A Multicenter Extension Trial to Evaluate the Safety of Testosterone Gel

Study Overview
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Brief Summary
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This is a multicenter extension trial in adult hypogonadal males. The purpose of this study is to evaluate the safety of testosterone gel delivered using an applicator over an extended period of time.

Official Title
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A Multicenter Extension Trial to Evaluate the Safety of FE 999303 (Testosterone Gel) in Adult Hypogonadal Males

Conditions
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Adult Male Hypogonadism

Intervention / Treatment
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* Drug: Testosterone Gel (FE 999093)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Completion of the Phase 3 protocol (NCT01665599) Exclusion Criteria: Use of another investigational product Use of any medications that could be considered anabolic or interfere with androgen metabolism Use of estrogens, gonadotropin releasing hormone agonists/antagonists, antiandrogens, or human growth hormone Use of another testosterone product Chronic use of any drug of abuse

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Testosterone gel (FE 999093)<br>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. | Drug: Testosterone Gel (FE 999093)<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects With a Serum Total Testosterone Level - Maximum Observed Concentration (Cmax) of 1500-1799, 1800-2499, or Above 2500 ng/dL | 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. | 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) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects With a Serum Total Testosterone Level (Average Steady State Concentration [Cave]) Between 300 and 1050 ng/dL. | 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. | 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) | 
| Domain Scores for the International Index of Erectile Function (IIEF) Questionnaire | Data collected from the five domains of sexual functions were summarized by descriptive statistics. The domains are: Erectile function (6 items, questions 1-5 and 15) (Score range: 1-30) Orgasmic function (2 items, questions 9-10) (Score range: 0-10) Sexual desire (2 items, questions 11-12) (Score range: 2-10) Intercourse satisfaction (3 items, questions 6-8) (Score range: 0-15) 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. | At Month 6 | 
| Percentage of Subjects With a Negative Androgen Deficiency in the Aging Male (ADAM) Questionnaire | 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. | At Month 6 | 
| Domain Scores for the Multidimensional Assessments of Fatigue (MAF) Questionnaire | The MAF contains four sub-domains: Severity (2 items, questions 1-2) (Score range: 2-20) Distress (1 item, question 3) (Score range: 1-10) Degree of interference in activities of daily living (11 items, questions 4-14) (Score range: 11-110) 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. | At Month 6 | 
| Domain Scores for the Short Form-12 (SF-12) Questionnaire | 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. | At Month 6 | 
| Percentage of Subjects With a Serum Total Testosterone Level of 1500-1799, 1800-2499, or Above 2500 ng/dL | The data were presented using descriptive statistics. | At Month 3 | 
| Percentage of Subjects With a Serum Total Testosterone Level of 1500-1799, 1800-2499, or Above 2500 ng/dL | The data were presented using descriptive statistics. | At Month 6 | 
| Area Under the Concentration-time Curve (AUCτ) for Total Testosterone and Dihydrotestosterone | 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. | 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) | 
| Time at Which the Maximum Concentration (Tmax) Occurs for Total Testosterone and Dihydrotestosterone | 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. | 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) | 
| Maximum Concentration Observed (Cmax) for Total Testosterone and Dihydrotestosterone | 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. | 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) | 
| Minimum Concentration Observed (Cmin) for Total Testosterone and Dihydrotestosterone | 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. | 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) | 
| Average Concentration (Cave) for Total Testosterone and Dihydrotestosterone | 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. | 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) |