Conditions: Urea Cycle Disorders
Keywords: Urea Cycle Disorder (UCD) UCD hyperammonemia Buphenyl (NaPBA) glycerol phenylbutyrate (GPB) Sodium Phenylbutyrate (NaPBA)
Allocation: RANDOMIZED | Intervention model: CROSSOVER
Enrollment: 46
Healthy volunteers: no

Brief summary:
This was a randomized, active-controlled, double-blind, cross-over study designed to enroll subjects with UCDs who are being treated with NaPBA.

Detailed description:
This was a randomized, active-controlled, double-blind, cross-over study designed to enroll subjects with UCDs who are being treated with NaPBA. Subjects were randomly assigned to receive either HPN-100 + NaPBA placebo or NaPBA + HPN 100 placebo for 2 weeks, and then crossed over to receive the other treatment for 2 weeks. Venous ammonia was the primary outcome measure. Subjects were admitted to the clinical research unit for 24 hours of pharmacokinetic (PK) blood and urine sampling (including an overnight stay) at the end of each treatment period, by which time the study drug had reached steady state.

Subjects followed a stable diet throughout the study as prescribed by the investigator and dietician. Throughout the study, diet diaries were completed by the subject and dietary protein intake were assessed by a dietician based on completed dietary diaries and consultation with the subject.

Subjects who completed this study and met the study entry criteria, were offered the opportunity to enroll in the HPN-100 open-label safety protocol (HPN-100-007).

Study acquired from Horizon in 2024.

Arms:
arm 1: Subjects in Arm A were randomly assigned to receive NaPBA + HPN 100 placebo for 2 weeks and then crossed over to receive HPN 100 + NaPBA Placebo for 2 weeks. arm 2: Subjects in Arm B were randomly assigned to receive HPN-100 + NaPBA placebo for 2 weeks and then crossed over to receive NaPBA + HPN 100 placebo for 2 weeks.

Interventions: intervention 1: HPN-100 intervention 2: Buphenyl (NaPBA)
Intervention descriptions: intervention 1: HPN-100 is a triglyceride that has a similar mechanism of action as NaPBA. It is a liquid with minimal taste and odor. Three teaspoons of HPN-100 (\~17.4mL) delivers equivalent amount of PBA in 40 tablets of NaPBA. intervention 2: Buphenyl (NaPBA) will be the comparator drug to HPN-100 in this study.

Protocol document: