A Pharmacokinetic (PK) Study to Compare the Absorption of Two Formulations of Transdermal Testosterone Spray and Intrinsa®

Study Overview
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Brief Summary
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The purpose of this study is to determine if the absorption of the testosterone spray is the same as the Intrinsa® Patch.

Official Title
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A Phase 1, Open-label, Randomized, Three-cohort, Two-period Crossover Study to Determine the Relative Bioavailability of Testosterone Following Application of Two Testosterone Transdermal Spray (TTS) Formulations Once Daily and Intrinsa® Patch Twice Weekly in Healthy, Surgically and Naturally Post-menopausal Women Receiving Estrogen Replacement Therapy

Conditions
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Hypoactive Sexual Desire Disorder

Intervention / Treatment
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* Drug: Testosterone Spray 5% and 1%
* Drug: Intrinsa® Patch and Testosterone Spray 5%
* Drug: Intrinsa® Patch and Testosterone Spray 1%


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written Informed Consent Naturally or surgically postmenopausal females, 45 - 65 years of age Subjects have spontaneous amenorrhea for at least 12 months Subjects have a serum total testosterone level of < 30 ng/dL Subjects currently on a stable dose of prescribed oral or transdermal estrogen replacement therapy (ERT) for a period of at least 8 to 12 weeks prior to screening, respectively, or not on ERT. A body weight of at least 50 kg and a body mass index (BMI) between 18 and 35 kg/m2, inclusive [BMI will be calculated as weight in kg/(height in m)2] Medically healthy, with clinically insignificant screening results (e.g., laboratory profiles, medical histories, ECGs, physical examination (including breast examination), in the opinion of the Investigator. Subjects are able to communicate with the Investigator, and to understand and to comply with all requirements of study participation. An adequate washout period prior to obtaining any baseline assessments in women who have been previously treated for postmenopausal symptoms. Calculated from study Day 1, the minimum washout period will be 2 and 4 weeks for prior treatment with testosterone oral and transdermal products, respectively, 3 months for prior treatment with testosterone implants and 2 weeks for treatment with estratest. Exclusion Criteria: A positive serum pregnancy test at screening A history or presence of significant cardiovascular, neurological, hematological, psychiatric, hepatic, gastrointestinal, pulmonary, endocrine, immunologic or renal disease or other condition known to interfere with the transdermal absorption, distribution, metabolism, or excretion of drugs or place the subjects at increased risk as determined by the Investigator Any clinically significant laboratory abnormalities as judged by the Investigator Subjects are experiencing > 20 hot flushes per week Subjects are suffering from severe acne, moderate to severe hirsutism or androgenic alopecia, or have a history of severe dermatological problems or drug-induced contact dermatitis Systolic blood pressure > 150 mm Hg or diastolic blood pressure > 95 mm Hg at screening or prior to the first dosing in this study (two rechecks are allowed) Any malignancy except basal cell carcinoma A significant psychiatric disorder (e.g., major depression, etc.) that might, in the Investigator's opinion, prevent the subject from completing the study Currently smoke more than 10 cigarettes a day A history of breast biopsy with atypical hyperplasia A prior history of breast cancer, suspected breast cancer, or other current or prior cancer within the past 10 years Exhibits anemia, defined as a hemoglobin level at screening below the laboratory's lower limit of normal reference range Diabetes mellitus Any chronic skin disorder (e.g., eczema, psoriasis) likely to interfere with transdermal drug absorption or assessments of skin tolerability Positive urine drug test and/or positive breath alcohol test at screening or prior to the first dosing in this study (Period 1 only) Positive testing for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C antibodies (HCV) at screening Any history or presence of alcoholism or drug or substance abuse as defined by the Investigator A history of hypersensitivity or idiosyncratic reaction to testosterone, octisalate, PEG 200, IPA, or other sunscreens, or alcohol-based skin products or Intrinsa® Use of any prescription (except estrogen replacement therapy) or over-the-counter (OTC) medication, within the 30 days prior to the first dosing in this study. Up to 2 g per day of acetaminophen is allowed at the discretion of the Investigator Use of any drugs known to have clinical significance in inhibiting or inducing liver enzymes involved in drug metabolism [CYP P450]) within 30 days prior to the first dosing in this study. Use of any systemic corticosteroids within 30 days prior to the first dosing in this study Blood donation or significant blood loss within 56 days prior to the first dosing in this study. Any contraindication to blood sampling Plasma donation within 7 days prior to the first dosing in this study Currently using or has a history of any androgen use within 6 months prior to screening, or uses dehydroepiandrosterone (DHEA) >/= 25 mg per day, or St. John's Wort within 4 weeks prior to baseline. Due to large number of herbal remedies available, all other herbal supplements will be reviewed by the Sponsor during screening Currently using estratest (esterified estrogens and methyltestosterone) Use of an investigational drug within 30 days or six half-lives, whichever is longer, prior to the first dosing in this study Clinical judgment by the Investigator that the subject should not participate in the study Involvement in the planning and conduct of the study (applies to both VIVUS and designee staff, and staff at the investigational site)

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Cohort 2<br>Testosterone Spray (5%) vs Intrinsa® Patch | Drug: Intrinsa® Patch and Testosterone Spray 5%<br>* Testosterone Spray 5% 2x90uL for 14 days Intrinsa® Patch for 14 days<br>|
| Active Comparator: Cohort 3<br>Testosterone Spray (1%) vs Intrinsa® Patch | Drug: Intrinsa® Patch and Testosterone Spray 1%<br>* Testosterone Spray 1% 2x90uL for 14 days Intrinsa® Patch for 14 days<br>|
| Active Comparator: Cohort 1<br>Testosterone Spray (5%) vs Testosterone Spray (1%) | Drug: Testosterone Spray 5% and 1%<br>* Testosterone Spray 5% 2x90uL for 14 days Testosterone Spray 1% 2x90uL for 14 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To measure the amount of testosterone in the blood after dosing | The following PK parameters of testosterone will be measured AUC0-24, AUC0-48, AUC0-72, AUC0-96, Cavg, Cmin, Cmax | 2 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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postmenopausal, hormone replacement therapy