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

Lilly

Status and phase: Completed; Phase 3

Conditions: Hypogonadism

Treatments: Drug: Testosterone MD-Lotion

Study type: Interventional

Funder types: Industry

Identifiers

NCT00702650

14272

I5E-MC-TSAH (Other Identifier)

MTE08 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 155 patients

Sex: Male

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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155 participants in 1 patient group

Testosterone MD-Lotion

Experimental group

Description:

Participants received Testosterone Metered Dose (MD)-Lotion for 120 days. Participants started by receiving 3.0 mL (60 mg) of 2% Testosterone MD-Lotion, and based upon restoration to eugonadal levels, may have had their dose of testosterone adjusted upwards or downwards on Days 45 and 90. Doses could be titrated to one of the following: 1.5 mL (30 mg) of 2% Testosterone MD-Lotion applied daily by 1 dose 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 1 x 1.5 mL to the other axilla). 6.0 mL (120 mg) of 2% Testosterone MD-Lotion applied daily by 4 doses to the axilla (2 x 1.5 mL to each axilla).

Treatment:

Drug: Testosterone MD-Lotion