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US-12616702-B2 - Use of reboxetine to treat narcolepsy

US12616702B2US 12616702 B2US12616702 B2US 12616702B2US-12616702-B2

Abstract

Described herein are methods of treating narcolepsy with cataplexy, comprising administering reboxetine (including esreboxetine) to a human being in need thereof. Reboxetine (including esreboxetine) may also be used in the manufacture of a medicament for the treatment of narcolepsy with cataplexy. Also disclosed herein are kits comprising a pharmaceutical composition comprising reboxetine (including esreboxetine) and instructions to use the pharmaceutical composition to treat narcolepsy with cataplexy in a human being.

Inventors

  • Herriot Tabuteau

Assignees

  • AXSOME THERAPEUTICS, INC.

Dates

Publication Date
20260505
Application Date
20240829

Claims (16)

  1. 1 . A method of reducing the number of inadvertent naps in a human being having narcolepsy with cataplexy, comprising administering from 5 mg to 10 mg of reboxetine, or a molar equivalent amount of a pharmaceutically acceptable salt thereof, daily for at least two weeks to a human being in need thereof, wherein the human being is experiencing narcolepsy with cataplexy, wherein the human being is selected for having experienced at least 7 cataplexy attacks in the week before the human being first received reboxetine, wherein during the second week that reboxetine is administered, the human being experiences at least 20% fewer inadvertent naps per week as compared to the week before the human being first received reboxetine.
  2. 2 . The method of claim 1 , wherein 5 mg of reboxetine, or a molar equivalent amount of a pharmaceutically acceptable salt thereof, is administered once a day.
  3. 3 . The method of claim 1 , wherein reboxetine, or a pharmaceutically acceptable salt thereof, is administered in a dosage form further containing a polymer.
  4. 4 . The method of claim 1 , wherein reboxetine, or a pharmaceutically acceptable salt thereof, is administered in a dosage form further containing a binder.
  5. 5 . The method of claim 1 , wherein reboxetine, or a pharmaceutically acceptable salt thereof, is administered in a dosage form further containing a lubricant.
  6. 6 . The method of claim 1 , wherein reboxetine, or a pharmaceutically acceptable salt thereof, is administered in a dosage form further containing a diluent.
  7. 7 . The method of claim 1 , wherein reboxetine, or a pharmaceutically acceptable salt thereof, is administered in a dosage form further containing a disintegrant.
  8. 8 . The method of claim 1 , wherein 5 mg of the reboxetine, or a molar equivalent amount of a pharmaceutically acceptable salt thereof, is administered twice a day to the human being for a first week.
  9. 9 . The method of claim 8 , wherein 5 mg of the reboxetine, or a molar equivalent amount of a pharmaceutically acceptable salt thereof, is administered to the human being in the morning and 5 mg of the reboxetine, or a molar equivalent amount of a pharmaceutically acceptable salt thereof, is administered to the human being in the afternoon.
  10. 10 . The method of claim 1 , wherein 6 mg to 7 mg of a pharmaceutically acceptable salt of reboxetine is administered to the human being in the morning and 6 mg to 7 mg of a pharmaceutically acceptable salt of reboxetine is administered to the human being in the afternoon.
  11. 11 . The method of claim 1 , wherein 6 mg to 7 mg of the pharmaceutically acceptable salt of reboxetine is administered to the human being in the morning.
  12. 12 . The method of claim 2 , wherein the 5 mg of the reboxetine, or a molar equivalent amount of a pharmaceutically acceptable salt thereof, is administered to the human being once daily for a first week.
  13. 13 . The method of claim 1 , wherein 5 mg of the reboxetine, or a molar equivalent amount of a pharmaceutically acceptable salt thereof, is administered to the human being once daily for a first week, and wherein 5 mg of the reboxetine, or a molar equivalent amount of a pharmaceutically acceptable salt thereof, is administered to the human being in the morning and 5 mg of the reboxetine, or a molar equivalent amount of a pharmaceutically acceptable salt thereof, is administered to the human being in the afternoon for a second week.
  14. 14 . The method of claim 1 , wherein the human being has a diagnosis of narcolepsy with cataplexy that meets International Classification of Sleep Disorders, Third Edition criteria.
  15. 15 . The method of claim 1 , wherein the human being has an Epworth Sleepiness Scale score that is greater than 10 prior to receiving the reboxetine.
  16. 16 . The method of claim 1 , wherein the reboxetine is in a pharmaceutically acceptable salt form.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS This application is a continuation of U.S. patent application Ser. No. 18/671,931, filed May 22, 2024; which is a continuation of U.S. patent application Ser. No. 17/845,767, filed Jun. 21, 2022; which is a continuation of U.S. patent application Ser. No. 17/398,368, filed Aug. 10, 2021, now U.S. Pat. No. 11,364,245; which is a continuation of Ser. No. 17/177,554, filed Feb. 17, 2021, now U.S. Pat. No. 11,135,226; which is a division of U.S. patent application Ser. No. 17/119,792, filed Dec. 11, 2020, now U.S. Pat. No. 11,020,402; which is a continuation-in-part of International Pat. App. No. PCT/US2020/062560, filed Nov. 30, 2020; which is a continuation-in-part of U.S. patents application Ser. No. 16/740,329, filed Jan. 10, 2020, now abandoned; Ser. No. 16/740,409, filed Jan. 11, 2020, now U.S. Pat. No. 11,351,175; Ser. No. 16/740,410, filed Jan. 11, 2020, now abandoned; and Ser. No. 16/740,411, filed Jan. 11, 2020, now abandoned; International Pat. App. No. PCT/US2020/062560 also claims the benefit of U.S. Prov. Pat. App. Nos. 62/943,077, filed Dec. 3, 2019; and 62/946,295, filed Dec. 10, 2019. All of the above applications, U.S. patents issued from, or U.S. publications of any of the above applications are incorporated by reference in their entirety. BACKGROUND Narcolepsy is a serious and debilitating neurological condition that causes dysregulation of the sleep-wake cycle and is characterized clinically by excessive daytime sleepiness (EDS), cataplexy, hypnagogic hallucinations, sleep paralysis, and disrupted nocturnal sleep. Narcolepsy is estimated to afflict an estimated 185,000 individuals in the U.S. Cataplexy is seen in an estimated 70% of narcolepsy patients and is a sudden reduction or loss of muscle tone while a patient is awake, typically triggered by strong emotions such as laughter, fear, anger, stress, or excitement. Type 1 narcolepsy includes cataplexy, while Type 2 narcolepsy does not include cataplexy. Narcolepsy interferes with cognitive, psychological, and social functioning, increases the risk of work- and driving-related accidents, and is associated with a 1.5 fold higher mortality rate. Depression is reported in up to 57% of patients. Unfortunately, currently approved treatments are few for this under-diagnosed orphan condition and are limited by variability in efficacy from patient to patient, tolerability issues and the need for Drug Enforce ministration (DEA) scheduling. SUMMARY Described herein are methods of treating a nervous system disorder, comprising administering an antidepressant, such as a selective norepinephrine inhibitor, e.g., atomoxetine, edivoxetine, reboxetine, or S,S-reboxetine to a human being in need thereof. Described herein are methods of treating narcolepsy with cataplexy, comprising administering an antidepressant, such as a selective norepinephrine inhibitor, e.g., atomoxetine, edivoxetine, or reboxetine (including S,S-reboxetine), to a human being in need thereof. Some embodiments include use of an antidepressant, such as a selective norepinephrine inhibitor, e.g., atomoxetine, edivoxetine, or reboxetine (including S,S-reboxetine), in the manufacture of a medicament for the treatment of narcolepsy with cataplexy. Some embodiments include a kit comprising a pharmaceutical composition comprising an antidepressant, such as a selective norepinephrine inhibitor, e.g., atomoxetine, edivoxetine, or reboxetine (including S,S-reboxetine), and instructions to use the pharmaceutical composition to treat narcolepsy with cataplexy in a human being. In some embodiments, an antidepressant, such as a selective norepinephrine inhibitor, e.g., atomoxetine, edivoxetine, or reboxetine (including S,S-reboxetine), is administered at least once daily for more than two weeks. In some embodiments, the human being experiences a reduction in the number of cataplexy attacks in a week, a reduction in the Epworth Sleepiness Scale (ESS) score, a reduction in the Maintenance of Wakefulness Test (MWT) score, a reduction in the Narcolepsy Symptom Assessment Score (NSAQ), a reduction in the Patient Global Impression of Severity (PGI-S) score, a score below 4 in the Patient Global Impression of Change (PGI-C), or a reduction in the Hamilton Depression Rating Scale (HAM-D), or improvement in the ability to concentrate (e.g. on the NSAQ) as a result of the treatment. Some embodiments include a method of rapidly reducing the number of cataplexy attacks in a human being having narcolepsy with cataplexy, comprising administering about 8 mg to about 10 mg of reboxetine daily for at least two weeks to a human being in need thereof, wherein one week after the start of the treatment, the human being has at least 30% fewer cataplexy attacks as compared to baseline and the reduction in the number of cataplexy attacks is statistically significant as compared to administering a placebo with p<0.01. In some embodiments, the reduction in the number of cataplexy atta