| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 12.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10020933 |
| E.1.2 | Term | Hypoactive sexual desire disorder |
|
| 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 evaluate the PK profile of TBS-2 administered BID in patients with HSDD or SA. |
|
| E.2.2 | Secondary objectives of the trial |
To evaluate the initial PD efficacy of TBS-2 administered BID in patients with HSDD or SA.
To evaluate the safety of intranasal TBS-2 BID versus Intrinsa® (patch) in patients with HSDD or placebo in patients with SA.
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Diagnosis and inclusion criteria: HSDD
- Females up to 65 years.
- HSDD with personal distress (A score of “15” or higher on the FSDS-R) -
- BMI 35.
- Women must have a score of >11 on the FSDS-R© at the Screen Visit together with a score of < 26.55 on the FSFI.
- Women in a steady relationship of at least 12 months.
- Physiological and surgical post-menopausal women - estrogen/progesterone substitution (low dose combined ET/P) for at least three (3) months before study entry or post-menopausal women naïve to ET/P substitution.
- Normal thyroid function, physiological prolactin concentration.
- Normal otorhinolaryngologic (ENT) examination.
- Provide written informed consent.
- Patients must have a clinically acceptable PAP smear as read by a central cytology facility (no evidence of malignancy or squamous intraepithelial lesions) within two (2) years before the Screen Visit.
Diagnosis and Inclusion Criteria: SA
- Females aged 18-65 years.
- Diagnosis of Secondary Female Orgasmic Disorder (Anorgasmia) according to the DSM-IV criteria.
- BMI 35.
- Women must have a score of >11 on the FSDS-R© at the Screen Visit together with a score of < 26.55 on the FSFI.
- Women in a steady relationship of at least 12 months.
- Pre-and post-menopausal women - for physiological and surgical post-menopausal women -estrogen/progesterone substitution (low dose combined ET/P) for at least three (3) months before study entry or post-menopausal women naïve to ET/P substitution.
- Premenopausal women will need to be on a reliable birth control method (i.e,, OCPs).
- Normal thyroid function, physiological prolactin concentration.
- Normal otorhinolaryngologic examination.
- Provide written informed consent.
- Patients must have a clinically acceptable PAP smear as read by a central cytology facility (no evidence of malignancy or squamous intraepithelial lesions) within two (2) years before the Screen Visit.
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| E.4 | Principal exclusion criteria |
HSDD
- History of any clinically relevant other psychiatric disorders that could impact sexual function, risks patient's safety, or may impact compliance.
- History of Major Depressive Disorder within 6 months prior the Screening Visit.
- Patients who meet DSM-IV criteria for Sexual Aversion Disorder, Substance-Induced Sexual Dysfunction, Dyspareunia, Vaginismus, Gender Identity Disorder, Paraphilia, or for Sexual Dysfunction due to a General Medical Condition.
- Patients with pelvic inflammatory disease, urinary tract or vaginal infection/vaginitis, cervicitis, interstitial cystitis, vulvodynia, or significant vaginal atrophy.
- Women with relationship discord as indicated by a score of > 20 on the Maudsley Marital Questionnaire.
- Treatment with selective serotonin re-uptake inhibitors.
- Treatment with systemic glucocorticoids.
- Treatment with sex steroid hormones such as androgens, estrogens other than in low dose combined ET/P, or gestagens.
- Treatment with thyroid hormones.
- Significant intercurrent disease of any type, in particular liver, kidney, or heart disease, any form of diabetes mellitus or psychiatric illness.
- History of nasal disorders or sleep apnea.
- Patients with a history of dementia or other neurodegenerative diseases, organic brain disease, stroke, transient ischemic attacks, brain surgery, significant brain trauma, multiple sclerosis, spinal cord injury, peripheral neuropathy, and epilepsy.
- History of cancer, excluding skin cancer.
- History of severe or multiple allergies, severe adverse drug reaction or leucopenia.
- History of abnormal bleeding tendencies or thrombophlebitis unrelated to venepuncture or intravenous cannulation, or a history of Hepatitis B, a positive test for Hepatitis B surface antigen, a history of Hepatitis C, a positive test for Hepatitis C antibody, a history of HIV infection or demonstration of HIV antibodies.
- History of sleeping problems, shift-workers.
- Regular drinkers of more than 3 units of alcohol daily.
- History of, or current evidence of, abuse of alcohol or any drug substance.
- Difficulty in abstaining from OTC medication for the duration of the study.
- Poor compliers or subjects unlikely to attend study visits.
- Receipt of any drug as part of a research study within 30 days of initial dose administration.
- Blood donation 12 week before the initial study dose.
SA
- History of any other clinically relevant psychiatric disorders that could impact sexual function, risks patient's safety, or may impact compliance.
- History of Major Depressive Disorder within 6 months prior the Screen Visit.
- Patients who meet DSM-IV criteria for Sexual Aversion Disorder, Substance-Induced Sexual Dysfunction, Dyspareunia, Vaginismus, Gender Identity Disorder, Paraphilia, or for Sexual Dysfunction Due to a General Medical Condition.
- Patients experiencing relational discord as indicated by a score of > 20 on the Maudsley Marital Questionnaire.
- Patients with pelvic inflammatory disease, urinary tract or vaginal infection/vaginitis, cervicitis, interstitial cystitis, vulvodynia, or significant vaginal atrophy.
- Patients who are breast feeding or have breastfed the last 6 months prior to Baseline Visit.
- Patients who are pregnant or have been pregnant within the last 12 months.
- Treatment with SSRIs.
- Treatment with systemic glucocorticoids.
- Treatment with sex steroid hormones such as androgens, estrogens other than in low dose combined ET/P, or gestagens.
- Treatment with thyroid hormones.
- Significant intercurrent disease of any type, in particular liver, kidney, or heart disease, any form of diabetes mellitus or psychiatric illness.
- History of nasal disorders or sleep apnea.
- Patients with a history of dementia or other neurodegenerative diseases, organic brain disease, stroke, transient ischemic attacks, brain surgery, significant brain trauma, multiple sclerosis, spinal cord injury, peripheral neuropathy, and epilepsy.
- History of cancer, excluding skin cancer.
- History of severe or multiple allergies, severe adverse drug reaction or leucopenia.
- History of abnormal bleeding tendencies or thrombophlebitis unrelated to venepuncture or intravenous cannulation, or a history of Hepatitis B, a positive test for Hepatitis B surface antigen, a history of Hepatitis C, a positive test for Hepatitis C antibody, a history of HIV infection or demonstration of HIV antibodies.
- History of sleeping problems, shift-workers.
- Regular drinkers of more than 3 units of alcohol daily.
- History of, or current evidence of, abuse of alcohol or any drug substance.
- Difficulty in abstaining from OTC medication for the duration of the study.
- Poor compliers or subjects unlikely to attend study visits.
- Receipt of any drug as part of a research study within 30 days of initial dose administration.
- Blood donation 12 week before the study.
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| E.5 End points |
| E.5.1 | Primary end point(s) |
a) To evaluate the PK profile of TBS-2 administered BID in patients with HSDD or SA
The serum concentrations of total testosterone and dihydrotestosterone will be measured using validated LC/MS/MS. The following pharmacokinetic parameters will be determined for all subjects:
- Cmin, Cmax, tmax, PTF and PTS will be determined, for each dosing interval.
- AUC0-τ, and Cavg, will be calculated for each dosing interval.
- The percentage of time within, below, and above the physiological reference range for serum testosterone and dihydrotestosterone
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| 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 | Yes |
| 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) | Yes |
| 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 | Yes |
| 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) | Yes |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
| 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 | Information not present in EudraCT |
| 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
|
| last visit of the last subject undergoing the trial |
|
| 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 | 0 |
| E.8.9.1 | In the Member State concerned days | 4 |
| 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 |
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