Methods of treating prader-willi syndrome with carbetocin
The application describes stable aqueous compositions comprising relatively high concentrations of carbetocin and a solubilizer and/or surface active agent. The disclosed carbetocin compositions are effective in the treatment of a neurodevelopmental disorder, such as Präder-Willi syndrome. Additionally, the disclosed carbetocin compositions show improved stability at room temperature and/or under accelerated conditions of stress.
1. A method of treating Präder-Willi syndrome comprising administering intranasally to a subject having Präder-Willi syndrome three doses per day of 3.2 mg/dose carbetocin, for at least one month, wherein the administration results in a decrease in hyperphagia compared to placebo.
2. The method of claim 1 , wherein the dose is administered before a meal.
3. The method of claim 2 , wherein each dose is administered within 30 minutes of a meal.
4. The method of claim 1 , wherein the carbetocin is administered for at least two months.
5. The method of claim 2 , wherein the carbetocin is administered for at least two months.
6. The method of claim 1 , wherein the administration of carbetocin further results in one or more of: (a) decrease in obsessive and compulsive behavior compared to placebo; (b) decrease in anxiety compared to placebo; or (c) improvement in global clinical impression compared to placebo.
7. The method of claim 2 , wherein the administration of carbetocin further results in one or more of: (a) decrease in obsessive and compulsive behavior compared to placebo; (b) decrease in anxiety compared to placebo; or (c) improvement in global clinical impression compared to placebo.
8. The method of claim 2 , wherein the administration of carbetocin results in a decrease in anxiety.
9. The method of claim 2 , wherein the administration of carbetocin results in a decrease in obsessive and compulsive behavior.
10. The method of claim 1 , wherein the administration of carbetocin results in a decrease in hyperphagia behavior and a decrease in obsessive and compulsive behavior.
11. The method of claim 1 , wherein the administration of carbetocin results in a decrease in anxiety.
12. The method of claim 1 , wherein the subject has an age ranging from seven (7) to eighteen (18) years old, inclusive.
13. The method of claim 1 , wherein the subject is aged seven (7) years old.
14. The method of claim 1 , wherein the administration of carbetocin results in a decrease in measurement of Hyperphagia Questionnaire for Clinical Trials (HQ-CT) Total Score.
15. The method of claim 1 , wherein the administration of carbetocin results in a decrease in measurement of the PWS Anxiety and Distress Questionnaire (PADQ) Total Score.
16. The method of claim 1 wherein the carbetocin is administered in an aqueous solution comprising:
(a) carbetocin or a pharmaceutically acceptable salt thereof, wherein the carbetocin is present in a concentration of about 10 mg/mL to about 70 mg/mL; and
(b) a hydrotrope, and wherein the solution has little to no visible solids.
17. The method of claim 16 , wherein the pharmaceutical preparation has little to no visible solids after shaking for 1, 2, or 3 days at 5° C. and/or 25° C.
18. The method of claim 16 , wherein the hydrotrope is nicotinamide.
19. The method of claim 1 wherein the carbetocin is administered in an aqueous solution comprising:
(a) carbetocin or a pharmaceutically acceptable salt thereof, wherein the carbetocin is present in a concentration of about 10 mg/mL to about 70 mg/mL;
(b) nicotinamide;
(c) HPMC; and
(d) one or more additional excipients.