A Titration Trial to Determine the Effectiveness of Testosterone MD-Lotion (Cutaneous Solution) Formulations

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

Testosterone replacement treatment is the most effective way of treating hypogonadism in men. Acrux has a propriety testosterone replacement product- Testosterone MD-Lotion (cutaneous solution), and this study will evaluate the efficacy via pharmacokinetics of various doses of this product. The study will also assess safety of the product.

Inclusion Criteria:

• Male subjects with a prior documented definitive diagnosis of hypogonadism as evidenced by previously documented:

  • Hypothalamic, pituitary or testicular disorder or age related idiopathic hypogonadism
  • Screening serum testosterone of less than or equal to 300 ng/dL (based on the average of two morning samples taken at least 30 minutes apart)

• Were currently receiving treatment for hypogonadism in accordance with approved labelling, or in the Investigator's opinion are eligible to receive such treatment

• Body Mass Index (BMI) < 35.0 kg/m^2

• Haemoglobin levels at screening greater than or equal to 11.5 g/dL

• Adequate venous access on left or right arm to allow collection of a number of samples by venipuncture

• Ability to communicate with the trial staff, understand the Trial Information Sheet and sign the Written Informed Consent Forms; willing to follow the Protocol requirements and comply with Protocol restrictions and procedures

Exclusion Criteria:

• Current use of long acting testosterone injectables such as Nebido®

• Any significant history of allergy and/or sensitivity to the drug products or their excipients, including any history of sensitivity to testosterone and/or sunscreens

• Any clinically significant chronic illness or finding on screening physical exam and/or laboratory testing that makes it undesirable for the Investigator to enrol the trial subject in the trial and/or that in the Investigator's opinion, would interfere with the trial objectives or safety of the subject

• Chronic skin disorder (e.g. eczema, psoriasis) likely to interfere with transdermal drug absorption

• Men with suspected reversible hypogonadism

• 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 obstruction and International Prostate Symptom Scores (IPSS) scores 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 > 51
  • Untreated moderate to severe depression

• Men with clinically significant prostate exam (such as irregularities or nodules palpated) or clinically significant elevated serum Prostate Specific Antigen (PSA) levels (>4 ng/mL), or age adjusted reference range of PSA values

• Current or history of drug or alcohol abuse (more than 4 standard drinks per day and/or abnormal liver function tests >2 times the upper limit of the normal range values)

• Men taking concomitant medications (prescribed, over-the-counter or complementary) that would affect sex hormone binding globulin (SHBG) or testosterone concentrations or metabolism, warfarin, insulin, opiates, Gonadotropin-releasing hormone (GnRH), 5 alpha reductase inhibitors, propanolol, oxyphenbutazone, corticosteroids (except for physiological replacement doses), estradiol

• Men involved in sport in which there is screening for anabolic steroids

• Men with uncontrolled diabetes (haemoglobin A1c [HbA1c] greater than or equal to 10%)

• Men currently taking any investigational product, or have received an investigational product within 28 days prior to screening or 5 half-lives

• Any contraindication to blood sampling

• 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