Phase 2
N=47
Short-Term Outcome of N-Carbamylglutamate in the Treatment of Acute Hyperammonemia
Propionic Acidemia, Type I and/or Type II · Methylmalonic Acidemia · Carbamoyl-Phosphate Synthase I Deficiency Disease · Ornithine Carbamoyltransferase Deficiency
Bottom Line
View on ClinicalTrials.gov: NCT01599286 ↗Enrolled (actual)
47
Serious AEs
28.6%
Results posted
Feb 2021
Primary outcome: Primary: Time to the Primary Outcome (Earlier of Ammonia <50 µmol/L or Hospital Discharge) — 1.37; 0.79 Hazard Ratio
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Carbaglu (Drug); Placebo (Drug)
- Age
- Pediatric, Adult, Older Adult · 0+ yrs
- Sex
- All
- Sponsor
- Mendel Tuchman
- Primary completion
- Apr 2019
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Time to the Primary Outcome (Earlier of Ammonia <50 µmol/L or Hospital Discharge) |
1.37; 0.79 | — |
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.
Eligibility Criteria
Inclusion Criteria
o Aged older than 1 week with an established diagnosis of CPSD or OTCD (as follows):
- Diagnosed with late-onset CPSD confirmed by detection of pathogenic mutation(s), and/or decreased ( 1 week of age
OR
o An established diagnosis of PA or MMA (as follows):
- Diagnosed with PA by semi-quantitative urine organic acid analysis, defined as the presence of elevated Methylcitric acid and normal methylmalonic acid levels and no evidence of biotin related disorders in the organic acid analysis
OR
- Diagnosed with MMA by semi-quantitative urine organic acid analysis, defined as an elevation of methylmalonic acid and no evidence of vitamin B12 dependent disorder on plasma amino acid analysis (B12 dependency is defined by documented B12 responsiveness)
AND: Subject or subject's first-degree relative had plasma ammonia level at any time ≥100 μmol/L
- Able to receive medications orally, by nasogastric (NG)-tube or by gastric (G)-tube
- No concomitant illness which would preclude safe participation as judged by the investigator
- If post-menarcheal must have a negative pregnancy test prior to administration of study drug at each episode
- Signed informed consent by the subject or the subject's legally acceptable representative
Exclusion Criteria
- Administration of NCG within 7 days of participation in the study
- Use of any other investigational drug, biologic, or therapy
- Planned participation in any other clinical trial
- Diagnosis of any medical condition causing hyperammonemia which is not PA/MMA, CPSD or OTCD. Other urea cycle disorders will be excluded from this study
- Any clinical or laboratory abnormality or medical condition that, at the discretion of the investigator, may put the subject at additional risk by participating in this study
- Has had a liver transplant
- Is not expected to be compliant with this study in terms of returning to the site for subsequent episodes of hyperammonemia crises
- Is pregnant
Data sourced from ClinicalTrials.gov (NCT01599286). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.