Oral Allopregnanolone Compositions and Methods of Use

A method of treating a CNS disorder in a human subject, said CNS disorder comprising at least one of a sleep disorder, a mood disorder, PND, PPD, postpartum psychosis, essential tremors, treatment resistant depression, perinatal depression, dysthymic disorder, bipolar disorder, GAD, social anxiety disorder, stress, PTSD, OCD, schizophrenia, schizoaffective disorder, epilepsy, SE, seizures, ADHD, dementia, Huntington's disease, Parkinson's disease, anti-social personality disorder, OCD, autism, synaptopathy, Rett syndrome, Fragile X syndrome, Angelman syndrome, neuropathic pain, an injury related pain syndrome, acute pain, chronic pain, TBI, stroke, ischemia, a vascular malformation, a substance abuse disorder, a withdrawal syndrome, and tinnitus,

• wherein said method comprises the step of orally administering to said subject an encapsulated or solid dosage form oral pharmaceutical composition comprising at least about 3% w/w of allopregnanolone, at least one hydrophilic additive, and at least one lipophilic additive, and
• wherein said administration of said composition to said subject results in at least one of:
• a Cmax of at least 10 ng/mL of allopregnanolone in said subject, and
• an effective dose of at least 10 mg of allopregnanolone in said subject.

A method of treating a CNS disorder in a human subject, said CNS disorder comprising at least one of a sleep disorder, a mood disorder, PND, PPD, postpartum psychosis, essential tremors, treatment resistant depression, perinatal depression, dysthymic disorder, bipolar disorder, GAD, social anxiety disorder, stress, PTSD, OCD, schizophrenia, schizoaffective disorder, epilepsy, SE, seizures, ADHD, dementia, Huntington's disease, Parkinson's disease, anti-social personality disorder, OCD, autism, synaptopathy, Rett syndrome, Fragile X syndrome, Angelman syndrome, neuropathic pain, an injury related pain syndrome, acute pain, chronic pain, TBI, stroke, ischemia, a vascular malformation, a substance abuse disorder, a withdrawal syndrome, and tinnitus,

• wherein said method comprises the step of orally administering to said subject an encapsulated or solid dosage form oral pharmaceutical composition comprising at least about 3% w/w of allopregnanolone, at least one hydrophilic additive, and at least one lipophilic additive, and
• wherein in response to at least two days of administration of said composition to said subject, said administration results in at least one of:
• a serum concentration level (SCL) of allopregnanolone in the range of about 0.47 ng/mL to about 134.5 ng/mL in said subject,
• an effective dose of allopregnanolone of at least 1311 mg in said subject,
• a comparable Cmax of allopregnanolone in said subject (Comp-Cmax) that is within +50%/−50% of a Cmax of allopregnanolone in said subject resulting from an intravenous administration at a concentration rate less than or equal to 90 μg kg−1 hr−1 over 60 hours of a pharmaceutical composition comprising allopregnanolone (IVA) (IVA-Cmax) to said subject, and
• a comparable AUC0-t of allopregnanolone in said subject (Comp-AUC) that is within +25%/−20% of an AUC in said subject resulting from said IVA (IVA-AUC) to said subject.

A method of treating a CNS disorder in a human subject, said CNS disorder comprising at least one of a sleep disorder, a mood disorder, PND, PPD, postpartum psychosis, essential tremors, treatment resistant depression, perinatal depression, dysthymic disorder, bipolar disorder, GAD, social anxiety disorder, stress, PTSD, OCD, schizophrenia, schizoaffective disorder, epilepsy, SE, seizures, ADHD, dementia, Huntington's disease, Parkinson's disease, anti-social personality disorder, OCD, autism, synaptopathy, Rett syndrome, Fragile X syndrome, Angelman syndrome, neuropathic pain, an injury related pain syndrome, acute pain, chronic pain, TBI, stroke, ischemia, a vascular malformation, a substance abuse disorder, a withdrawal syndrome, and tinnitus,

• wherein said method comprising the step of orally administering to said subject an encapsulated or solid dosage form oral pharmaceutical composition comprising at least about 3% w/w of allopregnanolone, at least one hydrophilic additive, and at least one lipophilic additive, and
• wherein said administration of said composition to said subject results in a substantial improvement, reduction, or elimination in said at least one CNS disorder of said subject and:
• a Cmax of at least 10 ng/mL of allopregnanolone in said subject, and
• an effective dose of at least 10 mg of allopregnanolone in said subject.

A method of treating a CNS disorder in a human subject, said CNS disorder comprising at least one of a sleep disorder, a mood disorder, PND, PPD, postpartum psychosis, essential tremors, treatment resistant depression, perinatal depression, dysthymic disorder, bipolar disorder, GAD, social anxiety disorder, stress, PTSD, OCD, schizophrenia, schizoaffective disorder, epilepsy, SE, seizures, ADHD, dementia, Huntington's disease, Parkinson's disease, anti-social personality disorder, OCD, autism, synaptopathy, Rett syndrome, Fragile X syndrome, Angelman syndrome, neuropathic pain, an injury related pain syndrome, acute pain, chronic pain, TBI, stroke, ischemia, a vascular malformation, a substance abuse disorder, a withdrawal syndrome, and tinnitus,

• wherein said method comprises the step of orally administering to said subject an encapsulated or solid dosage form oral pharmaceutical composition comprising at least about 3% w/w of allopregnanolone, at least one hydrophilic additive, and at least one lipophilic additive, and
• wherein in response to at least two days of administration of said composition to said subject, said administration results in a substantial improvement, reduction, or elimination in said at least one CNS disorder of said subject and:
• a serum concentration level (SCL) of allopregnanolone in the range of about 0.47 ng/mL to about 134.5 ng/mL in said subject,
• an effective dose of allopregnanolone of at least 1311 mg in said subject,
• a comparable Cmax of allopregnanolone in said subject (Comp-Cmax) that is within +50%/−50% of a Cmax of allopregnanolone in said subject resulting from an IVA (IVA-Cmax) to said subject, and
• a comparable AUC0-t of allopregnanolone in said subject (Comp-AUC) that is within +25%/−20% of an AUC in a said subject resulting from said IVA (IVA-AUC) to said subject.