Table 2. Small molecules used in clinical studies for treatment of mitochondrial diseases
Molecule nameTargeted diseaseClinical phaseClinical trial identifieraPrimary resultsSponsor
KH176MELASPhase 1 double‐blind, randomized, placebo‐controlled study of the safety, tolerability, pharmacokinetics, and pharmacodynamics in healthy volunteersNCT02544217KH176 is well tolerated and displays a promising PK profileKhondrion, Nijmegen, the Netherlands
Idebenone (a.k.a. Catena®, Raxone®, Sovrima®)LHONPhase 2 double‐blind, randomized, placebo‐controlled study of the efficacy, safety, and tolerabilityNCT00747487The primary end point did not reach statistical significance. In a subgroup of patients with discordant visual acuities at baseline, all secondary end points were significantly different between the idebenone and placebo groupsSanthera Pharmaceuticals, Liestal, Switzerland
FRDAPhase 3 double‐blind, randomized, placebo‐controlled study of the efficacy, safety, and tolerabilityNCT00537680Idebenone did not significantly alter neurological function in FRDA during the 6‐month study
MELASPhase 2a double‐blind, randomized, placebo‐controlled, dose‐finding studyNCT00887562No results reported
EPI‐743 (a.k.a. Vatiquinone®, Vincerinone®)LSPhase 2B randomized, placebo‐controlled, double‐blind clinical trialNCT01721733Study status unknownEdison Pharmaceuticals, Mountain View, USA
FRDASafety and efficacy study on visual functionNCT01728064Ongoing, not recruiting
MRCDEmergency use protocol for EPI‐743 in acutely ill patients with inherited MRCD (90 days of end‐of‐life care)NCT01370447Ongoing, not recruiting
PSOpen‐label phase 2 safety and efficacy studyNCT02104336Ongoing, not recruiting
FRDAPhase 2A clinical trial on visual function in patients with point mutationsNCT01962363Ongoing, not recruitingUniversity of South Florida, Tampa, USA
MTP‐131 (a.k.a. Bendavia®)MMPhase 1/2 multicenter, randomized, double‐blind, placebo‐controlled, multiple ascending‐dose clinical study investigating the safety, tolerability, and efficacy of intravenous MTP‐131 for the treatment of MM in subjects with genetically confirmed MDNCT02367014RecruitingStealth BioTherapeutics Inc., Newton, USA
SMMDEPhase 2 randomized, double‐blind, placebo‐controlled study to evaluate the impact of a single intravenous doseNCT02245620Recruiting
RP103 (Cysteamine bitartrate)Inherited MD including LSA phase 2/3 open‐label, dose‐escalating study to assess safety, tolerability, efficacy, PK, and PD of RP103 delayed‐release capsules in childrenNCT02023866 RP103‐MITO‐001RecruitingRaptor pharmaceuticals, Novato, USA
A phase 2 long‐term open‐label extension study of RP103‐MITO‐001 to assess the safety, tolerability and efficacy of RP103 delayed‐release capsules for treatment of childrenNCT02473445Recruiting
Coenzyme Q10Children inherited MD due to defects in specific ETC complexes or mtDNA mutationsPhase 3 trialNCT00432744Completed. No results reported yetUniversity of Florida; FDA office of orphan products development, USA
BezafibrateMD (Confirmed mt.3243A>G mutation)Open‐label phase 2 feasibility studyNCT02398201Recruiting not startedNewcastle‐upon‐Tyne Hospitals NHS foundation Trust, Newcastle, UK
RG2133 (2′,3′,5′‐tri‐O‐acetyluridine)MDOpen‐label dose‐escalation phase I study to assess the safety, tolerability, PK, and PD of RG2133 in treatment of inherited MDNCT00060515Terminated. No results reportedRepligen Corp, Waltham, USA
DCA (dichloroacetate)MELASPhase 2: investigation of clinical syndromes associated with mtDNA point mutationsNCT00068913Terminated prematurely because of peripheral nerve toxicityEunice Kennedy Shriver NICHD, Bethesda, USA
ARG and CITMELASOpen‐label phase 2: ARG flux and NO production in patients and the effect of dietary ARG and CIT supplementationNCT01339494UnknownBaylor College of Medicine, Houston, USA
ARGMELASOpen‐label phase 2 on 3 siblings: Efficacy of L‐arginine therapy on endothelium‐dependent vasodilation and mitochondrial metabolismNCT01603446Completed. A significant increase of the maximum work performed at anaerobic threshold was observedThe Hospital for Sick Children, Ontario, Canada
Lipoic acid (a.k.a. Thioctic acid)MMPilot compassionate use studyNCT00004770No results reportedNational Center for Research Resources (NCRR), Bethesda, USA
RTA408MMPhase 2 study of the safety, efficacy, and PD of the Nrf2‐activator RTA408NCT02255422RecruitingReata Pharmaceuticals Inc, Irving, USA
CurcuminLHONPhase 3 randomized, double‐blind, placebo‐controlled trialNCT00528151No results reportedMahidol University, Salaya, Thailand
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  • ARG, arginine; CIT, citrulline; ETC, electron transport chain; FDA, Food and Drug Administration; FRDA, Friedreich's Ataxia; GLC, glucose; LHON, Leber hereditary optic neuropathy; LS, Leigh syndrome; MD, mitochondrial disease; MELAS, mitochondrial encephalomyopathy, lactic acidosis, and stroke‐like episodes; MM, mitochondrial myopathy; MRCD, mitochondrial respiratory chain diseases; mtDNA, mitochondrial DNA: NICHD, National Institute of Child Health and Human Development; NO, nitric oxide; Nrf2 (a.k.a. NFE2L2), nuclear factor (erythroid‐derived 2)‐like 2; PD, pharmacodynamics; PK, pharmacokinetics; PS, Pearson syndrome; SMMDE, skeletal muscle mitochondrial dysfunction in the elderly.