Therapeutic treatment

• US 10,682,409 B2
• Filed: 09/26/2019
• Issued: 06/16/2020
• Est. Priority Date: 10/09/2012
• Status: Active Grant

• Current Assignee: Attentive Therapeutics, Inc.
• Original Assignee: Attentive Therapeutics, Inc.
• Inventors: Sears, Douglas, Reilly, Michael
• Primary Examiner(s): Ramachandran, Umamaheswari
• Application Number:
  US16/584,877
• Publication Number:
  US 20200030447A1
• Time in Patent Office: 264 Days
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/137 Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
• CPC Class Codes: A61K 31/165 having aromatic rings, e.g. colchicine, atenolol, progabide
• CPC Class Codes: A61K 31/4458 only substituted in position 2, e.g. methylphenidate
• CPC Class Codes: A61K 31/451 having a carbocyclic group directly attached to the heterocyclic ring, e.g. glutethimide, meperidine, loperamide, phencyclidine, piminodine
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system

Abstract

This invention discloses a treatment for a patient receiving medication to treat an attention deficit disorder such as ADHD wherein the treatment results in a loss of appetite and impairment of the patient'"'"'s attentiveness. The treatment combines a treatment for an attention deficit disorder with an appetite stimulant, wherein the appetite stimulant increases the caloric intake of a patient, which can increase the patient'"'"'s attentiveness. The combination treatment can be given for an indefinite, including, without limitation, life-long, to allow a patient to maintain normal caloric intake during treatment for an attention deficit disorder.

Claims

1. A method of increasing attentiveness and weight velocity in an individual having an attention deficit disorder, the method comprising:

coadministering to the individual a therapeutically effective amount of methylphenidate and a therapeutically effective amount of cyproheptadine;

wherein the methylphenidate and cyproheptadine are coadministered during at least one of the morning or afternoon;

wherein the cyproheptadine is not administered in the evening or before bedtime; and

wherein the method increases the individual'"'"'s weight velocity as compared to an individual receiving only methylphenidate; and

wherein the method increases the individual'"'"'s height velocity as compared to an individual receiving only methylphenidate.

2. The method of claim 1, wherein the method increases the individual'"'"'s weight velocity for up to 1,108 days or more.

3. The method of claim 1, wherein the cyproheptadine maintains mean peak plasma level for at least 6 hours during the individual'"'"'s waking hours.

4. The method of claim 1, wherein the method increases the individual'"'"'s baseline height by at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90% or at least 95%.

5. The method of claim 4, wherein the method increases the individual'"'"'s baseline height by at least 95%.

6. The method of claim 1, wherein the method increases the individual'"'"'s height velocity by 98%.

7. The method of claim 1, wherein the method reduces the individual'"'"'s baseline CGI-I score by 1 or more;

and wherein the method reduces the baseline CGI-S score by 1 or more, and attentiveness is increased by at least 10% as compared to an individual receiving only methylphenidate.

8. The method of claim 1, wherein the method reduces the individual'"'"'s baseline CGI-I by at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90% or at least 95%.

9. The method of claim 1, wherein the individual'"'"'s baseline CGI-S score is reduced by at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90% or at least 95%.

10. The method of claim 1, wherein the cyproheptadine is administered twice daily (b.i.d.).

11. The method of claim 1, wherein the therapeutically effective amount of cyproheptadine is 2 mg b.i.d or 4 mg b.i.d.

12. The method of claim 1, wherein the therapeutically effective amount of cyproheptadine is 2 mg/day.

13. The method of claim 1, wherein the therapeutically effective amount of cyproheptadine is 4 mg/day.

14. The method of claim 1, wherein the therapeutically effective amount of cyproheptadine is 8 mg/day.

15. The method of claim 1, wherein the method results in an increase in baseline weight by at least 0.5 pounds, at least 1 pound, at least 1.5 pounds, at least 2 pounds, at least 2.5 pounds, at least 3 pounds, at least 3.5 pounds, at least 4 pounds, at least 4.5 pounds, at least 5 pounds, at least 5.5 pounds, at least 6 pounds, at least 6.5 pounds, at least 7 pounds, at least 7.5 pounds, at least 8 pounds, at least 8.5 pounds, at least 9 pounds, at least 9.5 pounds, at least 10 pounds, at least 10.5 pounds, at least 11 pounds, at least 11.5 pounds, at least 12 pounds, at least 12.5 pounds, at least 13 pounds, at least 13.5 pounds, at least 14 pounds, at least 14.5 pounds, at least 15 pounds, at least 20 pounds, at least 25 pounds, at least 30 pounds, or at least 50 pounds.

16. The method of claim 1, wherein the methylphenidate and cyproheptadine are coadministered concomitantly.

17. The method of claim 1, wherein the increase in attentiveness is measured by the p academic performance rating scale, ADD evaluation scale-3rd edition (ADDES-3), ADHD rating scale-IV (ADHD-RS-IV), youth self-report (broadband instrument), Conners parent rating scale-revised (CPRS-R), Conners teacher rating scale-revised (CTRS-R), Conners 3 self-reporting scale (Conner 3-SR;

ages 8-18y), home situations questionnaire-revised, inattention/overactivity with aggression (IOWA) Conners teacher'"'"'s rating scale, Swanson Nolan and Pelham IV scale (SNAP-IV), Swanson Kotkin Agler M-Flynn and Pelham (SKAMP), Vanderbilt ADHD diagnostic parent rating scale (VADPRS), Vanderbilt ADHD diagnostic teacher rating scale (VADTRS), behavior assessment system for children-2nd edition (BASC-2) or the Conners rating scale long version.

18. The method of claim 1, wherein the cyproheptadine is administered in the morning and the mean peak plasma level of cyproheptadine is maintained through lunch.

19. A method of increasing attentiveness and weight velocity in an individual having an attention deficit disorder, the method comprising:

(i) coadministering to the individual methylphenidate and cyproheptadine on a first day during at least one of the morning or afternoon, wherein the cyproheptadine is not administered in the evening or before bedtime on the first day; and

(ii) coadministering the methylphenidate and the cyproheptadine on a second day during at least one of the morning or afternoon, wherein the cyproheptadine is not administered in the evening or before bedtime on the second day;

wherein the method increases the individual'"'"'s weight velocity and height velocity as compared to an individual receiving only methylphenidate;

wherein the methylphenidate and cyproheptadine are coadministered in therapeutically effective amounts;

wherein the dose of methylphenidate administered on the second day is increased relative to the dose of methylphenidate administered on the first day; and

wherein the dose of cyproheptadine administered on the first day and the second day is maintained without concomitant weight loss.