Safety and Efficacy of Intranasal TBS-1 Treatment of Male Hypogonadism
Safety and Efficacy of Intranasal TBS-1 Treatment of Male Hypogonadism
The purpose of this study is to determine the efficacy (based on the pharmacokinetic profile
 of testosterone) and safety of TBS-1 in the treatment of hypogonadal men
This study is a 4 Period study consists of 16 visits with overnight clinic stays that span
 over year to help determine the efficacy of TBS-1 gel administered twice daily (b.i.d) and
 three times daily (t.i.d)

 In addition, this study will investigate the safety and tolerability of TBS-1 after 90, 180
 and 360 days of treatment.
Inclusion Criteria

 -  Male between 18 and 80 years of age

 -  Able to understand and provide signed informed consent

 -  Have 2 fasting morning (0900 h ± 30 min) serum total testosterone levels <300 ng/dL

 -  Body mass index between 18.5 kg/m2 and 35 kg/m2

 -  Hemoglobin level > or = 13.0 g/dL

 -  Screening laboratory assessments within ±15% of the normal range, with the exception
 of liver function tests (which need to be within the normal range) and HbA1c (which
 must be <7.0% [9.5 mmol/L]); lipid profile and endocrine profile assessments are also
 exempt from this range unless the assessments indicate a significant intercurrent
 illness other than testosterone deficiency

 -  Ear, nose and throat examination including nasal endoscopy without clinically
 significant abnormal findings

 -  Normal prostate for age based on digital rectal exam and a serum PSA <4.0 ng/mL.

 Exclusion Criteria

 -  Significant intercurrent disease of any type, in particular liver, kidney, heart
 disease, or psychiatric illness

 -  Hyperparathyroidism, uncontrolled diabetes mellitus, hypothyroidism, or
 hyperthyroidism (thyroid stimulating hormone should be <1.5 times the upper limit of
 normal)

 -  Hematocrit >54% at screening

 -  History of pituitary or hypothalamic tumors or history of malignancy within the past 5
 years, excluding basal cell or squamous cell carcinoma of the skin curatively treated
 by surgery

 -  History of nasal surgery, specifically turbinoplasty, septoplasty, rhinoplasty, "nose
 job," or sinus surgery

 -  History of nasal fractures within the past 6 months and/or prior nasal fractures that
 caused a severely deviated anterior nasal septum

 -  Active allergies, such as rhinitis, rhinorrhea, and nasal congestion

 -  Mucosal inflammatory disorders, specifically pemphigus or Sjogren's syndrome

 -  Sinus disease, specifically acute sinusitis, chronic sinusitis, or allergic fungal
 sinusitis

 -  History of nasal disorders (eg, polyposis, recurrent epistaxis [>1 nose bleed per
 month], abuse of nasal decongestants) or sleep apnea

 -  Use of any form of intranasal medication delivery, specifically nasal corticosteroids
 and oxymetazoline-containing nasal sprays (eg, Dristan® 12-Hour Nasal Spray)

 -  History of severe adverse drug reaction or leukopenia

 -  A known hypersensitivity to lidocaine or any materials that may be used during the
 study

 -  History of abnormal bleeding tendencies or thrombophlebitis unrelated to venipuncture
 or intravenous cannulation

 -  History of hepatitis B, a positive test for hepatitis B surface antigen, a history of
 hepatitis C, or a positive test for hepatitis C antibody

 -  Presence of human immunodeficiency virus infection or antibodies

 -  History of asthma and ongoing asthma treatment

 -  History of sleeping problems or a shift worker

 -  Smoker of >10 cigarettes (or equivalent) per day

 -  Regular consumption of more than 4 units of alcohol daily (1 unit is defined as 300 mL
 of beer, 1 glass of wine, or 1 measure of spirit) or difficulty abstaining from
 alcohol during the 48 hours prior to the 24 hour blood sampling visits

 -  History or current evidence of abuse of alcohol or any drug substance, licit or
 illicit, or positive urine drug and alcohol screen

 -  Treatment with androgen therapy within at least 2 weeks prior to baseline evaluations
 (subjects on androgen therapy will require a washout period of 4 weeks for depot
 products administered intramuscularly [eg, testosterone enanthate 200 mg/mL] and 2
 weeks for products administered orally or topically [oral, patch, gel, or buccal])

 -  Current treatment with other androgens (eg, dehydroepiandrosterone [DHEA]), anabolic
 steroids, or other sex hormones

 -  Treatment with estrogens, gonadotropin-releasing hormone (GnRH) agonists, or growth
 hormone within previous 12 months

 -  Treatment with drugs that interfere with the metabolism of testosterone, such as
 anastrozole, clomiphene, dutasteride, finasteride, flutamide, ketoconazole,
 spironolactone, or testolactone

 -  Treatment with any antihypertensive, antidepressant, tranquilizer, or histamine 2 (H2)
 receptor blocker that is not part of a stable regimen (stable dose for at least 3
 months prior to baseline);

 -  Poor compliance history or low likelihood of maintaining attendance

 -  Participation in any other research study during the conduct of this study or 30 days
 prior to the initiation of this study or blood donation at any time during this study
 and within the 12 week period prior to screening