Compound for treatment of female sexual dysfunction

The compound for use according to any one of the preceding claims wherein the compound is exo-7-[(8-azabicyclo[3.2.1]octan-3-yl)oxy]-3-methoxy-chromen-2-one hydrochloride.

The compound for use according to any one of the preceding claims, wherein the female sexual dysfunction is female sexual interest/arousal disorder (FSIAD).

The compound for use according to any one of the preceding claims, wherein the hypoactive sexual desire dysfunction is lifelong hypoactive sexual desire dysfunction or acquired hypoactive sexual desire dysfunction.

The compound for use according to any one of the preceding claims, wherein the hypoactive sexual desire dysfunction is generalised hypoactive sexual desire dysfunction or situational hypoactive sexual desire dysfunction.

The compound for use according to any one of the preceding claims, wherein the hypoactive sexual desire dysfunction is unspecified hypoactive sexual desire dysfunction.

The compound for use according to any one of the preceding claims, wherein the hypoactive sexual desire dysfunction is characterised by:

• (i) reduced or absent spontaneous desire,
• (ii) reduced or absent responsive desire to erotic cues and stimulation, and/or
• (iii) inability to sustain desire or interest in sexual activity once initiated.

The compound for use according to any one of the preceding claims, wherein the inability to sustain desire or interest in sexual activity has occurred episodically or persistently over a period at least several months, such as 3, 4, 5, 6, 7, or 8 months, and/or is associated with clinically significant distress.

The compound for use according to any one of the preceding claims, wherein the female sexual arousal dysfunction is lifelong female sexual arousal dysfunction or acquired female sexual arousal dysfunction.

The compound for use according to any one of the preceding claims, wherein the female sexual arousal dysfunction is generalised female sexual arousal dysfunction or situational female sexual arousal dysfunction.

The compound for use according to any one of the preceding claims, wherein the female sexual arousal dysfunction is unspecified female sexual arousal dysfunction.

The compound for use according to any one of the preceding claims, wherein the female sexual arousal dysfunction is characterised by:

• (i) absence or marked reduction in genital response, including vulvovaginal lubrication, engorgement of the genitalia, and sensitivity of the genitalia,
• (ii) absence or marked reduction in non-genital responses such as hardening of the nipples, flushing of the skin, increased heart rate, increase blood pressure, and increased respiration rate, and/or
• (iii) absence or marked reduction in feelings of sexual arousal, such as sexual excclaiment and sexual pleasure, from any type of sexual stimulation.

The compound for use according to any one of the preceding claims, wherein the absence or marked reduction in response to sexual stimulation occurs despite the desire for sexual activity and adequate sexual stimulation, has occurred episodically or persistently over a period at least several months, such as 3, 4, 5, 6, 7, or 8 months, and/or is associated with clinically significant distress.

The compound for use according to any one of the preceding claims, wherein the orgasmic dysfunction is anorgasmia.

The compound for use according to any one of the preceding claims, wherein the anorgasmia is lifelong anorgasmia or acquired anorgasmia.

The compound for use according to any one of the preceding claims, wherein the anorgasmia is generalised anorgasmia or situational anorgasmia.

The compound for use according to any one of the preceding claims, wherein the anorgasmia is unspecified anorgasmia.

The compound for use according to any one of the preceding claims, wherein the anorgasmia is characterised by the absence or marked infrequency of the orgasm experience and/or markedly diminished intensity of orgasmic sensations.

The compound for use according to any one of the preceding claims, wherein the absence or marked infrequency of the orgasm experience and/or markedly diminished intensity of orgasmic sensations occurs despite adequate sexual stimulation, including the desire for sexual activity and orgasm, has occurred episodically or persistently over a period at least several months, such as 3, 4, 5, 6, 7, or 8 months, and/or is associated with clinically significant distress.

The compound for use according to any one of the preceding claims, wherein the sexual pain disorder is sexual pain-penetration disorder.

The compound for use according to any one of the preceding claims, wherein the sexual pain-penetration disorder is lifelong sexual pain-penetration disorder or acquired sexual pain-penetration disorder.

The compound for use according to any one of the preceding claims, wherein the sexual pain-penetration disorder is generalised sexual pain-penetration disorder or situational sexual pain-penetration disorder.

The compound for use according to any one of the preceding claims, wherein the sexual pain-penetration disorder is unspecified sexual pain-penetration disorder.

The compound for use according to any one of the preceding claims, wherein the sexual pain-penetration disorder is characterised by:

• (i) marked or persistent or recurrent difficulties with penetration, including due to involuntary tightening or tautness of the pelvis floor muscles during attempted penetration,
• (ii) marked and persistent or recurrent vulvovaginal or pelvic pain during penetration, and/or
• (iii) marked and persistent or recurrent fear or anxiety about vulvovaginal or pelvic pain in anticipation of, during, or as a result of penetration.

The compound for use according to any one of the preceding claims, wherein the sexual pain disorder is vulvodynia, or progressive vulvodynia.

The compound for use according to any one of the preceding claims, wherein the female sexual dysfunction is a hypoactive female sexual desire dysfunction.

The compound for use according to any one of the preceding claims, wherein the female sexual dysfunction is not caused by another disease, such as a psychiatric disorder.

The compound for use according to any one of the preceding claims, wherein the female sexual dysfunction is not caused by injury to the genitals.

The compound for use according to any one of the preceding claims, wherein the subject is not under treatment with a medicament known to cause female sexual dysfunction.

The compound for use according to any one of the preceding claims, wherein the female sexual disorder is not a hyperactive female sexual disorder, such as premature female orgasm.

The compound for use according to any one of the preceding claims, wherein the compound is capable of increasing the number of satisfying sexual events (SSE) in the subject.

The compound for use according to any one of the preceding claims, wherein the subject prior to treatment had a female sexual function index (FSFI) of less than 26.55, such as 25.00 to 26.55, such as 20.00 to 25.00, such as 15.00 to 20.00, such as 10.00 to 15.00, such as 5.00 to 10.00, such as 2.00 to 5.00.

The compound for use according to any one of the preceding claims, wherein the compound is capable of increasing the FSFI in the subject.

The compound for use according to any one of the preceding claims, wherein the compound is capable of increasing FSFI by at least 1 point, at least 2 points, at least 3 points, at least 4 points, at least 5 points, at least 6 points, at least 7 points, at least 8 points, at least 9 points, at least 10 points, at least 11 points, at least 12 points, at least 13 points, at least 14 points, at least 15 points, at least 16 points, at least 17 points, at least 18 points, at least 19 points, at least 20 points, at least 21 points, at least 22 points, at least 23 points, at least 24 points, at least 25 points, or at least 26 points.

The compound for use according to any one of the preceding claims, wherein the compound is capable of increasing FSFI to above 26.55.

The compound for use according to any one of the preceding claims, wherein the compound is capable of increasing the FSFI score of the pain domain by at least 0.3 points, at least 0.7 points, at least 1.0 points, at least 1.3 points, at least 1.7 points, at least 2.0 points, at least 2.3 points, at least 2.7 points, at least 3.0 points, at least 3.3 points, at least 3.7 points, at least 4.0 points, at least 4.3 points, at least 4.7 points, at least 5.0 points, at least 5.3 points, at least 5.7 points, or 6.0 points.

The compound for use according to any one of the preceding claims, wherein the compound is capable of increasing the FSFI score question 17 (1st pain question), such as increasing the score by 1, 2, 3, 4, or 5 points.

The compound for use according to any one of the preceding claims, wherein the compound is capable of increasing the FSFI score question 18 (2nd pain question), such as increasing the score by 1, 2, 3, 4, or 5 points.

The compound for use according to any one of the preceding claims, wherein the compound is capable of increasing the FSFI score question 19 (3rd pain question), such as increasing the score by 1, 2, 3, 4, or 5 points.

The compound for use according to any one of the preceding claims, wherein the compound is capable of increasing the FSFI score of on any one or more of the other five domains (desire, arousal, lubrication, orgasm, and satisfaction).

The compound for use according to any one of the preceding claims, wherein the compound is capable of increasing the FSFI score of a subject in the desire domain.

The compound for use according to any one of the preceding claims, wherein the compound is capable of increasing the FSFI score of a subject in the desire domain by at least 0.3 points, at least 0.7 points, at least 1.0 points, at least 1.3 points, at least 1.7 points, at least 2.0 points, at least 2.3 points, at least 2.7 points, at least 3.0 points, at least 3.3 points, at least 3.7 points, at least 4.0 points, at least 4.3 points, at least 4.7 points, at least 5.0 points.

The compound for use according to any one of the preceding claims, wherein the compound is capable of increasing the FSFI score of question 1 (1st desire question) in a subject, such as increasing the score by 1, 2, 3, 4, or 5 points.

The compound for use according to any one of the preceding claims, wherein the compound is capable of increasing the FSFI score of question 2 (2nd desire question) in a subject, such as increasing the score by 1, 2, 3, 4, or 5 points.

The compound for use according to any one of the preceding claims, wherein the compound is capable of increasing the FSFI score of the arousal domain, or increasing the score of any one of the questions in the FSFI arousal domain, for example increasing the score of any one of questions 3 to 6 of the FSFI.

The compound for use according to any one of the preceding claims, wherein the compound is capable of increasing the FSFI score of the lubrication domain, or increasing the score of any one of the questions in the FSFI lubrication domain, for example increasing the score of any one of questions 7 to 10 of the FSFI.

The compound for use according to any one of the preceding claims, wherein the compound is capable of increasing the FSFI score of the orgasm domain, or increasing the score of any one of the questions in the FSFI orgasm domain, for example increasing the score of any one of questions 11 to 13 of the FSFI.

The compound for use according to any one of the preceding claims, wherein the compound is capable is capable of increasing the FSFI score of the satisfaction domain, or increasing the score of any one of the questions in the FSFI satisfaction domain, for example increasing the score of any one of questions 14 to 16 of the FSFI.

The compound for use according to any one of the preceding claims, wherein the compound is capable of increasing the FSFI-6 in the subject.

The compound for use according to any one of the preceding claims, wherein the compound is capable of increasing the FSFI-6 by at least 1 point, at least 2 points, at least 3 points, at least 4 points, or at least 5 points.

The compound for use according to any one of the preceding claims, wherein the compound is capable of decreasing FSDS-DAO by at least 1 point, at least 2 points, at least 3 points, at least 4 points, at least 5 points, at least 6 points, at least 7 points, at least 8 points, at least 9 points, at least 10 points, at least 11 points, at least 12 points, at least 13 points, at least 14 points, at least 15 points, at least 16 points, at least 17 points, at least 18 points, at least 19 points, at least 20 points, at least 21 points, at least 22 points, at least 23 points, at least 24 points, at least 25 points, at least 26 points, at least 27 points, at least 28 points, at least 29 points, at least 30 points, at least 31 points, at least 32 points, at least 33 points, at least 34 points, at least 35 points, at least 36 points, at least 37 points, at least 38 points, at least 39 points, at least 40 points, at least 41 points, at least 42 points, at least 43 points, at least 44 points, at least 45 points, at least 46 points, at least 47 points, at least 48 points, at least 49 points, at least 50 points, at least 51 points, at least 52 points, at least 53 points, at least 54 points, at least 55 points, at least 56 points, at least 57 points, at least 58 points, at least 59 points, or at least 60 points.

The compound for use according to any one of the preceding claims, wherein the compound is capable of decreasing the FSDS-DAO question 13 (FSDS DAO Q13) score by at least 0.3 points, at least 0.7 points, at least 1.0 points, at least 1.3 points, at least 1.7 points, at least 2.0 points, at least 2.3 points, at least 2.7 points, at least 3.0 points, at least 3.3 points, at least 3.7 points, or at least 4.0 points.

The compound for use according to any one of the preceding claims, wherein the subject prior to treatment had a female sexual function index FSDS-DAO of less than 60, such as 55 to 60, such as 50 to 55, such as 45 to 50, such as 40 to 45, such as 35 to 40, such as 30 to 35, such as 25 to 30, such as 20 to 25, such as 15 to 20, such as 10 to 15, such as 5 to 10, such as 0 to 10.

The compound for use according to any one of the preceding claims, wherein the compound is capable of increasing the EDQ score of a subject.

The compound for use according to any one of the preceding claims, compound for use according to any one of the preceding claims, wherein the compound is capable of increasing the score of any one question of the EDQ.

The compound for use according to any one of the preceding claims, wherein the subject is female.

The compound for use according to any one of the preceding claims, wherein the subject is a mammal.

The compound for use according to any one of the preceding claims, wherein the subject is a human.

The compound for use according to any one of the preceding claims, wherein the subject is fertile.

The compound for use according to any one of the preceding claims, wherein the subject is pre-menopausal.

The compound for use according to any one of the preceding claims, wherein the subject is menopausal.

The compound for use according to any one of the preceding claims, wherein the subject is post-menopausal.

The compound for use according to any one of the preceding claims wherein the subject is over the age of 18, such as over the age of 20, such as over the age of 25, such as over the age of 30, such as over the age of 35, such as over the age of 40, such as over the age of 45, such as over the age of 50, such as over the age of 55, such as over the age of 60, such as over the age of 65, such as over the age of 70, such as over the age of 75.

The compound for use according to claim Fejl! Henvisningskilde ikke fundet., wherein the subject is below the age of 40, such as below the age of 35, such as below the age of 30, such as below the age of 25, such as below the age of 20.

The compound for use according to any one of the preceding claims, wherein the subject is 18 to 20 years of age, or 20 to 25, or 25 to 30, or 30 to 35, or 35 to 40, or 40 to 45, or 45 to 50, or 50 to 55, or 55 to 60, or 60 to 65, or 65 to 70, or 70 to 75, or older.

Use of a compound of formula (I),

• for the manufacture of a medicament for the treatment of female sexual dysfunction.

A method of treatment, prevention, or alleviation of female sexual dysfunction in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a compound of formula (I),

• or a pharmaceutically acceptable salt thereof.

A method of increasing the vaginal temperature in a subject, the method comprising administering a therapeutically effective amount of a compound of formula (I),

• or a pharmaceutically acceptable salt thereof.

A method of increasing genital blood flow in a subject, the method comprising administering a therapeutically effective amount of a compound of formula (I),

• or a pharmaceutically acceptable salt thereof.

A method of increasing the genital temperature in a subject, the method comprising administering a therapeutically effective amount of a compound of formula (I),

• or a pharmaceutically acceptable salt thereof.

A method of increasing sexual desire, method of increasing sexual desire, sexual interest, sexual arousal, lubrication, sexual satisfaction, or a combination thereof in a subject, the method comprising administering a therapeutically effective amount of a compound of formula (I),

• or a pharmaceutically acceptable salt thereof.

A method of reducing sexual pain in a subject, the method comprising administering a therapeutically effective amount of a compound of formula (I),

• or a pharmaceutically acceptable salt thereof.

A method of reducing difficulty in reaching orgasm upon sexual stimulation or intercourse in a subject, the method comprising administering a therapeutically effective amount of a compound of formula (I),

• or a pharmaceutically acceptable salt thereof.