Trial Outcomes & Findings for A Multicenter Extension Trial to Evaluate the Safety of Testosterone Gel (NCT NCT01703741)
NCT ID: NCT01703741
Last Updated: 2017-10-06
Results Overview
Measurement of total testosterone level occur after subjects have been on a stabilized dose of testosterone gel for at least one month in the period between Month 3 and Month 6. The data were presented using descriptive statistics.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
145 participants
Primary outcome timeframe
Samples were collected at pre-dose; 2, 4, 6, 8, 10, 12 (±15 min for all), 18 (±2 hr), and 24 (±1 hr) hours post-dose (between Month 3 and Month 6, after subjects had been on a stabilized dose of Testosterone gel for at least 1 month)
Results posted on
2017-10-06
Participant Flow
Subjects were recruited from 16 study centers in United States and 2 study centers in Canada.
Of the 172 subjects who completed study 000023 (NCT01665599), 145 subjects were enrolled into this extension study and continued to receive treatment (23 mg, 46 mg or 69 mg).
Participant milestones
| Measure |
Testosterone Gel (FE 999303)
Subjects received testosterone gel with initial dose as fixed on Day 56 (23 mg, 46 mg or 69 mg) during the 000023 study. The dose could further be down titrated based on serum testosterone levels at Day 90/91 of 000023 study. Testosterone gel was applied daily in morning using an applicator, to the shoulder/upper arm in a contralateral fashion for 6 months.
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|---|---|
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Overall Study
STARTED
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145
|
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Overall Study
Per Protocol (PP) Population
|
106
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Overall Study
COMPLETED
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127
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Overall Study
NOT COMPLETED
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18
|
Reasons for withdrawal
| Measure |
Testosterone Gel (FE 999303)
Subjects received testosterone gel with initial dose as fixed on Day 56 (23 mg, 46 mg or 69 mg) during the 000023 study. The dose could further be down titrated based on serum testosterone levels at Day 90/91 of 000023 study. Testosterone gel was applied daily in morning using an applicator, to the shoulder/upper arm in a contralateral fashion for 6 months.
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|---|---|
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Overall Study
Withdrawal by Subject
|
6
|
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Overall Study
Adverse Event
|
2
|
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Overall Study
Physician Decision
|
2
|
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Overall Study
Protocol Violation
|
1
|
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Overall Study
Lost to Follow-up
|
3
|
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Overall Study
Subject did not want to continue
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2
|
|
Overall Study
Subject cannot comply with study visits
|
1
|
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Overall Study
Subject started testosterone injections
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1
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Baseline Characteristics
A Multicenter Extension Trial to Evaluate the Safety of Testosterone Gel
Baseline characteristics by cohort
| Measure |
Testosterone Gel (FE 999303)
n=145 Participants
Subjects received testosterone gel with initial dose as fixed on Day 56 (23 mg, 46 mg or 69 mg) during the 000023 study. The dose could further be down titrated based on serum testosterone levels at Day 90/91 of 000023 study. Testosterone gel was applied daily in morning using an applicator, to the shoulder/upper arm in a contralateral fashion for 6 months.
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|---|---|
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Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
116 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
29 Participants
n=5 Participants
|
|
Age, Continuous
|
57.1 years
STANDARD_DEVIATION 9.4 • n=5 Participants
|
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Sex: Female, Male
Female
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0 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
145 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
12 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
133 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
14 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
127 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Samples were collected at pre-dose; 2, 4, 6, 8, 10, 12 (±15 min for all), 18 (±2 hr), and 24 (±1 hr) hours post-dose (between Month 3 and Month 6, after subjects had been on a stabilized dose of Testosterone gel for at least 1 month)Population: PP analysis population was used which comprises data from subjects who had 24 hr PK data for testosterone, with no major protocol violations.
Measurement of total testosterone level occur after subjects have been on a stabilized dose of testosterone gel for at least one month in the period between Month 3 and Month 6. The data were presented using descriptive statistics.
Outcome measures
| Measure |
Testosterone Gel (FE 999303)
n=106 Participants
Subjects received testosterone gel with initial dose as fixed on Day 56 (23 mg, 46 mg or 69 mg) during the 000023 study. The dose could further be down titrated based on serum testosterone levels at Day 90/91 of 000023 study. Testosterone gel was applied daily in morning using an applicator, to the shoulder/upper arm in a contralateral fashion for 6 months.
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|---|---|
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Percentage of Subjects With a Serum Total Testosterone Level - Maximum Observed Concentration (Cmax) of 1500-1799, 1800-2499, or Above 2500 ng/dL
Total testosterone level between 1500-1799 ng/dL
|
5.7 percentage of subjects
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|
Percentage of Subjects With a Serum Total Testosterone Level - Maximum Observed Concentration (Cmax) of 1500-1799, 1800-2499, or Above 2500 ng/dL
Total testosterone level between 1800-2499 ng/dL
|
2.8 percentage of subjects
|
|
Percentage of Subjects With a Serum Total Testosterone Level - Maximum Observed Concentration (Cmax) of 1500-1799, 1800-2499, or Above 2500 ng/dL
Total testosterone level above 2500 ng/dL
|
2.8 percentage of subjects
|
SECONDARY outcome
Timeframe: Samples were collected at pre-dose; 2, 4, 6, 8, 10, 12 (±15 min for all), 18 (±2 hr), and 24 (±1 hr) hours post-dose (between Month 3 and Month 6, after subjects had been on a stabilized dose of Testosterone gel for at least 1 month)Population: PP analysis population was used which comprises data from subjects who had 24 hr PK data for testosterone, with no major protocol violations.
Measurement of total testosterone level occur after subjects have been on a stabilized dose of testosterone gel for at least one month in the period between Month 3 and Month 6. The data were presented using descriptive statistics.
Outcome measures
| Measure |
Testosterone Gel (FE 999303)
n=106 Participants
Subjects received testosterone gel with initial dose as fixed on Day 56 (23 mg, 46 mg or 69 mg) during the 000023 study. The dose could further be down titrated based on serum testosterone levels at Day 90/91 of 000023 study. Testosterone gel was applied daily in morning using an applicator, to the shoulder/upper arm in a contralateral fashion for 6 months.
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|---|---|
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Percentage of Subjects With a Serum Total Testosterone Level (Average Steady State Concentration [Cave]) Between 300 and 1050 ng/dL.
|
82.1 percentage of subjects
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SECONDARY outcome
Timeframe: At Month 6Population: ITT population was used which consists of all subjects who received at least one dose of the IMP. Of 145 treated subjects, 127 had available IIEF questionnaire results.
Data collected from the five domains of sexual functions were summarized by descriptive statistics. The domains are: 1. Erectile function (6 items, questions 1-5 and 15) (Score range: 1-30) 2. Orgasmic function (2 items, questions 9-10) (Score range: 0-10) 3. Sexual desire (2 items, questions 11-12) (Score range: 2-10) 4. Intercourse satisfaction (3 items, questions 6-8) (Score range: 0-15) 5. Overall satisfaction (2 items, questions 13-14) (Score range: 2-10) A score of 0-5 is awarded to questions 1-10 and a score of 1-5 is awarded to questions 11-15. Low score indicates severe dysfunction and a high score indicates no dysfunction in sexual function, in each domain.
Outcome measures
| Measure |
Testosterone Gel (FE 999303)
n=127 Participants
Subjects received testosterone gel with initial dose as fixed on Day 56 (23 mg, 46 mg or 69 mg) during the 000023 study. The dose could further be down titrated based on serum testosterone levels at Day 90/91 of 000023 study. Testosterone gel was applied daily in morning using an applicator, to the shoulder/upper arm in a contralateral fashion for 6 months.
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|---|---|
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Domain Scores for the International Index of Erectile Function (IIEF) Questionnaire
Erectile function domain
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19.8 units on a scale
Standard Deviation 7.9
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Domain Scores for the International Index of Erectile Function (IIEF) Questionnaire
Orgasmic function domain
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7.3 units on a scale
Standard Deviation 3.2
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Domain Scores for the International Index of Erectile Function (IIEF) Questionnaire
Sexual desire domain
|
7.0 units on a scale
Standard Deviation 1.8
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Domain Scores for the International Index of Erectile Function (IIEF) Questionnaire
Intercourse satisfaction domain
|
8.7 units on a scale
Standard Deviation 4.4
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Domain Scores for the International Index of Erectile Function (IIEF) Questionnaire
Overall satisfaction domain
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6.7 units on a scale
Standard Deviation 2.3
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SECONDARY outcome
Timeframe: At Month 6Population: ITT population was used which consists of all the subjects who received at least one dose of the IMP. Of 145 treated subjects, 127 had available ADAM questionnaire results.
In ADAM questionnaire, subjects had to respond in "yes or no" to 10 questions. A positive result (with severity and symptoms of low testosterone) on the questionnaire was defined as an affirmative answer ("yes") to questions 1 or 7, or to any 3 other questions. The data were presented using descriptive statistics.
Outcome measures
| Measure |
Testosterone Gel (FE 999303)
n=127 Participants
Subjects received testosterone gel with initial dose as fixed on Day 56 (23 mg, 46 mg or 69 mg) during the 000023 study. The dose could further be down titrated based on serum testosterone levels at Day 90/91 of 000023 study. Testosterone gel was applied daily in morning using an applicator, to the shoulder/upper arm in a contralateral fashion for 6 months.
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|---|---|
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Percentage of Subjects With a Negative Androgen Deficiency in the Aging Male (ADAM) Questionnaire
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44.1 percentage of subjects
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SECONDARY outcome
Timeframe: At Month 6Population: ITT population was used which consists of all subjects who received at least one dose of the IMP. Of 145 treated subjects, 127 had available MAF questionnaire results.
The MAF contains four sub-domains: 1. Severity (2 items, questions 1-2) (Score range: 2-20) 2. Distress (1 item, question 3) (Score range: 1-10) 3. Degree of interference in activities of daily living (11 items, questions 4-14) (Score range: 11-110) 4. Timing (2 items, questions 15-16) (Score range: 5-20) A score of 1-10 is awarded to each of the 14 questions across the 3 domains. The timing domain is categorical and was converted to 1-10 scale by multiplying each score by 2.5. Lower score in each domain indicates improvement in fatigue. To calculate GFI : Score of question 15 is converted to a 0-10 scale by multiplying each score by 2.5 and then sum scores of questions 1, 2, 3, average of 4-14, and newly scored question 15. A score of zero is assigned to question 2-16, if patient select 'no fatigue' to question 1. Question 16 is not included in GFI calculation. Range of GFI: 1 (no fatigue) to 50 (severe fatigue). The data were presented using descriptive statistics.
Outcome measures
| Measure |
Testosterone Gel (FE 999303)
n=127 Participants
Subjects received testosterone gel with initial dose as fixed on Day 56 (23 mg, 46 mg or 69 mg) during the 000023 study. The dose could further be down titrated based on serum testosterone levels at Day 90/91 of 000023 study. Testosterone gel was applied daily in morning using an applicator, to the shoulder/upper arm in a contralateral fashion for 6 months.
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|---|---|
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Domain Scores for the Multidimensional Assessments of Fatigue (MAF) Questionnaire
Severity domain
|
6.6 units on a scale
Standard Deviation 5.0
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Domain Scores for the Multidimensional Assessments of Fatigue (MAF) Questionnaire
Distress domain
|
2.8 units on a scale
Standard Deviation 2.3
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Domain Scores for the Multidimensional Assessments of Fatigue (MAF) Questionnaire
Degree of interference in daily activities
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28.3 units on a scale
Standard Deviation 19.6
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|
Domain Scores for the Multidimensional Assessments of Fatigue (MAF) Questionnaire
Timing domain
|
10.1 units on a scale
Standard Deviation 3.2
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Domain Scores for the Multidimensional Assessments of Fatigue (MAF) Questionnaire
Global fatigue index score
|
15.3 units on a scale
Standard Deviation 11.2
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SECONDARY outcome
Timeframe: At Month 6Population: ITT population was used which consists of all the subjects who received at least one dose of the IMP. Of 145 treated subjects, 127 had available SF-12 questionnaire results.
Data collected from the SF-12 questionnaire was used to assess improvement in the psychometrically-based physical component summary (PCS) and mental component summary (MCS). Both PCS and MCS contains four sub-domains: PCS: General Health (1 item), Physical Functioning (2 items), Role-Physical (2 items), Bodily Pain (1 item) MCS: Role-Emotional (2 items), Mental Health (2 items), Vitality (1 item), Social Functioning (1 item) The scale scores are calculated by summing responses across scale items and then transforming these raw scores to a 0-100 scale. Computerized scoring algorithms are used to produce norm-based scores for each scale (mean of 50 and SD of 10) as well as the PCS and MCS summary scores. A zero score indicates the lowest level of health measured by the scales and 100 indicates the highest level of health. The data were presented using descriptive statistics.
Outcome measures
| Measure |
Testosterone Gel (FE 999303)
n=127 Participants
Subjects received testosterone gel with initial dose as fixed on Day 56 (23 mg, 46 mg or 69 mg) during the 000023 study. The dose could further be down titrated based on serum testosterone levels at Day 90/91 of 000023 study. Testosterone gel was applied daily in morning using an applicator, to the shoulder/upper arm in a contralateral fashion for 6 months.
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|---|---|
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Domain Scores for the Short Form-12 (SF-12) Questionnaire
General health domain
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54.3 units on a scale
Standard Deviation 8.2
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Domain Scores for the Short Form-12 (SF-12) Questionnaire
Physical functioning domain
|
51.7 units on a scale
Standard Deviation 8.6
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Domain Scores for the Short Form-12 (SF-12) Questionnaire
Role-physical domain
|
50.2 units on a scale
Standard Deviation 8.4
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|
Domain Scores for the Short Form-12 (SF-12) Questionnaire
Bodily pain domain
|
51.1 units on a scale
Standard Deviation 8.9
|
|
Domain Scores for the Short Form-12 (SF-12) Questionnaire
Physical component summary
|
51.9 units on a scale
Standard Deviation 8.1
|
|
Domain Scores for the Short Form-12 (SF-12) Questionnaire
Role-emotional domain
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48.8 units on a scale
Standard Deviation 9.1
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Domain Scores for the Short Form-12 (SF-12) Questionnaire
Mental health domain
|
52.7 units on a scale
Standard Deviation 8.0
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Domain Scores for the Short Form-12 (SF-12) Questionnaire
Vitality domain
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53.1 units on a scale
Standard Deviation 9.1
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Domain Scores for the Short Form-12 (SF-12) Questionnaire
Social functioning domain
|
51.2 units on a scale
Standard Deviation 8.8
|
|
Domain Scores for the Short Form-12 (SF-12) Questionnaire
Mental component summary
|
51.2 units on a scale
Standard Deviation 8.3
|
SECONDARY outcome
Timeframe: At Month 3Population: PP analysis population was used which comprises data from subjects who had 24 hr PK data for testosterone, with no major protocol violations.
The data were presented using descriptive statistics.
Outcome measures
| Measure |
Testosterone Gel (FE 999303)
n=106 Participants
Subjects received testosterone gel with initial dose as fixed on Day 56 (23 mg, 46 mg or 69 mg) during the 000023 study. The dose could further be down titrated based on serum testosterone levels at Day 90/91 of 000023 study. Testosterone gel was applied daily in morning using an applicator, to the shoulder/upper arm in a contralateral fashion for 6 months.
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|---|---|
|
Percentage of Subjects With a Serum Total Testosterone Level of 1500-1799, 1800-2499, or Above 2500 ng/dL
Total testosterone level between 1500-1799 ng/dL
|
6.6 percentage of subjects
|
|
Percentage of Subjects With a Serum Total Testosterone Level of 1500-1799, 1800-2499, or Above 2500 ng/dL
Total testosterone level between 1800-2499 ng/dL
|
5.7 percentage of subjects
|
|
Percentage of Subjects With a Serum Total Testosterone Level of 1500-1799, 1800-2499, or Above 2500 ng/dL
Total testosterone level above 2500 ng/dL
|
2.8 percentage of subjects
|
SECONDARY outcome
Timeframe: At Month 6Population: PP analysis population was used which comprises data from subjects who had 24 hr PK data for testosterone, with no major protocol violations.
The data were presented using descriptive statistics.
Outcome measures
| Measure |
Testosterone Gel (FE 999303)
n=105 Participants
Subjects received testosterone gel with initial dose as fixed on Day 56 (23 mg, 46 mg or 69 mg) during the 000023 study. The dose could further be down titrated based on serum testosterone levels at Day 90/91 of 000023 study. Testosterone gel was applied daily in morning using an applicator, to the shoulder/upper arm in a contralateral fashion for 6 months.
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|---|---|
|
Percentage of Subjects With a Serum Total Testosterone Level of 1500-1799, 1800-2499, or Above 2500 ng/dL
Total testosterone level between 1500-1799 ng/dL
|
6.7 percentage of subjects
|
|
Percentage of Subjects With a Serum Total Testosterone Level of 1500-1799, 1800-2499, or Above 2500 ng/dL
Total testosterone level between 1800-2499 ng/dL
|
2.9 percentage of subjects
|
|
Percentage of Subjects With a Serum Total Testosterone Level of 1500-1799, 1800-2499, or Above 2500 ng/dL
Total testosterone level above 2500 ng/dL
|
1.9 percentage of subjects
|
SECONDARY outcome
Timeframe: Samples were collected at pre-dose; 2, 4, 6, 8, 10, 12 (±15 min for all), 18 (±2 hr), and 24 (±1 hr) hours post-dose (between Month 3 and Month 6, after subjects had been on a stabilized dose of Testosterone gel for at least 1 month)Population: PP analysis population was used which comprises data from subjects who had 24 hr PK data for testosterone, with no major protocol violations.
Measurement of total testosterone and DHT levels occur after subjects have been on a stabilized dose of Testosterone Gel for at least one month in the period between Month 3 and Month 6. The data were presented using descriptive statistics.
Outcome measures
| Measure |
Testosterone Gel (FE 999303)
n=106 Participants
Subjects received testosterone gel with initial dose as fixed on Day 56 (23 mg, 46 mg or 69 mg) during the 000023 study. The dose could further be down titrated based on serum testosterone levels at Day 90/91 of 000023 study. Testosterone gel was applied daily in morning using an applicator, to the shoulder/upper arm in a contralateral fashion for 6 months.
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|---|---|
|
Area Under the Concentration-time Curve (AUCτ) for Total Testosterone and Dihydrotestosterone
Total testosterone at 23 mg
|
7732 ng*hr/dL
Standard Deviation 1874
|
|
Area Under the Concentration-time Curve (AUCτ) for Total Testosterone and Dihydrotestosterone
Total testosterone at 46 mg
|
10583 ng*hr/dL
Standard Deviation 3863
|
|
Area Under the Concentration-time Curve (AUCτ) for Total Testosterone and Dihydrotestosterone
Total testosterone at 69 mg
|
10842 ng*hr/dL
Standard Deviation 3927
|
|
Area Under the Concentration-time Curve (AUCτ) for Total Testosterone and Dihydrotestosterone
Total testosterone all doses
|
10451 ng*hr/dL
Standard Deviation 3836
|
|
Area Under the Concentration-time Curve (AUCτ) for Total Testosterone and Dihydrotestosterone
Dihydrotestosterone at 23 mg
|
1361 ng*hr/dL
Standard Deviation 233
|
|
Area Under the Concentration-time Curve (AUCτ) for Total Testosterone and Dihydrotestosterone
Dihydrotestosterone at 46 mg
|
1675 ng*hr/dL
Standard Deviation 944
|
|
Area Under the Concentration-time Curve (AUCτ) for Total Testosterone and Dihydrotestosterone
Dihydrotestosterone at 69 mg
|
1751 ng*hr/dL
Standard Deviation 801
|
|
Area Under the Concentration-time Curve (AUCτ) for Total Testosterone and Dihydrotestosterone
Dihydrotestosterone all doses
|
1685 ng*hr/dL
Standard Deviation 827
|
SECONDARY outcome
Timeframe: Samples were collected at pre-dose; 2, 4, 6, 8, 10, 12 (±15 min for all), 18 (±2 hr), and 24 (±1 hr) hours post-dose (between Month 3 and Month 6, after subjects had been on a stabilized dose of Testosterone gel for at least 1 month)Population: PP analysis population was used which comprises data from subjects who had 24 hr PK data for testosterone, with no major protocol violations.
Measurement of total testosterone and DHT levels occur after subjects have been on a stabilized dose of Testosterone Gel for at least one month in the period between Month 3 and Month 6. The data were presented using descriptive statistics.
Outcome measures
| Measure |
Testosterone Gel (FE 999303)
n=106 Participants
Subjects received testosterone gel with initial dose as fixed on Day 56 (23 mg, 46 mg or 69 mg) during the 000023 study. The dose could further be down titrated based on serum testosterone levels at Day 90/91 of 000023 study. Testosterone gel was applied daily in morning using an applicator, to the shoulder/upper arm in a contralateral fashion for 6 months.
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|---|---|
|
Time at Which the Maximum Concentration (Tmax) Occurs for Total Testosterone and Dihydrotestosterone
Total testosterone at 23 mg
|
3.09 hour
Interval 1.75 to 18.5
|
|
Time at Which the Maximum Concentration (Tmax) Occurs for Total Testosterone and Dihydrotestosterone
Total testosterone at 46 mg
|
2.11 hour
Interval 0.0 to 24.1
|
|
Time at Which the Maximum Concentration (Tmax) Occurs for Total Testosterone and Dihydrotestosterone
Total testosterone at 69 mg
|
3.97 hour
Interval 1.85 to 25.0
|
|
Time at Which the Maximum Concentration (Tmax) Occurs for Total Testosterone and Dihydrotestosterone
Total testosterone all doses
|
3.88 hour
Interval 0.0 to 25.0
|
|
Time at Which the Maximum Concentration (Tmax) Occurs for Total Testosterone and Dihydrotestosterone
Dihydrotestosterone at 23 mg
|
3.96 hour
Interval 0.0 to 24.9
|
|
Time at Which the Maximum Concentration (Tmax) Occurs for Total Testosterone and Dihydrotestosterone
Dihydrotestosterone at 46 mg
|
4.00 hour
Interval 0.0 to 24.1
|
|
Time at Which the Maximum Concentration (Tmax) Occurs for Total Testosterone and Dihydrotestosterone
Dihydrotestosterone at 69 mg
|
4.00 hour
Interval 0.0 to 25.0
|
|
Time at Which the Maximum Concentration (Tmax) Occurs for Total Testosterone and Dihydrotestosterone
Dihydrotestosterone all doses
|
4.00 hour
Interval 0.0 to 25.0
|
SECONDARY outcome
Timeframe: Samples were collected at pre-dose; 2, 4, 6, 8, 10, 12 (±15 min for all), 18 (±2 hr), and 24 (±1 hr) hours post-dose (between Month 3 and Month 6, after subjects had been on a stabilized dose of Testosterone gel for at least 1 month)Population: PP analysis population was used which comprises data from subjects who had 24 hr PK data for testosterone, with no major protocol violations.
Measurement of total testosterone and DHT levels occur after subjects have been on a stabilized dose of Testosterone Gel for at least one month in the period between Month 3 and Month 6. The data were presented using descriptive statistics.
Outcome measures
| Measure |
Testosterone Gel (FE 999303)
n=106 Participants
Subjects received testosterone gel with initial dose as fixed on Day 56 (23 mg, 46 mg or 69 mg) during the 000023 study. The dose could further be down titrated based on serum testosterone levels at Day 90/91 of 000023 study. Testosterone gel was applied daily in morning using an applicator, to the shoulder/upper arm in a contralateral fashion for 6 months.
|
|---|---|
|
Maximum Concentration Observed (Cmax) for Total Testosterone and Dihydrotestosterone
Total testosterone at 23 mg
|
747 ng/dL
Standard Deviation 236
|
|
Maximum Concentration Observed (Cmax) for Total Testosterone and Dihydrotestosterone
Total testosterone at 46 mg
|
1085 ng/dL
Standard Deviation 742
|
|
Maximum Concentration Observed (Cmax) for Total Testosterone and Dihydrotestosterone
Total testosterone at 69 mg
|
999 ng/dL
Standard Deviation 525
|
|
Maximum Concentration Observed (Cmax) for Total Testosterone and Dihydrotestosterone
Total testosterone all doses
|
1008 ng/dL
Standard Deviation 602
|
|
Maximum Concentration Observed (Cmax) for Total Testosterone and Dihydrotestosterone
Dihydrotestosterone at 23 mg
|
88.7 ng/dL
Standard Deviation 21.0
|
|
Maximum Concentration Observed (Cmax) for Total Testosterone and Dihydrotestosterone
Dihydrotestosterone at 46 mg
|
111 ng/dL
Standard Deviation 56
|
|
Maximum Concentration Observed (Cmax) for Total Testosterone and Dihydrotestosterone
Dihydrotestosterone at 69 mg
|
114 ng/dL
Standard Deviation 62
|
|
Maximum Concentration Observed (Cmax) for Total Testosterone and Dihydrotestosterone
Dihydrotestosterone all doses
|
111 ng/dL
Standard Deviation 57
|
SECONDARY outcome
Timeframe: Samples were collected at pre-dose; 2, 4, 6, 8, 10, 12 (±15 min for all), 18 (±2 hr), and 24 (±1 hr) hours post-dose (between Month 3 and Month 6, after subjects had been on a stabilized dose of Testosterone gel for at least 1 month)Population: PP analysis population was used which comprises data from subjects who had 24 hr PK data for testosterone, with no major protocol violations.
Measurement of total testosterone and DHT levels occur after subjects have been on a stabilized dose of Testosterone Gel for at least one month in the period between Month 3 and Month 6. The data were presented using descriptive statistics.
Outcome measures
| Measure |
Testosterone Gel (FE 999303)
n=106 Participants
Subjects received testosterone gel with initial dose as fixed on Day 56 (23 mg, 46 mg or 69 mg) during the 000023 study. The dose could further be down titrated based on serum testosterone levels at Day 90/91 of 000023 study. Testosterone gel was applied daily in morning using an applicator, to the shoulder/upper arm in a contralateral fashion for 6 months.
|
|---|---|
|
Minimum Concentration Observed (Cmin) for Total Testosterone and Dihydrotestosterone
Total testosterone at 23 mg
|
162 ng/dL
Standard Deviation 65
|
|
Minimum Concentration Observed (Cmin) for Total Testosterone and Dihydrotestosterone
Total testosterone at 46 mg
|
201 ng/dL
Standard Deviation 98
|
|
Minimum Concentration Observed (Cmin) for Total Testosterone and Dihydrotestosterone
Total testosterone at 69 mg
|
219 ng/dL
Standard Deviation 106
|
|
Minimum Concentration Observed (Cmin) for Total Testosterone and Dihydrotestosterone
Total testosterone all doses
|
207 ng/dL
Standard Deviation 101
|
|
Minimum Concentration Observed (Cmin) for Total Testosterone and Dihydrotestosterone
Dihydrotestosterone at 23 mg
|
34.8 ng/dL
Standard Deviation 7.5
|
|
Minimum Concentration Observed (Cmin) for Total Testosterone and Dihydrotestosterone
Dihydrotestosterone at 46 mg
|
43.5 ng/dL
Standard Deviation 32.8
|
|
Minimum Concentration Observed (Cmin) for Total Testosterone and Dihydrotestosterone
Dihydrotestosterone at 69 mg
|
44.8 ng/dL
Standard Deviation 26.9
|
|
Minimum Concentration Observed (Cmin) for Total Testosterone and Dihydrotestosterone
Dihydrotestosterone all doses
|
43.4 ng/dL
Standard Deviation 28.1
|
SECONDARY outcome
Timeframe: Samples were collected at pre-dose; 2, 4, 6, 8, 10, 12 (±15 min for all), 18 (±2 hr), and 24 (±1 hr) hours post-dose (between Month 3 and Month 6, after subjects had been on a stabilized dose of Testosterone gel for at least 1 month)Population: PP analysis population was used which comprises data from subjects who had 24 hr PK data for testosterone, with no major protocol violations.
Measurement of total testosterone and DHT levels occur after subjects have been on a stabilized dose of Testosterone Gel for at least one month in the period between Month 3 and Month 6. The data were presented using descriptive statistics.
Outcome measures
| Measure |
Testosterone Gel (FE 999303)
n=106 Participants
Subjects received testosterone gel with initial dose as fixed on Day 56 (23 mg, 46 mg or 69 mg) during the 000023 study. The dose could further be down titrated based on serum testosterone levels at Day 90/91 of 000023 study. Testosterone gel was applied daily in morning using an applicator, to the shoulder/upper arm in a contralateral fashion for 6 months.
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|---|---|
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Average Concentration (Cave) for Total Testosterone and Dihydrotestosterone
Total testosterone at 23 mg
|
322 ng/dL
Standard Deviation 78
|
|
Average Concentration (Cave) for Total Testosterone and Dihydrotestosterone
Total testosterone at 46 mg
|
438 ng/dL
Standard Deviation 161
|
|
Average Concentration (Cave) for Total Testosterone and Dihydrotestosterone
Total testosterone at 69 mg
|
449 ng/dL
Standard Deviation 165
|
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Average Concentration (Cave) for Total Testosterone and Dihydrotestosterone
Total testosterone all doses
|
433 ng/dL
Standard Deviation 160
|
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Average Concentration (Cave) for Total Testosterone and Dihydrotestosterone
Dihydrotestosterone at 23 mg
|
56.6 ng/dL
Standard Deviation 9.6
|
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Average Concentration (Cave) for Total Testosterone and Dihydrotestosterone
Dihydrotestosterone at 46 mg
|
69.3 ng/dL
Standard Deviation 39.5
|
|
Average Concentration (Cave) for Total Testosterone and Dihydrotestosterone
Dihydrotestosterone at 69 mg
|
72.4 ng/dL
Standard Deviation 33.4
|
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Average Concentration (Cave) for Total Testosterone and Dihydrotestosterone
Dihydrotestosterone all doses
|
69.7 ng/dL
Standard Deviation 34.5
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Adverse Events
Testosterone Gel (FE 999303)
Serious events: 1 serious events
Other events: 28 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Testosterone Gel (FE 999303)
n=145 participants at risk
Subjects received testosterone gel with initial dose as fixed on Day 56 during the 000023 study. The dose was further down titrated based on serum testosterone levels. Testosterone gel was applied using an applicator, to the shoulder/upper arm in a contralateral fashion.
|
|---|---|
|
Metabolism and nutrition disorders
Dehydration
|
0.69%
1/145 • Number of events 1 • Overall study period (From Day 1 to Month 6)
The treatment-emergent adverse event (TEAE), defined as any adverse event (AE) occurring after start of IMP administration and within the time of residual drug effect (5 days of the last dosing), or a pretreatment AE or pre-existing medical condition that worsens in intensity after treatment with the IMP and within the time of residual drug effect, were presented.
|
|
Infections and infestations
Diverticulitis
|
0.69%
1/145 • Number of events 2 • Overall study period (From Day 1 to Month 6)
The treatment-emergent adverse event (TEAE), defined as any adverse event (AE) occurring after start of IMP administration and within the time of residual drug effect (5 days of the last dosing), or a pretreatment AE or pre-existing medical condition that worsens in intensity after treatment with the IMP and within the time of residual drug effect, were presented.
|
Other adverse events
| Measure |
Testosterone Gel (FE 999303)
n=145 participants at risk
Subjects received testosterone gel with initial dose as fixed on Day 56 during the 000023 study. The dose was further down titrated based on serum testosterone levels. Testosterone gel was applied using an applicator, to the shoulder/upper arm in a contralateral fashion.
|
|---|---|
|
Cardiac disorders
Ventricular extrasystoles
|
0.69%
1/145 • Overall study period (From Day 1 to Month 6)
The treatment-emergent adverse event (TEAE), defined as any adverse event (AE) occurring after start of IMP administration and within the time of residual drug effect (5 days of the last dosing), or a pretreatment AE or pre-existing medical condition that worsens in intensity after treatment with the IMP and within the time of residual drug effect, were presented.
|
|
Gastrointestinal disorders
Dyspepsia
|
0.69%
1/145 • Overall study period (From Day 1 to Month 6)
The treatment-emergent adverse event (TEAE), defined as any adverse event (AE) occurring after start of IMP administration and within the time of residual drug effect (5 days of the last dosing), or a pretreatment AE or pre-existing medical condition that worsens in intensity after treatment with the IMP and within the time of residual drug effect, were presented.
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
0.69%
1/145 • Overall study period (From Day 1 to Month 6)
The treatment-emergent adverse event (TEAE), defined as any adverse event (AE) occurring after start of IMP administration and within the time of residual drug effect (5 days of the last dosing), or a pretreatment AE or pre-existing medical condition that worsens in intensity after treatment with the IMP and within the time of residual drug effect, were presented.
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
0.69%
1/145 • Overall study period (From Day 1 to Month 6)
The treatment-emergent adverse event (TEAE), defined as any adverse event (AE) occurring after start of IMP administration and within the time of residual drug effect (5 days of the last dosing), or a pretreatment AE or pre-existing medical condition that worsens in intensity after treatment with the IMP and within the time of residual drug effect, were presented.
|
|
Gastrointestinal disorders
Periodontal disease
|
0.69%
1/145 • Overall study period (From Day 1 to Month 6)
The treatment-emergent adverse event (TEAE), defined as any adverse event (AE) occurring after start of IMP administration and within the time of residual drug effect (5 days of the last dosing), or a pretreatment AE or pre-existing medical condition that worsens in intensity after treatment with the IMP and within the time of residual drug effect, were presented.
|
|
Infections and infestations
Bronchitis
|
0.69%
1/145 • Overall study period (From Day 1 to Month 6)
The treatment-emergent adverse event (TEAE), defined as any adverse event (AE) occurring after start of IMP administration and within the time of residual drug effect (5 days of the last dosing), or a pretreatment AE or pre-existing medical condition that worsens in intensity after treatment with the IMP and within the time of residual drug effect, were presented.
|
|
Infections and infestations
Orchitis
|
0.69%
1/145 • Overall study period (From Day 1 to Month 6)
The treatment-emergent adverse event (TEAE), defined as any adverse event (AE) occurring after start of IMP administration and within the time of residual drug effect (5 days of the last dosing), or a pretreatment AE or pre-existing medical condition that worsens in intensity after treatment with the IMP and within the time of residual drug effect, were presented.
|
|
Infections and infestations
Pneumonia
|
0.69%
1/145 • Overall study period (From Day 1 to Month 6)
The treatment-emergent adverse event (TEAE), defined as any adverse event (AE) occurring after start of IMP administration and within the time of residual drug effect (5 days of the last dosing), or a pretreatment AE or pre-existing medical condition that worsens in intensity after treatment with the IMP and within the time of residual drug effect, were presented.
|
|
Injury, poisoning and procedural complications
Contusion
|
0.69%
1/145 • Overall study period (From Day 1 to Month 6)
The treatment-emergent adverse event (TEAE), defined as any adverse event (AE) occurring after start of IMP administration and within the time of residual drug effect (5 days of the last dosing), or a pretreatment AE or pre-existing medical condition that worsens in intensity after treatment with the IMP and within the time of residual drug effect, were presented.
|
|
Injury, poisoning and procedural complications
Meniscus lesion
|
0.69%
1/145 • Overall study period (From Day 1 to Month 6)
The treatment-emergent adverse event (TEAE), defined as any adverse event (AE) occurring after start of IMP administration and within the time of residual drug effect (5 days of the last dosing), or a pretreatment AE or pre-existing medical condition that worsens in intensity after treatment with the IMP and within the time of residual drug effect, were presented.
|
|
Injury, poisoning and procedural complications
Procedural pain
|
0.69%
1/145 • Overall study period (From Day 1 to Month 6)
The treatment-emergent adverse event (TEAE), defined as any adverse event (AE) occurring after start of IMP administration and within the time of residual drug effect (5 days of the last dosing), or a pretreatment AE or pre-existing medical condition that worsens in intensity after treatment with the IMP and within the time of residual drug effect, were presented.
|
|
Injury, poisoning and procedural complications
Tendon rupture
|
0.69%
1/145 • Overall study period (From Day 1 to Month 6)
The treatment-emergent adverse event (TEAE), defined as any adverse event (AE) occurring after start of IMP administration and within the time of residual drug effect (5 days of the last dosing), or a pretreatment AE or pre-existing medical condition that worsens in intensity after treatment with the IMP and within the time of residual drug effect, were presented.
|
|
Injury, poisoning and procedural complications
Tooth fracture
|
0.69%
1/145 • Overall study period (From Day 1 to Month 6)
The treatment-emergent adverse event (TEAE), defined as any adverse event (AE) occurring after start of IMP administration and within the time of residual drug effect (5 days of the last dosing), or a pretreatment AE or pre-existing medical condition that worsens in intensity after treatment with the IMP and within the time of residual drug effect, were presented.
|
|
Investigations
Alanine aminotransferase abnormal
|
0.69%
1/145 • Overall study period (From Day 1 to Month 6)
The treatment-emergent adverse event (TEAE), defined as any adverse event (AE) occurring after start of IMP administration and within the time of residual drug effect (5 days of the last dosing), or a pretreatment AE or pre-existing medical condition that worsens in intensity after treatment with the IMP and within the time of residual drug effect, were presented.
|
|
Investigations
Aspartate aminotransferase abnormal
|
0.69%
1/145 • Overall study period (From Day 1 to Month 6)
The treatment-emergent adverse event (TEAE), defined as any adverse event (AE) occurring after start of IMP administration and within the time of residual drug effect (5 days of the last dosing), or a pretreatment AE or pre-existing medical condition that worsens in intensity after treatment with the IMP and within the time of residual drug effect, were presented.
|
|
Investigations
Haematocrit abnormal
|
0.69%
1/145 • Overall study period (From Day 1 to Month 6)
The treatment-emergent adverse event (TEAE), defined as any adverse event (AE) occurring after start of IMP administration and within the time of residual drug effect (5 days of the last dosing), or a pretreatment AE or pre-existing medical condition that worsens in intensity after treatment with the IMP and within the time of residual drug effect, were presented.
|
|
Investigations
Haematocrit increased
|
2.8%
4/145 • Overall study period (From Day 1 to Month 6)
The treatment-emergent adverse event (TEAE), defined as any adverse event (AE) occurring after start of IMP administration and within the time of residual drug effect (5 days of the last dosing), or a pretreatment AE or pre-existing medical condition that worsens in intensity after treatment with the IMP and within the time of residual drug effect, were presented.
|
|
Investigations
Haemoglobin abnormal
|
0.69%
1/145 • Overall study period (From Day 1 to Month 6)
The treatment-emergent adverse event (TEAE), defined as any adverse event (AE) occurring after start of IMP administration and within the time of residual drug effect (5 days of the last dosing), or a pretreatment AE or pre-existing medical condition that worsens in intensity after treatment with the IMP and within the time of residual drug effect, were presented.
|
|
Investigations
Haemoglobin increased
|
1.4%
2/145 • Overall study period (From Day 1 to Month 6)
The treatment-emergent adverse event (TEAE), defined as any adverse event (AE) occurring after start of IMP administration and within the time of residual drug effect (5 days of the last dosing), or a pretreatment AE or pre-existing medical condition that worsens in intensity after treatment with the IMP and within the time of residual drug effect, were presented.
|
|
Investigations
Red blood cell count abnormal
|
0.69%
1/145 • Overall study period (From Day 1 to Month 6)
The treatment-emergent adverse event (TEAE), defined as any adverse event (AE) occurring after start of IMP administration and within the time of residual drug effect (5 days of the last dosing), or a pretreatment AE or pre-existing medical condition that worsens in intensity after treatment with the IMP and within the time of residual drug effect, were presented.
|
|
Metabolism and nutrition disorders
Hyperlipidaemia
|
0.69%
1/145 • Overall study period (From Day 1 to Month 6)
The treatment-emergent adverse event (TEAE), defined as any adverse event (AE) occurring after start of IMP administration and within the time of residual drug effect (5 days of the last dosing), or a pretreatment AE or pre-existing medical condition that worsens in intensity after treatment with the IMP and within the time of residual drug effect, were presented.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.69%
1/145 • Overall study period (From Day 1 to Month 6)
The treatment-emergent adverse event (TEAE), defined as any adverse event (AE) occurring after start of IMP administration and within the time of residual drug effect (5 days of the last dosing), or a pretreatment AE or pre-existing medical condition that worsens in intensity after treatment with the IMP and within the time of residual drug effect, were presented.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.69%
1/145 • Overall study period (From Day 1 to Month 6)
The treatment-emergent adverse event (TEAE), defined as any adverse event (AE) occurring after start of IMP administration and within the time of residual drug effect (5 days of the last dosing), or a pretreatment AE or pre-existing medical condition that worsens in intensity after treatment with the IMP and within the time of residual drug effect, were presented.
|
|
Musculoskeletal and connective tissue disorders
Osteopenia
|
0.69%
1/145 • Overall study period (From Day 1 to Month 6)
The treatment-emergent adverse event (TEAE), defined as any adverse event (AE) occurring after start of IMP administration and within the time of residual drug effect (5 days of the last dosing), or a pretreatment AE or pre-existing medical condition that worsens in intensity after treatment with the IMP and within the time of residual drug effect, were presented.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Thyroid neoplasm
|
0.69%
1/145 • Overall study period (From Day 1 to Month 6)
The treatment-emergent adverse event (TEAE), defined as any adverse event (AE) occurring after start of IMP administration and within the time of residual drug effect (5 days of the last dosing), or a pretreatment AE or pre-existing medical condition that worsens in intensity after treatment with the IMP and within the time of residual drug effect, were presented.
|
|
Nervous system disorders
Presyncope
|
0.69%
1/145 • Overall study period (From Day 1 to Month 6)
The treatment-emergent adverse event (TEAE), defined as any adverse event (AE) occurring after start of IMP administration and within the time of residual drug effect (5 days of the last dosing), or a pretreatment AE or pre-existing medical condition that worsens in intensity after treatment with the IMP and within the time of residual drug effect, were presented.
|
|
Psychiatric disorders
Libido increased
|
0.69%
1/145 • Overall study period (From Day 1 to Month 6)
The treatment-emergent adverse event (TEAE), defined as any adverse event (AE) occurring after start of IMP administration and within the time of residual drug effect (5 days of the last dosing), or a pretreatment AE or pre-existing medical condition that worsens in intensity after treatment with the IMP and within the time of residual drug effect, were presented.
|
|
Renal and urinary disorders
Hypertonic bladder
|
1.4%
2/145 • Overall study period (From Day 1 to Month 6)
The treatment-emergent adverse event (TEAE), defined as any adverse event (AE) occurring after start of IMP administration and within the time of residual drug effect (5 days of the last dosing), or a pretreatment AE or pre-existing medical condition that worsens in intensity after treatment with the IMP and within the time of residual drug effect, were presented.
|
|
Reproductive system and breast disorders
Epididymitis
|
0.69%
1/145 • Overall study period (From Day 1 to Month 6)
The treatment-emergent adverse event (TEAE), defined as any adverse event (AE) occurring after start of IMP administration and within the time of residual drug effect (5 days of the last dosing), or a pretreatment AE or pre-existing medical condition that worsens in intensity after treatment with the IMP and within the time of residual drug effect, were presented.
|
|
Reproductive system and breast disorders
Testicular pain
|
0.69%
1/145 • Overall study period (From Day 1 to Month 6)
The treatment-emergent adverse event (TEAE), defined as any adverse event (AE) occurring after start of IMP administration and within the time of residual drug effect (5 days of the last dosing), or a pretreatment AE or pre-existing medical condition that worsens in intensity after treatment with the IMP and within the time of residual drug effect, were presented.
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
0.69%
1/145 • Overall study period (From Day 1 to Month 6)
The treatment-emergent adverse event (TEAE), defined as any adverse event (AE) occurring after start of IMP administration and within the time of residual drug effect (5 days of the last dosing), or a pretreatment AE or pre-existing medical condition that worsens in intensity after treatment with the IMP and within the time of residual drug effect, were presented.
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
0.69%
1/145 • Overall study period (From Day 1 to Month 6)
The treatment-emergent adverse event (TEAE), defined as any adverse event (AE) occurring after start of IMP administration and within the time of residual drug effect (5 days of the last dosing), or a pretreatment AE or pre-existing medical condition that worsens in intensity after treatment with the IMP and within the time of residual drug effect, were presented.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.69%
1/145 • Overall study period (From Day 1 to Month 6)
The treatment-emergent adverse event (TEAE), defined as any adverse event (AE) occurring after start of IMP administration and within the time of residual drug effect (5 days of the last dosing), or a pretreatment AE or pre-existing medical condition that worsens in intensity after treatment with the IMP and within the time of residual drug effect, were presented.
|
|
Respiratory, thoracic and mediastinal disorders
Paranasal sinus hypersecretion
|
0.69%
1/145 • Overall study period (From Day 1 to Month 6)
The treatment-emergent adverse event (TEAE), defined as any adverse event (AE) occurring after start of IMP administration and within the time of residual drug effect (5 days of the last dosing), or a pretreatment AE or pre-existing medical condition that worsens in intensity after treatment with the IMP and within the time of residual drug effect, were presented.
|
|
Skin and subcutaneous tissue disorders
Lichen planus
|
0.69%
1/145 • Overall study period (From Day 1 to Month 6)
The treatment-emergent adverse event (TEAE), defined as any adverse event (AE) occurring after start of IMP administration and within the time of residual drug effect (5 days of the last dosing), or a pretreatment AE or pre-existing medical condition that worsens in intensity after treatment with the IMP and within the time of residual drug effect, were presented.
|
|
Skin and subcutaneous tissue disorders
Urticaria
|
0.69%
1/145 • Overall study period (From Day 1 to Month 6)
The treatment-emergent adverse event (TEAE), defined as any adverse event (AE) occurring after start of IMP administration and within the time of residual drug effect (5 days of the last dosing), or a pretreatment AE or pre-existing medical condition that worsens in intensity after treatment with the IMP and within the time of residual drug effect, were presented.
|
|
Vascular disorders
Flushing
|
0.69%
1/145 • Overall study period (From Day 1 to Month 6)
The treatment-emergent adverse event (TEAE), defined as any adverse event (AE) occurring after start of IMP administration and within the time of residual drug effect (5 days of the last dosing), or a pretreatment AE or pre-existing medical condition that worsens in intensity after treatment with the IMP and within the time of residual drug effect, were presented.
|
|
Vascular disorders
Hypertension
|
1.4%
2/145 • Overall study period (From Day 1 to Month 6)
The treatment-emergent adverse event (TEAE), defined as any adverse event (AE) occurring after start of IMP administration and within the time of residual drug effect (5 days of the last dosing), or a pretreatment AE or pre-existing medical condition that worsens in intensity after treatment with the IMP and within the time of residual drug effect, were presented.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The only disclosure restriction on the PI is that the sponsor can review the draft manuscript prior to publication and can request delay of publication where any contents are deemed patentable by the sponsor or confidential to the sponsor. Comments will be given within four weeks from receipt of the draft manuscript. Additional time may be required to allow Ferring to seek patent protection of the invention.
- Publication restrictions are in place
Restriction type: OTHER