Claims for Patent: 12,606,869

Summary for Patent: 12,606,869

Title:	Methods for the administration of iloperidone
Abstract:	The present invention relates to methods for the identification of genetic polymorphisms that may be associated with a risk for QT prolongation after treatment with iloperidone and related methods of administering iloperidone to patients with such polymorphisms.
Inventor(s):	Curt Wolfgang, Mihael Polymeropoulos, Christian Lavedan, Simona Volpi
Assignee:	Vanda Pharmaceutials Inc , Vanda Pharmaceuticals Inc
Application Number:	US17/716,968
Patent Claims:	1. A method for treating a patient with a compound that is iloperidone or a metabolite thereof, wherein the patient is suffering from schizophrenia, the method comprising the steps of: determining that the patient demonstrates reduced CYP2D6-mediated metabolism relative to wild type by: obtaining or having obtained a biological sample from the patient; performing or having performed a genotyping assay on the biological sample; and determining that the patient has a genotype associated with reduced CYP2D6-mediated metabolism, wherein the genotype includes two CYP2D6*41 alleles; and administering the compound to the patient in a first amount that is one of 25%, 50%, or 75% of a second amount of 24 mg/day, that would be administered to a patient demonstrating CYP2D6-mediated metabolism consistent with a wild type CYP2D6 genotype, and wherein a risk of QTc prolongation for the patient is lower following the administration of the first amount of the compound than it would be if the compound were administered in the second amount. 2. The method of claim 1, wherein the performing or having performed the genotyping assay step comprises: extracting or having extracted genomic DNA or mRNA from the biological sample, and sequencing or having sequenced CYP2D6 DNA derived from the extracted genomic DNA or from the extracted mRNA, wherein the sequencing or having sequenced step further comprises: amplifying or having amplified a CYP2D6 region in the extracted genomic DNA or mRNA to prepare a DNA sample enriched in DNA from the CYP2D6 gene region; and sequencing or having sequenced the DNA sample by hybridizing the DNA sample to nucleic acid probes to determine if the patient has the genotype including two CYP2D6*41 alleles. 3. The method of claim 1, wherein the first amount of the compound is about 12 mg/day. 4. A method of treating a patient who is suffering from a schizoaffective disorder, depression, Tourette's syndrome, a psychotic disorder or a delusional disorder, the method comprising: determining that the patient has a genotype associated with reduced CYP2D6-mediated metabolism by: obtaining or having obtained a biological sample from the patient, and performing or having performed a genotyping assay on the biological sample to determine that the patient has a genotype associated with reduced CYP2D6-mediated metabolism, wherein the genotype includes two CYP2D6 *41 alleles; and administering a compound that is iloperidone or a metabolite thereof to the patient in a first amount, wherein the first amount of the compound is 25%, 50%, or 75% of a second amount of 24 mg/day of the compound that would be administered to a patient demonstrating CYP2D6-mediated metabolism consistent with a wild type CYP2D6 genotype, wherein a risk of QTc prolongation for the patient is lower following the administration of the first amount of the compound than it would be if the compound were administered in the second amount. 5. The method of claim 4, wherein the patient is at risk for a prolonged QT interval. 6. The method of claim 4, wherein the first amount of the compound is about 12 mg/day. 7. A method of treating a patient who is suffering from a schizoaffective disorder, depression, Tourette's syndrome, a psychotic disorder or a delusional disorder, the method comprising: determining that the patient is at risk for iloperidone-induced QTc prolongation by: obtaining or having obtained a biological sample from the patient, and performing or having performed a genotyping assay on the biological sample to determine whether the patient has a CYP2D6 poor metabolizer genotype that includes two CYP2D6 *41 alleles, wherein the presence of the CYP2D6 poor metabolizer genotype indicates risk for iloperidone-induced QTc prolongation, and administering a compound that is or a metabolite thereof, to the patient in a first amount, wherein the first amount of the compound is one of 25%, 50%, or 75% of a second amount of 24 mg/day of the compound, wherein the second amount causes an iloperidone blood exposure level that is therapeutically effective in a patient not having a CYP2D6 poor metabolizer genotype. 8. The method of claim 7, wherein the patient is at risk for iloperidone-induced QTc prolongation. 9. The method of claim 7, wherein the first amount of iloperidone is about 12 mg/day. 10. The method of claim 1, wherein the compound comprises the metabolite of iloperidone, the metabolite being (1-[4-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl] propoxy]-3-methoxyphenyl] ethanol) (P88). 11. The method of claim 1, wherein the first amount of the compound is about 6 mg/day. 12. The method of claim 1, wherein the first amount of the compound is about 18 mg/day. 13. The method of claim 4, wherein the compound comprises the metabolite of iloperidone, the metabolite being (1-[4-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl] propoxy]-3-methoxyphenyl] ethanol) (P88). 14. The method of claim 4, wherein the first amount of the compound is about 6 mg/day. 15. The method of claim 4, wherein the first amount of the compound is about 18 mg/day. 16. The method of claim 7, wherein the compound comprises the metabolite of iloperidone, the metabolite being (1-[4-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl] propoxy]-3-methoxyphenyl] ethanol) (P88). 17. The method of claim 7, wherein the first amount of the compound is about 6 mg/day. 18. The method of claim 7, wherein the first amount of the compound is about 18 mg/day. 19. The method of claim 1, wherein the first amount of the compound is administered in twice daily (bid) divided doses. 20. The method of claim 4, wherein the first amount of the compound is administered in twice daily (bid) divided doses.