Oral Testosterone for the Treatment of Hypogonadism in Males

Study Overview
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Brief Summary
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Low testosterone is a condition that occurs when the body is unable to produce sufficient quantities of testosterone. The medical name for low testosterone is hypogonadism. Hypogonadism can be caused by many factors. Symptoms include: decrease in libido, lack of energy and mood swings. The goal of testosterone replacement therapy is to return testosterone levels to the normal range and relieve symptoms.

Detailed Description
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The purpose of this study is to evaluate the pharmacokinetic (PK) parameters of testosterone after administration of TSX-002 (easy to swallow testosterone capsules) to hypogonadal men. This will be determined by blood sampling at specified times during the study. The study is also intended to evaluate the PK parameters of the testosterone metabolite, dihydrotestosterone (DHT), as well as the safety and tolerability of TSX-002. The study consists of three (3) periods, for which TSX-002 will be taken orally at various doses. Study duration is approximately 9 weeks.

Official Title
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A Phase 2B Study to Determine the Dose Response Pharmacokinetics of TSX-002 (Testosterone) in Hypogonadal Males

Conditions
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Hypogonadism

Intervention / Treatment
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* Drug: TSX-002


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Symptomatic hypogonadal male subjects (Testosterone > 100 and <300 ng/dL, two separate 10 am samples one week apart), 18-70 years old, Willing and able to provide informed consent and to participate in all 3 periods of the study. BMI < 35 kg/m2. Exclusion Criteria: Malabsorption conditions (e.g. history of cholecystectomy, Inflammatory Bowel Disease, Pancreatitis, Celiac disease, Sprue, Dumping syndrome, Bariatric surgery; Short bowel syndrome, Lactose intolerance); Alcoholics or substance abuse; Gastroparesis; IPSS (International Prostate Symptom score) > 19; PSA (prostate-specific antigen)> 4 ng/ml; Congestive Heart Failure, uncontrolled (NYHC >1); Uncontrolled sleep apnea; Topical or injectable testosterone replacement therapy (any kind including dehydroepiandrosterone (DHEA) and nutritional supplements) within past 4 weeks; Testopel excluded if within 2 years; Aveed excluded if within past 6 months; Hematocrit > 50.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Period 1: Single Dose<br>Period 1: Each study subject will receive an escalating single dose of TSX-002 (60, 90, 120, 180, 240 mg), with a minimum 3 day wash-out between each of the 5 escalating doses. After completing the 240 mg dose, a 7 day wash-out period will occur prior to Period 2. | Drug: TSX-002<br>* TSX-002 are capsules with testosterone as the active ingredient.<br>* Other names: Testosterone;|
| Experimental: Period 2: Two Times Daily Dosing 90 mg<br>Period 2: Each study subject dose is 90 mg twice daily of TSX-002, fasted for 17 days. | Drug: TSX-002<br>* TSX-002 are capsules with testosterone as the active ingredient.<br>* Other names: Testosterone;|
| Experimental: Period 3: Two Times Daily Dosing 120 mg<br>Period 2: Each study subject dose is 90 mg twice daily of TSX-002, fasted for 17 days. On Day 15, a serum Testosterone level will be drawn and used to dose titrate and randomized to BID or TID (as eligible). The TSX-002 dose will be down or up titrated. Period 3: Begins Day 18 with the first adjusted TSX-002 dose administered fasted two times daily. The Testosterone level on Day 22 will be used to perform the final, TSX-002 dose adjustment. | Drug: TSX-002<br>* TSX-002 are capsules with testosterone as the active ingredient.<br>* Other names: Testosterone;|
| Experimental: Period 3: Three Times Daily Dosing 90 mg<br>Period 2: Each study subject dose is 90 mg twice daily of TSX-002, fasted for 17 days. On Day 15, a serum Testosterone level will be drawn and used to dose titrate and randomized to BID or TID (as eligible). The TSX-002 dose will be down or up titrated. Period 3: Begins Day 18 with the first adjusted TSX-002 dose administered fasted three times daily. The Testosterone level on Day 22 will be used to perform the final, TSX-002 dose adjustment. | Drug: TSX-002<br>* TSX-002 are capsules with testosterone as the active ingredient.<br>* Other names: Testosterone;|
| Experimental: Period 3: Two Times Daily Dosing 180 mg<br>Period 2: Each study subject dose is 90 mg twice daily of TSX-002, fasted for 17 days. On Day 15, a serum Testosterone level will be drawn and used to dose titrate and randomized to BID or TID (as eligible). The TSX-002 dose will be down or up titrated. Period 3: Begins Day 18 with the first adjusted TSX-002 dose administered fasted two times daily. The Testosterone level on Day 22 will be used to perform the final, TSX-002 dose adjustment. | Drug: TSX-002<br>* TSX-002 are capsules with testosterone as the active ingredient.<br>* Other names: Testosterone;|
| Experimental: Period 3: Three Times Daily Dosing 120 mg<br>Period 2: Each study subject dose is 90 mg twice daily of TSX-002, fasted for 17 days. On Day 15, a serum Testosterone level will be drawn and used to dose titrate and randomized to BID or TID (as eligible). The TSX-002 dose will be down or up titrated. Period 3: Begins Day 18 with the first adjusted TSX-002 dose administered fasted three times daily. The Testosterone level on Day 22 will be used to perform the final, TSX-002 dose adjustment. | Drug: TSX-002<br>* TSX-002 are capsules with testosterone as the active ingredient.<br>* Other names: Testosterone;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Responders | Percentage of subjects with response to treatment within each period. Response to treatment was considered when Testosterone Cavg was within the physiological range of Testosterone concentration, i.e. 300 - 1050 ng/dL. | Cavg from samples at Period 1: post dose hrs 0,1,2,3,4,5,6,8,12,16,24; Period 2: hrs 0,2,3,4,5,6,8,12,14,15,16,17,18,20,24; Period 3 BID: hrs 0,2,3,4,5,6,8,12,14,15,16,17,18,20,24; Period 3 TID: hrs 0,2,3,4,5,6,8,10,11,12,13,14,16,18,19,20,21,22,24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hypogonadism, Gonadal Disorders, Endocrine System Diseases, Testosterone, Testosterone enanthate, Testosterone undecanoate, Testosterone 17 beta-cypionate, Methyltestosterone, Androgens, Hormones, Hormones,, Hormone Substitutes,, Hormone Antagonists, Physiological Effects of Drugs, Pharmacologic Actions, Therapeutic Uses, Anabolic Agents, dihydrotestosterone