Oral Testosterone for the Treatment of Hypogonadism

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. The purpose of this study is to evaluate the ability of TSX-002, which is testosterone provided in easy to swallow capsules, to maintain serum (blood) testosterone levels within the normal range in hypogonadal men. This will be determined by blood sampling at specified times during the study. The study is also intended to evaluate the tolerability of TSX-002, which will be taken orally twice per day for 15 days. In addition, the study is intended to determine a dosing regimen(s) that achieves testosterone levels within the normal range. Related Outcome Measures will be reported for Parts 1, 2, and 4. A portion of the study (Part 3) to also assess the effect of a high-calorie, high-fat meal on the single dose pharmacokinetic exposure of TSX-002. Related outcome measures to be reported for Part 3.

Official Title
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A Phase 2, Randomized, Double-blind, Dose Response Study of Oral Testosterone in Subjects With Hypogonadism

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: Prior documentation of a diagnosis of hypogonadism as evidenced by a screening serum testosterone < 300 ng/dL (based on the average of 2 morning samples taken at least 1 week apart) Men over the age of 18 years with a body mass index (BMI) < 39.0 kg/m2 and weighing ≥ 55 kg Hemoglobin levels at screening and baseline > 12.5 g/dL Testosterone treatment not contraindicated No evidence of suspected reversible hypogonadism Willing to abstain from current treatment for hypogonadism in accordance with approved labeling to facilitate an appropriate washout period before study participation (for nondepot formulations of testosterone only) Understands the requirements of the study and voluntarily consents to participate in the study Exclusion Criteria: -

Ages Eligible for Study
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Minimum Age: 18 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: Part 1: 120 mg BID<br>Oral TSX-002 120 mg BID (total dose = 240 mg/day) for a duration of 15 days | Drug: TSX-002<br>* TSX-002 are capsules with testosterone as the active ingredient.<br>* Other names: Testosterone;|
| Experimental: Part 1: 240 mg BID<br>Oral TSX-002 240 mg BID (total dose = 480 mg/day) for a duration of 15 days | Drug: TSX-002<br>* TSX-002 are capsules with testosterone as the active ingredient.<br>* Other names: Testosterone;|
| Experimental: Part 2: 120 mg BID<br>Single cohort, open-label, nonrandomized oral TSX 002 120 mg BID (total dose = 240 mg/day) for a duration of 15 days | Drug: TSX-002<br>* TSX-002 are capsules with testosterone as the active ingredient.<br>* Other names: Testosterone;|
| Experimental: Part 3: A-B-C 120 mg QD<br>Open-label, randomized, 3-way crossover of 3 treatments, A, B, and C. Treatment A: Oral TSX-002 (1 x 120-mg capsules) administered 30 minutes after a high-calorie, high-fat meal. No food was allowed 4 hours before the high calorie, high-fat meal and no food was allowed for at least 10 hours after dosing. Treatment B: Oral TSX-002 (1 x 120-mg capsules) administered 4 hours after a high-calorie, high fat meal. No food was allowed 4 hours before the high calorie, high-fat meal and no food was allowed for at least 10 hours after dosing. Treatment C: Oral TSX-002 (1 x 120-mg capsules) administered 30 minutes before a high-calorie, high-fat meal. No food was allowed 4 hours before the high-calorie, high-fat meal and no food was allowed for at least 10 hours after dosing. | Drug: TSX-002<br>* TSX-002 are capsules with testosterone as the active ingredient.<br>* Other names: Testosterone;|
| Experimental: Part 3: B-C-A 120 mg QD<br>Open-label, randomized, 3-way crossover of 3 treatments, A, B, and C. Treatment A: Oral TSX-002 (1 x 120-mg capsules) administered 30 minutes after a high-calorie, high-fat meal. No food was allowed 4 hours before the high calorie, high-fat meal and no food was allowed for at least 10 hours after dosing. Treatment B: Oral TSX-002 (1 x 120-mg capsules) administered 4 hours after a high-calorie, high fat meal. No food was allowed 4 hours before the high calorie, high-fat meal and no food was allowed for at least 10 hours after dosing. Treatment C: Oral TSX-002 (1 x 120-mg capsules) administered 30 minutes before a high-calorie, high-fat meal. No food was allowed 4 hours before the high-calorie, high-fat meal and no food was allowed for at least 10 hours after dosing. | Drug: TSX-002<br>* TSX-002 are capsules with testosterone as the active ingredient.<br>* Other names: Testosterone;|
| Experimental: Part 3: C-A-B 120 mg QD<br>Open-label, randomized, 3-way crossover of 3 treatments, A, B, and C. Treatment A: Oral TSX-002 (1 x 120-mg capsules) administered 30 minutes after a high-calorie, high-fat meal. No food was allowed 4 hours before the high calorie, high-fat meal and no food was allowed for at least 10 hours after dosing. Treatment B: Oral TSX-002 (1 x 120-mg capsules) administered 4 hours after a high-calorie, high fat meal. No food was allowed 4 hours before the high calorie, high-fat meal and no food was allowed for at least 10 hours after dosing. Treatment C: Oral TSX-002 (1 x 120-mg capsules) administered 30 minutes before a high-calorie, high-fat meal. No food was allowed 4 hours before the high-calorie, high-fat meal and no food was allowed for at least 10 hours after dosing. | Drug: TSX-002<br>* TSX-002 are capsules with testosterone as the active ingredient.<br>* Other names: Testosterone;|
| Experimental: Part 4 Cohort 1: 60 mg BID/ 60 mg TID<br>Oral TSX-002 60 mg BID for 15 days then 60 mg TID for 15 days | Drug: TSX-002<br>* TSX-002 are capsules with testosterone as the active ingredient.<br>* Other names: Testosterone;|
| Experimental: Part 4 Cohort 2: 90 mg BID/ 90 mg TID<br>Oral TSX-002 90 mg BID for 15 days then 90 mg TID for 15 days | Drug: TSX-002<br>* TSX-002 are capsules with testosterone as the active ingredient.<br>* Other names: Testosterone;|
| Experimental: Part 4 Cohort 3: 180 mg QD<br>Oral TSX-002 180 mg once daily (QD) for 15 days | Drug: TSX-002<br>* TSX-002 are capsules with testosterone as the active ingredient.<br>* Other names: Testosterone;|
| Experimental: Part 4 Cohort 4: 120 mg BID<br>Oral TSX-002 120 mg BID for 15 days | 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 Subjects Achieving a 24 Hour Average Total Serum Testosterone Concentration (Cavg,0-24h) in the Range of 300 to 1050 ng/dL After 15 Days of Treatment With TSX-002 | Percentage of subjects achieving a 24-hour average total serum testosterone concentration (Cavg,0-24h) in the range of 300 to 1050 ng/dL after 15 days of treatment with TSX-002. PK samples taken at 0 ,2 ,4, 5 ,6, 7, 9, 12, 14, 16, 17, 18, 21, 24 hours post-dose after 15 days of treatment for Part 1. PK samples taken at 0, 1, 2, 3, 4, 5, 6, 8, 12, 16, 17, 18, 19, 20, 21, 22, 24 hours post-dose after 15 days of treatment for Part 2. PK samples taken at 0, 1, 2, 3, 4, 5, 6, 8 ,12, 13, 14, 15, 16, 17, 18, 20, 24 hours post-dose after 15 days of treatment for Part 4. | 15 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects With Cmax ≤ 1500 ng/dL After 15 Days of Treatment 2. Percentage of Subjects With Cmax ≥ 1800 and ≤ 2500 ng/dL After 15 Days of BID Treatment 3. Percentage of Subjects With Cmax > 2500 ng/dL After 15 Days of BID Treatment | Cmax. PK samples taken at 0, 2, 4, 5, 6, 7, 9, 12, 14, 16, 17, 18, 21, 24 hours post-dose after 15 days of treatment for Part 1. PK samples taken at 0, 1, 2, 3, 4, 5, 6, 8, 12, 16, 17, 18, 19, 20, 21, 22, 24 hours post-dose after 15 days of treatment for Part 2. PK samples taken at 0, 1, 2, 3, 4, 5, 6, 8, 12, 13, 14, 15, 16, 17,18, 20, 24 hours post-dose after 15 days of treatment for Part 4. | 15 days | 

 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, and Hormone Antagonists, Physiological Effects of Drugs, Pharmacologic Actions, Therapeutic Uses, Anabolic Agents