N-Carbamylglutamate (Carbaglu) In The Treatment Of Hyperammonemia
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||N-Carbamylglutamate (Carbaglu) In The Treatment Of Hyperammonemia|
- Rate of ureagenesis as determined by 13C enrichment of urea [ Time Frame: 3 days of treatment ] [ Designated as safety issue: Yes ]
- Plasma ammonia concentration [ Time Frame: 3 days ] [ Designated as safety issue: Yes ]
- Plasma amino acid levels [ Time Frame: 3 days ] [ Designated as safety issue: Yes ]
- Urine Orotic Acid [ Time Frame: 3 days ] [ Designated as safety issue: No ]Only in patients with OTC deficiency
- Blood Urea Nitrogen (BUN) [ Time Frame: 3 days ] [ Designated as safety issue: Yes ]
- Routine safety laboratory tests (CBC, LFTs, Creatinine) [ Time Frame: 3 days ] [ Designated as safety issue: Yes ]
|Study Start Date:||August 2008|
|Estimated Study Completion Date:||July 2018|
|Estimated Primary Completion Date:||July 2017 (Final data collection date for primary outcome measure)|
Investigate whether a 3-day treatment with NCG can improve or restore urea genesis capacity in patients with NAGS, CPSI, or OTC deficiency or PA or MMA using surrogate markers: [13C] label incorporation into urea and plasma levels of ammonia, urea nitrogen (BUN) and amino acids
100 mg/kg/day or 2.2 g/M2/day in 3-4 divided doses for 3 days
Other Name: Carglumic acid, Carbaglu
Hyperammonemia associated with several rare inherited disorders frequently causes mental retardation, developmental disabilities and death. The overall goal of this study is to investigate the short-term efficacy and safety of the orphan drug, N-Carbamyl-L-glutamate (Carbaglu®, abbreviated as NCG), for the treatment of hyperammonemia in rare inherited disorders: carbamyl phosphate synthetase I (CPSI) deficiency, NAGS deficiency, ornithine transcarbamylase (OTC) deficiency, propionic acidemia (PA) and methylmalonic acidemia (MMA).
The primary aims are:
- To investigate whether 3-day treatment with NCG can improve or restore ureagenesis capacity in patients with NAGS, CPSI or OTC deficiency using as surrogate markers: [13C] label incorporation into urea and plasma levels of ammonia, urea and glutamine. In addition, to determine whether treatment with NCG in OTC deficiency increases the production of a nitrogen containing intermediate, orotic acid, as a mechanism for eliminating nitrogen in lieu of urea.
- To investigate whether ureagenesis capacity is deficient in patients with PA and MMA and whether 3-day treatment with NCG can improve or restore ureagenesis capacity in all or some of these patients.
- To evaluate the safety of short-term (3-day) treatment with NCG in the above patients using clinical and laboratory parameters.
The hypothesis is that ureagenesis capacity as evidenced by [13C] incorporation into urea is deficient in each of these five disorders and that treatment with NCG will improve or restore ureagenesis in patients affected by them. The study will be conducted in the General Clinical Research Centers (GCRC) of the Children's National Medical Center, Washington, D.C. and the Children's Hospital of Philadelphia. Patients (1 day to 70 years of age) with any of the five disorders are eligible for the study. They will all be tested in a short-term trial using surrogate markers (incorporation of [13C] label from Na-acetate into urea, and plasma levels of ammonia, urea and glutamine) before and immediately following 3 days of treatment with NCG. The patients will also be evaluated for short-term safety of NCG using clinical and laboratory parameters. The results of this study will provide important efficacy data, which should help to bring Carbaglu®) to the US market for the benefit of patients with any of these orphan diseases found to be responsive to NCG in this trial.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00843921
|Contact: Mendel Tuchman, MDemail@example.com|
|United States, District of Columbia|
|Childrens Research Institute||Recruiting|
|Washington, District of Columbia, United States, 20010|
|Contact: Mendel Tuchman, MD 202-476-2549 firstname.lastname@example.org|
|Principal Investigator: Mendel Tuchman, MD|
|Principal Investigator:||Mendel Tuchman, MD||Children's Research Institute|