Clinical trial NCT00857961: A Study of the Pharmacokinetics of Testosterone Metered Dose (MD)-Lotion Formulations
Official title: A Phase II, Randomised, Four-way Crossover Study to Compare the Steady State Pharmacokinetics of Testosterone Following Application of Different Testosterone Metered Dose (MD) Lotion® Formulations and Doses in Hypogonadal Men
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hypogonadism
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2009-03-09
Enrollment: 21
Sex: MALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

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

Primary outcomes:
measure: Pharmacokinetics of Total Testosterone, Dihydrotestosterone, Free Testosterone: Time of Maximal Concentration (Tmax)
timeFrame: Day 7 (0, 2, 4, 8, 12, 16, 20, 24 hours) of each of the four 7 day cycles of treatment
measure: Pharmacokinetics of Total Testosterone: Maximal Concentration (Cmax), Minimum Concentration (Cmin), and Average Concentration (Cavg)
timeFrame: Day 7 (0, 2, 4, 8, 12, 16, 20, 24 hours) of each of the four 7 day cycles of treatment
measure: Pharmacokinetics of Dihydrotestosterone: Maximal Concentration (Cmax), Minimum Concentration (Cmin), and Average Concentration (Cavg)
timeFrame: Day 7 (0, 2, 4, 8, 12, 16, 20, 24 hours) of each of the four 7 day cycles of treatment
measure: Pharmacokinetics of Free Testosterone: Maximal Concentration (Cmax), Minimum Concentration (Cmin), and Average Concentration (Cavg)
timeFrame: Day 7 (0, 2, 4, 8, 12, 16, 20, 24 hours) of each of the four 7 day cycles of treatment
measure: Pharmacokinetics of Total Testosterone, Dihydrotestosterone, Free Testosterone: Degree of Fluctuation (DF)
timeFrame: Day 7 (0, 2, 4, 8, 12, 16, 20, 24 hours) of each of the four 7 day cycles of treatment
measure: Pharmacokinetics of Total Testosterone, Dihydrotestosterone, Free Testosterone: Area Under the Time Concentration Curve [AUC(0-24h)]
timeFrame: Day 7 (0, 2, 4, 8, 12, 16, 20, 24 hours) of each of the four 7 day cycles of treatment
Secondary outcomes:
measure: Number of Participants With Adverse Events
timeFrame: Baseline through 7 days of each cycle of four treatments and follow-up (up to 38 days)
Other outcomes:
Locations:
city: Tuscon
country: United States
facility: 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.
state: Arizona
city: Burbank
country: United States
facility: 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.
state: California
city: New Britain
country: United States
facility: 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.
state: Connecticut
city: San Antonio
country: United States
facility: 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.
state: Texas
Study officials:
affiliation: Eli Lilly and Company
name: Call 1-877-CTLILLY (1-877-285-4559) or 1-31- Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
role: STUDY_DIRECTOR
References: