Efficacy, Pharmacokinetics and Safety of Testosterone

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

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01370369

Enrollment

Registered

2011-06-09

Start date

2011-05-31

Completion date

2011-07-31

Last updated

2017-09-13

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Testicular Hypogonadism

Brief summary

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.

Interventions

DRUGTestosterone gel (FE 99903)

Study design

Allocation

NON_RANDOMIZED

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

MALE

Age

18 Years to 65 Years

Healthy volunteers

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)

Design outcomes

Primary

Measure	Time frame	Description
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.	From Baseline to Day 43	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.

Secondary

Measure	Time frame	Description
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.	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	The data were presented using descriptive statistics for this outcome.
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.	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	The data were presented using descriptive statistics for this outcome.
Pharmacokinetic Parameter - Cmax for Total Testosterone With Multiple-dose Profile of IMP After 10 Days of Treatment to Shoulder/Upper Arm.	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	The data were presented using descriptive statistics for this outcome.
Pharmacokinetic Parameter - Tmax for Total Testosterone With Multiple-dose Profile of IMP After 10 Days of Treatment to Shoulder/Upper Arm.	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	The data were presented using descriptive statistics for this outcome.
Pharmacokinetic Parameter : AUC0-24 Observed for Total Testosterone With Multiple-dose Profile of IMP After 10 Days of Treatment to Shoulder/Upper Arm.	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	The data were presented using descriptive statistics for this outcome.
Pharmacokinetic Parameter - Cmax for Free Testosterone With Multiple-dose Profile of IMP After 10 Days of Treatment to Shoulder/Upper Arm.	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	The data were presented using descriptive statistics for this outcome.
Pharmacokinetic Parameter : Maximum Concentration Observed (Cmax) for Total Testosterone, After an Initial Single Treatment (Testosterone) on the Abdomen, Inner Thigh and Shoulder/Upper Arm.	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	The data were presented using descriptive statistics for this outcome.
Pharmacokinetic Parameter : AUC0-24 Observed for Free Testosterone With Multiple-dose Profile of IMP After 10 Days of Treatment to Shoulder/Upper Arm.	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	The data were presented using descriptive statistics for this outcome.
Pharmacokinetic Parameter - Cmax for Dihydrotestosterone (DHT) With Multiple-dose Profile of IMP After 10 Days of Treatment to Shoulder/Upper Arm.	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	The data were presented using descriptive statistics for this outcome.
Pharmacokinetic Parameter - Tmax for DHT With Multiple-dose Profile of IMP After 10 Days of Treatment to Shoulder/Upper Arm.	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	The data were presented using descriptive statistics for this outcome.
Pharmacokinetic Parameter : AUC0-24 Observed for DHT With Multiple-dose Profile of IMP After 10 Days of Treatment to Shoulder/Upper Arm.	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	The data were presented using descriptive statistics for this outcome.
Frequency of Adverse Events (AEs)	From Baseline to Day 43	The data were presented using descriptive statistics for this outcome.
Pharmacokinetic Parameter - Tmax for Free Testosterone With Multiple-dose Profile of IMP After 10 Days of Treatment to Shoulder/Upper Arm.	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	The data were presented using descriptive statistics for this outcome.

Countries

United States

Participant flow

Recruitment details

The study was conducted at one study site in the US. Out of 42 subjects screened, 20 subjects were enrolled in the study.

Pre-assignment details

Apart from having history of hypogonadism, the study subjects were required to present with one or more symptoms of low testosterone (i.e. fatigue, decreased muscle mass, reduced libido, reduced sexual functioning of a non-mechanical nature). The study subjects needed to be in good health despite exhibiting hypogonadism.

Participants by arm

Arm	Count
Testosterone Topical For single dose PKs, a single application of 2.50 mL (two strokes) of the testosterone gel 2% was applied to the inner thigh followed by a 7-day washout period. After this washout period, the second single application of 2.50 mL (two strokes) of the testosterone gel 2% was applied to the abdomen followed by another 7-day washout period. After this washout period, the third single application of 2.50 mL (2 strokes) of the testosterone gel 2% was applied to the shoulder/upper arm. After the last 24 hour PK sampling from the shoulder/upper arm, 3 ascending doses of testosterone gel 2%, 1.25, 2.50 and 3.75 mL (1 stroke, 2 strokes and 3 strokes, respectively), were sequentially applied once daily for 10 consecutive days to the shoulder/upper arm. Steady-state PK evaluations were performed starting on the morning of the last administered dose. There was no washout between each of the 10-day treatments.	20
Total	20

Arm

Count

Testosterone Topical

For single dose PKs, a single application of 2.50 mL (two strokes) of the testosterone gel 2% was applied to the inner thigh followed by a 7-day washout period. After this washout period, the second single application of 2.50 mL (two strokes) of the testosterone gel 2% was applied to the abdomen followed by another 7-day washout period. After this washout period, the third single application of 2.50 mL (2 strokes) of the testosterone gel 2% was applied to the shoulder/upper arm. After the last 24 hour PK sampling from the shoulder/upper arm, 3 ascending doses of testosterone gel 2%, 1.25, 2.50 and 3.75 mL (1 stroke, 2 strokes and 3 strokes, respectively), were sequentially applied once daily for 10 consecutive days to the shoulder/upper arm. Steady-state PK evaluations were performed starting on the morning of the last administered dose. There was no washout between each of the 10-day treatments.

Total

Baseline characteristics

Characteristic	Testosterone Topical
Age, Continuous	47.9 year STANDARD_DEVIATION 9.9
Body Mass Index (BMI)	28.3 Kg/m^2 STANDARD_DEVIATION 2.3
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	17 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants
Height	69.7 Inch STANDARD_DEVIATION 3.2
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	1 Participants
Race (NIH/OMB) Black or African American	6 Participants
Race (NIH/OMB) More than one race	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) White	13 Participants
Sex: Female, Male Female	0 Participants
Sex: Female, Male Male	20 Participants
Weight	196.2 lbs STANDARD_DEVIATION 23.3

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —
other Total, other adverse events	1 / 20	2 / 20	2 / 20
serious Total, serious adverse events	0 / 20	0 / 20	0 / 20

Outcome results

Primary

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.

Time frame: From Baseline to Day 43

Population: ITT population was used for this analysis, which comprised of all subjects who received at least one dose of the IMP.

Arm	Measure	Group	Value (NUMBER)
Testosterone 1.25	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.	Cave	73.7 percentage of subjects
Testosterone 1.25	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.	Cmin	20.0 percentage of subjects
Testosterone 2.50	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.	Cave	77.7 percentage of subjects
Testosterone 2.50	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.	Cmin	40.0 percentage of subjects
Testosterone 3.75	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.	Cave	75.0 percentage of subjects
Testosterone 3.75	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.	Cmin	55.0 percentage of subjects

Secondary