Polymorphic and amorphous forms of (R)-2-hydroxy-2-methyl-4-(2,4,5-trimethyl-3,6-dioxocyclohexa-1,4-dienyl)butanamide

1. An polymorph of an anhydrate, a hydrate, or a solvate of (R)-2-hydroxy-2-methyl-4-(2,4,5-trimethyl-3,6-dioxocyclohexa-1,4-dienyl)butanamide, wherein the polymorph is selected from the group consisting of Form I, Form V, Form III, Form II, Form IV, or Form VI; wherein a powder X-ray diffraction pattern for polymorph Form I comprises characteristic peaks at least at the following angular positions, wherein the angular positions may vary by ±0.2: 12.06, 17.03, and 17.26; wherein a powder X-ray diffraction pattern for polymorph Form V comprises characteristic peaks at least at the following angular positions, wherein the angular positions may vary by ±0.2: 9.61, 11.49, and 15.45; wherein a powder X-ray diffraction pattern for polymorph Form III comprises characteristic peaks at least at the following angular positions, wherein the angular positions may vary by ±0.2: 14.02, 15.23, and 21.10; wherein a powder X-ray diffraction pattern for polymorph Form II comprises characteristic peaks at least at the following angular positions, wherein the angular positions may vary by ±0.2: 9.63, 11.33, and 19.33; wherein a powder X-ray diffraction pattern for polymorph Form IV comprises characteristic peaks at least at the following angular positions, wherein the angular positions may vary by ±0.2: 4.31, 12.97, and 13.20; and wherein a powder X-ray diffraction pattern for polymorph Form VI comprises characteristic peaks at least at the following angular positions, wherein the angular positions may vary by ±0.2: 6.27, 9.91, and 12.94.

2. The polymorph of claim 1 , wherein the polymorph is Form I, wherein a powder X-ray diffraction pattern for the polymorph comprises characteristic peaks at least at the following angular positions, wherein the angular positions may vary by ±0.2: 12.06, 17.03, and 17.26.

3. The polymorph of claim 1 , wherein the polymorph is Form I, wherein a powder X-ray diffraction pattern for the polymorph comprises characteristic peaks at least at the following angular positions, wherein the angular positions may vary by ±0.2: 12.06, 15.33, 17.03, 17.26, and 18.72.

4. The polymorph of claim 1 , wherein the polymorph is Form I, wherein the polymorph has a powder x-ray diffraction pattern substantially as shown in FIG. 10 .

5. A composition comprising the polymorph of claim 2 , wherein the composition is essentially free of Forms II-VI.

6. A composition comprising the polymorph of claim 2 , wherein at least about 95% by mole of the composition is the polymorph Form I, exclusive of any solvents, carriers or excipients.

7. A pharmaceutical composition comprising the polymorph of claim 2 and a pharmaceutically acceptable carrier.

8. The pharmaceutical composition of claim 7 , wherein the pharmaceutical composition has an HPLC purity of more than about 95% for the anhydrate of (R)-2-hydroxy-2-methyl-4-(2,4,5-trimethyl-3,6-dioxocyclohexa-1,4-dienyl)butanamide, exclusive of any solvents, carriers or excipients.

9. The pharmaceutical composition of claim 7 , wherein the pharmaceutical composition has an HPLC purity of more than about 99% for the anhydrate of (R)-2-hydroxy-2-methyl-4-(2,4,5-trimethyl-3,6-dioxocyclohexa-1,4-dienyl)butanamide, exclusive of any solvents, carriers or excipients.

10. A method of treating or suppressing an oxidative stress disorder, modulating one or more energy biomarkers, normalizing one or more energy biomarkers, or enhancing one or more energy biomarkers, comprising administering to an individual in need thereof a therapeutically effective amount or effective amount of the polymorph of claim 2 .

11. The method of claim 10 , wherein the method is a method of treating or suppressing an oxidative stress disorder selected from the group consisting of: a mitochondrial disorder; an inherited mitochondrial disease; Alpers Disease; Barth syndrome; a Beta-oxidation Defect; Carnitine-Acyl-Carnitine Deficiency; Carnitine Deficiency; a Creatine Deficiency Syndrome; Co-Enzyme Q10 Deficiency; Complex I Deficiency; Complex II Deficiency; Complex III Deficiency; Complex IV Deficiency; Complex V Deficiency; COX Deficiency; chronic progressive external ophthalmoplegia (CPEO); CPT I Deficiency; CPT II Deficiency; Friedreich's Ataxia (FA); Glutaric Aciduria Type II; Kearns-Sayre Syndrome (KSS); Lactic Acidosis; Long-Chain Acyl-CoA Dehydrogenase Deficiency (LCAD); LCHAD; Leigh Syndrome; Leigh-like Syndrome; Leber's Hereditary Optic Neuropathy (LHON); Lethal Infantile Cardiomyopathy (LIC); Luft Disease; Multiple Acyl-CoA Dehydrogenase Deficiency (MAD); Medium-Chain Acyl-CoA Dehydrogenase Deficiency (MCAD); Mitochondrial Myopathy, Encephalopathy, Lactacidosis, Stroke (MELAS); Myoclonic Epilepsy with Ragged Red Fibers (MERRF); Mitochondrial Recessive Ataxia Syndrome (MIRAS); Mitochondrial Cytopathy, Mitochondrial DNA Depletion; Mitochondrial Encephalopathy; Mitochondrial Myopathy; Myoneurogastrointestina Disorder and Encephalopathy (MNGIE); Neuropathy, Ataxia, and Retinitis Pigmentosa (NARP); Pearson Syndrome; Pyruvate Carboxylase Deficiency; Pyruvate Dehydrogenase Deficiency; a POLG Mutation; a Respiratory Chain Disorder; Short-Chain Acyl-CoA Dehydrogenase Deficiency (SCAD); SCHAD; Very Long-Chain Acyl-CoA Dehydrogenase Deficiency (VLCAD); a myopathy; cardiomyopathy; encephalomyopathy; a neurodegenerative disease; Parkinson's disease; Alzheimer's disease; amyotrophic lateral sclerosis (ALS); a motor neuron disease; a neurological disease; epilepsy; an age-associated disease; macular degeneration; diabetes; metabolic syndrome; cancer; brain cancer; a genetic disease; Huntington's Disease; a mood disorder; schizophrenia; bipolar disorder; a pervasive developmental disorder; autistic disorder; Asperger's syndrome; childhood disintegrative disorder (CDD); Rett's disorder; PDD-not otherwise specified (PDD-NOS); a cerebrovascular accident; stroke; a vision impairment; optic neuropathy; dominant inherited juvenile optic atrophy; optic neuropathy caused by a toxic agent; glaucoma; Stargardt's macular dystrophy; diabetic retinopathy; diabetic maculopathy; retinopathy of prematurity; ischemic reperfusion-related retinal injury; oxygen poisoning; a haemoglobinopathy; thalassemia; sickle cell anemia; seizures; ischemia; renal tubular acidosis; attention deficit/hyperactivity disorder (ADHD); a neurodegenerative disorder resulting in hearing or balance impairment; Dominant Optic Atrophy (DOA); Maternally inherited diabetes and deafness (MIDD); chronic fatigue; contrast-induced kidney damage; contrast-induced retinopathy damage; Abetalipoproteinemia; retinitis pigmentosum; Wolfram's disease; Tourette syndrome; cobalamin c defect; methylmalonic aciduria; glioblastoma; Down's syndrome; acute tubular necrosis; a muscular dystrophy; a leukodystrophy; Progressive Supranuclear Palsy; spinal muscular atrophy; hearing loss; noise induced hearing loss; traumatic brain injury; Juvenile Huntington's Disease; Multiple Sclerosis; NGLY1; Multiple System Atrophy; Adrenoleukodystrophy; and Adrenomyeloneuropathy.

12. The method of claim 11 , wherein the oxidative stress disorder is amyotrophic lateral sclerosis (ALS).

13. The method of claim 11 , wherein the oxidative stress disorder is Parkinson's disease.

14. The polymorph of claim 1 , wherein the polymorph is Form I, having a differential scanning calorimetry (DSC) thermogram substantially as shown in FIG. 12 .

15. The polymorph of claim 14 , wherein the DSC thermogram has a single endothermic peak at about 152.9° C.

16. The polymorph of claim 1 , wherein the polymorph is Form I, having a thermogravimetric analysis (TGA) thermogram substantially as shown in FIG. 13 .

17. The polymorph of claim 1 , wherein the polymorph is Form I, having a 1 H NMR spectrum substantially as shown in FIG. 40 .

18. A composition comprising the polymorph of claim 14 , wherein the composition is essentially free of Forms II-VI.

19. A composition comprising the polymorph of claim 14 , wherein at least about 95% by mole of the composition is the polymorph Form I, exclusive of any solvents, carriers or excipients.

20. A method of treating or suppressing an oxidative stress disorder, modulating one or more energy biomarkers, normalizing one or more energy biomarkers, or enhancing one or more energy biomarkers, comprising administering to an individual in need thereof a therapeutically effective amount or effective amount of the pharmaceutical composition of claim 7 .

21. A polymorph of an anhydrate of (R)-2-hydroxy-2-methyl-4-(2,4,5-trimethyl-3,6-dioxocyclohexa-1,4-dienyl)butanamide, wherein TGA analysis shows no weight loss between 45-160° C., and wherein the polymorph has a single endothermic event and a melting point higher than about 151.3° C.