Secondary Hypogonadism
Conditions
Keywords
Adult Onset Idiopathic Hypothalamic Hypogonadism (AIHH), Secondary hypogonadism, Semen volume, Sperm count, Sperm motility
Brief summary
The study was designed to determine if Androxal® would affect sperm parameters (count, concentration, volume) in men with secondary hypogonadism who have been previously treated with topical testosterone.
Detailed description
The study was designed to determine if Androxal® would affect sperm parameters (count, concentration, volume) in men with secondary hypogonadism who have been previously treated with topical testosterone. A maximum of twelve subjects per group were randomized to daily treatments of Androxal® or topical testosterone (Testim®) for six months. The protocol was later amended to include a treatment group who received Androxal after a 3 month wash out period.
Interventions
DRUG25 mg Androxal
25 mg Androxal capsules, 1 capsule daily for 6 months
DRUGTestim 1%
Testim 1% gel, dosage to be titrated according to manufacturer's instructions, once daily for 6 months
Sponsors
Repros Therapeutics Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
21 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* Healthy adult males between 21 and 60 years of age who have been diagnosed with AIHH. * Subjects must have been treated with a topical testosterone replacement therapy (typically AndroGel® or Testim®) for at least 6 months at enrollment and for not more than 2 years.
Exclusion criteria
* A history of idiopathic infertility due to primary hypogonadism, testicular failure, Kallmann's syndrome or any other infertility condition. * Subjects demonstrating any clinically significant medical condition rendering the subjects infertile or marginally fertile other than AIHH. * Men with a history of, known, or suspected prostate disease not ruled out by a prostate biopsy, or a prostate specific antigen (PSA)\>3.6 or clinical suspicion of current prostate disease. * Men with a hematocrit in excess of 50 % or hemoglobin \>17 g/dl
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Sperm Concentration | Baseline, Month 3, Month 6, Follow-Up (Month 7) | Total sperm concentration was measured. |
| Motile Total Sperm Count | Baseline, Month 3, Month 6, Follow-Up (Month 7) | Motile total sperm count was measured. |
| Semen Volume | Baseline, Month 3, Month 6, Follow-Up (Month 7) | Semen volume was measured. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Luteinizing Hormone (LH) Levels | Baseline, Month 3, Month 6, Follow-Up (Month 7) | LH levels were measured. |
| Follicle Stimulating Hormone (FSH) Levels | Baseline, Month 3, Month 6, Follow-Up (Month 7) | FSH levels were measured. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Group A Testim 1% Testim gel applied daily | 5 |
| Group B Androxal no Wash Out 25 mg Androxal 1 capsule per day in men who have not previously washed out topical testosterone for 3 months | 7 |
| Group C Androxal Wash Out 25 mg 1 capsule per day in men who have undergone a 3 month wash out period of topical testosterone | 5 |
| Total | 17 |
Baseline characteristics
| Characteristic | Group B Androxal no Wash Out | Group C Androxal Wash Out | Group A Testim | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants | 5 Participants | 5 Participants | 17 Participants |
| Age, Continuous | 48.9 years STANDARD_DEVIATION 8.99 | 56.4 years STANDARD_DEVIATION 23.8 | 54.4 years STANDARD_DEVIATION 4.88 | 52.7 years STANDARD_DEVIATION 7.72 |
| Region of Enrollment United States | 7 participants | 5 participants | 5 participants | 17 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 7 Participants | 5 Participants | 5 Participants | 17 Participants |
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 | 0 / 5 | 2 / 7 | 4 / 5 |
| serious Total, serious adverse events | 0 / 5 | 0 / 7 | 0 / 5 |
Outcome results
Primary
Motile Total Sperm Count
Motile total sperm count was measured.
Time frame: Baseline, Month 3, Month 6, Follow-Up (Month 7)
Population: Subjects in Group A and B who completed the study. No analysis was performed for subjects in Group C because only 1 subject completed the study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group A Testim | Motile Total Sperm Count | Baseline | 0.3 millions sperm | Standard Deviation 0.48 |
| Group A Testim | Motile Total Sperm Count | Month 3 | 2.42 millions sperm | Standard Deviation 5.41 |
| Group A Testim | Motile Total Sperm Count | Month 6 | 40.4 millions sperm | Standard Deviation 55.3 |
| Group A Testim | Motile Total Sperm Count | Follow-Up (Month 7) | 38 millions sperm | Standard Deviation 52.5 |
| Group B Androxal no Wash Out | Motile Total Sperm Count | Follow-Up (Month 7) | 100.3 millions sperm | Standard Deviation 103.8 |
| Group B Androxal no Wash Out | Motile Total Sperm Count | Baseline | 99.0 millions sperm | Standard Deviation 159.6 |
| Group B Androxal no Wash Out | Motile Total Sperm Count | Month 6 | 146.9 millions sperm | Standard Deviation 120 |
| Group B Androxal no Wash Out | Motile Total Sperm Count | Month 3 | 214.7 millions sperm | Standard Deviation 166 |
Comparison: Comparison of Group A and B observed values at Baseline.p-value: 0.15Wilcoxon (Mann-Whitney)
Comparison: Comparison of Group A and B observed values at Month 3.p-value: 0.0067Wilcoxon (Mann-Whitney)
Comparison: Comparison of Group A and B observed values at Month 6.p-value: 0.1Wilcoxon (Mann-Whitney)
Comparison: Comparison of Group A and B observed values at Follow-up (Month 7).p-value: 0.26t-test, 2 sided
Primary
Semen Volume
Semen volume was measured.
Time frame: Baseline, Month 3, Month 6, Follow-Up (Month 7)
Population: Subjects in Group A and B who completed the study. No analysis was performed for subjects in Group C because only 1 subject completed the study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group A Testim | Semen Volume | Baseline | 2.34 mL | Standard Deviation 1.43 |
| Group A Testim | Semen Volume | Month 6 | 1.90 mL | Standard Deviation 1.03 |
| Group A Testim | Semen Volume | Month 3 | 2.88 mL | Standard Deviation 1.4 |
| Group A Testim | Semen Volume | Follow-Up (Month 7) | 3.34 mL | Standard Deviation 0.83 |
| Group B Androxal no Wash Out | Semen Volume | Follow-Up (Month 7) | 2.40 mL | Standard Deviation 0.58 |
| Group B Androxal no Wash Out | Semen Volume | Baseline | 2.23 mL | Standard Deviation 0.81 |
| Group B Androxal no Wash Out | Semen Volume | Month 3 | 2.45 mL | Standard Deviation 1.31 |
| Group B Androxal no Wash Out | Semen Volume | Month 6 | 2.48 mL | Standard Deviation 1.53 |
Comparison: Comparison of Group A and B observed values at Baseline.p-value: 0.88t-test, 2 sided
Comparison: Comparison of Group A and B observed values at Month 3.p-value: 0.612t-test, 2 sided
Comparison: Comparison of Group A and B observed values at Month 6.p-value: 0.488t-test, 2 sided
Comparison: Comparison of Group A and B observed values at Follow-up (Month 7).p-value: 0.054t-test, 2 sided
Primary
Sperm Concentration
Total sperm concentration was measured.
Time frame: Baseline, Month 3, Month 6, Follow-Up (Month 7)
Population: Subjects in Group A and B who completed the study. No analysis was performed for subjects in Group C because only 1 subject completed the study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group A Testim | Sperm Concentration | Baseline | 0.54 millions sperm/mL | Standard Deviation 0.74 |
| Group A Testim | Sperm Concentration | Month 3 | 3.00 millions sperm/mL | Standard Deviation 5.2 |
| Group A Testim | Sperm Concentration | Month 6 | 23.14 millions sperm/mL | Standard Deviation 30.67 |
| Group A Testim | Sperm Concentration | Follow-Up (Month 7) | 21.03 millions sperm/mL | Standard Deviation 28.9 |
| Group B Androxal no Wash Out | Sperm Concentration | Follow-Up (Month 7) | 164.0 millions sperm/mL | Standard Deviation 71.2 |
| Group B Androxal no Wash Out | Sperm Concentration | Baseline | 72.8 millions sperm/mL | Standard Deviation 92.7 |
| Group B Androxal no Wash Out | Sperm Concentration | Month 6 | 168.5 millions sperm/mL | Standard Deviation 92.9 |
| Group B Androxal no Wash Out | Sperm Concentration | Month 3 | 182.6 millions sperm/mL | Standard Deviation 115.5 |
Comparison: Comparison of Group A and B observed values at Baseline.p-value: 0.118t-test, 2 sided
Comparison: Comparison of Group A and B observed values at Month 3.p-value: 0.006t-test, 2 sided
Comparison: Comparison of Group A and B observed values at Month 6.p-value: 0.009t-test, 2 sided
Comparison: Comparison of Group A and B observed values at Follow-up (Month 7).p-value: 0.0024t-test, 2 sided
Secondary
Follicle Stimulating Hormone (FSH) Levels
FSH levels were measured.
Time frame: Baseline, Month 3, Month 6, Follow-Up (Month 7)
Population: Subjects in Group A and B who completed the study. No analysis was performed for subjects in Group C because only 1 subject completed the study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group A Testim | Follicle Stimulating Hormone (FSH) Levels | Month 3 | 1.06 mIU/mL | Standard Deviation 1.12 |
| Group A Testim | Follicle Stimulating Hormone (FSH) Levels | Baseline | 3.38 mIU/mL | Standard Deviation 0.74 |
| Group A Testim | Follicle Stimulating Hormone (FSH) Levels | Follow-Up (Month 7) | 3.6 mIU/mL | Standard Deviation 1.2 |
| Group A Testim | Follicle Stimulating Hormone (FSH) Levels | Month 6 | 0.9 mIU/mL | Standard Deviation 0.51 |
| Group B Androxal no Wash Out | Follicle Stimulating Hormone (FSH) Levels | Follow-Up (Month 7) | 2.38 mIU/mL | Standard Deviation 0.95 |
| Group B Androxal no Wash Out | Follicle Stimulating Hormone (FSH) Levels | Baseline | 1.58 mIU/mL | Standard Deviation 0.74 |
| Group B Androxal no Wash Out | Follicle Stimulating Hormone (FSH) Levels | Month 6 | 5.48 mIU/mL | Standard Deviation 2.46 |
| Group B Androxal no Wash Out | Follicle Stimulating Hormone (FSH) Levels | Month 3 | 4.53 mIU/mL | Standard Deviation 2.36 |
Comparison: Comparison of Group A and B observed values at Month 3.p-value: 0.015t-test, 2 sided
Comparison: Comparison of Group A and B observed values at Month 6.p-value: 0.003t-test, 2 sided
Comparison: Comparison of Group A and B observed values at Baseline.p-value: 0.008t-test, 2 sided
Comparison: Comparison of Group A and B observed values at Follow-up (Month 7).p-value: 0.109t-test, 2 sided
Secondary
Luteinizing Hormone (LH) Levels
LH levels were measured.
Time frame: Baseline, Month 3, Month 6, Follow-Up (Month 7)
Population: Subjects in Group A and B who completed the study. No analysis was performed for subjects in Group C because only 1 subject completed the study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group A Testim | Luteinizing Hormone (LH) Levels | Baseline | 3.40 mIU/mL | Standard Deviation 2.14 |
| Group A Testim | Luteinizing Hormone (LH) Levels | Month 3 | 0.88 mIU/mL | Standard Deviation 1.39 |
| Group A Testim | Luteinizing Hormone (LH) Levels | Month 6 | 0.60 mIU/mL | Standard Deviation 0.58 |
| Group A Testim | Luteinizing Hormone (LH) Levels | Follow-Up (Month 7) | 2.68 mIU/mL | Standard Deviation 0.48 |
| Group B Androxal no Wash Out | Luteinizing Hormone (LH) Levels | Follow-Up (Month 7) | 2.47 mIU/mL | Standard Deviation 1.58 |
| Group B Androxal no Wash Out | Luteinizing Hormone (LH) Levels | Baseline | 2.92 mIU/mL | Standard Deviation 1.69 |
| Group B Androxal no Wash Out | Luteinizing Hormone (LH) Levels | Month 6 | 6.12 mIU/mL | Standard Deviation 3.15 |
| Group B Androxal no Wash Out | Luteinizing Hormone (LH) Levels | Month 3 | 5.70 mIU/mL | Standard Deviation 3.22 |
Comparison: Comparison of Group A and B observed values at Baseline.p-value: 0.705t-test, 2 sided
Comparison: Comparison of Group A and B observed values at Month 3.p-value: 0.013t-test, 2 sided
Comparison: Comparison of Group A and B observed values at Month 6.p-value: 0.004t-test, 2 sided
Comparison: Comparison of Group A and B observed values at Follow-up (Month 7).p-value: 0.808t-test, 2 sided