PK Study of Testosterone Nasal Gel (TBS-2) in Healthy Premenopausal Women
Condition: Female Sexual Dysfunction
Intervention: Low dose testosterone nasal gel, single dose; Medium dose testosterone nasal gel, single dose; High dose testosterone nasal gel, single dose; Medium dose testosterone nasal gel, multiple dose
Intervention description: Low dose testosterone nasal gel, single dose; Medium dose testosterone nasal gel, single dose; High dose testosterone nasal gel, single dose; Medium dose testosterone nasal gel, multiple dose
Intervention MeSH terms: Methyltestosterone; Testosterone; Testosterone undecanoate; Testosterone enanthate; Testosterone 17 beta-cypionate
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 24.0
Sex: Female
Minimum age: 18 Years
Maximum age: 40 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: testosterone; pharmacokinetics

Summary:

      The purpose of this study was to assess the bioavailability of total testosterone through
      pharmacokinetic profiles obtained following (a) single administration of three doses of TBS-2
      b) multiple administration TBS-2.

      In addition, assessing the bioavailability of free testosterone, dihydrotestosterone, SHBG
      and estradiol through pharmacokinetic profiles was also conducted.
    

Eligibility criteria:

        Inclusion Criteria

          -  Subjects having regular menstrual cycles between 26-32 days.

          -  Women of childbearing potential must agree to use one of the following reliable birth
             control methods prior to the study, during the study and up until one month after the
             end of the study:

               -  Surgically sterile

               -  Intrauterine device in place for at least 3 months prior to study initiation

               -  Barrier method (condom with spermicidal agent use by partner)

               -  Abstinence

          -  Negative for drugs of abuse, hepatitis B-surface antigen, hepatitis C, HIV, and
             pregnancy (serum ß-HCG).

          -  Body Mass Index greater than or equal to 18.5 kg/m² and less than or equal to 35
             kg/m².

          -  Subjects with a normal ENT exam.

          -  Subjects with normal TSH values.

          -  No clinically significant findings in the physical examination, 12-lead ECG and vital
             signs

          -  Normal thyroid function. Physiological prolactin concentration.

          -  All clinical laboratory test values within the acceptable ranges (any clinically
             significant findings will require investigator/sponsor approval)

          -  Able to understand and provide written informed consent.

          -  Availability of the subject for the entire study period and willingness of the subject
             to adhere to protocol requirements, as evidenced by a signed ICF

        Exclusion Criteria

          -  Known history of hypersensitivity to Testosterone (e.g. Intrinsa patch) and/or related
             drugs.

          -  Known history of polycystic ovarian syndrome.

          -  Known history or presence of cardiac, pulmonary, gastrointestinal, endocrine,
             musculoskeletal, neurological, psychiatric, hematological, reproductive, liver or
             kidney disease, unless judged not clinically significant by the Principal Investigator
             or medical designate.

          -  Presence of or known history of Estrogen-responsive tumors such as breast cancer and
             /or history of any cancer, excluding basal cell carcinoma.

          -  Known history of frequent clinically significant acne.

          -  Known history of hirsutism

          -  History of nasal surgery, specifically turbinoplasty, septoplasty, rhinoplasty, "nose
             job", or sinus surgery.

          -  Prior nasal fractures.

          -  Active allergies, such as rhinitis, rhinorrhea, and nasal congestion.

          -  Mucosal inflammatory disorders, specifically pemphigus, and Sjogren's syndrome.

          -  Sinus disease, specifically acute sinusitis, chronic sinusitis, or allergic fungal
             sinusitis.

          -  History of nasal disorders or sleep apnea.

          -  Use of any form of intra-nasal medication delivery, specifically nasal corticosteroids
             and oxymetazoline containing nasal sprays

          -  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.

          -  Any history of severe allergic reaction (including drugs, food, insect bites,
             environmental allergens or any condition known to interfere with the absorption,
             distribution, metabolism or excretion of drugs.

          -  Any history of drug abuse or alcohol abuse as per DSM-IV criteria within 6 months of
             study drug administration.

          -  Current treatment with any hormone replacement therapy within previous 12 months,
             treatment with drugs which interfere with metabolism of Testosterone within 30 days of
             study drug administration and/or any other prescription medications. Difficulty in
             abstaining from OTC medication for the duration of study.

          -  Use of oral, transdermal and implant contraceptives within 30 days prior to drug
             administration or a depot contraceptives injection within one year prior to drug
             administration.

          -  Evidence of pregnancy or lactation.

          -  Subjects who are breast feeding or have breast fed within the last six (6) months
             prior to the Screening Visit.

          -  Administration of another investigational drug within 30 days prior to study
             medication administration.

          -  Blood donation within 56 days prior to study medication administration.

          -  Any participation as a plasma donor in a plasmapheresis program within seven days
             preceding screening in this study.

          -  Intolerance to venipuncture.

          -  History of abnormal bleeding tendencies or thrombophlebitis unrelated to venipuncture
             or intravenous cannulation.

          -  History of Deep Venous Thrombosis or coagulation disorders.