A Clinical Trial to Evaluate the Efficacy and Safety of Testosterone Gel

Study Overview
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Brief Summary
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This is a Phase 3 clinical trial in adult hypogonadal males with baseline serum testosterone concentrations <300 ng/dL. The purpose of this study is to evaluate the safety and efficacy of testosterone gel (2%) delivered using an applicator.

Official Title
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A Phase 3, Open-label, Non-randomized, Clinical Trial to Evaluate the Efficacy and 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 999303)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males between 18-75 years of age Two screening serum testosterone values less than 300 ng/dL One or more symptoms of testosterone deficiency Exclusion Criteria: Previous use of the investigational product Use of any investigational product within 30 days prior to screening and during the study BMI less than 18 kg/m^2 or more than 35 kg/m^2 Prostatic mass(es) Generalized skin irritation or skin disease Lower urinary tract obstruction Myocardial infarction or cerebrovascular accident in the last 6 months Unstable angina or congestive heart failure Thromboembolic disorders Sleep apnea Hyperparathyroidism or uncontrolled diabetes Untreated moderate to severe depression History of testicular, prostate, or breast cancer HIV, Hepatitis B, or Hepatitis C positive PSA more or equal to 3 ng/mL Use of any medications that could be considered anabolic Use of estrogens, Gonadotropin Releasing Hormone agonists/antagonists, antiandrogens, or human Growth Hormone Chronic use of any drug of abuse Involvement in a sport in which there is a screening for anabolic steroids Not willing to use adequate contraception during the study Partner is pregnant and/or breast feeding Partner has a history of breast, uterine or ovarian cancer

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 999303)<br>Subjects received a starting dose of 46 mg (two actuations) of testosterone gel (2%) daily in the morning. The dose was further titrated (increased or decreased - three actuations [69 mg] or single actuation [23 mg], respectively) based on serum testosterone concentrations. Testosterone gel was applied using an applicator, to the shoulder/upper arm in a contralateral fashion. | Drug: Testosterone gel (FE 999303)<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Percentage of Subjects on Day 90 Whose Cavg (0-24) Serum Total Testosterone Levels Are Between 300 and 1050 ng/dL | The data were presented using descriptive statistics. No statistical analysis was performed. | Day 90 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Percentage of Participants on Day 1 Whose Serum Cavg (0-24) Serum Total Testosterone Levels Are Between 300 and 1050 ng/dL | The data were presented using descriptive statistics. No statistical analysis was performed. | Day 1 | 
| Pharmacokinetics of Total Testosterone Measuring Area Under the Concentration-time Curve From the Last Dose and 24 Hours Post-dose (AUCτ) | A validated high pressure liquid chromatography with tandem mass spectrometry detection (LC/MS/MS) method was used to determine the levels of total testosterone. | Day 1; Day 90 | 
| Pharmacokinetics of Total Testosterone Measuring Time of Maximum Observed Concentration (Tmax) | A validated LC/MS/MS method was used to determine the levels of total testosterone. | Day 1; Day 90 | 
| Pharmacokinetics of Total Testosterone Measuring Maximum Concentration Observed (Cmax) | A validated LC/MS/MS method was used to determine the levels of total testosterone. | Day 1; Day 90 | 
| Pharmacokinetics of Total Testosterone Measuring Average Steady State Concentration (Cave) | A validated LC/MS/MS method was used to determine the levels of total testosterone. | Day 1; Day 90 | 
| Pharmacokinetics of Total Testosterone Measuring Minimum Concentration Observed (Cmin) | A validated LC/MS/MS method was used to determine the levels of total testosterone. | Day 1; Day 90 | 
| Pharmacokinetics of Total Testosterone Measuring Time of Minimum Observed Concentration (Tmin) | A validated LC/MS/MS method was used to determine the levels of total testosterone. | Day 1; Day 90 | 
| Pharmacokinetics of DHT (Dihydrotestosterone) Measuring AUCτ | A validated LC/MS/MS method was used to determine the levels of DHT. | Day 1; Day 90 | 
| Pharmacokinetics of DHT Measuring Tmax | A validated LC/MS/MS method was used to determine the levels of DHT. | Day 1; Day 90 | 
| Pharmacokinetics of DHT Measuring Cmax | A validated LC/MS/MS method was used to determine the levels of DHT. | Day 1; Day 90 | 
| Pharmacokinetics of DHT Measuring Cave | A validated LC/MS/MS method was used to determine the levels of DHT. | Day 1; Day 90 | 
| Pharmacokinetics of DHT Measuring Cmin | A validated LC/MS/MS method was used to determine the levels of DHT. | Day 1; Day 90 | 
| Pharmacokinetics of DHT Measuring Tmin | A validated LC/MS/MS method was used to determine the levels of DHT. | Day 1; Day 90 | 
| Change From Baseline in the International Index of Erectile Dysfunction (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 to 10 and a score of 1-5 is awarded to questions 11 to 15. Total score was calculated by summing up scores of each domain and ranged from 5 to 75. Low score indicates severe dysfunction and a high score indicates no dysfunction in sexual function. | Day 91 | 
| Change From Baseline in the Multidimensional Assessment 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 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. | Day 91 | 
| Change From Baseline in the SF-12 Health 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 standard deviation 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. | Day 91 |