E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Hypoactive Sexual Desire Disorder |
|
E.1.1.1 | Medical condition in easily understood language |
Problems with sexual desire |
|
E.1.1.2 | Therapeutic area | Psychiatry and Psychology [F] - Psychological processes [F02] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 13.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10059272 |
E.1.2 | Term | Sexual desire decreased |
E.1.2 | System Organ Class | 10037175 - Psychiatric disorders |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 13.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10020933 |
E.1.2 | Term | Hypoactive sexual desire disorder |
E.1.2 | System Organ Class | 10037175 - Psychiatric disorders |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 13.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10037228 |
E.1.2 | Term | Psychosexual dysfunction with inhibited sexual desire |
E.1.2 | System Organ Class | 10037175 - Psychiatric disorders |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 13.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10040465 |
E.1.2 | Term | Sexual arousal decreased |
E.1.2 | System Organ Class | 10037175 - Psychiatric disorders |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To investigate the efficacy of combined administration of 0.5 mg sublingual testosterone and 10 mg tadalafil in increasing sexual satisfaction during sexual activity in the domestic setting in healthy female subjects with hypoactive sexual desire disorder (HSDD). |
|
E.2.2 | Secondary objectives of the trial |
• To investigate the efficacy of combined administration of 0.5 mg sublingual testosterone and 10 mg tadalafil in increasing vaginal pulse amplitude (VPA), clitoral blood volume (CBV) and subjective ratings of sexual desire and arousal in the laboratory, in healthy female subjects with hypoactive sexual desire disorder (HSDD). • To evaluate the safety of combined administration of 0.5 mg sublingual testosterone and 10 mg tadalafil
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Provision of written informed consent 2. Female 21 to 45 years of age, inclusive, premenopausal, with HSDD (comorbidity with female sexual arousal disorder and/or female orgasmic disorder [FOD; only as secondary diagnosis] is allowed). The diagnosis of HSDD will be established by a trained professional. 3. Heterosexual orientation 4. Be involved in a stable relationship 5. Healthy according to normal results of medical history, physical examination, laboratory values, and vital signs; exceptions may be made if the investigator considers an abnormality to be clinically irrelevant
|
|
E.4 | Principal exclusion criteria |
Cardiovascular Conditions 1. Any underlying cardiovascular condition, including unstable angina pectoris, that would preclude sexual activity 2. History of myocardial infarction, stroke, transient ischemic attack or life threatening arrhythmia within the prior 6 months 3. Uncontrolled atrial fibrillation/flutter at screening or other significant abnormality observed on electrocardiogram (ECG) 4. 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 5. Systolic blood pressure < 90 mmHg and/or diastolic blood pressure < 50 mmHg Gynecological and Obstetric Conditions 6. Use of oral contraceptive containing anti androgens 7. Use of oral contraceptive containing 50 μg estrogen or more 8. Positive test result for Chlamydia or Gonorrhea 9. Pregnancy or intention to become pregnant during this study (Note: A urine pregnancy test will be performed in all women prior to the administration of study medications.) 10. Lactating or delivery in the previous 6 months 11. Significant abnormal pap smear in the previous 12 months 12. History of bilateral oophorectomy 13. Other unexplained gynecological complaints, such as clinically relevant abnormal uterine bleeding patterns Other Medical Conditions 14. Liver and/or renal insufficiency (aspartate aminotransferase and alanine aminotransferase > 3 times the upper limit of normal and/or glomerular filtration rate < 29 mL/min based on the Cockcroft and Gault formula) 15. Current clinically relevant endocrine disease or uncontrolled diabetes mellitus 16. Current clinically relevant neurological disease which, in the opinion of the investigator, would compromise the validity of study results, or which could form a contraindication for tadalafil and/or testosterone use 17. History of hormone dependent malignancy 18. Vision impairment, such as partial or complete blindness or color blindness 19. Dyslexia 20. Positive test result for human immunodeficiency virus, hepatitis B, or hepatitis C (acute and chronic hepatitis infection) Psychological/Psychiatric Factors 21. History of (childhood) sexual abuse that, in the opinion of the investigator, could have negative psychological effects when testosterone is administered 22. 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 tadalafil and/or testosterone use 23. Current psychotherapeutic treatment for female sexual dysfunction 24. Current sexual disorder of vaginismus or dyspareunia according to the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (text revision). 25. 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. 26. Positive test result for illicit drugs Concomitant Medications 27. Use of potent CYP3A4 inhibitors (eg, ritonavir, ketoconazol, itraconazol claritromycine, erytromycine, saquinavir and grapefruitjuice) 28. Use of potent CYP3A4 inducers (eg, carbamazepine, phenytoin, phenobarbital, St Johns Wort, rifampicin) 29. Use of nitrates or nitric oxide donor compounds 30. Use of SSRIs 31. Use of any other medication that interferes with study medication (eg, monoamine oxidase [MAO] inhibitors [includes classic MAO inhibitors and linezolid) 32. Use of medication (including herbs) that would compromise the validity of study results 33. Use of testosterone therapy within 6 months before study entry General 34. Illiteracy, unwillingness, or inability to follow study procedures 35. Participation in other clinical trials within the last 90 days 36. 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 tadalafil and/or testosterone use
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the increase in sexual satisfaction of a single coital event, measured using the Sexual Satisfaction of an Event Questionnaire (SSEQ), and through a psychological interview discussing in depth (at follow up but whilst still blinded) the difference between two sexual events experienced at home whilst using study medication. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
Physiological sexual response o VPA in response to erotic film clips o CBV in response to erotic film clips
Subjective sexual response o Subjective rating of sexual desire and arousal in response to an erotic film clip (SARSAQ)
Safety assessments
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
Final visit of last subject |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |