Postmenopause
Conditions
Keywords
Postmenopausal Symptoms e.g., Hot flushes, Sweating episodes, Vaginal dryness
Brief summary
The study is designed to investigate the safety of the investigational product for the lining of the uterus (endometrium).
Interventions
One capsule \[0.25mg drospirenone/0.5mg 17β-estradiol (DRSP/E2)\] per day taken orally for 13 cycles (28 days per cycle).
DRUG0.5mg NETA / 1.0mg E2 (Activella)
One capsule \[0.5mg norethisterone acetate/1.0mg 17β-estradiol (NETA/E2)\] per day taken orally for 13 cycles (28 days per cycle).
Sponsors
Laboratorium für Klinische Forschung
Diagnostic Cytology Laboratory
University of California, San Francisco
Bayer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
40 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Postmenopausal women between 40 and 65 years of age with hormone therapy indication (symptoms and need for treatment) * Non-hysterectomized women.
Exclusion criteria
* Usual
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants in the DRSP/E2 Group With an Assessment of Endometrial Hyperplasia or Worse at End of Study (EoS) (1 Year of Treatment) | Up to one year | The number of women who had a biopsy classified as 'hyperplasia or worse' at any time during the study. According to the protocol this endpoint was defined as primary for the DRSP/E2 group only. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Amenorrhea During Month 1 to 3 of Treatment | Month 1 to Month 3 | The women were to record daily in a diary, indicating 'no bleeding', 'spotting', 'light bleeding', 'normal bleeding' or 'heavy bleeding'. Women were considered to have amenorrhea if they had no bleeding and no spotting day within the given time interval. |
| Number of Participants With Amenorrhea During Month 10 to 12 of Treatment | Month 10 to Month 12 | The women were to record any bleeding daily in a diary, indicating 'no bleeding', 'spotting', 'light bleeding', 'normal bleeding' or 'heavy bleeding'. Women were considered to have amenorrhea if they had no bleeding and no spotting day within the given time interval. |
Countries
Argentina, Austria, Brazil, Denmark, Italy, Mexico, Russia, United States
Participant flow
Recruitment details
Only non-hysterectomized, postmenopausal women could take part in this study. The women had to have symptoms requiring hormone therapy in the opinion of the investigator. An endometrial biopsy at screening was to show no evidence of endometrial hyperplasia or cancer.
Pre-assignment details
944 women screened, 661 treated. 282 failed screening: consent withdrawn (55), in-/exclusion criteria not met (209), lost to follow-up (3), other (15). 1 woman was randomized but not treated (own decision). 5 women completed the study but not study medication, i.e. they stopped medication early but remained in the study for final assessments.
Participants by arm
| Arm | Count |
|---|---|
| 0.25mg DRSP / 0.5mg E2 (BAY86-4891) One capsule \[0.25mg drospirenone/0.5mg 17β-estradiol (DRSP/E2)\] per day taken orally for 13 cycles (28 days per cycle). | 489 |
| 0.5mg NETA / 1.0mg E2 (Activella) One capsule \[0.5mg norethisterone acetate/1.0mg 17β-estradiol (NETA/E2)\] per day taken orally for 13 cycles (28 days per cycle). | 172 |
| Total | 661 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 41 | 26 |
| Overall Study | Lost to Follow-up | 11 | 3 |
| Overall Study | Medication Errors | 1 | 1 |
| Overall Study | Never Received Medication | 1 | 0 |
| Overall Study | Personal Reasons | 8 | 1 |
| Overall Study | Protocol Violation | 14 | 4 |
| Overall Study | Withdrawal by Subject | 20 | 9 |
Baseline characteristics
| Characteristic | 0.25mg DRSP / 0.5mg E2 (BAY86-4891) | 0.5mg NETA / 1.0mg E2 (Activella) | Total |
|---|---|---|---|
| Age, Continuous | 53.5 Years STANDARD_DEVIATION 5.1 | 53.5 Years STANDARD_DEVIATION 4.5 | 53.5 Years STANDARD_DEVIATION 4.9 |
| Body Mass Index (BMI) | 26.315 kg/m^2 STANDARD_DEVIATION 4.851 | 26.020 kg/m^2 STANDARD_DEVIATION 5.476 | 26.184 kg/m^2 STANDARD_DEVIATION 5.008 |
| Number of participants with hysterectomy/oophorectomy Hysterectomized | 0 Participants | 0 Participants | 0 Participants |
| Number of participants with hysterectomy/oophorectomy Oophorectomized | 25 Participants | 5 Participants | 30 Participants |
| Sex: Female, Male Female | 489 Participants | 172 Participants | 661 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
| Years since last menstruation at baseline | 5.109 years STANDARD_DEVIATION 4.528 | 4.807 years STANDARD_DEVIATION 4.287 | 5.031 years STANDARD_DEVIATION 4.465 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 172 / 489 | 63 / 172 |
| serious Total, serious adverse events | 16 / 489 | 6 / 172 |
Outcome results
Primary
Number of Participants in the DRSP/E2 Group With an Assessment of Endometrial Hyperplasia or Worse at End of Study (EoS) (1 Year of Treatment)
The number of women who had a biopsy classified as 'hyperplasia or worse' at any time during the study. According to the protocol this endpoint was defined as primary for the DRSP/E2 group only.
Time frame: Up to one year
Population: For the DRSP/E2 group only - Primary analysis set (PAS): All subjects from the full analysis set (FAS) who either had a biopsy result classified as 'normal' or 'hyperplasia or worse' after a year of treatment or who prematurely discontinued the study before Cycle 13 with a biopsy classified as 'hyperplasia or worse'.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 0.25mg DRSP / 0.5mg E2 (BAY86-4891) | Number of Participants in the DRSP/E2 Group With an Assessment of Endometrial Hyperplasia or Worse at End of Study (EoS) (1 Year of Treatment) | 0 Participants |
Comparison: Exact 95% confidence interval for proportion of participants with hyperplasia or worse at EoS95% CI: [0, 0.0119]
Secondary
Number of Participants With Amenorrhea During Month 10 to 12 of Treatment
The women were to record any bleeding daily in a diary, indicating 'no bleeding', 'spotting', 'light bleeding', 'normal bleeding' or 'heavy bleeding'. Women were considered to have amenorrhea if they had no bleeding and no spotting day within the given time interval.
Time frame: Month 10 to Month 12
Population: Per protocol set (PPS): All subjects from the FAS who had at least 75% overall study drug compliance and no major protocol violations
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 0.25mg DRSP / 0.5mg E2 (BAY86-4891) | Number of Participants With Amenorrhea During Month 10 to 12 of Treatment | 280 Participants |
| 0.5mg NETA / 1.0mg E2 (Activella) | Number of Participants With Amenorrhea During Month 10 to 12 of Treatment | 89 Participants |
Comparison: exact 95% confidence intervall (Clopper-Pearson) for proportion of participants with amenorrhea95% CI: [0.743, 0.83]
Comparison: exact 95% confidence intervall (Clopper-Pearson) for proportion of participants with amenorrhea95% CI: [0.756, 0.904]
Secondary
Number of Participants With Amenorrhea During Month 1 to 3 of Treatment
The women were to record daily in a diary, indicating 'no bleeding', 'spotting', 'light bleeding', 'normal bleeding' or 'heavy bleeding'. Women were considered to have amenorrhea if they had no bleeding and no spotting day within the given time interval.
Time frame: Month 1 to Month 3
Population: Per protocol set (PPS): All subjects from the FAS who had at least 75% overall study drug compliance and no major protocol violations
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 0.25mg DRSP / 0.5mg E2 (BAY86-4891) | Number of Participants With Amenorrhea During Month 1 to 3 of Treatment | 255 Participants |
| 0.5mg NETA / 1.0mg E2 (Activella) | Number of Participants With Amenorrhea During Month 1 to 3 of Treatment | 67 Participants |
Comparison: exact 95% confidence intervall (Clopper-Pearson) for proportion of participants with amenorrhea95% CI: [0.637, 0.734]
Comparison: exact 95% confidence intervall (Clopper-Pearson) for proportion of participants with amenorrhea95% CI: [0.496, 0.684]