Efficacy, Pharmacokinetics and Safety of Testosterone

Study Overview
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Brief Summary
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This is an open-label study of a single and repeated application of three dose levels of topical testosterone in hypogonadal males with morning serum testosterone concentrations < 297 ng/dL.

Official Title
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A Phase 2 Open-Label, Sequential Dose Escalation Study to Evaluate the Efficacy, Pharmacokinetics and Safety of Three Volumes (1.25, 2.50 and 3.75 mL) of Testosterone Gel 2% (FE 999303) Equivalent to 23, 46 And 70 mg of Testosterone in Hypogonadal Males

Conditions
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Testicular Hypogonadism

Intervention / Treatment
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* Drug: Testosterone gel (FE 99903)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ages 18-65 History of hypogonadism In good health based on medical history, physical examination and clinical laboratory tests Screening morning serum testosterone ≤ 297 ng/dL One or more symptoms of testosterone deficiency (i.e. fatigue, reduced libido or reduced sexual functioning of non-vasculogenic or neurogenic nature) Body mass index (BMI) between 18 and 31 Exclusion Criteria: Prostate cancer Palpable prostatic mass(es) Generalized skin irritation or significant skin disease Use of any medications that could be considered anabolic (e.g. dehydroepiandrosterone (DHEA)) or could interfere with androgen metabolism (e.g. spironolactone, finasteride, ketoconazole) Clinically significant anemia or renal dysfunction Hyperparathyroidism or uncontrolled diabetes Serum PSA Levels; ≥ 4ng/mL History of cardiovascular disease Use of estrogens, Gonadotropin-releasing hormone (GnRH) agonists/antagonist, human growth hormone (hGH), (within previous 12 months) Use of testosterone products (within eight months for parenteral products, or six weeks for other preparations)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single Testosterone Dose (Inner Thigh)<br>Subjects received a single application of 2.50 mL (two strokes) of the testosterone gel 2% applied to the inner thigh followed by a seven day washout period. | Drug: Testosterone gel (FE 99903)<br> <br> |
| Experimental: Single Testosterone Dose (Abdomen)<br>Subjects received a single application of 2.50 mL (two strokes) of the testosterone gel 2% applied to the abdomen followed by a seven day washout period. | Drug: Testosterone gel (FE 99903)<br> <br> |
| Experimental: Single Testosterone Dose (shoulder/upper arm)<br>Subjects received a single application of 2.50 mL (two strokes) of the testosterone gel 2% applied to the shoulder/upper arm. | Drug: Testosterone gel (FE 99903)<br> <br> |
| Experimental: Testosterone 1.25<br>Subjects received testosterone gel 2% at dose of 1.25 mL (one stroke) applied once daily for 10 consecutive days to the shoulder/upper arm. | Drug: Testosterone gel (FE 99903)<br> <br> |
| Experimental: Testosterone 2.50<br>Subjects received testosterone gel 2% at dose of 2.50 mL (two strokes) applied once daily for 10 consecutive days to the shoulder/upper arm. | Drug: Testosterone gel (FE 99903)<br> <br> |
| Experimental: Testosterone 3.75<br>Subjects received testosterone gel 2% at dose of 3.75 mL (three strokes) applied once daily for 10 consecutive days to the shoulder/upper arm. | Drug: Testosterone gel (FE 99903)<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Responder Rate - the Percentage of Subjects Whose Minimum Concentration Observed (Cmin) and Average Steady State Concentration (Cave) of Serum Testosterone Levels Were Between 298 and 1043 ng/dL. | Responder rate was calculated for the subjects who received 10 days of treatment with three doses of testosterone gel; 1.25 mL, 2.50 mL, and 3.75 mL, respectively. The data were presented using descriptive statistics for this outcome. | From Baseline to Day 43 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic Parameter : Maximum Concentration Observed (Cmax) for Total Testosterone, After an Initial Single Treatment (Testosterone) on the Abdomen, Inner Thigh and Shoulder/Upper Arm. | The data were presented using descriptive statistics for this outcome. | Samples were collected at pre-dose and at 2, 4, 6, 8, 10, 12, and 24 hr post-dose on Days 1, 7 and 13 | 
| Pharmacokinetic Parameter : Time of Maximum Observed Concentration (Tmax) for Total Testosterone, After an Initial Single Treatment (Testosterone) on the Abdomen, Inner Thigh, and Shoulder/Upper Arm. | The data were presented using descriptive statistics for this outcome. | Samples were collected at pre-dose and at 2, 4, 6, 8, 10, 12, and 24 hr post-dose on Days 1, 7 and 13 | 
| Pharmacokinetic Parameter : Area Under the Plasma Concentration Time Curve From 0 to 24 hr (AUC0-24) Observed for Total Testosterone, After an Initial Single Treatment (Testosterone) on the Abdomen, Inner Thigh and Shoulder/Upper Arm. | The data were presented using descriptive statistics for this outcome. | Samples were collected at pre-dose and at 2, 4, 6, 8, 10, 12, and 24 hr post-dose on Days 1, 7 and 13 | 
| Pharmacokinetic Parameter - Cmax for Total Testosterone With Multiple-dose Profile of IMP After 10 Days of Treatment to Shoulder/Upper Arm. | The data were presented using descriptive statistics for this outcome. | Samples were collected at pre-dose and at 2, 4, 6, 8, 10, 12, and 24 hr post-dose on Days 23, 33, and 43 | 
| Pharmacokinetic Parameter - Tmax for Total Testosterone With Multiple-dose Profile of IMP After 10 Days of Treatment to Shoulder/Upper Arm. | The data were presented using descriptive statistics for this outcome. | Samples were collected at pre-dose and at 2, 4, 6, 8, 10, 12, and 24 hr post-dose on Days 23, 33, and 43 | 
| Pharmacokinetic Parameter : AUC0-24 Observed for Total Testosterone With Multiple-dose Profile of IMP After 10 Days of Treatment to Shoulder/Upper Arm. | The data were presented using descriptive statistics for this outcome. | Samples were collected at pre-dose and at 2, 4, 6, 8, 10, 12, and 24 hr post-dose on Days 23, 33, and 43 | 
| Pharmacokinetic Parameter - Cmax for Free Testosterone With Multiple-dose Profile of IMP After 10 Days of Treatment to Shoulder/Upper Arm. | The data were presented using descriptive statistics for this outcome. | Samples were collected at pre-dose and at 2, 4, 6, 8, 10, 12, and 24 hr post-dose on Days 23, 33, and 43 | 
| Pharmacokinetic Parameter - Tmax for Free Testosterone With Multiple-dose Profile of IMP After 10 Days of Treatment to Shoulder/Upper Arm. | The data were presented using descriptive statistics for this outcome. | Samples were collected at pre-dose and at 2, 4, 6, 8, 10, 12, and 24 hr post-dose on Days 23, 33, and 43 | 
| Pharmacokinetic Parameter : AUC0-24 Observed for Free Testosterone With Multiple-dose Profile of IMP After 10 Days of Treatment to Shoulder/Upper Arm. | The data were presented using descriptive statistics for this outcome. | Samples were collected at pre-dose and at 2, 4, 6, 8, 10, 12, and 24 hr post-dose on Days 23, 33, and 43 | 
| Pharmacokinetic Parameter - Cmax for Dihydrotestosterone (DHT) With Multiple-dose Profile of IMP After 10 Days of Treatment to Shoulder/Upper Arm. | The data were presented using descriptive statistics for this outcome. | Samples were collected at pre-dose and at 2, 4, 6, 8, 10, 12, and 24 hr post-dose on Days 23, 33, and 43 | 
| Pharmacokinetic Parameter - Tmax for DHT With Multiple-dose Profile of IMP After 10 Days of Treatment to Shoulder/Upper Arm. | The data were presented using descriptive statistics for this outcome. | Samples were collected at pre-dose and at 2, 4, 6, 8, 10, 12, and 24 hr post-dose on Days 23, 33, and 43 | 
| Pharmacokinetic Parameter : AUC0-24 Observed for DHT With Multiple-dose Profile of IMP After 10 Days of Treatment to Shoulder/Upper Arm. | The data were presented using descriptive statistics for this outcome. | Samples were collected at pre-dose and at 2, 4, 6, 8, 10, 12, and 24 hr post-dose on Days 23, 33, and 43 | 
| Frequency of Adverse Events (AEs) | The data were presented using descriptive statistics for this outcome. | From Baseline to Day 43 |