Long-term Efficacy of Carglumic Acid in Organic Acidemia.

Study Overview
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Brief Summary
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Evaluate the Long Term Effectiveness & Safety of the use of Carglumic Acid (Carbaglu®) in Patients with Propionic Acidemia (PA) or Methylmalonic Acidemia (MMA).

Detailed Description
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Study procedures: A. Study period: 24 months; treatment period: 12 months. B. Patients will receive Carglumic Acid (Carbaglu®) 50 mg/kg/day in addition to standard therapy (protein restricted diet, L-carnitine, metronidazole and vitamin B12). C. Patients need to regularly come back for follow up examination on Day 0, month 3, month 6, and month 12. D. Patients should report any adverse event that occur during treatment period. E. Patients' number of emergency visits due to hyperammonemia, ammonia level, acylcarnitine, urinary organic acid analysis, plasma amino acid analysis will be recorded during treatment period.

Official Title
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Evaluate the Long Term Effectiveness & Safety of the Use of Carglumic Acid (Carbaglu®) in Patients With Propionic Acidemia (PA) or Methylmalonic Acidemia (MMA).

Conditions
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Propionic Acidemia (PA) , Methylmalonic Acidemia (MMA)

Intervention / Treatment
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* Drug: Carglumic Acid (Carbaglu®)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: PA or MMA confirmed using the following criteria: PA confirmed by the measurement of acylcarnitine profile, urine organic acid, measurement of propionyl Co-A carboxylase in leukocytes or cultured fibroblasts or by DNA molecular testing of PCCA (Propionyl CoA Carboxylase, Alpha Polypeptide) or PCCB (propionyl CoA carboxylase, beta polypeptide) gene MMA confirmed by the measurement of acylcarnitine profile, urine organic acid, measurement of methymalonyl Co-A mutase in culture fibroblasts or DNA molecular testing of mutgene. Male or female Children of 18 years old or less. Had experienced Hyperammonemia(NH3 ≧100 uM) before. Not participating in any other clinical trial in the previous 30 days Exclusion Criteria: Patients with other organic acidemia or any other cause of hyperammonemia Patient receiving other investigational therapy for PA or MMA Patient with PA or MMA and other inherited genetic conditions or congenital anomalies Past history of hypersensitivity or drug allergy to Carbaglu®

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Receive Carglumic Acid<br>Experimental Case_ Carglumic Acid | Drug: Carglumic Acid (Carbaglu®)<br>* A. Study period: 24 months; treatment period: 12 months. B. Patients will receive Carglumic Acid (Carbaglu®) 50 mg/kg/day in addition to standard therapy (protein restricted diet, L-carnitine, metronidazole and vitamin B12) C. Patients need to regularly come back for follow up examination on Day 0, month 3, month 6, and month 12. (Check Plasma Amino Acid Analysis, Ammonia, acylcarnitine profile, Urinary organic acid analysis.) D. Patients should report any adverse event that occur during treatment period. E. Patients' number of emergency visits due to hyperammonemia, ammonia level, acylcarnitine, urinary organic acid analysis, plasma amino acid analysis will be recorded during treatment period.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of emergency visits due to hyperammonemia within 12 months period | Adverse Events | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to first visit to the ER due to hyperammonemia from starting the treatment | Adverse Events | 12 months | 
| Assessment of Plasma ammonia level | Plasma ammonia level over the study treatment period. | Baseline,3,6,9 and 12,months after receiving Carbaglu. | 
| Number of days of hospitalization | Number of days of hospitalization during study treatment period. | 12 months | 
| Assessment of Acylcarnitine level | Acylcarnitine level for all patients | Baseline,3,6,9 and 12,months after receiving Carbaglu. | 
| Assessment of urine organic acid level | Measuring urine organic acid level for both diseases. | Baseline,3,6,9 and 12,months after receiving Carbaglu. | 
| Assessment of Plasma aminoacids' level | Measuring Plasma aminoacids' level for both diseases. | Baseline,3,6,9 and 12,months after receiving Carbaglu. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Carglumic Acid (Carbaglu®)