The KHENERGY Study

Exclusion Criteria

• •1. Motoric abnormalities other than related to the mitochondrial disease interfering with the outcome parameters.
• •2. CPEO patients with clinical signs and symptoms restricted to the eye only
• •3. Heteroplasmy level as measured in urine \< 20%
• •4. Poor nutritional state as judged by the investigator
• •5. Body Mass Index (BMI) not within 18.0-30.0 kg/m2 at screening.
• •6. History of cancer
• •7. Surgery or active illness of gastro-intestinal tract that might interfere with absorption.
• •8. Participation in a trial of an investigational product in the preceding 3 months prior to the first dose or during this trial.
• •9. Positive drug, alcohol or cotinine test at screening and/or admission (Day 1 of the first dosing period).
• •10. Clinically relevant abnormal laboratory, ECG recordings, cardiac echo (within 1 year prior to screening), vital signs or physical or mental findings at screening as judged by the Investigator.
• •11. Clinically relevant abnormal ECG or cardiac functioning as judged by a cardiologist.
• •12. ECG: QTc \> 450 ms, abnormal T-wave
• •13. Symptomatic heart failure or signs of ischemic heart disease
• •14. Left Ventricular Ejection Fraction \<45%
• •15. History or family history of congenital Long QT syndrome
• •16. Increased or decreased potassium (local laboratory normal range)
• •17. Inadequate contraception use, pregnancy or breast feeding (females)
• •18. Clinically significant presence or history of allergy as judged by the Investigator.
• •19. History of hypersensitivity or idiosyncrasy to any of the components of the investigational drug.
• •20. Within 4 weeks prior to dosing, the use of:
• •* (multi)vitamins, co-enzyme Q10, Vitamine E, riboflavin, and anti-oxidant supplements (and idebenone/EPI-743),
• •* as well as any medication negatively influencing mitochondrial functioning (including but not limited to valproic acid, glitazones, statins, anti-virals, amiodarone, and NSAID's)
• •* as well as any strong Cytochrome P450 inhibitors (all 'conazoles-anti-fungals', HIV antivirals, grapefruit)
• •* and strong Cytochrome P450 inducers (a.o. carbamazepine, phenobarbital, phenytoin, rifampicin, St Johns wort, pioglitazone, troglitazone)
• •* as well as any medication known to affect cardiac repolarization (all anti-psychotics, several anti-depressants: nor/amitriptyline, fluoxetine, anti-emetics: domperidone (motilium) granisetron, ondansetron)
• •* as well as any medication metabolized by Cytochrome P450 with a narrow therapeutical width. (for reference: drug interaction table of Indiana University http://medicine.iupui.edu/clinpharm/ddis/clinical-table/)