A Clinical Trial to Evaluate the Efficacy and Safety of Testosterone Gel in Adult Hypogonadal Males

Study Overview
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Brief Summary
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This is a phase 3, open-label, non-randomized, clinical trial to evaluate the efficacy and safety of FE 999303 (Testosterone gel) in adult hypogonadal males.

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 fasting serum testosterone levels <300 ng/dL Exclusion Criteria: Previous use of the study drug History of prostate or breast cancer Prostate-Specific Antigen (PSA) ≥3 ng/mL Subject is sexually active and not willing to use adequate contraception

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 at least one dose of testosterone gel (23 mg), which was further titrated, if needed (upto three doses [69 mg]), based on serum testosterone concentrations. Testosterone gel was delivered using an applicator to the contralateral shoulder/upper arm. | 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 Whose Average Concentration (Cave(0-24)) Serum Total Testosterone Levels Are ≥300 and ≤1050 ng/dL | The data were presented using descriptive statistics. The 95% confidence interval (CI) of the proportion (response) was estimated using the normal approximation to the binomial distribution. The study was considered to have met its efficacy criteria if the percentage was ≥ 75% and the lower bound of the 95% CI was ≥ 65%. | At Day 90 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Percentage of Subjects Whose Cave(0-24) Serum Total Testosterone Levels Are ≥300 and ≤1050 ng/dL | The data were presented using descriptive statistics. No statistical analysis was performed. | At 14, 35 and 56 | 
| Change From Baseline in International Index of Erectile Function (IIEF) Score | Data collected from the five domains of sexual functions were summarized by descriptive statistics. The domains were: 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. | At Days 35 and 90 | 
| Change From Baseline in Multidimensional Assessment of Fatigue (MAF) Score | 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 (categorical in nature) are scored from 1-4. The scores are 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. The GFI ranged from 1 (no fatigue) to 50 (severe fatigue). | At Days 35 and 90 | 
| Change From Baseline in Short Form-12 Health Survey (SF-12) Score | Data collected from the SF-12 questionnaire, based on the norm-based scores was used to assess improvement in the psychometrically-based physical component summary (PCS) and mental component summary (MCS). Both PCS and MCS contained four sub-domains: PCS: Physical Functioning (2 items, questions 2-3) Role-Physical (2 items, questions 4-5) Bodily Pain (1 item, question 8) General Health (1 item, question 1) MCS: Vitality (1 item, question 10) Social Functioning (1 item, question 12) Role-Emotional (2 items, questions 6-7) Mental Health (2 items, questions 9 and 11) PCS and MCS composite scores are computed using the scores of the 12 questions and range from 0-100, where a zero score indicates the lowest level of health measured by the scales and 100 indicates the highest level of health. Positive change from baseline indicated improvement in physical and mental health. | At Days 35 and 90 | 
| Pharmacokinetic Parameter - Average Concentration (Cave) for Total Testosterone and Dihydrotestosterone | A validated high pressure liquid chromatography with tandem mass spectrometry detection (LC/MS/MS) method was used to determine the levels of total testosterone and dihydrotestosterone. | Samples collected at pre-dose, 2, 4, 6, 8 & 24 hours post-dose on Days 14, 35 & 56, and at pre-dose, 2, 4, 6, 8, 10, 12, 18 & 24 hours post-dose on Day 90 | 
| Pharmacokinetic Parameter - Area Under the Concentration-time Curve (AUCτ) for Total Testosterone and Dihydrotestosterone | A validated LC/MS/MS method was used to determine the levels of total testosterone and dihydrotestosterone. | Samples collected at pre-dose, 2, 4, 6, 8 & 24 hours post-dose on Days 14, 35 & 56, and at pre-dose, 2, 4, 6, 8, 10, 12, 18 & 24 hours post-dose on Day 90 | 
| Pharmacokinetic Parameter - Time at Which the Maximum Concentration Occurs (Tmax) for Total Testosterone and Dihydrotestosterone | A validated LC/MS/MS method was used to determine the levels of total testosterone and dihydrotestosterone. | Samples collected at pre-dose, 2, 4, 6, 8 & 24 hours post-dose on Days 14, 35 & 56, and at pre-dose, 2, 4, 6, 8, 10, 12, 18 & 24 hours post-dose on Day 90 | 
| Pharmacokinetic Parameter - Maximum Concentration Observed (Cmax) for Total Testosterone and Dihydrotestosterone | A validated LC/MS/MS method was used to determine the levels of total testosterone and dihydrotestosterone. | Samples collected at pre-dose, 2, 4, 6, 8 & 24 hours post-dose on Days 14, 35 & 56, and at pre-dose, 2, 4, 6, 8, 10, 12, 18 & 24 hours post-dose on Day 90 | 
| Pharmacokinetic Parameter - Minimum Concentration Observed (Cmin) for Total Testosterone and Dihydrotestosterone | A validated LC/MS/MS method was used to determine the levels of total testosterone and dihydrotestosterone. | Samples collected at pre-dose, 2, 4, 6, 8 & 24 hours post-dose on Days 14, 35 & 56, and at pre-dose, 2, 4, 6, 8, 10, 12, 18 & 24 hours post-dose on Day 90 |