Short-Term Outcome of N-Carbamylglutamate in the Treatment of Acute Hyperammonemia

Summary

The overall objective of this drug trial is to determine whether the treatment of acute hyperammonemia with N-carbamyl-L-glutamate (NCG, Carglumic acid) in propionic acidemia (PA), methylmalonic acidemia (MMA), late-onset CPS1 deficiency (CPSD) and late-onset Ornithine transcarbamylase deficiency (OTCD) accelerates the resolution of hyperammonemia efficiently and safely.

The primary goal is to determine if the study drug (NCG) efficiently reduces ammonia levels following a hyperammonemia episode(s).

Secondly, the investigators want to know if treatment with this study drug (NCG) efficiently improves neurologic function, reduces plasma glutamine levels and lessens the duration of hospitalization after each episode of hyperammonemia.

Conditions

• Propionic Acidemia, Type I and/or Type II
• Methylmalonic Acidemia
• Carbamoyl-Phosphate Synthase I Deficiency Disease
• Ornithine Carbamoyltransferase Deficiency

Interventions

DRUG

Carbaglu

Carbaglu Chemical Composition: N-carbamoyl-L-glutamic acid (NCG) The daily dose will be 150 mg/kg/ day or 3.3 g/m2/day for patients \>15 kg and will be administered for 7 days or until discharge, whichever is sooner. The doses are to be divided into 2 equal doses and administered orally or enterally by nasogastric or gastrostomy tube. Standard of care will prevail when choosing the mode of drug administration. The tablets must be dispersed in a minimum of 2.5-10 ml of water and ingested immediately or administered by fast-push through a syringe via a nasogastric or gastrostomy tube. The suspension has a slightly acidic taste.

DRUG

Placebo

Placebo that looks/tastes the same as NCG and is administered on the same schedule as the NCG intervention

Sponsors & Collaborators

• Children's National Research Institute

  collaborator OTHER

• Boston Children's Hospital

  collaborator OTHER

• University Hospitals Cleveland Medical Center

  collaborator OTHER

• University of California, Los Angeles

  collaborator OTHER

• Children's Hospital of Philadelphia

  collaborator OTHER

• Stanford University

  collaborator OTHER

• Icahn School of Medicine at Mount Sinai

  collaborator OTHER

• University of Pittsburgh

  collaborator OTHER

• Children's Hospital Colorado

  collaborator OTHER

• Mendel Tuchman

  lead OTHER

Principal Investigators

• Mendel Tuchman, MD · Children's National Research Institute

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

1 Week

Max Age

99 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2012-09-01

Primary Completion

2019-04-30

Completion

2020-04-30

Countries

• United States

Study Locations