A Titration Trial to Determine the Effectiveness of Testo... | NCT00702650

ID	Type	Description	Link
MTE08	Other Identifier	Acrux
I5E-MC-TSAH	Other Identifier	Eli Lilly and Company

Label	Type	Description	Intervention Names
Testosterone MD-Lotion	Experimental	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).	Drug: Testosterone MD-Lotion

Name	Type	Description	Arm Group Labels	Other Names
Testosterone MD-Lotion	Drug	30 mg to 120 mg administered topically once daily for 120 days	Testosterone MD-Lotion

Measure	Description	Time Frame
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

Measure	Description	Time Frame
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
Percentage of Participants With Cmax Between 1800 and 2500 ng/dL

Eligibility Module

Eligibility Criteria

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

Name	Affiliation	Role
Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)	Eli Lilly and Company	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
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

PubMed Identifier	Type	Citation	Retractions
21689131	Result	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.1365-2265.2011.04152.x.
26549704	Derived	Muram D, Ni X. Utility of a single serum testosterone measurement to determine response to topical testosterone replacement in hypogonadal men. Curr Med Res Opin. 2016;32(2):263-9. doi: 10.1185/03007995.2015.1117434. Epub 2015 Dec 15.

ID	Title	Description
FG000	Testosterone MD-Lotion	30 mg to 120 mg of 2% Testosterone MD-Lotion administered topically once daily for 120 days.

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

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).

All participants who received at least one dose of study drug, had on-treatment data for at least one efficacy variable, and completed the Day 120 visit. Participants were also included if they withdrew prior to Day 120 because of adverse event or lack of efficacy (considered as treatment failures).

Posted

Number

95% Confidence Interval

percentage of participants

Day 120

ID	Title	Description
OG000	Testosterone MD-Lotion	30 mg to 120 mg of 2% Testosterone MD-Lotion administered topically once daily for 120 days.

Units	Counts
Participants	OG000138

Title

Denominators

Categories

Title	Measurements
	OG00084.1(77.95 to 90.17)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000		One-Sample Binomial (Wald) test, 2-sided		<0.001							95						No	Superiority or Other

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.

All participants who received at least one dose of study drug, had on-treatment data for at least one efficacy variable, and completed the Day 120 visit.

Posted

Number

percentage of participants

Day 120

ID	Title	Description
OG000	Testosterone MD-Lotion	30 mg to 120 mg of 2% Testosterone MD-Lotion administered topically once daily for 120 days.

Units	Counts
Participants	OG000

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.

All participants who received at least one dose of study drug, had on-treatment data for at least one efficacy variable, and completed the Day 120 visit.

Posted

Number

percentage of participants

Day 120

ID	Title	Description
OG000	Testosterone MD-Lotion	30 mg to 120 mg of 2% Testosterone MD-Lotion administered topically once daily for 120 days.

Units	Counts
Participants	OG000

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.

All participants who received at least one dose of study drug, had on-treatment data for at least one efficacy variable, and completed the Day 120 visit.

Posted

Number

percentage of participants

Day 120

ID	Title	Description
OG000	Testosterone MD-Lotion	30 mg to 120 mg of 2% Testosterone MD-Lotion administered topically once daily for 120 days.

Units	Counts
Participants	OG000135

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.

All participants who received at least one dose of study drug, had on-treatment data for at least one efficacy variable, and completed the Day 120 visit.

Posted

Number

percentage of participants

Day 120

ID	Title	Description
OG000	Testosterone MD-Lotion	30 mg to 120 mg of 2% Testosterone MD-Lotion administered topically once daily for 120 days.

Units	Counts
Participants	OG000

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).

All participants who received at least one dose of study drug, had baseline and on-treatment data for at least one efficacy variable, and completed the Day 120 visit.

Posted

Mean

Standard Deviation

units on a scale

Baseline, Day 120

ID	Title	Description
OG000	Testosterone MD-Lotion	30 mg to 120 mg of 2% Testosterone MD-Lotion administered topically once daily for 120 days.

Units	Counts
Participants	OG000

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).

All participants who received at least one dose of study drug, had baseline and on-treatment data for at least one efficacy variable, and completed the Day 120 visit.

Posted

Mean

Standard Deviation

units on a scale

Baseline, Day 120

ID	Title	Description
OG000	Testosterone MD-Lotion	30 mg to 120 mg of 2% Testosterone MD-Lotion administered topically once daily for 120 days.

Units	Counts
Participants	OG000

Secondary

Change From Baseline to Endpoint in Fasting Insulin

Participants enrolled in the study who had a baseline and a measurement at endpoint: Day 120, follow-up, or early withdrawal.

Posted

Mean

Standard Deviation

uIU/mL

Baseline, up to Day 120

ID	Title	Description
OG000	Testosterone MD-Lotion	30 mg to 120 mg of 2% Testosterone MD-Lotion administered topically once daily for 120 days.

Units	Counts
Participants	OG00063

Secondary

Change From Baseline to Endpoint in Fasting Glucose

Participants enrolled in the study who had a baseline and a measurement at endpoint: Day 120, follow-up, or early withdrawal.

Posted

Mean

Standard Deviation

mg/dL

Baseline, up to Day 120

ID	Title	Description
OG000	Testosterone MD-Lotion	30 mg to 120 mg of 2% Testosterone MD-Lotion administered topically once daily for 120 days.

Units	Counts
Participants	OG00064

Secondary

Change From Baseline to Endpoint in Prostate Specific Antigen (PSA)

Participants enrolled in the study who had a baseline and a measurement at endpoint: Day 120.

Posted

Mean

Standard Deviation

ng/mL

Baseline, Day 120

ID	Title	Description
OG000	Testosterone MD-Lotion	30 mg to 120 mg of 2% Testosterone MD-Lotion administered topically once daily for 120 days.

Units	Counts
Participants	OG00070

Title

Secondary

Change From Baseline to Endpoint in Luteinizing Hormone (LH) and Follicle Stimulating Hormone (FSH)

Participants enrolled in the study who had a baseline and a measurement at endpoint: Day 120, follow-up, or early withdrawal.

Posted

Mean

Standard Deviation

mIU/mL

Baseline, up to Day 120

ID	Title	Description
OG000	Testosterone MD-Lotion	30 mg to 120 mg of 2% Testosterone MD-Lotion administered topically once daily for 120 days.

Units	Counts
Participants	OG00054

Secondary

Change From Baseline to Endpoint in Estradiol

Participants enrolled in the study who had a baseline and a measurement at endpoint: Day 120, follow-up, or early withdrawal.

Posted

Mean

Standard Deviation

pg/mL

Baseline, up to Day 120

ID	Title	Description
OG000	Testosterone MD-Lotion	30 mg to 120 mg of 2% Testosterone MD-Lotion administered topically once daily for 120 days.

Units	Counts
Participants	OG00039

Secondary

Change From Baseline to Endpoint in Haemoglobin

Participants enrolled in the study who had a baseline and a measurement at endpoint: Day 120, follow-up, or early withdrawal.

Posted

Mean

Standard Deviation

g/dL

Baseline, up to Day 120

ID	Title	Description
OG000	Testosterone MD-Lotion	30 mg to 120 mg of 2% Testosterone MD-Lotion administered topically once daily for 120 days.

Units	Counts
Participants	OG00064

Secondary

Change From Baseline to Endpoint in Haematocrit

Haematocrit: percentage of total blood volume made up of blood cells

Participants enrolled in the study who had a baseline and a measurement at endpoint: Day 120, follow-up, or early withdrawal.

Posted

Mean

Standard Deviation

percentage of red blood cells

Baseline, up to Day 120

ID	Title	Description
OG000	Testosterone MD-Lotion	30 mg to 120 mg of 2% Testosterone MD-Lotion administered topically once daily for 120 days.

Units	Counts
Participants	OG00064

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.

Participants enrolled in the study who had a baseline and a measurement at endpoint: Day 120.

Posted

Mean

Standard Deviation

units on a scale

Baseline, Day 120

ID	Title	Description
OG000	Testosterone MD-Lotion	30 mg to 120 mg of 2% Testosterone MD-Lotion administered topically once daily for 120 days.

Units	Counts
Participants	OG000

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Diarrhoea	Gastrointestinal disorders	MedDRA (11.1)	Systematic Assessment	EG0004 events4 affected155 at risk
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA (11.1)	Systematic Assessment	EG0002 events2 affected155 at risk
Nausea	Gastrointestinal disorders	MedDRA (11.1)	Systematic Assessment	EG0003 events2 affected155 at risk
Vomiting	Gastrointestinal disorders	MedDRA (11.1)	Systematic Assessment	EG0004 events4 affected155 at risk
Application site erythema	General disorders	MedDRA (11.1)	Systematic Assessment	EG0009 events8 affected155 at risk
Application site irritation	General disorders	MedDRA (11.1)	Systematic Assessment	EG00019 events11 affected155 at risk
Application site oedema	General disorders	MedDRA (11.1)	Systematic Assessment	EG0002 events2 affected155 at risk
Application site warmth	General disorders	MedDRA (11.1)	Systematic Assessment	EG0004 events2 affected155 at risk
Fatigue	General disorders	MedDRA (11.1)	Systematic Assessment	EG0003 events3 affected155 at risk
Pyrexia	General disorders	MedDRA (11.1)	Systematic Assessment	EG0003 events3 affected155 at risk
Fungal infection	Infections and infestations	MedDRA (11.1)	Systematic Assessment	EG0002 events2 affected155 at risk
Influenza	Infections and infestations	MedDRA (11.1)	Systematic Assessment	EG0003 events3 affected155 at risk
Nasopharyngitis	Infections and infestations	MedDRA (11.1)	Systematic Assessment	EG0008 events6 affected155 at risk
Rhinitis	Infections and infestations	MedDRA (11.1)	Systematic Assessment	EG0002 events2 affected155 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA (11.1)	Systematic Assessment	EG0003 events3 affected155 at risk
Epicondylitis	Injury, poisoning and procedural complications	MedDRA (11.1)	Systematic Assessment	EG0002 events2 affected155 at risk
Blood glucose increased	Investigations	MedDRA (11.1)	Systematic Assessment	EG0002 events2 affected155 at risk
Haematocrit increased	Investigations	MedDRA (11.1)	Systematic Assessment	EG0006 events6 affected155 at risk
Haemoglobin increased	Investigations	MedDRA (11.1)	Systematic Assessment	EG0002 events2 affected155 at risk
Prostatic specific antigen increased	Investigations	MedDRA (11.1)	Systematic Assessment	EG0002 events2 affected155 at risk
Hypercholesterolaemia	Metabolism and nutrition disorders	MedDRA (11.1)	Systematic Assessment	EG0002 events2 affected155 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA (11.1)	Systematic Assessment	EG0005 events3 affected155 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (11.1)	Systematic Assessment	EG0002 events2 affected155 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA (11.1)	Systematic Assessment	EG0002 events2 affected155 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA (11.1)	Systematic Assessment	EG0002 events2 affected155 at risk
Dizziness	Nervous system disorders	MedDRA (11.1)	Systematic Assessment	EG0002 events2 affected155 at risk
Headache	Nervous system disorders	MedDRA (11.1)	Systematic Assessment	EG00011 events8 affected155 at risk
Migraine	Nervous system disorders	MedDRA (11.1)	Systematic Assessment	EG0002 events2 affected155 at risk
Presyncope	Nervous system disorders	MedDRA (11.1)	Systematic Assessment	EG0002 events2 affected155 at risk
Anger	Psychiatric disorders	MedDRA (11.1)	Systematic Assessment	EG0004 events2 affected155 at risk
Anxiety	Psychiatric disorders	MedDRA (11.1)	Systematic Assessment	EG0003 events2 affected155 at risk
Insomnia	Psychiatric disorders	MedDRA (11.1)	Systematic Assessment	EG0003 events3 affected155 at risk
Stress	Psychiatric disorders	MedDRA (11.1)	Systematic Assessment	EG0002 events2 affected155 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA (11.1)	Systematic Assessment	EG0002 events2 affected155 at risk
Paranasal sinus hypersecretion	Respiratory, thoracic and mediastinal disorders	MedDRA (11.1)	Systematic Assessment	EG0003 events3 affected155 at risk
Sinus congestion	Respiratory, thoracic and mediastinal disorders	MedDRA (11.1)	Systematic Assessment	EG0002 events2 affected155 at risk
Acne	Skin and subcutaneous tissue disorders	MedDRA (11.1)	Systematic Assessment	EG0002 events2 affected155 at risk
Erythema	Skin and subcutaneous tissue disorders	MedDRA (11.1)	Systematic Assessment	EG0002 events2 affected155 at risk
Hyperkeratosis	Skin and subcutaneous tissue disorders	MedDRA (11.1)	Systematic Assessment	EG0002 events2 affected155 at risk
Hypertension	Vascular disorders	MedDRA (11.1)	Systematic Assessment	EG0004 events3 affected155 at risk

ID	Term
D006058	Gonadal Disorders
D004700	Endocrine System Diseases

ID	Term
D013739	Testosterone
D000737	Androstenols
D000736	Androstenes
D000731	Androstanes
D013256	Steroids
D000072473	Fused-Ring Compounds
D011083	Polycyclic Compounds
D045165	Testosterone Congeners
D012739	Gonadal Steroid Hormones
D042341	Gonadal Hormones
D006728	Hormones
D006730	Hormones, Hormone Substitutes, and Hormone Antagonists