Trial Outcomes & Findings for A Titration Trial to Determine the Effectiveness of Testosterone MD-Lotion (Cutaneous Solution) Formulations (NCT NCT00702650)

NCT ID: NCT00702650

Last Updated: 2011-07-25

Results Overview

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).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

155 participants

Primary outcome timeframe

Day 120

Results posted on

2011-07-25

Participant Flow

Subjects received Testosterone Metered Dose (MD)-Lotion for 120 days, at initial dose of 60 mg; may have had their dose adjusted up or down on Days 45 and 90 (3 were on 30mg; 97 on 60mg; 25 on 90mg; and 10 on 120mg). As primary outcome=subjects with normal testosterone at Day 120, results are presented for overall treatment group rather than dose.

Participant milestones

Participant milestones
Measure
Testosterone MD-Lotion
30 mg to 120 mg of 2% Testosterone MD-Lotion administered topically once daily for 120 days.
Overall Study
STARTED
155
Overall Study
COMPLETED
135
Overall Study
NOT COMPLETED
20

Reasons for withdrawal

Reasons for withdrawal
Measure
Testosterone MD-Lotion
30 mg to 120 mg of 2% Testosterone MD-Lotion administered topically once daily for 120 days.
Overall Study
Withdrawal by Subject
9
Overall Study
Non-Compliance of Study Drug
3
Overall Study
Lost to Follow-up
2
Overall Study
Non-Compliance with Site Directives
1
Overall Study
Sponsor Request
1
Overall Study
Screening Testosterone Levels >300 ng/dL
1
Overall Study
Adverse Event
3

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Testosterone MD-Lotion
n=155 Participants
30 mg to 120 mg of 2% Testosterone MD-Lotion administered topically once daily for 120 days.
Age Continuous
51.5 years
STANDARD_DEVIATION 12.7 • n=99 Participants
Sex: Female, Male
Female
0 Participants
n=99 Participants
Sex: Female, Male
Male
155 Participants
n=99 Participants
Race/Ethnicity, Customized
Asian
1 participants
n=99 Participants
Race/Ethnicity, Customized
Caucasian
122 participants
n=99 Participants
Race/Ethnicity, Customized
African American
6 participants
n=99 Participants
Race/Ethnicity, Customized
Hispanic
13 participants
n=99 Participants
Race/Ethnicity, Customized
Other - Not Specified
2 participants
n=99 Participants
Race/Ethnicity, Customized
Missing
11 participants
n=99 Participants
Region of Enrollment
France
11 participants
n=99 Participants
Region of Enrollment
United States
104 participants
n=99 Participants
Region of Enrollment
Australia
10 participants
n=99 Participants
Region of Enrollment
Germany
9 participants
n=99 Participants
Region of Enrollment
United Kingdom
10 participants
n=99 Participants
Region of Enrollment
Sweden
11 participants
n=99 Participants
Body Mass Index (BMI)
29.53 kilograms per square meter (kg/m^2)
STANDARD_DEVIATION 3.60 • n=99 Participants
Baseline Total Testosterone Level
196.73 nanograms per deciliter (ng/dL)
STANDARD_DEVIATION 91.04 • n=99 Participants

PRIMARY outcome

Timeframe: Day 120

Population: 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).

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).

Outcome measures

Outcome measures
Measure
Testosterone MD-Lotion
n=138 Participants
30 mg to 120 mg of 2% Testosterone MD-Lotion administered topically once daily for 120 days.
Percentage of Participants With 24-Hour Average Concentration [Cavg(0-24h)] Total Testosterone Within Normal Range at Day 120
84.1 percentage of participants
Interval 77.95 to 90.17

SECONDARY outcome

Timeframe: Day 120

Population: 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.

Cmax is the maximum observed serum concentration (\>1500 ng/dL) during the 24 hour period on Day 120.

Outcome measures

Outcome measures
Measure
Testosterone MD-Lotion
n=135 Participants
30 mg to 120 mg of 2% Testosterone MD-Lotion administered topically once daily for 120 days.
Percentage of Participants With Maximum Serum Concentration (Cmax) >1500 ng/dL
5.2 percentage of participants

SECONDARY outcome

Timeframe: Day 120

Population: 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.

Cmax is the maximum observed serum concentration (between 1800 and 2500 ng/dL) during the 24 hour period on Day 120.

Outcome measures

Outcome measures
Measure
Testosterone MD-Lotion
n=135 Participants
30 mg to 120 mg of 2% Testosterone MD-Lotion administered topically once daily for 120 days.
Percentage of Participants With Cmax Between 1800 and 2500 ng/dL
3.0 percentage of participants

SECONDARY outcome

Timeframe: Day 120

Population: 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.

Cmax is the maximum observed serum concentration (\>2500 ng/dL) during the 24 hour period on Day 120.

Outcome measures

Outcome measures
Measure
Testosterone MD-Lotion
n=135 Participants
30 mg to 120 mg of 2% Testosterone MD-Lotion administered topically once daily for 120 days.
Percentage of Participants With Cmax >2500 ng/dL
0.7 percentage of participants

SECONDARY outcome

Timeframe: Day 120

Population: 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.

Cmin is the minimum observed serum concentration (\<300 ng/dL) during the 24 hour period on Day 120.

Outcome measures

Outcome measures
Measure
Testosterone MD-Lotion
n=135 Participants
30 mg to 120 mg of 2% Testosterone MD-Lotion administered topically once daily for 120 days.
Percentage of Participants With Minimum Concentration (Cmin) <300 ng/dL
64.4 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Day 120

Population: 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.

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).

Outcome measures

Outcome measures
Measure
Testosterone MD-Lotion
n=131 Participants
30 mg to 120 mg of 2% Testosterone MD-Lotion administered topically once daily for 120 days.
Change From Baseline to Endpoint in Psychosexual Daily Questionnaire
Sexual Desire
1.49 units on a scale
Standard Deviation 1.84
Change From Baseline to Endpoint in Psychosexual Daily Questionnaire
Overall Sexual Activity Score
0.94 units on a scale
Standard Deviation 1.43
Change From Baseline to Endpoint in Psychosexual Daily Questionnaire
Erection Maintained for Satisfactory Duration
1.11 units on a scale
Standard Deviation 2.0
Change From Baseline to Endpoint in Psychosexual Daily Questionnaire
Positive Mood
0.56 units on a scale
Standard Deviation 1.25
Change From Baseline to Endpoint in Psychosexual Daily Questionnaire
Negative Mood
-0.50 units on a scale
Standard Deviation 1.33

SECONDARY outcome

Timeframe: Baseline, Day 120

Population: 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.

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).

Outcome measures

Outcome measures
Measure
Testosterone MD-Lotion
n=133 Participants
30 mg to 120 mg of 2% Testosterone MD-Lotion administered topically once daily for 120 days.
Change From Baseline to Endpoint in the 36-Item Short-Form Health Survey (SF-36)
Physical Component Score
1.55 units on a scale
Standard Deviation 7.72
Change From Baseline to Endpoint in the 36-Item Short-Form Health Survey (SF-36)
Mental Component Score
4.54 units on a scale
Standard Deviation 9.20

SECONDARY outcome

Timeframe: Baseline, up to Day 120

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

Outcome measures

Outcome measures
Measure
Testosterone MD-Lotion
n=63 Participants
30 mg to 120 mg of 2% Testosterone MD-Lotion administered topically once daily for 120 days.
Change From Baseline to Endpoint in Fasting Insulin
1.93 uIU/mL
Standard Deviation 12.02

SECONDARY outcome

Timeframe: Baseline, up to Day 120

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

Outcome measures

Outcome measures
Measure
Testosterone MD-Lotion
n=64 Participants
30 mg to 120 mg of 2% Testosterone MD-Lotion administered topically once daily for 120 days.
Change From Baseline to Endpoint in Fasting Glucose
-0.41 mg/dL
Standard Deviation 20.02

SECONDARY outcome

Timeframe: Baseline, Day 120

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

Outcome measures

Outcome measures
Measure
Testosterone MD-Lotion
n=70 Participants
30 mg to 120 mg of 2% Testosterone MD-Lotion administered topically once daily for 120 days.
Change From Baseline to Endpoint in Prostate Specific Antigen (PSA)
0.13 ng/mL
Standard Deviation 0.68

SECONDARY outcome

Timeframe: Baseline, up to Day 120

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

Outcome measures

Outcome measures
Measure
Testosterone MD-Lotion
n=54 Participants
30 mg to 120 mg of 2% Testosterone MD-Lotion administered topically once daily for 120 days.
Change From Baseline to Endpoint in Luteinizing Hormone (LH) and Follicle Stimulating Hormone (FSH)
Luteinizing Hormone (N=48)
-2.04 mIU/mL
Standard Deviation 5.36
Change From Baseline to Endpoint in Luteinizing Hormone (LH) and Follicle Stimulating Hormone (FSH)
Follicle Stimulating Hormone (N=54)
-2.41 mIU/mL
Standard Deviation 9.72

SECONDARY outcome

Timeframe: Baseline, up to Day 120

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

Outcome measures

Outcome measures
Measure
Testosterone MD-Lotion
n=39 Participants
30 mg to 120 mg of 2% Testosterone MD-Lotion administered topically once daily for 120 days.
Change From Baseline to Endpoint in Estradiol
-2.16 pg/mL
Standard Deviation 12.32

SECONDARY outcome

Timeframe: Baseline, up to Day 120

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

Outcome measures

Outcome measures
Measure
Testosterone MD-Lotion
n=64 Participants
30 mg to 120 mg of 2% Testosterone MD-Lotion administered topically once daily for 120 days.
Change From Baseline to Endpoint in Haemoglobin
0.51 g/dL
Standard Deviation 1.08

SECONDARY outcome

Timeframe: Baseline, up to Day 120

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

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

Outcome measures

Outcome measures
Measure
Testosterone MD-Lotion
n=64 Participants
30 mg to 120 mg of 2% Testosterone MD-Lotion administered topically once daily for 120 days.
Change From Baseline to Endpoint in Haematocrit
0.02 percentage of red blood cells
Standard Deviation 0.04

SECONDARY outcome

Timeframe: Baseline, Day 120

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

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.

Outcome measures

Outcome measures
Measure
Testosterone MD-Lotion
n=135 Participants
30 mg to 120 mg of 2% Testosterone MD-Lotion administered topically once daily for 120 days.
Change From Baseline to Endpoint in Draize Score
0 units on a scale
Standard Deviation 0.17

Adverse Events

Testosterone MD-Lotion

Serious events: 1 serious events
Other events: 80 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Testosterone MD-Lotion
n=155 participants at risk
30 mg to 120 mg of 2% Testosterone MD-Lotion administered topically once daily for 120 days.
Infections and infestations
Appendicitis
0.65%
1/155 • Number of events 1

Other adverse events

Other adverse events
Measure
Testosterone MD-Lotion
n=155 participants at risk
30 mg to 120 mg of 2% Testosterone MD-Lotion administered topically once daily for 120 days.
Gastrointestinal disorders
Diarrhoea
2.6%
4/155 • Number of events 4
Gastrointestinal disorders
Gastrooesophageal reflux disease
1.3%
2/155 • Number of events 2
Gastrointestinal disorders
Nausea
1.3%
2/155 • Number of events 3
Gastrointestinal disorders
Vomiting
2.6%
4/155 • Number of events 4
General disorders
Application site erythema
5.2%
8/155 • Number of events 9
General disorders
Application site irritation
7.1%
11/155 • Number of events 19
General disorders
Application site oedema
1.3%
2/155 • Number of events 2
General disorders
Application site warmth
1.3%
2/155 • Number of events 4
General disorders
Fatigue
1.9%
3/155 • Number of events 3
General disorders
Pyrexia
1.9%
3/155 • Number of events 3
Infections and infestations
Fungal infection
1.3%
2/155 • Number of events 2
Infections and infestations
Influenza
1.9%
3/155 • Number of events 3
Infections and infestations
Nasopharyngitis
3.9%
6/155 • Number of events 8
Infections and infestations
Rhinitis
1.3%
2/155 • Number of events 2
Infections and infestations
Upper respiratory tract infection
1.9%
3/155 • Number of events 3
Injury, poisoning and procedural complications
Epicondylitis
1.3%
2/155 • Number of events 2
Investigations
Blood glucose increased
1.3%
2/155 • Number of events 2
Investigations
Haematocrit increased
3.9%
6/155 • Number of events 6
Investigations
Haemoglobin increased
1.3%
2/155 • Number of events 2
Investigations
Prostatic specific antigen increased
1.3%
2/155 • Number of events 2
Metabolism and nutrition disorders
Hypercholesterolaemia
1.3%
2/155 • Number of events 2
Musculoskeletal and connective tissue disorders
Arthralgia
1.9%
3/155 • Number of events 5
Musculoskeletal and connective tissue disorders
Back pain
1.3%
2/155 • Number of events 2
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
1.3%
2/155 • Number of events 2
Musculoskeletal and connective tissue disorders
Myalgia
1.3%
2/155 • Number of events 2
Nervous system disorders
Dizziness
1.3%
2/155 • Number of events 2
Nervous system disorders
Headache
5.2%
8/155 • Number of events 11
Nervous system disorders
Migraine
1.3%
2/155 • Number of events 2
Nervous system disorders
Presyncope
1.3%
2/155 • Number of events 2
Psychiatric disorders
Anger
1.3%
2/155 • Number of events 4
Psychiatric disorders
Anxiety
1.3%
2/155 • Number of events 3
Psychiatric disorders
Insomnia
1.9%
3/155 • Number of events 3
Psychiatric disorders
Stress
1.3%
2/155 • Number of events 2
Respiratory, thoracic and mediastinal disorders
Cough
1.3%
2/155 • Number of events 2
Respiratory, thoracic and mediastinal disorders
Paranasal sinus hypersecretion
1.9%
3/155 • Number of events 3
Respiratory, thoracic and mediastinal disorders
Sinus congestion
1.3%
2/155 • Number of events 2
Skin and subcutaneous tissue disorders
Acne
1.3%
2/155 • Number of events 2
Skin and subcutaneous tissue disorders
Erythema
1.3%
2/155 • Number of events 2
Skin and subcutaneous tissue disorders
Hyperkeratosis
1.3%
2/155 • Number of events 2
Vascular disorders
Hypertension
1.9%
3/155 • Number of events 4

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place

Restriction type: GT60