MELAS: mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes
Conditions
Interventions
Single-dose as Step 1 (Table 1), repeated-dose as Step 2 (Table 2). In Step 1, the drug is administered orally during breakfast, and after confirming no safety problems during 7 days of observation, t
No. of Doses, Once
No. of Cases, 5
Observation after dosing, 7 days Adults (aged 16-59): Dosage 100mg
Observation after dosing, 7 days Table 2 Step2: Repeated-Dose Children (aged 6-15): Dosage 15mg/kg up to 200 mg
No. of Dosing days, 3 times per day for 12 weeks
Final Observation, 1 day after last dose Adults (aged 16-59): Dosage 300mg each time
Final Observation, 1 day after last dose
Sponsors
National Center of Neurology and Psychiatry, Japan
Edison Pharmaceuticals, Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Patients diagnosed with MELAS syndrome 2) Patients aged 6 to 59 at the time of consent 3) After adequate explanation regarding trial participation, patients who have adequately understood the explanation and have freely provided written agreement (or assent) and for whom a legal representative's written consent has been obtained 4) Patients that have a care provider who can ensure that the trial protocol is followed 5) Patients for whom the use of general pharmaceuticals can be prohibited 6) Patients for whom the ingestion of foods or beverages fortified with coenzyme Q10 or vitamin E can be prohibited for over 8 weeks prior to the administration start and for the duration of the trial. 7) Patients for whom the use of ubidecarenone, idebenone, and dichloroacetate can be prohibited for over 8 weeks prior to the administration start and for the duration of the trial.
Exclusion criteria
Exclusion criteria: 1) Patients for whom the MELAS syndrome genetic mutation has not been confirmed 2) Patients who cannot undergo magnetic resonance spectroscopy (MRS) 3) Patients allergic to EPI-743 or to sesame oil 4) Patients with a bleeding tendency, or with abnormal PT/PTT values (INR 1.5 or higher) 5) Patients with AST or ALT values of more than double the institutional limit 6) Patients with renal failure and who require dialysis 7) Patients with fat malabsorption syndrome that impedes drug absorption 8) Patients with pyruvate dehydrogenase (PDH) deficiency or other inborn error of metabolism 9) Patients who are pregnant or planning to become pregnant 10) Patients with an alcohol dependency or who are illegal drug users 11) Patients with severe heart failure accompanied by lactate acidosis 12) Patients who have received another trial drug or test drug within three months of the start of dosing of the test drug in this trial 13) Patients with a history of severe drug hypersensitivity 14) Other patients deemed by the researchers to be unsuitable for this trial
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Tabulate EPI-743 blood concentrations and calculate fundamental pharmacokinetic parameters | — |
Secondary
| Measure | Time frame |
|---|---|
| 1) Lactate levels at MRS testing 2) blood and CSF concentrations of lactate and pyruvate 3) QOL values (SF-36, PedsQL) 4) Mitochondrial disease evaluation scale scores (NPMDS or NMDAS) 5) Incidence of abnormal brain waves 6) Incidence of epileptiform seisures 7) Fatigue level 8) Safety evaluation | — |
Countries
Japan
Contacts
Public ContactAkemi Tamaura
National Center Hospital, National Center of Neurology and Psychiatry Clinical Research Unit
Outcome results
None listed