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

Hypogonadism Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00702650
• Other study ID #: 14272
• Secondary ID: MTE08I5E-MC-TSAH
• Status: Completed
• Phase: Phase 3
• First received: June 19, 2008
• Last updated: July 21, 2011
• Start date: June 2008
• Est. completion date: July 2009

Study information

• Verified date: July 2011
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationAustralia: Department of Health and Ageing Therapeutic Goods AdministrationUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyGermany: Federal Institute for Drugs and Medical DevicesSweden: Medical Products AgencyFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 155
• Est. completion date: July 2009
• Est. primary completion date: July 2009
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hypogonadism

Intervention

Drug:
• Testosterone MD-Lotion
30 mg to 120 mg administered topically once daily for 120 days

Locations

Country	Name	City	State
Australia	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.	Adelaide	South Australia
Australia	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.	Melbourne	Victoria
Australia	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.	Perth	Western Australia
Australia	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.	Sydney	New South Wales
France	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.	Lyon
France	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.	Nice
France	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.	Nimes
Germany	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.	Bonn
Germany	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.	Freiburg
Germany	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.	Halle
Sweden	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.	Malmo
Sweden	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.	Stockholm
United Kingdom	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.	Barnsley
United Kingdom	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.	Newcastle Upon Tyne
United Kingdom	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.	Swansea
United States	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.	Birmingham	Alabama
United States	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.	Boise	Idaho
United States	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.	Burbank	California
United States	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.	Colorado Springs	Colorado
United States	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.	New Britain	Connecticut
United States	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.	Ocala	Florida
United States	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.	Omaha	Nebraska
United States	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.	San Antonio	Texas
United States	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.	Shawnee Mission	Kansas
United States	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.	Shreveport	Louisiana
United States	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.	Torrance	California
United States	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.	Tuscon	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Eli Lilly and Company

Countries where clinical trial is conducted

United States,  Australia,  France,  Germany,  Sweden,  United Kingdom, 

References & Publications (1)

Wang C, Ilani N, Arver S, McLachlan RI, Soulis T, Watkinson A. Efficacy and safety of the 2% formulation of testosterone topical solution applied to the axillae in androgen-deficient men. Clin Endocrinol (Oxf). 2011 Dec;75(6):836-43. doi: 10.1111/j.1365-2 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With 24-Hour Average Concentration [Cavg(0-24h)] Total Testosterone Within Normal Range at Day 120	Cavg(0-24) is the average serum concentration calculated over the 24 hour period on Day 120. Calculated as the AUC(0-24) divided by 24 hours. Normal range for Total Testosterone was defined as 300 - 1050 nanograms per deciliter (ng/dL).	Day 120	No
Secondary	Percentage of Participants With Maximum Serum Concentration (Cmax) >1500 ng/dL	Cmax is the maximum observed serum concentration (>1500 ng/dL) during the 24 hour period on Day 120.	Day 120	No
Secondary	Percentage of Participants With Cmax Between 1800 and 2500 ng/dL	Cmax is the maximum observed serum concentration (between 1800 and 2500 ng/dL) during the 24 hour period on Day 120.	Day 120	No
Secondary	Percentage of Participants With Cmax >2500 ng/dL	Cmax is the maximum observed serum concentration (>2500 ng/dL) during the 24 hour period on Day 120.	Day 120	No
Secondary	Percentage of Participants With Minimum Concentration (Cmin) <300 ng/dL	Cmin is the minimum observed serum concentration (<300 ng/dL) during the 24 hour period on Day 120.	Day 120	No
Secondary	Change From Baseline to Endpoint in Psychosexual Daily Questionnaire	Questions included: Sexual Desire (0=none to 7=very high), Overall Sexual Activity Score (calculated as average of weekly values on scale from 0=none to 7=Frequent), Erection Maintained for Satisfactory Duration (0=not satisfactory to 7=very satisfactory), and Positive and Negative Mood (individual mood variables on scale from 0=Not at all true to 7=very true). Positive mood: sum of 4 positive mood variables-alert, full of pep/energetic, friendly, and well/good (range from 0-28). Negative mood: sum of 5 negative mood variables-angry, irritable, sad/blue, tired, and nervous (range from 0-35).	Baseline, Day 120	No
Secondary	Change From Baseline to Endpoint in the 36-Item Short-Form Health Survey (SF-36)	The SF-36 Health Status Survey is a generic, health-related scale assessing subjects' quality of life on 8 domains: physical functioning, social functioning, bodily pain, vitality, mental health, role-physical, role-emotional and general health and 2 summary scores (mental component summary [MCS] and physical component summary [PCS]). MCS and PCS scores=0-100 (higher scores indicate better health status).	Baseline, Day 120	No
Secondary	Change From Baseline to Endpoint in Fasting Insulin		Baseline, up to Day 120	No
Secondary	Change From Baseline to Endpoint in Fasting Glucose		Baseline, up to Day 120	No
Secondary	Change From Baseline to Endpoint in Prostate Specific Antigen (PSA)		Baseline, Day 120	No
Secondary	Change From Baseline to Endpoint in Luteinizing Hormone (LH) and Follicle Stimulating Hormone (FSH)		Baseline, up to Day 120	No
Secondary	Change From Baseline to Endpoint in Estradiol		Baseline, up to Day 120	No
Secondary	Change From Baseline to Endpoint in Haemoglobin		Baseline, up to Day 120	No
Secondary	Change From Baseline to Endpoint in Haematocrit	Haematocrit: percentage of total blood volume made up of blood cells	Baseline, up to Day 120	No
Secondary	Change From Baseline to Endpoint in Draize Score	Draize score is a measurement of skin irritability of the application site based on erythema/eschar 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.	Baseline, Day 120	No