Use of a ppar-delta agonist for reducing loss of muscle strength, muscle mass, or type I muscle fibers in an immobilized limb

Patent metadata

Field	Value
Publication number	US-9968613-B2
Application number	US-201615286661-A
Country	US
Kind code	B2
Filing date	Oct 6, 2016
Priority date	Sep 9, 2013
Publication date	May 15, 2018
Grant date	May 15, 2018

Abstract

The present invention provides methods for reducing loss of muscle strength, muscle mass, or Type I muscle fibers in an immobilized limb by administering (E)-[4-[3-(4-Fluorophenyl)-3-[4-[3-(morpholin-4-yl)propynyl]phenyl]allyloxy]-2-methyl-phenoxy]acetic acid or a pharmaceutically acceptable salt thereof.

First claim

We claim:

1. A method of treatment comprising administering to a human subject (E)-[4-[3-(4-Fluorophenyl)-3-[4-[3-(morpholin-4-yl)propynyl]phenyl]allyloxy]-2-methyl-phenoxy]acetic acid or a pharmaceutically acceptable salt thereof,
wherein the human subject has an immobilized limb, and
wherein the amount of (E)-[4-[3-(4-Fluorophenyl)-3-[4-[3-(morpholin-4-yl)propynyl]phenyl]allyloxy]-2-methyl-phenoxy]acetic acid or a pharmaceutically acceptable salt thereof administered is sufficient to reduce the rate of loss of muscle strength in the muscle tissue of the immobilized limb of the subject relative to a control,
wherein muscle strength is measured by a muscle strength test.

2. The method of claim 1 , wherein the rate of loss of muscle strength comprises a comparison of muscle strength in the subject's immobilized limb to a baseline measurement of muscle strength in the same limb prior to a period of immobilization.

3. The method of claim 1 , wherein reducing the rate of loss of muscle strength in the subject comprises a return to the subject's baseline measurement of muscle strength faster than the control following a period of immobilization.

4. The method of claim 1 , wherein reducing the rate of loss of muscle strength in the subject comprises a return to the subject's baseline measurement of muscle strength following a period of disuse in less than 90% of the time to return to baseline for a control.

5. The method of claim 1 , wherein the loss of muscle strength in the subject's immobilized limb is less than the loss of muscle strength relative to the control during a period of immobilization.

6. The method of claim 1 , wherein (E)-[4-[3-(4-Fluorophenyl)-3-[4-[3-(morpholin-4-yl)propynyl]phenyl]allyloxy]-2-methyl-phenoxy]acetic acid or a pharmaceutically acceptable salt thereof is administered orally.

7. A method of treatment comprising administering to a human subject (E)-[4-[3-(4-Fluorophenyl)-3-[4-[3-(morpholin-4-yl)propynyl]phenyl]allyloxy]-2-methyl-phenoxy]acetic acid or a pharmaceutically acceptable salt thereof,
wherein the human subject has an immobilized limb, and
wherein the amount of (E)-[4-[3-(4-Fluorophenyl)-3-[4-[3-(morpholin-4-yl)propynyl]phenyl]allyloxy]-2-methyl-phenoxy]acetic acid or a pharmaceutically acceptable salt thereof administered is sufficient to reduce the rate of loss of muscle mass in the muscle tissue of the immobilized limb of the subject relative to a control,
wherein the rate of loss of muscle mass comprises a comparison of one or more measurements of muscle volume in the subject to a baseline measurement of muscle volume in the same subject, wherein muscle volume is measured by the cross-section area of a muscle.

8. The method of claim 7 , wherein reducing the rate of loss of muscle mass in the subject's immobilized limb comprises a return to the subject's baseline measurement of muscle mass faster than the control.

9. The method of claim 7 , wherein reducing the rate of loss of muscle mass in the subject's immobilized limb comprises a return to the subject's baseline measurement of muscle mass following a period of limb immobilization in less than 90% of the time to return to baseline for a control.

10. The method of claim 7 , wherein the loss of muscle mass in the subject is less than the loss of muscle mass relative to the control.

11. The method of claim 7 , wherein the loss of muscle mass in the subject's immobilized limb comprises less than a 10% loss of muscle mass relative to the subject's baseline measurement of muscle mass prior to a period of immobilization.

12. The method of claim 7 , wherein (E)-[4-[3-(4-Fluorophenyl)-3-[4-[3-(morpholin-4-yl)propynyl]phenyl]allyloxy]-2-methyl-phenoxy]acetic acid or a pharmaceutically acceptable salt thereof is administered orally.

13. A method of treatment comprising administering to a human subject (E)-[4-[3-(4-Fluorophenyl)-3-[4-[3-(morpholin-4-yl)propynyl]phenyl]allyloxy]-2-methyl-phenoxy]acetic acid or a pharmaceutically acceptable salt thereof,
wherein the human subject has an immobilized limb, and
wherein the amount of (E)-[4-[3-(4-Fluorophenyl)-3-[4-[3-(morpholin-4-yl)propynyl]phenyl]allyloxy]-2-methyl-phenoxy]acetic acid or a pharmaceutically acceptable salt thereof administered is sufficient to reduce the rate of loss of Type I muscle fibers in immobilized muscle tissue of the subject relative to a control,
wherein the measure of the rate of loss of Type I muscle fibers in the immobilized muscle tissue comprises a comparison of one or more measurements of Type I muscle fibers in the subject to a baseline measurement of Type I muscle fibers in the same subject.

14. The method of claim 13 , wherein (E)-[4-[3-(4-Fluorophenyl)-3-[4-[3-(morpholin-4-yl)propynyl]phenyl]allyloxy]-2-methyl-phenoxy]acetic acid or a pharmaceutically acceptable salt thereof is administered orally.

Assignees

• Vtv Therapeutics Llc

Inventors

• Valcarce Lopez Maria Carmen
• Ohlstein Eliot

Classifications

• A61P21/00

  Drugs for disorders of the muscular or neuromuscular system · CPC title

• C07D295/096

  with the ring nitrogen atoms and the oxygen or sulfur atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings · CPC title

• A61K31/5375 Primary

  1,4-Oxazines, e.g. morpholine · CPC title

• A61K9/0053

  Mouth and digestive tract, i.e. intraoral and peroral administration · CPC title

• A61K31/192

  having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid  {(cannabinoids A61K31/658)} · CPC title