Safety and Efficacy of Intranasal TBS-1 Treatment of Male Hypogonadism

Study Overview
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Brief Summary
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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

Detailed Description
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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.

Official Title
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A 90-Day, Randomized, Dose-Ranging Study, Including Potential Dose Titration, Evaluating the Efficacy and Safety of Intranasal TBS-1 in the Treatment of Male Hypogonadism With Sequential Safety Extension Periods of 90 and 180 Days

Conditions
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Male Hypogonadism

Intervention / Treatment
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* Drug: Testosterone
* Drug: Testosterone


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TBS-1 - b.i.d.<br>5.5 mg per nostril of 4.5% TBS-1 BID | Drug: Testosterone<br>* Intranasal testosterone<br>|
| Experimental: TBS-1 - t.i.d.<br>5.5 mg per nostril of 4.5% TBS-1 TID | Drug: Testosterone<br>* Intranasal testosterone<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum Testosterone Cavg | The percentage of patients with an average serum total testosterone concentration (Cavg) within the normal range (300 to 1050 ng/dL) | 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patients With a Certain Serum Total Testosterone Maximum Concentration on Day 90 | To determine the efficacy of 4.5% TBS-1 gel, administered 2 or 3 times daily at a dose of 5.5 mg per nostril, in achieving the following serum total testosterone maximum concentration (Cmax) on Day 90: A Cmax (maximum testosterone concentration) value of 1500 ng/dL or more in at least 85% of the participants analyzed A Cmax (maximum testosterone concentration) value of 1800 to 2500 ng/dL in fewer than 5% of participants analyzed No analyzed participants with a Cmax (maximum testosterone concentration) >2500 ng/dL | 90 days |