Study of the Safety of HPN (Hyperion)-100 for the Long-Term Treatment of Urea Cycle Disorders (Treat UCD)

Urea Cycle Disorders Clinical Trial

Official title:

A Phase 3, Open-Label Study of the Safety of HPN-100 for the Long-Term Treatment of Urea Cycle Disorders (Treat UCD)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00947297
• Other study ID #: HPN-100-007
• Status: Completed
• Phase: Phase 3
• First received: July 24, 2009
• Last updated: January 13, 2017
• Start date: November 2009
• Est. completion date: November 2011

Study information

• Verified date: June 2015
• Source: Horizon Pharma Ireland, Ltd., Dublin Ireland
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This was a long-term safety study HPN-100 in urea cycle disorder (UCD) subjects. Subjects were assessed regularly for safety and control of their venous ammonia. Hyperammonemic events were characterized with respect to contributing factors, such as intercurrent illness, diet, and noncompliance with medication.

Description:

This was a one year long-term safety study of HPN-100 in UCD subjects. Subjects were assessed regularly for safety and control of their venous ammonia. Hyperammonemic events were characterized with respect to contributing factors, such as intercurrent illness, diet, and noncompliance with medication.

Forty subjects with a diagnosis of UCD who completed Study HPN-100-006 were enrolled.

Twenty additional UCD subjects ≥ 6 years of age were enrolled. These subjects included those who did not qualify for HPN-100-006 [e.g., subjects between the ages of 6-17; subjects with other UCD subtypes or adult subjects who have not taken sodium phenylbutyrate (NaPBA) in the past 6 months, etc.]. For adult subjects not receiving NaPBA in the past 6 months, subjects must, in the judgment of the investigator, be anticipated to benefit from the addition of a nitrogen-scavenging agent to their current treatment. See the inclusion criteria for examples of clinical evidence of potential benefit.

Monthly assessments included safety laboratory tests, amino acid panel, vital signs, electrocardiogram (ECG) monitoring, venous ammonia, and blood and urine metabolites. Adverse events (AEs) and concomitant medications were recorded on an ongoing basis.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: November 2011
• Est. primary completion date: September 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years and older

Eligibility

Inclusion Criteria:

• Male and female subjects who completed HPN-100-006:

*Additionally, approximately 20 UCD subjects = 6 years of age may be enrolled who have not participated in HPN-100-006. These subjects may include those who did not qualify HPN-100-006 (e.g., subjects between the ages of 6-17 years, subjects with other UCD subtypes, or adult subjects who have not taken sodium phenylbutyrate (NaPBA) in the past 6 months, etc.). For adult subjects not receiving NaPBA in the past 6 months, subjects must, in the judgment of the investigator, be anticipated to benefit from the addition of a nitrogen-scavenging agent to their current treatment. Clinical evidence of potential benefit from introduction of an ammonia-scavenging agent might include a recent history (in the past year) of clinically overt hyperammonemia accompanied by a venous ammonia = 100 µmol/L, a recent history (within the past year) of protein intolerance, or a history of abnormally high venous ammonia levels accompanied by symptoms (e.g., headache) that might reasonably be attributed to hyperammonemia.

• 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.

• Able to perform and comply with study activities, including blood draws.

• 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.

Exclusion Criteria:

• Screening venous ammonia level of = 100 µmol/L or signs and symptoms indicative of hyperammonemia; subjects may be re-screened after their venous ammonia is controlled, at the discretion of the investigator.

• History of 4 or more hyperammonemic events as defined in Section 3.5.1 in the preceding 12 months.

• Active infection (viral or bacterial) or any other condition that may increase venous ammonia levels.

• Any clinical or laboratory abnormality or medical condition that, at the discretion of the investigator, may put the subject at increased risk by participating in this study.

• Use of any medication known to significantly affect renal clearance (e.g., probenecid) or to increase protein catabolism (e.g., corticosteroids), or other medication known to increase venous ammonia levels (e.g., valproate), within the 24 hours prior to Day 1 and throughout the study.

• History of QTc (QT interval corrected) prolongation, or a QTc interval = 450 msec or an increase of = 60 msec during the previous HPN-100 study if applicable.

• Known hypersensitivity to PAA or PBA.

• Liver transplant, including hepatocellular transplant.

• Breastfeeding or lactating females.

Related Conditions & MeSH terms

• Disease
• Urea Cycle Disorders
• Urea Cycle Disorders, Inborn

Intervention

Drug:
• HPN-100
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 (~17.4 mL) delivers equivalent of PBA that 40 tablets of NaPBA do.

Locations

Country	Name	City	State
Canada	The Hospital for Sick Children	Toronto	Ontario
United States	Children's Hospital Colorado	Aurora	Colorado
United States	SNBL-Clinical Pharmacology Center	Baltimore	Maryland
United States	Tufts-New England Medical Center	Boston	Massachusetts
United States	University Hospitals Case Medical Center	Cleveland	Ohio
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	University of Florida	Gainesville	Florida
United States	Baylor College of Medicine	Houston	Texas
United States	Univeristy of Iowa	Iowa City	Iowa
United States	Long Beach Memorial	Long Beach	California
United States	UCLA	Los Angeles	California
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	University of Minnesota Medical Center	Minneapolis	Minnesota
United States	Yale School of Medicine	New Haven	Connecticut
United States	Mount Sinai School of Medicine	New York	New York
United States	University of Pittsburgh	Pittsburgh	Pennsylvania
United States	Maine Medical Center	Portland	Maine
United States	Oregon Health & Science University	Portland	Oregon
United States	University of Utah	Salt Lake City	Utah
United States	Stanford University	Stanford	California
United States	Westchester Medical Center	Valhalla	New York
United States	Children's National Medical Center	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Horizon Pharma Ireland, Ltd., Dublin Ireland

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of Adverse Events (Number of Participants Who Experienced Any AE Considered Related to Study Drug)		1 year
Secondary	Number and Causes of Hyperammonemic Events	Number of hyperammonemic crises per patient	1 year
Secondary	Blood Ammonia Levels	Venous Ammonia levels over time	1 Year
Secondary	Patient Satisfaction With HPN-100	Drug preference will be noted at week 3	Month 1 post dose