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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hyperion Therapeutics, Inc.
ClinicalTrials.gov Identifier:
NCT00947297
First received: July 24, 2009
Last updated: July 15, 2013
Last verified: July 2013

July 24, 2009
July 15, 2013
November 2009
September 2011   (final data collection date for primary outcome measure)
Rate of Adverse Events (Number of Participants Who Experienced Any AE Considered Related to Study Drug) [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
Long-term safety data [ Time Frame: 1 year ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00947297 on ClinicalTrials.gov Archive Site
Number and Causes of Hyperammonemic Events [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
Number of hyperammonemic crises per patient
Not Provided
Not Provided
Not Provided
 
Study of the Safety of HPN-100 for the Long-Term Treatment of Urea Cycle Disorders (Treat UCD)
A Phase 3, Open-Label Study of the Safety of HPN-100 for the Long-Term Treatment of Urea Cycle Disorders (Treat UCD)

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.

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.

Interventional
Phase 3
Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Urea Cycle Disorders
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.
Experimental: HPN-100
Patients who were treated with HPN-100
Intervention: Drug: HPN-100
Mokhtarani M, Diaz GA, Rhead W, Berry SA, Lichter-Konecki U, Feigenbaum A, Schulze A, Longo N, Bartley J, Berquist W, Gallagher R, Smith W, McCandless SE, Harding C, Rockey DC, Vierling JM, Mantry P, Ghabril M, Brown RS Jr, Dickinson K, Moors T, Norris C, Coakley D, Milikien DA, Nagamani SC, Lemons C, Lee B, Scharschmidt BF. Elevated phenylacetic acid levels do not correlate with adverse events in patients with urea cycle disorders or hepatic encephalopathy and can be predicted based on the plasma PAA to PAGN ratio. Mol Genet Metab. 2013 Dec;110(4):446-53. doi: 10.1016/j.ymgme.2013.09.017. Epub 2013 Oct 8.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
60
November 2011
September 2011   (final data collection date for primary outcome measure)

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 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.
Both
6 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Canada
 
NCT00947297
HPN-100-007
Yes
Hyperion Therapeutics, Inc.
Hyperion Therapeutics, Inc.
Not Provided
Not Provided
Hyperion Therapeutics, Inc.
July 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP