A study to validate the demarcation formula for Lybrido and Lybridos

1. Provision of written informed consent;

2. Females between 18 and 70 years of age, inclusive, pre or postmenopausal, with FSIAD (comorbidity with female orgasmic disorder [FOD]; only as secondary diagnosis) is allowed. The diagnosis of FSIAD will be established by a trained health care professional;

3. Be involved in a stable, communicative, monogamous relationship and have a sexually functional partner who will be at home for the majority of the study duration;

4. 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;

5. Use of highly effective contraception.

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 (supine blood pressure). 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 (supine blood pressure);

Gynecological and Obstetric Conditions

4. Use of any contraceptive containing anti-androgens (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. 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);

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

8. History of bilateral oophorectomy;

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

10. 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) and/or 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

11. 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);

12. Any current endocrine disease or endocrinopathy (e.g. uncontrolled thyroid function) 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%);

13. Free- and/or total testosterone levels outside the upper limit of the reference range of the central laboratory;

14. 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 sildenafil, buspirone and/or testosterone;

15. History of hormone dependent malignancy (including all types of breast cancer);

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

Psychological/Psychiatric Factors

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

18. (Psychotherapeutic and/or pharmacological treatment for) a psychiatric disorder (other than those under inclusion criterion 6) that, in the opinion of the investigator, would compromise the validity of study results or which could be a contraindication for sildenafil, buspirone and/or testosterone use;

19. Current psychotherapeutic treatment for female sexual dysfunction;

20. Current genito-pelvic pain/ penetration disorder according to the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM 5);

21. 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;

Concomitant Medications

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

23. Use of potent CYP3A4 inducers (eg, carbamazepine, phenytoin, phenobarbital, St John’s wort, rifampin);

25. Use of antidepressants including SSRIs, tricyclic and other;

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

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

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

General

30. Illiteracy, unwillingness, or inability to follow study procedures;

31. Participation in other clinical trials within the last 30 days;

32. 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 sildenafil and/or testosterone use.