FORMULATIONS OF GABOXADOL FOR TREATMENT OF ANGELMAN SYNDROME, FRAGILE X SYNDROME AND FRAGILE X-ASSOCIATED TREMOR/ATAXIA SYNDROME
Methods and pharmaceutical compositions for treating Angelman syndrome, Fragile X syndrome and Fragile X-associated tremor/ataxia syndrome with gaboxadol or a pharmaceutically acceptable salt thereof are provided.
1 . A method of treating a disorder selected from the group consisting of Angelman syndrome, Fragile X syndrome and Fragile X-associated tremor/ataxia syndrome comprising administering to a patient in need thereof a pharmaceutical composition comprising about 0.05 mg to about 100 mg gaboxadol or a pharmaceutically acceptable salt thereof wherein the composition provides a T max of less than 20 minutes.
2 . The method of treating a disorder selected from the group consisting of Angelman syndrome, Fragile X syndrome and Fragile X-associated tremor/ataxia syndrome according to claim 1 , wherein the composition is a modified release dosage form.
3 . The method of treating a disorder selected from the group consisting of Angelman syndrome, Fragile X syndrome and Fragile X-associated tremor/ataxia syndrome according to claim 2 , wherein the modified release dosage form comprises an orally disintegrating dosage form.
4 . The method of treating a disorder selected from the group consisting of Angelman syndrome, Fragile X syndrome and Fragile X-associated tremor/ataxia syndrome according to claim 2 , wherein the modified release dosage form comprises an extended release dosage form.
5 . The method of treating a disorder selected from the group consisting of Angelman syndrome, Fragile X syndrome and Fragile X-associated tremor/ataxia syndrome according to claim 2 , wherein the modified release dosage form comprises a delayed release dosage form.
6 . The method of treating a disorder selected from the group consisting of Angelman syndrome, Fragile X syndrome and Fragile X-associated tremor/ataxia syndrome according to claim 2 , wherein the modified release dosage form comprises a pulsatile release dosage form.
7 . The method of treating a disorder selected from the group consisting of Angelman syndrome, Fragile X syndrome and Fragile X-associated tremor/ataxia syndrome according to claim 1 , wherein the composition comprises 15 mg gaboxadol or a pharmaceutically acceptable salt thereof.
8 . The method of treating a disorder selected from the group consisting of Angelman syndrome, Fragile X syndrome and Fragile X-associated tremor/ataxia syndrome according to claim 1 , wherein the composition comprises 10 mg gaboxadol or a pharmaceutically acceptable salt thereof.
9 . The method of treating a disorder selected from the group consisting of Angelman syndrome, Fragile X syndrome and Fragile X-associated tremor/ataxia syndrome according to claim 1 , wherein the composition comprises 5 mg gaboxadol or a pharmaceutically acceptable salt thereof.
10 . The method of treating a disorder selected from the group consisting of Angelman syndrome, Fragile X syndrome and Fragile X-associated tremor/ataxia syndrome according to claim 1 , wherein the composition provides a C max of less than 400 ng/ml.
11 . The method of treating a disorder selected from the group consisting of Angelman syndrome, Fragile X syndrome and Fragile X-associated tremor/ataxia syndrome according to claim 2 , wherein the amount of gaboxadol or a pharmaceutically acceptable salt thereof within the patient 4 hours after administration of the pharmaceutical composition is between about 65% to about 85% less than the administered dose.
12 . The method of treating a disorder selected from the group consisting of Angelman syndrome, Fragile X syndrome and Fragile X-associated tremor/ataxia syndrome according to claim 2 , wherein the amount of gaboxadol or a pharmaceutically acceptable salt thereof within the patient 4 hours after administration of the pharmaceutical composition is more than 50% of the administered dose.
13 . The method of treating a disorder selected from the group consisting of Angelman syndrome, Fragile X syndrome and Fragile X-associated tremor/ataxia syndrome according to claim 1 wherein the composition provides improvement in at least one symptom selected from the group consisting of tremors, rigidity, ataxia, bradykinesia, gait, speech impairment, vocalization difficulties, cognition impairment, impaired motor activity, clinical seizure, hypotonia, hypertonia, feeding difficulty, drooling, mouthing behavior, sleep difficulties, hand flapping, easily provoked laughter, short attention span, reduced sensation, numbness or tingling, pain, muscle weakness in the lower limbs, inability to control the bladder or bowel, chronic pain syndromes, fibromyalgia, migraine, hypothyroidism, hypertension, sleep apnea, vertigo, olfactory dysfunction, hearing loss, short-term memory loss, loss of executive function, impulse control difficulties, self- monitoring difficulties, attention focusing difficulties, cognitive inflexibility, anxiety, depression, moodiness, irritability.
14 . A pharmaceutical dosage form comprising: a) a therapeutically effective amount of gaboxadol or a pharmaceutically acceptable salt thereof; and b) at least one pharmaceutically acceptable excipient, wherein the dosage form provides a T max of less than about 20 minutes and a C max greater than about 50 ng/mL.
15 . The pharmaceutical dosage form according to claim 14 , wherein the C max is less than about 400 ng/ml.
16 . The pharmaceutical dosage form according to claim 14 , wherein the dosage form is a modified release dosage form.
17 . The pharmaceutical dosage form according to claim 16 , wherein the modified release dosage form comprises an orally disintegrating dosage form.
18 . The pharmaceutical dosage form according to claim 16 , wherein the modified release dosage form comprises an extended release dosage form.
19 . The pharmaceutical dosage form according to claim 16 , wherein the modified release dosage form comprises a delayed release dosage form.
20 . The pharmaceutical dosage form according to claim 16 , wherein the modified release dosage form comprises a pulsatile release dosage form.
21 . The pharmaceutical dosage form according to claim 14 , wherein the amount of gaboxadol or a pharmaceutically acceptable salt thereof ranges from 0.05 mg to 100 mg.
22 . The pharmaceutical dosage form according to claim 21 , wherein the dosage form provides delivery of gab oxadol or a pharmaceutically acceptable salt thereof such that the amount of gaboxadol or a pharmaceutically acceptable salt thereof within the patient 4 hours after administration of the pharmaceutical composition is between about 65% to about 85% less than the administered dose.
23 . The pharmaceutical dosage form according to claim 21 , wherein the dosage form provides delivery of gab oxadol or a pharmaceutically acceptable salt thereof such that the amount of gaboxadol or pharmaceutically acceptable salt thereof within the patient 4 hours after administration of the pharmaceutical composition is more than 50% of the administered dose.