Time Frame: during the period subjects on 100% Buphenyl (up to 4 weeks) or HPN-100 (up to 10 weeks) ]
- Pharmacokinetics (Plasma and Urine PK Parameters of Study Drugs and Their Metabolites) [ Time Frame: 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.
- Drug Preference for HPN-100 or Buphenyl® (as Assessed by Global Preference Question) [ Time Frame: End of Study ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00551200
|United States, Minnesota|
|University of Minnesota|
|Minneapolis, Minnesota, United States, 55455|
|United States, Texas|
|Baylor College of Medicine|
|Houston, Texas, United States, 77030|
|Study Director:||Bruce Scharschmidt, MD||Horizon Pharma Ireland, Ltd., Dublin Ireland|