Lybridos in Pre- and Postmenopausal Women With Hypoactive Sexual Desire Disorder Due to Maladaptive Activation of Sexual Inhibitory Systems

Inclusion Criteria:

Subjects must meet all of the following criteria:

1. Provision of written informed consent

2. Females between 21 and 70 years of age, inclusive, pre- or postmenopausal, with HSDD
(comorbidity with female sexual arousal disorder [FSAD] and/or female orgasmic
disorder [FOD; only as secondary diagnosis] is allowed). The diagnosis of HSDD will
be established by a trained health care professional.

3. Maladaptive activity of sexual inhibitory mechanism(s) (see appendix 5 for
definition)

4. Be involved in a stable relationship and have a partner who will be accessible for
the majority of the study duration

5. Healthy with normal medical history, physical examination, laboratory values, and
vital signs; exceptions may be made if the investigator considers an abnormality to
be clinically irrelevant

Exclusion Criteria:

Subjects who meet any of the following criteria are not eligible to participate in the
study:

Cardiovascular Conditions

1. Any underlying cardiovascular condition, including unstable angina pectoris, that
would preclude sexual activity

2. Systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg. For
subjects ≥ 60 years old and without diabetes mellitus, familial hypercholesterolemia,
or cardiovascular disease: systolic blood pressure ≥ 160 mmHg and/or diastolic blood
pressure ≥ 90 mmHg

3. Systolic blood pressure ≤ 90 mmHg and/or diastolic blood pressure ≤ 50 mmHg.
Gynecological and Obstetric Conditions

4. Use of any contraceptive containing antiandrogens (e.g. Cyproteron acetate)
or(anti)androgenic progestogens (drospirenone, dienogest, chlormadinone acetate and
norgestrel)

5. Use of any contraceptive or hormone replacement therapy (HRT) containing more than 50
μg/day of estrogen

6. Positive test result for Chlamydia or gonorrhea

7. Pregnancy or intention to become pregnant during this study (Note: A urine pregnancy
test will be performed in all women of child bearing potential prior to the
administration of study medications.)

8. Lactating or delivery in the previous 6 months prior to signing Informed Consent Form

9. Significant abnormal Pap smear in the previous 12 months prior to signing Informed
Consent Form

10. History of bilateral oophorectomy

11. Other unexplained gynecological complaints, such as clinically relevant abnormal
uterine bleeding patterns

12. Perimenopausal status (cycle shortening/irregular menstrual bleeding in the last 12
consecutive months and/or occurrence of vasomotor symptoms (e.g. hot flashes, night
sweating) in combination with elevated FSH levels (>40 IU/L) for women from age 40
onwards; in women with a history of hysterectomy, perimenopausality can be assessed
by FSH levels (> 40 IU/L) and/or vasomotor symptoms) Other Medical Conditions

13. Liver and/or renal insufficiency (aspartate aminotransferase, alanine
aminotransferase and gamma glutamyltransferase > 3 times the upper limit of normal
and/or estimated glomerular filtration rate (eGFR) < 60.00 mL/min based on the
Cockcroft-Gault formula)

14. Any current endocrine disease or endocrinopathy (e.g. uncontrolled thyroid
dysfunction) as determined by medical history, basic physical examination and/or
laboratory values significantly outside normal range of the central laboratory; or
uncontrolled diabetes mellitus (HbA1c > 7.5%)

15. Free- and/or total testosterone levels outside the upper limit of the reference range
of the central laboratory (free testosterone: > 1.1 ng/dL, and total testosterone >
80 ng/dL)

16. Any current clinically relevant neurological disease which, in the opinion of the
investigator, would compromise the validity of study results or which exclude from
use of buspirone and/or testosterone

17. History of hormone-dependent malignancy (including all types of breast cancer)

18. Vision impairment, such as partial or complete blindness or color blindness

19. Dyslexia

20. Positive test result for immunodeficiency virus, hepatitis B, or hepatitis C (acute
and chronic hepatitis infection)

21. History of serotonin syndrome Psychological/Psychiatric Factors

22. History of (childhood) sexual abuse that, in the opinion of the investigator, could
result in negative psychological effects when testosterone is administered

23. (Psychotherapeutic and/or pharmacological treatment for) a psychiatric disorder that,
in the opinion of the investigator, would compromise the validity of study results or
which could be a contraindication for buspirone and/or testosterone use

24. Current psychotherapeutic treatment for female sexual dysfunction

25. Current sexual disorder of vaginismus or dyspareunia according to the Diagnostic and
Statistical Manual of Mental Disorders, fourth edition (text revision (DSM-IV-TR))

26. A substance abuse disorder that, in the opinion of the investigator, is likely to
affect the subject's ability to complete the study or precludes the subject‟s
participation in the study (mild or moderate alcohol consumption is allowed but must
be stopped 12 hours before the Stroop task).

27. A score of > 65 at the STAI-Y2 questionnaire

28. Positive test result for illicit drugs Concomitant Medications

29. Use of potent CYP3A4 inhibitors (eg, ritonavir, ketoconazole, itraconazole
clarithromycin, erythromycin and saquinavir)

30. Use of potent CYP3A4 inducers (eg, carbamazepine, phenytoin, phenobarbital, St John‟s
wort, rifampin)

31. Use of selective serotonin reuptake inhibitors, tricyclic antidepressants or other
antidepressants

32. Use of any other medication that interferes with study medication (eg, monoamine
oxidase [MAO] inhibitors [includes classic MAO inhibitors and
linezolid],spironolactone)

33. Use of medication (including herbs) that would compromise the validity of study
results

34. Use of testosterone therapy within 6 months before study entry prior to signing the
Informed Consent Form General

35. Illiteracy, unwillingness, or inability to follow study procedures

36. Participation in other clinical trials within the last 30 days

37. Any other clinically significant abnormality or condition which, in the opinion of
the investigator, might interfere with the participant‟s ability to provide informed
consent or comply with study instructions, compromise the validity of study results,
or be a contraindication for buspirone and/or testosterone use