A Phase 2, Switch-Over, Dose-Escalation Study of the Safety and Tolerability of HPN-100 (glyceryl tri-[4-phenylbutyrate]) Compared to Sodium Phenylbutyrate in Adult and Pediatric Subjects with Urea Cycle Disorders

• Conditions: rea Cycle Disorder (urea cycle enzyme or transporter deficiency); MedDRA version: 9.1Level: LLTClassification code 10013373Term: Disorders of urea cycle metabolism

• Registration Number: EUCTR2008-003865-23-GB
• Lead Sponsor: Hyperion Therapeutics Limited

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2008-07-25
• Last Update Posted: 14 August 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 16

Inclusion Criteria

•Male and female subjects = 6 years old
•Signed informed consent by subject and/or subject’s legally acceptable representative
•Diagnosis of urea cycle disorder (enzyme or transporter deficiency) confirmed via enzymatic, biochemical or genetic testing
•Currently being treated with sodium PBA for a diagnosis of UCD for at least one week prior to the screening visit
•Able to perform and comply with study activities (including the ability to adhere to 24-hour urine collections both in the clinic and after discharge; i.e., no subjects in diapers)
•Willing to maintain a constant diet throughout the study (unless the investigator recommends a change based on safety considerations)
•Negative pregnancy test for all females of childbearing potential
•All females of childbearing potential and all sexually active males must agree to use an acceptable method of contraception throughout the study

Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

•Use of any investigational drug (sodium PBA excepted) within 30 days prior to Day 1
•Active infection (viral or bacterial) or any other condition that may increase ammonia levels
•Laboratory values outside the normal range that are determined to be clinically significant by the investigator
•Any clinical or laboratory abnormality of Grade 3 or greater severity according to the CTCAE v3.0 (or for conditions not covered by the CTCAE, a severe or life-threatening toxicity); except that Grade 3 elevations in liver enzymes are allowed in an otherwise clinically stable subject
•Use of any medication known to significantly affect renal clearance (e.g., probenecid) or to increase protein catabolism (e.g., corticosteroids), or other medication (e.g., valproate) known to increase ammonia levels, within the 24 hours prior to Day 1
•History of diagnosis with long QT syndrome or QTc interval > 450 msec at screening
•Other medical conditions which in the judgment of the investigator preclude entry
•Known hypersensitivity to PAA or PBA
•Creatinine levels = 1.5 ? upper limit of normal (ULN)
•Liver transplant, including hepatocellular transplant
•Currently treated with sodium benzoate or Carbaglu® (carglumic acid)

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary objective of this study is to evaluate the safety and tolerability of escalating doses of HPN-100 compared to a constant dose of sodium PBA (European Trade name: AMMONAPS®; United States trade name BUPHENYL®) in adult and pediatric subjects with UCDs.;Secondary Objective: Secondary objectives are to assess:<br>•plasma and urine PK characteristics of HPN-100 and sodium phenylbutyrate (sodium PBA) metabolites<br>•preliminary evidence of efficacy (as assessed by venous ammonia levels and urinary excretion of PAGN)<br>•compliance with diet and study drug treatment<br>•subject-reported outcomes of symptoms and drug preference<br>;Primary end point(s): The primary objective of this study is to evaluate the safety and tolerability of escalating doses of HPN-100 compared to a constant dose of sodium PBA (European Trade name: AMMONAPS®; United States trade name BUPHENYL®) in adult and pediatric subjects with UCDs.