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

• ClinicalTrials.gov Identifier: NCT01743235
• Recruitment Status: Completed
• First Posted: December 6, 2012
• Last Update Posted: March 31, 2014
• Sponsor: Emotional Brain NY Inc.
• Information provided by (Responsible Party): Emotional Brain NY Inc.

Study Description

Brief Summary:

A double-blind, randomized, placebo-controlled, dose-finding study to investigate the safety and efficacy of Lybridos in the domestic setting in healthy female subjects with hypoactive sexual desire disorder and maladaptive activity of sexual inhibitory mechanisms.

In the present study, the efficacy of Lybridos will be evaluated in the domestic setting in healthy female subjects with HSDD and maladaptive activity of sexual inhibitory mechanism(s). Sexual satisfaction and other aspects of sexual functioning will be measured within 24 hours after each sexual activity. The following hypotheses will be tested:

Lybridos, as compared to placebo, will significantly increase the number of satisfying sexual events.

The number of satisfying sexual events will not differ significantly between subjects treated with placebo and subjects treated with 0.5 mg testosterone alone and/or 10 mg buspirone alone.

Lybridos, as compared to placebo, will significantly increase sexual desire/arousal.

Sexual desire/arousal will not differ significantly between subjects treated with placebo and subjects treated with 0.5 mg testosterone alone and/or 10 mg buspirone alone.

Lybridos, as compared to testosterone alone and buspirone alone, will significantly increase the number of satisfying sexual events and sexual desire/arousal.

Condition or disease	Intervention/treatment	Phase
Hypoactive Sexual Desire Disorder	Drug: Placebo; Drug: Testosterone; Drug: Buspirone hydrochloride	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 207 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Double-blind, Randomized, Placebo-controlled, Dose-finding Study to Investigate the Safety and Efficacy of Lybridos in the Domestic Setting in Healthy Female Subjects With Hypoactive Sexual Desire Disorder and Maladaptive Activity of Sexual Inhibitory Mechanisms
• Study Start Date: July 2012
• Actual Primary Completion Date: June 2013
• Actual Study Completion Date: June 2013

Arms and Interventions

Arm	Intervention/treatment
Experimental: Placebo; 30 subjects administered a placebo	Drug: Placebo; Solid Oral Dosage. Maximum every other day (on an as needed basis)
Experimental: Testosterone + Buspirone hydrochloride combination drug; 30 subjects are given combination drug (0.25 mg Testosterone + 5 mg Buspirone hydrochloride)	Drug: Testosterone; Solid Oral Dosage. Maximum every other day (on an as needed basis); Drug: Buspirone hydrochloride; Solid Oral Dosage. Maximum every other day (on an as needed basis)
Experimental: Testosterone + Buspirone hydrochloride combinat; 30 subjects are given combination drug (0.25 mg Testosterone + 10 mg Buspirone hydrochloride)	Drug: Testosterone; Solid Oral Dosage. Maximum every other day (on an as needed basis); Drug: Buspirone hydrochloride; Solid Oral Dosage. Maximum every other day (on an as needed basis)
Experimental: Testosterone + Buspirone Combination Drug; 30 subjects are given combination drug (0.5 mg Testosterone + 5 mg Buspirone hydrochloride)	Drug: Testosterone; Solid Oral Dosage. Maximum every other day (on an as needed basis); Drug: Buspirone hydrochloride; Solid Oral Dosage. Maximum every other day (on an as needed basis)
Experimental: Testosterone +Buspirone Combination Drug; 30 subjects are given combination drug (0.5 mg Testosterone + 10 mg Buspirone hydrochloride)	Drug: Testosterone; Solid Oral Dosage. Maximum every other day (on an as needed basis); Drug: Buspirone hydrochloride; Solid Oral Dosage. Maximum every other day (on an as needed basis)
Experimental: Testosterone; 30 subjects are given 0.5 mg Testosterone	Drug: Testosterone; Solid Oral Dosage. Maximum every other day (on an as needed basis)
Experimental: Buspirone; 30 subjects are given 10 mg Buspirone hydrochloride	Drug: Buspirone hydrochloride; Solid Oral Dosage. Maximum every other day (on an as needed basis)

Outcome Measures

Primary Outcome Measures :

1. Satisfactory Sexual Episodes [ Time Frame: 20 Weeks ]
   To investigate the efficacy of Lybridos as compared to placebo in increasing the number of satisfactory sexual episodes in healthy female subjects with hypoactive sexual desire disorder(HSDD) and maladaptive activity of sexual inhibitory mechanisms

Secondary Outcome Measures :

1. Sexual satisfaction [ Time Frame: 20 Weeks ]
   Sexual satisfaction will be evaluated based on a global satisfaction assessment comparing the 4-week establishment period with the 8 week DB treatment period. In addition there is a 8 week run in period between the establishment period and the double blind treatment period for a total treatment period of 20 weeks.
2. Sexual desire and arousal [ Time Frame: 20 Weeks ]
   Sexual desire and arousal will be evaluated based on the 'desire' and 'arousal' domains of the Sexual Anamnesis Questionnaire, the Sexual Function questionnaire and weekly diaries throughout the course of the study.
3. Sexual motivation and inhibition [ Time Frame: 20 weeks ]
   Sexual motivation and inhibition will be assessed using the Sexual Motivation Questionnaire and comparing sexual motivation and inhibition between the 4-week establishment period and the 8-week DB treatment period. In addition there is a 8 week run in period between the establishment period and the double blind treatment period for a total treatment period of 20 weeks.
4. Safety and toleration [ Time Frame: 20 weeks ]
   Safety will be evaluated by: 1) AEs [Number of patients reporting AEs, number of patients reporting drug related AEs] 2)SAE [Number of patients reporting SAEs, number of patients reporting drug related SAEs]and 3) Changes in laboratory safety data [Number of patients reporting abnormal lab safety data, number of patients reporting drug related abnormal lab safety data]. These will be evaluated throughout the course of the study.

Eligibility Criteria

• Ages Eligible for Study: 21 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

Criteria

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

Contacts and Locations

Locations

United States, California

San Diego Sexual Medicine

San Diego, California, United States, 92120

United States, Florida

Meridien Research

Bradenton, Florida, United States, 34208

Segal Insitute for Clinical Research

North Miami, Florida, United States, 33161

Compass Research

Orlando, Florida, United States, 32806

Meridien Research

St Petersburg, Florida, United States, 34203

United States, Maryland

Annapolis Sexual Wellness Center

Annapolis, Maryland, United States, 21401

Maryland Prime Care Physicians

Stevensville, Maryland, United States, 21666

Center for Sexual Medicine at Sheppard Pratt

Townson, Maryland, United States, 22104

United States, Massachusetts

Boston Clinical Trials

Boston, Massachusetts, United States, 02135

NECCR Fall River LLC

Fall River, Massachusetts, United States, 02720

United States, New York

Michael A. Werner, MD PC

Purchase, New York, United States, 10577

United States, Pennsylvania

Philadelphia Clinical Research, LLC

Philadelphia, Pennsylvania, United States, 19114

Sponsors and Collaborators

Emotional Brain NY Inc.

More Information

• Responsible Party: Emotional Brain NY Inc.
• ClinicalTrials.gov Identifier: NCT01743235
• Other Study ID Numbers: EB90; EB90 ( Other Identifier: Emotional Brain NY Inc. )
• First Posted: December 6, 2012
• Last Update Posted: March 31, 2014
• Last Verified: March 2014

Keywords provided by Emotional Brain NY Inc.:

HSDD

Additional relevant MeSH terms:

Hypokinesia; Sexual Dysfunctions, Psychological; Dyskinesias; Neurologic Manifestations; Nervous System Diseases; Mental Disorders; Buspirone; Testosterone; Androgens; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Anti-Anxiety Agents; Tranquilizing Agents; Central Nervous System Depressants; Psychotropic Drugs; Serotonin Receptor Agonists; Serotonin Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action