A Trial to Evaluate the Ongoing Skin Safety of Testosterone MD-Lotion Formulations

Study Overview
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Brief Summary
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Testosterone replacement treatment is the most effective way of treating hypogonadism in men. Acrux has a propriety testosterone replacement product, Testosterone MD-Lotion and this study will assess the occurrence of skin safety events for a further two months of continuous use of the Testosterone MD-Lotion® (cutaneous solution) after completion of the MTE08 (NCT00702650) trial.

Official Title
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A Phase III Open-label Extension of the MTE08 Trial (A Phase III Open-label Titration Trial to Evaluate the Effectiveness and Safety of Different Doses of a Dermal Application of Testosterone MD-Lotion® (Cutaneous Solution) in Hypogonadal Men) to Evaluate Skin-safety

Conditions
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Hypogonadism

Intervention / Treatment
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* Drug: Testosterone MD-Lotion


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Hypogonadal males with a qualifying general medical health who have Completed the MTE08 trial up to and including Day 120/121 in a compliant manner Were able to communicate with the trial staff, understand the Trial Information Sheet and sign the Written Informed Consent Forms; were willing to follow the Protocol requirements and comply with Protocol restrictions and procedures Exclusion Criteria: Any clinically significant chronic illness or finding and/or laboratory testing that would interfere with the trial objectives or safety of the subject Any man in whom testosterone therapy was contraindicated, which included those with: Known or suspected carcinoma (or history of carcinoma) of the prostate or clinically significant symptoms of benign prostatic hyperplasia and/or clinically significant symptoms of lower urinary obstructions and with a International Prostate Symptoms Score (IPSS) score of greater than or equal to 19 Known or suspected carcinoma (or history of carcinoma) of the breast Severe liver disease (i.e. cirrhosis, hepatitis or liver tumours or liver function tests >2 times the upper limit of the normal range values Active deep vein thrombosis, thromboembolic disorders or a documented history of these conditions Current significant cerebrovascular or coronary artery disease Untreated sleep apnoea Haematocrit of >54% Untreated moderate to severe depression Men with clinically significant prostate exam or clinically significant elevated serum Prostate Specific Antigen (PSA) level (> 4 ng/mL) or age adjusted reference range of PSA values Men taking concomitant medications (prescribed, over-the-counter or complementary) that would affect Sex Hormone Binding Globulin (SHBG) or testosterone concentrations (excluding Testosterone MD-Lotion (cutaneous solution)) or metabolism such as warfarin, insulin, opiates, gonadotropin-releasing hormone analogues (GnRH), 5 alpha reductase inhibitors, propanolol, oxyphenbutazone, corticosteroids (except for physiological replacement doses), estradiol Men with uncontrolled diabetes (Hemoglobin A1c [HbA1c] greater than or equal to 10%) Subjects intending to have any surgical procedure during the course of the trial Subjects with a partner of child bearing potential who are not willing to use adequate contraception for the duration of the trial Subjects whose partners are pregnant

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
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Testosterone MD-lotion<br>In this open-label extension of the MTE08 trial, participants received Testosterone Metered Dose (MD)-Lotion for 60 days (dosing from Day 121 of the MTE08 trial to Day 180 of the MTE09 trial). Participants in MTE08 initially received 3.0 milliliters (mL) (60 micrograms [mg]) of 2% Testosterone MD-Lotion, and may have had their dose of testosterone adjusted upwards or downwards. Doses could be titrated to one of the following: 1.5 mL (30 mg) of 2% Testosterone MD-Lotion applied daily by 2 doses to the axilla (1.5 mL to one axilla). 3.0 mL (60 mg)of 2% Testosterone MD-Lotion applied daily by 2 doses to the axilla (1.5 mL to each axilla). 4.5 mL (90 mg)of 2% Testosterone MD-Lotion applied daily by 3 doses to the axilla (2 x 1.5 mL to one axilla and 2 x 1.5 mL to the other axilla). 6.0 (120 mg)of 2% Testosterone MD-Lotion applied daily by 4 doses to the axilla (2 x 1.5 mL to each axilla). | Drug: Testosterone MD-Lotion<br>* 30 mg to 120 mg administered topically once daily for 60 days<br>* Other names: Axiron;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline MTE08 to MTE09 Endpoint in Draize Score | Draize score is a measurement of skin irritability of the application site based on erythema/escar and oedema. Erythema/eschar scoring ranges from 0 (no erythema) to 4 (severe erythema [beet redness] to slight eschar formation [injuries in depth]). Oedema scoring ranges from 0 (no oedema) to 4 (severe oedema [raised more than 1 millimeter and extending beyond area of exposure]. The total Draize score ranges from 0 to 8. | Day 1, Day 190 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline MTE08 to MTE09 Follow-up in Fasting Insulin |  | Day 1, up to Day 190 | 
| Change From Baseline MTE08 to MTE09 Follow-up in Fasting Glucose |  | Day 1, up to Day 190 | 
| Change From Baseline MTE08 to MTE09 Follow-up in Prostatic Specific Antigen (PSA) |  | Day 1, up to Day 190 | 
| Change From Baseline MTE08 to MTE09 Follow-up in Luteinizing Hormone (LH) and Follicle Stimulating Hormone (FSH) |  | Day 1, up to Day 190 | 
| Change From Baseline MTE08 to MTE09 Follow-up in Estradiol |  | Day 1, up to Day 190 | 
| Change From Baseline MTE08 to MTE09 Follow-up in Hemoglobin |  | Day 1, up to Day 190 | 
| Change From Baseline MTE08 to MTE09 Follow-up in Hematocrit |  | Day 1, up to Day 190 |