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A Study of the Pharmacokinetics of Testosterone Metered Dose (MD)-Lotion Formulations

Phase 2
Completed
Conditions
Hypogonadism
Interventions
Registration Number
NCT00857961
Lead Sponsor
Eli Lilly and Company
Brief Summary

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 evaluate pharmacokinetics of testosterone MD-Lotion formulations.The study will also assess safety of the product.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
Male
Target Recruitment
21
Inclusion Criteria
  • Male study participants with a prior documented diagnosis of hypoandrogenism as evidenced by previously documented: Hypothalamic, pituitary or testicular disorder or a Serum testosterone less than or equal to 300 ng/dL
  • Were receiving, or in the investigator's opinion were eligible to receive treatment for hypoandrogenism
  • Body Mass Index (BMI) less than 35 kg/m^2
  • Passed the required laboratory and physical screening tests
  • Haemoglobin levels at screening greater than or equal to 13.0 g/dL
  • Adequate venous access on left or right arm
  • Able to communicate with study staff, understand the study information sheet and sign the written Informed Consent forms; willing to follow and comply with study procedures
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Exclusion Criteria
  • 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

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

  • Men with suspected reversible hypoandrogenism (i.e. due to medications, stress)

  • Any man in whom testosterone therapy is contraindicated, which included those with:

    • Known or suspected carcinoma (or history of carcinoma) of the prostate or symptoms of benign prostatic hyperplasia and/or symptoms of lower urinary obstruction,
    • Known or suspected carcinoma (or history of carcinoma) of the breast,
    • Severe liver damage i.e. cirrhosis, hepatitis or liver tumours,
    • Active deep vein thrombosis, thromboembolic disorders or a documented history of these conditions,
    • Significant cerebrovascular or coronary artery disease,
    • Known or suspected sleep apnoea,
    • Hematocrit > 51%
  • Men with clinically significant prostate exam or clinically significant elevated serum prostate specific antigen (PSA) level, or age adjusted reference range of PSA values.

  • Current history of drug or alcohol abuse (more than 4 standard drinks per day and/or abnormal liver function tests 3 times the upper limit of the normal range values)

  • Men taking concomitant medications that affect sex hormone binding globulin (SHBG) or testosterone concentrations or metabolism, or that were cytochrome P450 inducers or inhibitors, anti-coagulants (warfarin), or diabetic medications (insulin), anti-histamines

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

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

  • Men taking any Investigational Product, or who had received an Investigational Product within 28 days prior to screening or 5 half-lives (whichever was the longer)

  • Any contraindication to blood sampling

  • Study participants who planned to have a surgical procedure during the course of the study

  • Study participants with a partner of child bearing potential who was not willing to use adequate contraception (i.e. condoms) for the duration of the study

  • Study participants whose partners were pregnant

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Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
4.5 mL (90 mg) of 2% Testosterone MD-LotionTestosterone MD-LotionApplied once daily for 7 days by three doses to both axilla (2 x 1.5 mL to one axilla and 1 x 1.5 mL to the other axilla). All study participants are randomized to each of the 4 study treatments.
3 mL (30 mg) of 1% Testosterone MD-LotionTestosterone MD-LotionApplied once daily for 7 days to both axilla (1.5 mL to each axilla). All study participants are randomized to each of the 4 study treatments.
1.5 mL (30 mg) of 2% Testosterone MD-LotionTestosterone MD-LotionApplied once daily for 7 days to one axilla. All study participants are randomized to each of the 4 study treatments.
3 mL (60 mg) of 2% Testosterone MD-LotionTestosterone MD-LotionApplied once daily for 7 days to both axilla (1.5 mL to each axilla). All study participants are randomized to each of the 4 study treatments.
Primary Outcome Measures
NameTimeMethod
Pharmacokinetics of Total Testosterone, Dihydrotestosterone, Free Testosterone: Time of Maximal Concentration (Tmax)Day 7 (0, 2, 4, 8, 12, 16, 20, 24 hours) of each of the four 7 day cycles of treatment

Tmax is the time at which the maximum concentration (Cmax) was attained during the 24 hour period on Day 7.

Pharmacokinetics of Total Testosterone: Maximal Concentration (Cmax), Minimum Concentration (Cmin), and Average Concentration (Cavg)Day 7 (0, 2, 4, 8, 12, 16, 20, 24 hours) of each of the four 7 day cycles of treatment

Cmax is the maximum observed serum concentration of total testosterone during the 24 hour period on Day 7. Cmin is the minimum observed serum concentration during the 24 hour period on Day 7. Cavg(0-24) is the average serum concentration calculated during the 24 hour period on Day 7. Calculated as the AUC(0-24) divided by 24 hours.

Pharmacokinetics of Dihydrotestosterone: Maximal Concentration (Cmax), Minimum Concentration (Cmin), and Average Concentration (Cavg)Day 7 (0, 2, 4, 8, 12, 16, 20, 24 hours) of each of the four 7 day cycles of treatment

Cmax is the maximum observed serum concentration of dihydrotestosterone during the 24 hour period on Day 7. Cmin is the minimum observed serum concentration during the 24 hour period on Day 7. Cavg(0-24) is the average serum concentration calculated during the 24 hour period on Day 7. Calculated as the AUC(0-24) divided by 24 hours.

Pharmacokinetics of Free Testosterone: Maximal Concentration (Cmax), Minimum Concentration (Cmin), and Average Concentration (Cavg)Day 7 (0, 2, 4, 8, 12, 16, 20, 24 hours) of each of the four 7 day cycles of treatment

Cmax is the maximum observed serum concentration of free testosterone during the 24 hour period on Day 7. Cmin is the minimum observed serum concentration during the 24 hour period on Day 7. Cavg(0-24) is the average serum concentration calculated during the 24 hour period on Day 7. Calculated as the AUC(0-24) divided by 24 hours.

Pharmacokinetics of Total Testosterone, Dihydrotestosterone, Free Testosterone: Degree of Fluctuation (DF)Day 7 (0, 2, 4, 8, 12, 16, 20, 24 hours) of each of the four 7 day cycles of treatment

Degree of fluctuation in serum concentration calculated as ((Cmax-Cmin)/Cavg) x 100%.

Pharmacokinetics of Total Testosterone, Dihydrotestosterone, Free Testosterone: Area Under the Time Concentration Curve [AUC(0-24h)]Day 7 (0, 2, 4, 8, 12, 16, 20, 24 hours) of each of the four 7 day cycles of treatment

Area under the serum concentration versus time curve was calculated using the linear trapezoidal rule from time 0 to 24 hours on Day 7.

Secondary Outcome Measures
NameTimeMethod
Number of Participants With Adverse EventsBaseline through 7 days of each cycle of four treatments and follow-up (up to 38 days)

A listing of adverse events is located in the Reported Adverse Events module.

Trial Locations

Locations (1)

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

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San Antonio, Texas, United States

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