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

A Phase 3, Open-label, Non-randomized, Clinical Trial to Evaluate the Efficacy and Safety of FE 999303 (Testosterone Gel) in Adult Hypogonadal Males

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01665599

Enrollment

180

Registered

2012-08-15

Start date

2012-07-31

Completion date

2013-05-31

Last updated

2017-10-26

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

Conditions

Adult Male Hypogonadism

Brief summary

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.

Interventions

DRUGTestosterone gel (FE 999303)

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

MALE

Age

18 Years to 75 Years

Healthy volunteers

Inclusion criteria

1. Males between 18-75 years of age 2. Two screening serum testosterone values less than 300 ng/dL 3. One or more symptoms of testosterone deficiency

Exclusion criteria

1. Previous use of the investigational product 2. Use of any investigational product within 30 days prior to screening and during the study 3. BMI less than 18 kg/m\^2 or more than 35 kg/m\^2 4. Prostatic mass(es) 5. Generalized skin irritation or skin disease 6. Lower urinary tract obstruction 7. Myocardial infarction or cerebrovascular accident in the last 6 months 8. Unstable angina or congestive heart failure 9. Thromboembolic disorders 10. Sleep apnea 11. Hyperparathyroidism or uncontrolled diabetes 12. Untreated moderate to severe depression 13. History of testicular, prostate, or breast cancer 14. HIV, Hepatitis B, or Hepatitis C positive 15. PSA more or equal to 3 ng/mL 16. Use of any medications that could be considered anabolic 17. Use of estrogens, Gonadotropin Releasing Hormone agonists/antagonists, antiandrogens, or human Growth Hormone 18. Chronic use of any drug of abuse 19. Involvement in a sport in which there is a screening for anabolic steroids 20. Not willing to use adequate contraception during the study 21. Partner is pregnant and/or breast feeding 22. Partner has a history of breast, uterine or ovarian cancer

Design outcomes

Primary

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

Secondary

Measure	Time frame	Description
Pharmacokinetics of Total Testosterone Measuring Area Under the Concentration-time Curve From the Last Dose and 24 Hours Post-dose (AUCτ)	Day 1; Day 90	A validated high pressure liquid chromatography with tandem mass spectrometry detection (LC/MS/MS) method was used to determine the levels of total testosterone.
Pharmacokinetics of Total Testosterone Measuring Time of Maximum Observed Concentration (Tmax)	Day 1; Day 90	A validated LC/MS/MS method was used to determine the levels of total testosterone.
Pharmacokinetics of Total Testosterone Measuring Maximum Concentration Observed (Cmax)	Day 1; Day 90	A validated LC/MS/MS method was used to determine the levels of total testosterone.
Pharmacokinetics of Total Testosterone Measuring Average Steady State Concentration (Cave)	Day 1; Day 90	A validated LC/MS/MS method was used to determine the levels of total testosterone.
Pharmacokinetics of Total Testosterone Measuring Minimum Concentration Observed (Cmin)	Day 1; Day 90	A validated LC/MS/MS method was used to determine the levels of total testosterone.
Pharmacokinetics of Total Testosterone Measuring Time of Minimum Observed Concentration (Tmin)	Day 1; Day 90	A validated LC/MS/MS method was used to determine the levels of total testosterone.
Pharmacokinetics of DHT (Dihydrotestosterone) Measuring AUCτ	Day 1; Day 90	A validated LC/MS/MS method was used to determine the levels of DHT.
The Percentage of Participants on Day 1 Whose Serum Cavg (0-24) Serum Total Testosterone Levels Are Between 300 and 1050 ng/dL	Day 1	The data were presented using descriptive statistics. No statistical analysis was performed.
Pharmacokinetics of DHT Measuring Cmax	Day 1; Day 90	A validated LC/MS/MS method was used to determine the levels of DHT.
Pharmacokinetics of DHT Measuring Cave	Day 1; Day 90	A validated LC/MS/MS method was used to determine the levels of DHT.
Pharmacokinetics of DHT Measuring Cmin	Day 1; Day 90	A validated LC/MS/MS method was used to determine the levels of DHT.
Pharmacokinetics of DHT Measuring Tmin	Day 1; Day 90	A validated LC/MS/MS method was used to determine the levels of DHT.
Change From Baseline in the International Index of Erectile Dysfunction (IIEF) Questionnaire	Day 91	Data collected from the five domains of sexual functions were summarized by descriptive statistics. The domains are: 1. Erectile function (6 items, questions 1-5 and 15) (Score range: 1-30) 2. Orgasmic function (2 items, questions 9-10) (Score range: 0-10) 3. Sexual desire (2 items, questions 11-12) (Score range: 2-10) 4. Intercourse satisfaction (3 items, questions 6-8) (Score range: 0-15) 5. 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.
Change From Baseline in the Multidimensional Assessment of Fatigue (MAF) Questionnaire	Day 91	The MAF contains four sub-domains: 1. Severity (2 items, questions 1-2) (Score range: 2-20) 2. Distress (1 item, question 3) (Score range: 1-10) 3. Degree of interference in activities of daily living (11 items, questions 4-14) (Score range: 11-110) 4. 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.
Change From Baseline in the SF-12 Health Questionnaire	Day 91	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.
Pharmacokinetics of DHT Measuring Tmax	Day 1; Day 90	A validated LC/MS/MS method was used to determine the levels of DHT.

Countries

Canada, United States

Participant flow

Recruitment details

Subjects were recruited from 19 study centers (17 in the US and 2 in Canada).

Pre-assignment details

Of the 656 screened subjects, 180 subjects were enrolled into the study.

Participants by arm

Arm	Count
Testosterone Gel (FE 999303) 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.	180
Total	180

Arm

Count

Testosterone Gel (FE 999303)

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.

180

Total

180

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Adverse Event	1
Overall Study	Consent Withdrawn	1
Overall Study	Could Not Continue Due to Time Constrain	1
Overall Study	Death	1
Overall Study	Investigator/Sponsor decision	1
Overall Study	Lost to Follow-up	2
Overall Study	Participant Left for More Than 3 Months	1

Baseline characteristics

Characteristic	Testosterone Gel (FE 999303)
Age, Categorical <=18 years	0 Participants
Age, Categorical >=65 years	35 Participants
Age, Categorical Between 18 and 65 years	145 Participants
Age, Continuous	56.8 years STANDARD_DEVIATION 9.4
BMI, Continuous	30 kg/m^2 STANDARD_DEVIATION 3.4
Ethnicity (NIH/OMB) Hispanic or Latino	16 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	164 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants
Height, Continuous	70.3 Inches STANDARD_DEVIATION 2.8
Multidimensional Assessment of Fatigue Degree of interference domain	48.9 units on a scale STANDARD_DEVIATION 24.3
Multidimensional Assessment of Fatigue Distress domain	4.9 units on a scale STANDARD_DEVIATION 2.8
Multidimensional Assessment of Fatigue Global Fatigue Index (GFI)	27.2 units on a scale STANDARD_DEVIATION 12.6
Multidimensional Assessment of Fatigue Severity domain	11.9 units on a scale STANDARD_DEVIATION 5.5
Multidimensional Assessment of Fatigue Timing domain	12.8 units on a scale STANDARD_DEVIATION 3.1
Race (NIH/OMB) American Indian or Alaska Native	1 Participants
Race (NIH/OMB) Asian	2 Participants
Race (NIH/OMB) Black or African American	19 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	1 Participants
Race (NIH/OMB) White	157 Participants
Sex: Female, Male Female	0 Participants
Sex: Female, Male Male	180 Participants
Short Form -12 (SF-12) Health survey Mental Component Summary	43.0 units on a scale STANDARD_DEVIATION 10.2
Short Form -12 (SF-12) Health survey Physical Component Summary	47.5 units on a scale STANDARD_DEVIATION 9.6
Total International Index of Erectile Function (IIEF) Score	31.9 units on a scale STANDARD_DEVIATION 18.4
Weight, Continuous	211.3 pounds STANDARD_DEVIATION 30.1

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	— / —
other Total, other adverse events	62 / 180
serious Total, serious adverse events	3 / 180

Outcome results

Primary

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.

Time frame: Day 90

Population: Full Analysis set (FAS) population was used which comprised of subjects who had any available pharmacokinetic (PK) data for testosterone on Day 90.

Arm	Measure	Group	Value (NUMBER)
Testosterone Gel (FE 999303)	The Percentage of Subjects on Day 90 Whose Cavg (0-24) Serum Total Testosterone Levels Are Between 300 and 1050 ng/dL	23 mg	2.9 percentage of participants
Testosterone Gel (FE 999303)	The Percentage of Subjects on Day 90 Whose Cavg (0-24) Serum Total Testosterone Levels Are Between 300 and 1050 ng/dL	46 mg	4.7 percentage of participants
Testosterone Gel (FE 999303)	The Percentage of Subjects on Day 90 Whose Cavg (0-24) Serum Total Testosterone Levels Are Between 300 and 1050 ng/dL	69 mg	77.9 percentage of participants
Testosterone Gel (FE 999303)	The Percentage of Subjects on Day 90 Whose Cavg (0-24) Serum Total Testosterone Levels Are Between 300 and 1050 ng/dL	Overall	85.5 percentage of participants

Secondary

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: 1. Erectile function (6 items, questions 1-5 and 15) (Score range: 1-30) 2. Orgasmic function (2 items, questions 9-10) (Score range: 0-10) 3. Sexual desire (2 items, questions 11-12) (Score range: 2-10) 4. Intercourse satisfaction (3 items, questions 6-8) (Score range: 0-15) 5. 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.

Time frame: Day 91