Evaluation of long-term effectiveness of the use of carglumic acid in patients with propionic acidemia (PA) or methylmalonic acidemia (MMA): study protocol for a randomized controlled trial.

Abstract

INTRODUCTION:

Propionic acidemia (PA) and methylmalonic acidemia (MMA) are rare autosomal recessive inborn errors of metabolism characterized by hyperammonemia due to N-acetylglutamate synthase (NAGS) dysfunction. Carglumic acid (Carbaglu®; Orphan Europe Ltd.) is approved by the US Food and Drug Administration (USFDA) for the treatment of hyperammonemia due hepatic NAGS deficiency. Here we report the rationale and design of a phase IIIb trial that is aimed at determining the long-term efficacy and safety of carglumic acid in the management of PA and MMA.

METHODS:

This prospective, multicenter, open-label, randomized, parallel group phase IIIb study will be conducted in Saudi Arabia. Patients with PA or MMA (≤15 years of age) will be randomized 1:1 to receive twice daily carglumic acid (50 mg/kg/day) plus standard therapy (protein-restricted diet, L-carnitine, and metronidazole) or standard therapy alone for a 2-year treatment period. The primary efficacy outcome is the number of emergency room visits due to hyperammonemia. Safety will be assessed throughout the study and during the 1 month follow-up period after the study.

DISCUSSION:

Current guidelines recommend conservative medical treatment as the main strategy for the management of PA and MMA. Although retrospective studies have suggested that long-term carglumic acid may be beneficial in the management of PA and MMA, current literature lacks evidence for this indication. This clinical trial will determine the long-term safety and efficacy of carglumic acid in the management of PA and MMA.

TRIAL REGISTRATION:

King Abdullah International Medical Research Center ( KAIMRC ): (RC13/116) 09/1/2014. Saudi Food and Drug Authority (SFDA) (33066) 08/14/2014. ClinicalTrials.gov (identifier: NCT02426775) 04/22/2015.

• Authors: Marwan Nashabat, Abdulrahman Obaid, Fuad Al Mutairi, Mohammed Saleh, Mohammed Elamin, Hind Ahmed, Faroug Ababneh, Wafaa Eyaid, Abdulrahman Alswaid, Lina Alohali, Eissa Faqeih, Majed Aljeraisy, Mohamed A Hussein, Ali Alasmari, Majid Alfadhel
• Journal: BMC pediatrics (BMC Pediatr) Vol. 19 Issue 1 Pg. 195 (06 13 2019) ISSN: 1471-2431 [Electronic] England
• PMID: 31196016 (Publication Type: Clinical Trial Protocol, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Glutamates
• Metronidazole
• carglumic acid
• Carnitine

Topics

• Adolescent
• Amino Acid Metabolism, Inborn Errors (drug therapy)
• Carnitine (therapeutic use)
• Child
• Clinical Trials, Phase III as Topic
• Diet, Protein-Restricted
• Drug Administration Schedule
• Early Termination of Clinical Trials
• Glutamates (adverse effects, therapeutic use)
• Humans
• Metronidazole (therapeutic use)
• Multicenter Studies as Topic
• Propionic Acidemia (drug therapy, therapy)
• Prospective Studies
• Randomized Controlled Trials as Topic
• Sample Size
• Saudi Arabia