Trial Outcomes & Findings for Phase III Study to Evaluated Morning Testosterone Normalization in Men With Secondary Hypogonadism (NCT NCT01532414)
NCT ID: NCT01532414
Last Updated: 2015-05-27
Results Overview
Proportion of pooled Androxal subjects with average serum concentration (Cavg) for T in the normal range (300 - 1040 ng/dL) after 12 weeks of treatment. Cavg will be calculated as the numerical average of 24-hour serial testosterone assessments at 0, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours after dosing. If the lower limit of the 95% confidence interval for the Androxal treatment group at Week 12 is at least 67%, then the co-primary endpoint based on the Cavg for testosterone has been achieved. FDA specified primary endpoint did not include comparison to placebo, thus the proportion of placebo subjects with average serum concentration (Cavg) for T in the normal range (300 - 1040 ng/dL) after 12 weeks of treatment was not calculated.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
151 participants
Primary outcome timeframe
3 months
Results posted on
2015-05-27
Participant Flow
Participant milestones
| Measure |
Androxal 12.5 mg
Androxal (enclomiphene citrate), 12.5 mg oral capsules taken once daily
enclomiphene citrate: oral, capsules, taken one time daily, for 3 months Subjects with morning testosterone \<300ng/dL after 6 weeks of treatment were up-titrated to 25 mg/day
|
Androxal 25 mg
Androxal (enclomiphene citrate), 25 mg oral capsules taken once daily
enclomiphene citrate: oral, capsules, taken one time daily, for 3 months
|
Placebo
Placebo oral capsules taken one time daily
Placebo: Oral capsule taken one time daily for 3 months
|
|---|---|---|---|
|
Overall Study
STARTED
|
92
|
21
|
38
|
|
Overall Study
COMPLETED
|
85
|
19
|
35
|
|
Overall Study
NOT COMPLETED
|
7
|
2
|
3
|
Reasons for withdrawal
| Measure |
Androxal 12.5 mg
Androxal (enclomiphene citrate), 12.5 mg oral capsules taken once daily
enclomiphene citrate: oral, capsules, taken one time daily, for 3 months Subjects with morning testosterone \<300ng/dL after 6 weeks of treatment were up-titrated to 25 mg/day
|
Androxal 25 mg
Androxal (enclomiphene citrate), 25 mg oral capsules taken once daily
enclomiphene citrate: oral, capsules, taken one time daily, for 3 months
|
Placebo
Placebo oral capsules taken one time daily
Placebo: Oral capsule taken one time daily for 3 months
|
|---|---|---|---|
|
Overall Study
Lost to Follow-up
|
3
|
0
|
1
|
|
Overall Study
Withdrawal by Subject
|
3
|
0
|
0
|
|
Overall Study
No V6 semen sample
|
0
|
1
|
0
|
|
Overall Study
Adverse Event
|
0
|
1
|
1
|
|
Overall Study
Unable to complete 24 hour PK
|
0
|
0
|
1
|
|
Overall Study
Withdrawn by sponsor
|
1
|
0
|
0
|
Baseline Characteristics
Phase III Study to Evaluated Morning Testosterone Normalization in Men With Secondary Hypogonadism
Baseline characteristics by cohort
| Measure |
Androxal 12.5 mg
n=92 Participants
Androxal (enclomiphene citrate), 12.5 mg oral capsules taken once daily
enclomiphene citrate: oral, capsules, taken one time daily, for 3 months Subjects with morning testosterone \<300ng/dL after 6 weeks of treatment were up-titrated to 25 mg/day
|
Androxal 25 mg
n=21 Participants
Androxal (enclomiphene citrate), 25 mg oral capsules taken once daily
enclomiphene citrate: oral, capsules, taken one time daily, for 3 months
|
Placebo
n=38 Participants
Placebo oral capsules taken one time daily
Placebo: Oral capsule taken one time daily for 3 months
|
Total
n=151 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
47.2 years
STANDARD_DEVIATION 9.6 • n=5 Participants
|
43.6 years
STANDARD_DEVIATION 10.1 • n=7 Participants
|
47.8 years
STANDARD_DEVIATION 9.5 • n=5 Participants
|
46.9 years
STANDARD_DEVIATION 9.7 • n=4 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
92 Participants
n=5 Participants
|
21 Participants
n=7 Participants
|
38 Participants
n=5 Participants
|
151 Participants
n=4 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Asian
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Black or African American
|
11 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
12 Participants
n=4 Participants
|
|
Race (NIH/OMB)
White
|
79 Participants
n=5 Participants
|
20 Participants
n=7 Participants
|
36 Participants
n=5 Participants
|
135 Participants
n=4 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Region of Enrollment
United States
|
92 participants
n=5 Participants
|
21 participants
n=7 Participants
|
38 participants
n=5 Participants
|
151 participants
n=4 Participants
|
|
BMI
|
31.5 Kg/m^2
STANDARD_DEVIATION 4.3 • n=5 Participants
|
32.8 Kg/m^2
STANDARD_DEVIATION 5.0 • n=7 Participants
|
31.3 Kg/m^2
STANDARD_DEVIATION 3.8 • n=5 Participants
|
31.6 Kg/m^2
STANDARD_DEVIATION 4.3 • n=4 Participants
|
PRIMARY outcome
Timeframe: 3 monthsPopulation: ITT population.
Proportion of pooled Androxal subjects with average serum concentration (Cavg) for T in the normal range (300 - 1040 ng/dL) after 12 weeks of treatment. Cavg will be calculated as the numerical average of 24-hour serial testosterone assessments at 0, 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours after dosing. If the lower limit of the 95% confidence interval for the Androxal treatment group at Week 12 is at least 67%, then the co-primary endpoint based on the Cavg for testosterone has been achieved. FDA specified primary endpoint did not include comparison to placebo, thus the proportion of placebo subjects with average serum concentration (Cavg) for T in the normal range (300 - 1040 ng/dL) after 12 weeks of treatment was not calculated.
Outcome measures
| Measure |
Androxal Treated Subjects Pooled
n=113 12.5 and 25 mg pooled
Androxal (enclomiphene citrate), 12.5 mg or 25 mg oral capsules taken once daily
enclomiphene citrate: oral, capsules, taken one time daily, for 3 months
|
Placebo
Placebo oral capsules taken one time daily
Placebo: Oral capsule taken one time daily for 3 months
|
|---|---|---|
|
Proportion (Percentage) of Androxal Treated Subjects With Testosterone in the Normal Range
|
78.8 Percentage of Subjects
Interval 70.3 to 85.3
|
—
|
PRIMARY outcome
Timeframe: 3 monthsPopulation: ITT.
Proportion of subjects with a 50% or greater decrease in sperm concentration from baseline after 12 weeks of treatment in Androxal treated subjects to placebo. The difference between the proportions (placebo minus Androxal) and corresponding 95% confidence interval was determined and compared to the equivalence limit of -20%. If the lower limit of the 95% confidence interval was greater than -20%, then Androxal would be concluded to be non-inferior to placebo in causing a 50% reduction in sperm concentrations.
Outcome measures
| Measure |
Androxal Treated Subjects Pooled
n=113 Participants
Androxal (enclomiphene citrate), 12.5 mg or 25 mg oral capsules taken once daily
enclomiphene citrate: oral, capsules, taken one time daily, for 3 months
|
Placebo
n=38 Participants
Placebo oral capsules taken one time daily
Placebo: Oral capsule taken one time daily for 3 months
|
|---|---|---|
|
Subjects With 50% or Greater Decrease in Sperm Concentration Comparison of Proportion of Subjects With 50% or Greater Decrease in Sperm
|
14.2 percentage of participants
|
2.6 percentage of participants
|
Adverse Events
Androxal 12.5 mg
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Androxal 25 mg
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
Placebo
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Androxal 12.5 mg
n=92 participants at risk
Androxal (enclomiphene citrate), 12.5 mg oral capsules taken once daily
enclomiphene citrate: oral, capsules, taken one time daily, for 3 months
|
Androxal 25 mg
n=21 participants at risk
Androxal (enclomiphene citrate), 25 mg oral capsules taken once daily
enclomiphene citrate: oral, capsules, taken one time daily, for 3 months
|
Placebo
n=38 participants at risk
Placebo oral capsules taken one time daily
Placebo: Oral capsule taken one time daily for 3 months
|
|---|---|---|---|
|
Eye disorders
Ocular discomfort
|
0.00%
0/92 • For subjects not up-titrated 13 weeks (one week follow up after end of treatment). For subjects up-titrated 18 weeks plus one week of follow up.
|
4.8%
1/21 • For subjects not up-titrated 13 weeks (one week follow up after end of treatment). For subjects up-titrated 18 weeks plus one week of follow up.
|
0.00%
0/38 • For subjects not up-titrated 13 weeks (one week follow up after end of treatment). For subjects up-titrated 18 weeks plus one week of follow up.
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/92 • For subjects not up-titrated 13 weeks (one week follow up after end of treatment). For subjects up-titrated 18 weeks plus one week of follow up.
|
0.00%
0/21 • For subjects not up-titrated 13 weeks (one week follow up after end of treatment). For subjects up-titrated 18 weeks plus one week of follow up.
|
5.3%
2/38 • For subjects not up-titrated 13 weeks (one week follow up after end of treatment). For subjects up-titrated 18 weeks plus one week of follow up.
|
|
Infections and infestations
Upper respiratort tract infection
|
5.4%
5/92 • For subjects not up-titrated 13 weeks (one week follow up after end of treatment). For subjects up-titrated 18 weeks plus one week of follow up.
|
4.8%
1/21 • For subjects not up-titrated 13 weeks (one week follow up after end of treatment). For subjects up-titrated 18 weeks plus one week of follow up.
|
0.00%
0/38 • For subjects not up-titrated 13 weeks (one week follow up after end of treatment). For subjects up-titrated 18 weeks plus one week of follow up.
|
|
Nervous system disorders
Headache
|
3.3%
3/92 • For subjects not up-titrated 13 weeks (one week follow up after end of treatment). For subjects up-titrated 18 weeks plus one week of follow up.
|
9.5%
2/21 • For subjects not up-titrated 13 weeks (one week follow up after end of treatment). For subjects up-titrated 18 weeks plus one week of follow up.
|
5.3%
2/38 • For subjects not up-titrated 13 weeks (one week follow up after end of treatment). For subjects up-titrated 18 weeks plus one week of follow up.
|
|
Vascular disorders
Hypertension
|
1.1%
1/92 • For subjects not up-titrated 13 weeks (one week follow up after end of treatment). For subjects up-titrated 18 weeks plus one week of follow up.
|
4.8%
1/21 • For subjects not up-titrated 13 weeks (one week follow up after end of treatment). For subjects up-titrated 18 weeks plus one week of follow up.
|
0.00%
0/38 • For subjects not up-titrated 13 weeks (one week follow up after end of treatment). For subjects up-titrated 18 weeks plus one week of follow up.
|
|
Cardiac disorders
Palpitations
|
0.00%
0/92 • For subjects not up-titrated 13 weeks (one week follow up after end of treatment). For subjects up-titrated 18 weeks plus one week of follow up.
|
4.8%
1/21 • For subjects not up-titrated 13 weeks (one week follow up after end of treatment). For subjects up-titrated 18 weeks plus one week of follow up.
|
2.6%
1/38 • For subjects not up-titrated 13 weeks (one week follow up after end of treatment). For subjects up-titrated 18 weeks plus one week of follow up.
|
Additional Information
Jennifer L Wike, Director of Regulatory Affairs
Repros Therapeutics Inc.
Phone: 281-719-3402
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee Investigator shall submit a copy of proposed publication. Sponsor shall have sixty (60) days (or such longer period as Sponsor shall determine is necessary) to review the proposed publication and, upon request, Investigator shall delete any of Sponsor's Confidential Information or withhold submission of such publication.
- Publication restrictions are in place
Restriction type: OTHER