Secondary Amenorrhea
Conditions
Keywords
To collect additional data on 300 and 400 mg doses of PROMETRIUM in women with secondary amenorrhea
Brief summary
To evaluate the efficacy and safety of 300 mg and 400 mg doses of PROMETRIUM® capsules in women of reproductive age with secondary amenorrhea
Interventions
DRUGPROMETRIUM® 300 mg
300 mg (3x100mg capsules) by mouth once daily at bedtime for 10 days X 3 cycles
DRUGPROMETRIUM® 400 mg
400 mg (4x100mg capsules) by mouth once daily at bedtime for 10 days X 3 cycles
Sponsors
Solvay Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
No
Inclusion criteria
* Women with secondary amenorrhea * Normal serum Dehydroepiandrosterone (DHEA), prolactin, testosterone, Thyroid Stimulating Hormone (TSH) and thyroxine
Exclusion criteria
* Primary amenorrhea * Other medical conditions resulting in amenorrhea (e.g. Asherman's syndrome) * Peanut allergy * Allergy to progestational steroids
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Secretory Conversion of the Endometrium | End of the study (Days 85) | Endometrial biopsy results were classified as : Secretory (Complete or partial), Non-secretory, Unable to determine or Unknown after an evaluation of morphologic criteria. |
| Number of Subjects With Withdrawal Bleeding | After first and second cycle (cycle=28 days) | This measure is the number of subjects with withdrawal bleeding using Last Observation Carried Forward (LOCF) after first and second cycle. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Duration of Withdrawal Bleeding After Second Treatment Cycle | End of the second cycle of treatment (cycle=28 days) | The numbers of days the subjects actually bled after the end of the second treatment cycle |
| Maximum Intensity of Withdrawal Bleeding After Any Cycle | Duration of withdrawal bleed | The intensity of withdrawal bleeding was classified by: None, Spotting, Light, Moderate, Heavy |
| Time to Withdrawal Bleeding After Second Treatment Cycle | End of the second cycle of treatment (cycle=28 days) | The number of days between the second cycle of treatment and the withdrawal bleeding |
| Time to Withdrawal Bleeding After First Treatment Cycle | End of the first cycle of treatment (cycle=28 days) | The number of days between the first cycle of treatment and the withdrawal bleeding. |
| The Duration of Withdrawal Bleeding After the First Treatment Cycle | End of the first cycle of treatment (cycle=28 days) | The numbers of days the subjects actually bled after the end of the first treatment cycle. |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited in 42 centers in US between November 2004 and February 2009. Before the randomization, subjects were evaluated for eligibility. In total 240 subjects were randomized.
Pre-assignment details
The Baseline characteristics are presented using the Full Analysis Sample (FAS) to be online with the Efficacy analysis results.
Participants by arm
| Arm | Count |
|---|---|
| Prometrium 300 mg/Day | 107 |
| Prometrium 400 mg/Day | 99 |
| Total | 206 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Administrative | 0 | 1 |
| Overall Study | Adverse Event | 5 | 14 |
| Overall Study | Lack of Efficacy | 0 | 1 |
| Overall Study | Lost to Follow-up | 7 | 7 |
| Overall Study | Protocol Violation | 8 | 8 |
| Overall Study | Withdrawal by Subject | 4 | 6 |
Baseline characteristics
| Characteristic | Prometrium 300 mg/Day | Prometrium 400 mg/Day | Total |
|---|---|---|---|
| Age Continuous | 29.2 years STANDARD_DEVIATION 6.63 | 28.7 years STANDARD_DEVIATION 6.35 | 29.0 years STANDARD_DEVIATION 6.49 |
| Region of Enrollment United States | 107 participants | 99 participants | 206 participants |
| Sex: Female, Male Female | 107 Participants | 99 Participants | 206 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 72 / 113 | 70 / 107 |
| serious Total, serious adverse events | 2 / 113 | 1 / 107 |
Outcome results
Primary
Number of Subjects With Withdrawal Bleeding
This measure is the number of subjects with withdrawal bleeding using Last Observation Carried Forward (LOCF) after first and second cycle.
Time frame: After first and second cycle (cycle=28 days)
Population: The analysis was done on the Full Analysis Sample defined as subjects who received at least one dose of treatment and with at least one post-baseline evaluable efficacy assessment. Only summary statistics were generated.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Prometrium 300 mg/Day | Number of Subjects With Withdrawal Bleeding | 93 participants |
| Prometrium 400 mg/Day | Number of Subjects With Withdrawal Bleeding | 90 participants |
Primary
Secretory Conversion of the Endometrium
Endometrial biopsy results were classified as : Secretory (Complete or partial), Non-secretory, Unable to determine or Unknown after an evaluation of morphologic criteria.
Time frame: End of the study (Days 85)
Population: The analysis was done on the Full Analysis Sample defined as subjects who received at least one dose of treatment and with at least one post-baseline evaluable efficacy assessment. Only summary statistics were generated.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Prometrium 300 mg/Day | Secretory Conversion of the Endometrium | Secretory | 23 participants |
| Prometrium 300 mg/Day | Secretory Conversion of the Endometrium | Non-Secretory | 70 participants |
| Prometrium 300 mg/Day | Secretory Conversion of the Endometrium | Unable to determine | 7 participants |
| Prometrium 300 mg/Day | Secretory Conversion of the Endometrium | Unknown | 4 participants |
| Prometrium 400 mg/Day | Secretory Conversion of the Endometrium | Unknown | 2 participants |
| Prometrium 400 mg/Day | Secretory Conversion of the Endometrium | Secretory | 28 participants |
| Prometrium 400 mg/Day | Secretory Conversion of the Endometrium | Unable to determine | 9 participants |
| Prometrium 400 mg/Day | Secretory Conversion of the Endometrium | Non-Secretory | 53 participants |
Secondary
Maximum Intensity of Withdrawal Bleeding After Any Cycle
The intensity of withdrawal bleeding was classified by: None, Spotting, Light, Moderate, Heavy
Time frame: Duration of withdrawal bleed
Population: The analysis was done on the Full Analysis Sample defined as subjects who received at least one dose of treatment and with at least one post-baseline evaluable efficacy assessment. Only summary statistics were generated.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Prometrium 300 mg/Day | Maximum Intensity of Withdrawal Bleeding After Any Cycle | Spotting (Intermittent Staining) | 10 participants |
| Prometrium 300 mg/Day | Maximum Intensity of Withdrawal Bleeding After Any Cycle | Moderate (Modest amount-continuous staining) | 25 participants |
| Prometrium 300 mg/Day | Maximum Intensity of Withdrawal Bleeding After Any Cycle | Light (Slight amount-continuous staining) | 18 participants |
| Prometrium 300 mg/Day | Maximum Intensity of Withdrawal Bleeding After Any Cycle | Heavy (Large amount-heavy clots) | 40 participants |
| Prometrium 300 mg/Day | Maximum Intensity of Withdrawal Bleeding After Any Cycle | None | 13 participants |
| Prometrium 400 mg/Day | Maximum Intensity of Withdrawal Bleeding After Any Cycle | Heavy (Large amount-heavy clots) | 33 participants |
| Prometrium 400 mg/Day | Maximum Intensity of Withdrawal Bleeding After Any Cycle | None | 8 participants |
| Prometrium 400 mg/Day | Maximum Intensity of Withdrawal Bleeding After Any Cycle | Spotting (Intermittent Staining) | 3 participants |
| Prometrium 400 mg/Day | Maximum Intensity of Withdrawal Bleeding After Any Cycle | Light (Slight amount-continuous staining) | 14 participants |
| Prometrium 400 mg/Day | Maximum Intensity of Withdrawal Bleeding After Any Cycle | Moderate (Modest amount-continuous staining) | 40 participants |
Secondary
The Duration of Withdrawal Bleeding After Second Treatment Cycle
The numbers of days the subjects actually bled after the end of the second treatment cycle
Time frame: End of the second cycle of treatment (cycle=28 days)
Population: The analysis was done on the Full Analysis Sample defined as subjects who received at least one dose of treatment and with at least one post-baseline evaluable efficacy assessment. Only summary statistics were generated.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prometrium 300 mg/Day | The Duration of Withdrawal Bleeding After Second Treatment Cycle | 3.5 Days | Standard Deviation 2.15 |
| Prometrium 400 mg/Day | The Duration of Withdrawal Bleeding After Second Treatment Cycle | 3.8 Days | Standard Deviation 1.62 |
Secondary
The Duration of Withdrawal Bleeding After the First Treatment Cycle
The numbers of days the subjects actually bled after the end of the first treatment cycle.
Time frame: End of the first cycle of treatment (cycle=28 days)
Population: The analysis was done on the Full Analysis Sample defined as subjects who received at least one dose of treatment and with at least one post-baseline evaluable efficacy assessment. Only summary statistics were generated.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prometrium 300 mg/Day | The Duration of Withdrawal Bleeding After the First Treatment Cycle | 4.0 Days | Standard Deviation 2.03 |
| Prometrium 400 mg/Day | The Duration of Withdrawal Bleeding After the First Treatment Cycle | 3.8 Days | Standard Deviation 1.88 |
Secondary
Time to Withdrawal Bleeding After First Treatment Cycle
The number of days between the first cycle of treatment and the withdrawal bleeding.
Time frame: End of the first cycle of treatment (cycle=28 days)
Population: The analysis was done on the Full Analysis Sample defined as subjects who received at least one dose of treatment and with at least one post-baseline evaluable efficacy assessment. Only summary statistics were generated.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prometrium 300 mg/Day | Time to Withdrawal Bleeding After First Treatment Cycle | 1.9 Days | Standard Deviation 1.89 |
| Prometrium 400 mg/Day | Time to Withdrawal Bleeding After First Treatment Cycle | 2.2 Days | Standard Deviation 1.81 |
Secondary
Time to Withdrawal Bleeding After Second Treatment Cycle
The number of days between the second cycle of treatment and the withdrawal bleeding
Time frame: End of the second cycle of treatment (cycle=28 days)
Population: The analysis was done on the Full Analysis Sample defined as subjects who received at least one dose of treatment and with at least one post-baseline evaluable efficacy assessment. Only summary statistics were generated.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prometrium 300 mg/Day | Time to Withdrawal Bleeding After Second Treatment Cycle | 1.6 Days | Standard Deviation 1.99 |
| Prometrium 400 mg/Day | Time to Withdrawal Bleeding After Second Treatment Cycle | 2.21 Days | Standard Deviation 1.72 |