Dose-Escalation Safety Study of HPN-100 to Treat Urea Cycle Disorders
|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 ]
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|