This pharmacokinetic trial will be conducted in healthy women, but it is a part of a developmental program for medicine for Hypoactive Sexual Desire Disorder (comorbidity with other sexual dysfunctions e.g Female Sexual Arousal Disorder (FSAD) is allowed) MedDRA version: 12.1 Level: HLT Classification code 10040466 Term: Sexual arousal disorders MedDRA version: 12.1 Level: HLT Classification code 10040470 Term: Sexual desire disorders MedDRA version: 12.1 Level: HLT Classification code 100404
Conditions
Sponsors
Emotional Brain
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: -Healthy sexually functional premenopausal women. -Provision of written informed consent; -Female 21-40 years of age; -Healthy according to normal results of medical history, physical examination, laboratory values and vital signs, unless the investigator considers an abnormality to be clinically relevant; -Subject must be heterosexually oriented; -Venous access sufficient to allow blood sampling as per protocol. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1 Sexual dysfunction as determined SFQ diagnostic scores (within ‘high probability of dysfunction’ or ‘possibility of dysfunction’ ranges) for all functional domains (desire, arousal-lubrication, arousal-sensation, orgasm and pain) as described by Quirk et al. 2005; 2 Subjects who had used testosterone therapy within 6 months before study entry; 3 (A history of) hormone-dependant malignancy ; 4 Use of oral contraception containing anti-androgens (e.g. Diane 35; Minerva); 5 Use of oral contraception containing 50 µg estrogen or more; 6 Pregnancy, or intention to become pregnant during this study (Note: a serum or urine pregnancy test will be performed in all women prior to the administration of study medications); 7 A pelvic inflammatory disease or an untreated vaginal infection at screening; 8 Lactating, or subjects who have given birth in the previous 6 months; 9 Previous prolapse and incontinence surgery affecting the vaginal wall, which in the opinion of investigator would interfere with the VPA measurement; 10 Women with other unexplained gynecological complaints, such as abnormal uterine bleeding patterns; 11 (History of) endocrine disease; 12 (History of) severe neurological problems, current severe neurological problems, or other mild or moderate neurological problems which in the opinion of investigator would interfere with the participant’s ability to provide informed consent, comply with study instructions, confound interpretation of study results, or endanger the participant if she took part in the trial; 13 Treatment for a current serious psychiatric disorder (e.g., schizophrenia, psychosis ) or treatment for obsessive compulsive disorder, anorexia nervosa, bulimia nervosa and/or social anxiety neurosis. 14 Any underlying cardiovascular condition including unstable angina pectoris, that would preclude sexual activity; 15 (History of) myocardial infarction, stroke or life-threatening arrhythmia within the prior 6 months; 16 Uncontrolled atrial fibrillation/flutter at screening (ventricular response rate > 60-80 bpm in rest, > 90-115 bpm in moderate exercise), or other significant abnormality observed on ECG; 17 Systolic blood pressure = 130 mmHg and/or diastolic blood pressure > 80 mmHg; 18 Subjects who are taking CYP3A4-inhibitors: ritonavir (HIV-proteaseremmer), ketoconazol en itraconazol claritromycine, erytromycine and saquinavir; 19 Subjects who are taking CYP3A4-inducers: carbamazepine, fenytoïne, fenobarbital, st Johns Wort, rifampicine; 20 Acute/chronic liver disease: ASAT and ALAT > 3x the upper limit of normal; 21 Renal insufficiency (< 29 ml/min): based on the Cockcroft and Gault formula; 22 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 moderately alcohol drinking behavior is allowed, only 12 hours before the experimental days is alcohol drinking not allowed. Three weeks before the start of the experimental day is the taking of any recreational drug not allowed. Smoking is allowed. 23 Subjects who are illiterate, unwilling or unable to understand and complete the questionnaires; 24 Any other clinically significant abnormality or condition which in the opinion of investigator would interfere with the participant’s ability to provide informed consent, comply with study instructions, possibly confound interpretation of study results, or endanger the participant
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To establish the lowest effective dose using physiological and subjective measures of sexual arousal. To evaluate and compare the pharmacokinetics of testosterone and its metabolites following administration of three (3) doses (0.25, 0.50 & 0.75 mg) of testosterone sublingual. ;Secondary Objective: To investigate the effect of three (3) different doses (0.25, 0.50 & 0.75 mg) of testosterone sublingual on the duration of increased physiological and subjective measures of sexual arousal.;Primary end point(s): Primary pharmacodynamic endpoints • Vaginal Pulse Amplitude (VPA): difference between pre- and post dose relative increases to erotic stimuli (as compared to neutral stimuli) between treatments (placebo vs. 0.25, 0.50 mg. & 0.75 mg; 0.50 mg. vs. 0.75 mg). • SARSAQ questionnaire: difference between pre- and post dose increases to erotic stimuli (as compared to neutral stimuli) between treatments (placebo vs. 0.25, 0.50 mg. & 0.75 mg; 0.50 mg. vs. 0.75 mg). Primary pharmacokinetic endpoints (total and free testosterone) • Maximum concentration (Cmax): difference between treatments (0.25 vs. 0.50 mg. vs. 0.75 mg). • Area under the curve (AUC0-240): difference between treatments (0.25 vs. 0.50 mg. vs. 0.75 mg). • Time to Cmax (Tmax): difference between treatments (0.25 vs. 0.50 mg. vs. 0.75 mg). | — |
Countries
Netherlands
Outcome results
None listed