Contraception
Conditions
Keywords
Birth Control, Heavy menstrual bleeding
Brief summary
The study is performed to assess if Mirena is effective and safe as a birth control method beyond 5 years of use. Further the menstrual blood loss (in women that had Mirena inserted for the indication heavy menstrual bleeding \[HMB\]) and safety will be assessed.
Interventions
Levonorgestrel (LNG) intrauterine delivery system (IUS) with an initial in vitro release rate of 20 μg levonorgestrel per day.
Sponsors
Bayer
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 35 Years
Healthy volunteers
No
Inclusion criteria
* Signed and dated informed consent * Women, 18 to 35 years of age at the time of screening (visit 1) who are currently using Mirena for contraception or for contraception and heavy menstrual bleeding. The duration of use of the current Mirena has to be at least 4 years 6 months at the start of screening phase but not more than 5 years at visit 2 and the woman is willing to continue with its use and has a continuing need for contraception. * Normal or clinically insignificant cervical smear not requiring further follow up
Exclusion criteria
* Menopausal symptoms with Follicle-stimulating hormone\>30 mIU/ml * Pregnancy or suspicion of pregnancy * Uterine bleeding of unknown etiology * Untreated acute cervicitis or vaginitis or other lower genital tract infections * Increased susceptibility to pelvic infection * Acute pelvic inflammatory disease (PID) or a history of PID unless successfully treated and which, in the investigator's opinion, has not negatively affected subject's fertility * Congenital or acquired uterine anomaly if it distorts the uterine cavity * History of, diagnosed or suspected genital or other malignancy and untreated cervical dysplasia * Any active acute liver disease or liver tumor (benign or malignant) * Clinically significant endometrial polyp(s)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Pregnancies Per 100 Women Years (Pearl Index [PI]) Within Years 6 Thru 8 of Mirena Use | Years 6 to 8 of Mirena use | The Pearl Index (PI) is defined as the number of pregnancies per 100 women years. The 3-year PI (Years 6 to 8) was obtained by dividing the number of pregnancies the occurred during that time (starting at Day 1 Year 6 and up to Day 365 of Year 8) by the time (in 100 women years) that the women were at risk of getting pregnant during that time. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Menstrual Blood Loss (MBL) During a 30-day Period Starting at the Baseline Visit and at the End of Years 6, 7 and 8 | Baseline and end of Years 6, 7 and 8 of Mirena use | Menstrual blood loss (MBL) during a 30-day period starting at the baseline visit and at the end of Year 6, Year 7, and Year 8, measured by the alkaline hematin method. The assessment of this variable was restricted to women who had Mirena inserted for heavy menstrual bleeding (HMB). |
| Number of Participants With Menstrual Blood Loss (MBL) (>= 80 ml Per 30 Days) at End of Year 6, 7 and 8 of Mirena Use | At end of Year 6, 7 and 8 of Mirena use | Categorized menstrual blood loss (MBL) (≥ 80 mL per 30 days) at end of Year 6, Year 7, and Year 8. The assessment of this variable was restricted to women who had Mirena inserted for HMB. |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Years 6 to 8 of Mirena use | Adverse event (AE) was defined as any untoward medical occurrence (ie any unfavorable and unintended sign \[including abnormal laboratory findings\], symptom or disease) in a patient or clinical investigation subject after providing written informed consent for participation in the study. Serious adverse event (SAE) was defined as any untoward medical occurrence that, at any dose 1) resulted in death, 2) was life-threatening, 3) required inpatient hospitalization or prolongation of existing hospitalization, 4) resulted in persistent or significant disability/incapacity, 5) was a congenital anomaly/birth defect, or 6) was another medically important serious event as judged by the investigator. Treatment-emergent adverse event (TEAE) was defined as an AE that occurred on Day 1 Year 6 of Mirena use or later. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Total LNG Concentrations in Plasma Estimated Based on the Final 8-year Population Pharmacokinetics (popPK) Model | At the beginning of Year 6 (baseline) and at the end of Years 6, 7, and 8 of Mirena use | A population pharmacokinetic (popPK) analysis was performed including sparse data from the study. |
| Participant's Satisfaction With Mirena by Visit | Baseline, at end of Year 6, 7 and 8 of Mirena use | Participants were asked to evaluate their satisfaction with Mirena on a 5-point scale as very satisfied, somewhat satisfied, neither satisfied or dissatisfied, dissatisfied or very dissatisfied. |
Countries
United States
Participant flow
Pre-assignment details
A total of 364 women entered treatment period. Of these, 2 women were not valid for FAS (full analysis set)/SAF (safety analysis set)/PAS(primary analysis set) due to incomplete source data verification.
Participants by arm
| Arm | Count |
|---|---|
| Levonorgestrel IUS (Mirena, BAY86-5028) Mirena during extended use (Years 6 to 8). | 362 |
| Total | 362 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 27 |
| Overall Study | Lost to Follow-up | 26 |
| Overall Study | Not valid for analysis | 2 |
| Overall Study | Other reason | 5 |
| Overall Study | Physician Decision | 2 |
| Overall Study | Pregnancy | 2 |
| Overall Study | Wish for pregnancy | 44 |
| Overall Study | Withdrawal by Subject | 33 |
Baseline characteristics
| Characteristic | Levonorgestrel IUS (Mirena, BAY86-5028) |
|---|---|
| Age, Continuous | 29.4 years STANDARD_DEVIATION 3.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 41 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 319 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Parity Nulliparous | 171 Participants |
| Parity Parous | 191 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants |
| Race (NIH/OMB) Asian | 9 Participants |
| Race (NIH/OMB) Black or African American | 51 Participants |
| Race (NIH/OMB) More than one race | 14 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 13 Participants |
| Race (NIH/OMB) White | 273 Participants |
| Sex: Female, Male Female | 362 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 362 |
| other Total, other adverse events | 107 / 362 |
| serious Total, serious adverse events | 14 / 362 |
Outcome results
Primary
Number of Pregnancies Per 100 Women Years (Pearl Index [PI]) Within Years 6 Thru 8 of Mirena Use
The Pearl Index (PI) is defined as the number of pregnancies per 100 women years. The 3-year PI (Years 6 to 8) was obtained by dividing the number of pregnancies the occurred during that time (starting at Day 1 Year 6 and up to Day 365 of Year 8) by the time (in 100 women years) that the women were at risk of getting pregnant during that time.
Time frame: Years 6 to 8 of Mirena use
Population: All women in the full analysis set (FAS) with an age of 33 years or younger at baseline visit (i.e. an age of 36 or younger at end of year 8).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Levonorgestrel IUS (Mirena, BAY86-5028) | Number of Pregnancies Per 100 Women Years (Pearl Index [PI]) Within Years 6 Thru 8 of Mirena Use | 0.28 Pregnancies per 100 women years |
Comparison: Cumulative failure rate (Kaplan-Meier) during Years 6-895% CI: [0.17, 2.71]
Secondary
Menstrual Blood Loss (MBL) During a 30-day Period Starting at the Baseline Visit and at the End of Years 6, 7 and 8
Menstrual blood loss (MBL) during a 30-day period starting at the baseline visit and at the end of Year 6, Year 7, and Year 8, measured by the alkaline hematin method. The assessment of this variable was restricted to women who had Mirena inserted for heavy menstrual bleeding (HMB).
Time frame: Baseline and end of Years 6, 7 and 8 of Mirena use
Population: Women who had Mirena inserted for HMB
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Levonorgestrel IUS (Mirena, BAY86-5028) | Menstrual Blood Loss (MBL) During a 30-day Period Starting at the Baseline Visit and at the End of Years 6, 7 and 8 | Beginning of Year 6 (baseline) | 0.000 mL/30 days |
| Levonorgestrel IUS (Mirena, BAY86-5028) | Menstrual Blood Loss (MBL) During a 30-day Period Starting at the Baseline Visit and at the End of Years 6, 7 and 8 | End of Year 6 | 0.000 mL/30 days |
| Levonorgestrel IUS (Mirena, BAY86-5028) | Menstrual Blood Loss (MBL) During a 30-day Period Starting at the Baseline Visit and at the End of Years 6, 7 and 8 | End of Year 7 | 0.000 mL/30 days |
| Levonorgestrel IUS (Mirena, BAY86-5028) | Menstrual Blood Loss (MBL) During a 30-day Period Starting at the Baseline Visit and at the End of Years 6, 7 and 8 | End of Year 8 | 0.000 mL/30 days |
Secondary
Number of Participants With Menstrual Blood Loss (MBL) (>= 80 ml Per 30 Days) at End of Year 6, 7 and 8 of Mirena Use
Categorized menstrual blood loss (MBL) (≥ 80 mL per 30 days) at end of Year 6, Year 7, and Year 8. The assessment of this variable was restricted to women who had Mirena inserted for HMB.
Time frame: At end of Year 6, 7 and 8 of Mirena use
Population: Women who had Mirena inserted for HMB
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Levonorgestrel IUS (Mirena, BAY86-5028) | Number of Participants With Menstrual Blood Loss (MBL) (>= 80 ml Per 30 Days) at End of Year 6, 7 and 8 of Mirena Use | End of Year 6 | 0 Participants |
| Levonorgestrel IUS (Mirena, BAY86-5028) | Number of Participants With Menstrual Blood Loss (MBL) (>= 80 ml Per 30 Days) at End of Year 6, 7 and 8 of Mirena Use | End of Year 7 | 0 Participants |
| Levonorgestrel IUS (Mirena, BAY86-5028) | Number of Participants With Menstrual Blood Loss (MBL) (>= 80 ml Per 30 Days) at End of Year 6, 7 and 8 of Mirena Use | End of Year 8 | 0 Participants |
Secondary
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Adverse event (AE) was defined as any untoward medical occurrence (ie any unfavorable and unintended sign \[including abnormal laboratory findings\], symptom or disease) in a patient or clinical investigation subject after providing written informed consent for participation in the study. Serious adverse event (SAE) was defined as any untoward medical occurrence that, at any dose 1) resulted in death, 2) was life-threatening, 3) required inpatient hospitalization or prolongation of existing hospitalization, 4) resulted in persistent or significant disability/incapacity, 5) was a congenital anomaly/birth defect, or 6) was another medically important serious event as judged by the investigator. Treatment-emergent adverse event (TEAE) was defined as an AE that occurred on Day 1 Year 6 of Mirena use or later.
Time frame: Years 6 to 8 of Mirena use
Population: Safety analysis set (SAF): All women who completed the baseline visit of the study, analyzed for the FAS.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Levonorgestrel IUS (Mirena, BAY86-5028) | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Any AE | 249 Participants |
| Levonorgestrel IUS (Mirena, BAY86-5028) | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Any SAE | 14 Participants |
Other Pre-specified
Participant's Satisfaction With Mirena by Visit
Participants were asked to evaluate their satisfaction with Mirena on a 5-point scale as very satisfied, somewhat satisfied, neither satisfied or dissatisfied, dissatisfied or very dissatisfied.
Time frame: Baseline, at end of Year 6, 7 and 8 of Mirena use
Population: Full analysis set (FAS): All women who completed the baseline visit of the study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Levonorgestrel IUS (Mirena, BAY86-5028) | Participant's Satisfaction With Mirena by Visit | Baseline (very satisfied) | 342 Participants |
| Levonorgestrel IUS (Mirena, BAY86-5028) | Participant's Satisfaction With Mirena by Visit | Baseline (somewhat satisfied) | 20 Participants |
| Levonorgestrel IUS (Mirena, BAY86-5028) | Participant's Satisfaction With Mirena by Visit | Baseline (neither satisfied nor dissatisfied) | 0 Participants |
| Levonorgestrel IUS (Mirena, BAY86-5028) | Participant's Satisfaction With Mirena by Visit | Baseline (dissatisfied) | 0 Participants |
| Levonorgestrel IUS (Mirena, BAY86-5028) | Participant's Satisfaction With Mirena by Visit | Baseline (very dissatisfied) | 0 Participants |
| Levonorgestrel IUS (Mirena, BAY86-5028) | Participant's Satisfaction With Mirena by Visit | Year 6 (very satisfied) | 279 Participants |
| Levonorgestrel IUS (Mirena, BAY86-5028) | Participant's Satisfaction With Mirena by Visit | Year 6 (somewhat satisfied) | 20 Participants |
| Levonorgestrel IUS (Mirena, BAY86-5028) | Participant's Satisfaction With Mirena by Visit | Year 6 (neither satisfied nor dissatisfied) | 3 Participants |
| Levonorgestrel IUS (Mirena, BAY86-5028) | Participant's Satisfaction With Mirena by Visit | Year 6 (dissatisfied) | 0 Participants |
| Levonorgestrel IUS (Mirena, BAY86-5028) | Participant's Satisfaction With Mirena by Visit | Year 6 (very dissatisfied) | 0 Participants |
| Levonorgestrel IUS (Mirena, BAY86-5028) | Participant's Satisfaction With Mirena by Visit | Year 7 (very satisfied) | 218 Participants |
| Levonorgestrel IUS (Mirena, BAY86-5028) | Participant's Satisfaction With Mirena by Visit | Year 7 (somewhat satisfied) | 20 Participants |
| Levonorgestrel IUS (Mirena, BAY86-5028) | Participant's Satisfaction With Mirena by Visit | Year 7 (neither satisfied nor dissatisfied) | 1 Participants |
| Levonorgestrel IUS (Mirena, BAY86-5028) | Participant's Satisfaction With Mirena by Visit | Year 7 (dissatisfied) | 3 Participants |
| Levonorgestrel IUS (Mirena, BAY86-5028) | Participant's Satisfaction With Mirena by Visit | Year 7 (very dissatisfied) | 1 Participants |
| Levonorgestrel IUS (Mirena, BAY86-5028) | Participant's Satisfaction With Mirena by Visit | Year 8 (very satisfied) | 207 Participants |
| Levonorgestrel IUS (Mirena, BAY86-5028) | Participant's Satisfaction With Mirena by Visit | Year 8 (somewhat satisfied) | 13 Participants |
| Levonorgestrel IUS (Mirena, BAY86-5028) | Participant's Satisfaction With Mirena by Visit | Year 8 (neither satisfied nor dissatisfied) | 3 Participants |
| Levonorgestrel IUS (Mirena, BAY86-5028) | Participant's Satisfaction With Mirena by Visit | Year 8 (dissatisfied) | 0 Participants |
| Levonorgestrel IUS (Mirena, BAY86-5028) | Participant's Satisfaction With Mirena by Visit | Year 8 (very dissatisfied) | 0 Participants |
Other Pre-specified
Total LNG Concentrations in Plasma Estimated Based on the Final 8-year Population Pharmacokinetics (popPK) Model
A population pharmacokinetic (popPK) analysis was performed including sparse data from the study.
Time frame: At the beginning of Year 6 (baseline) and at the end of Years 6, 7, and 8 of Mirena use
Population: Concentrations were estimated for women who had Mirena still in place.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Levonorgestrel IUS (Mirena, BAY86-5028) | Total LNG Concentrations in Plasma Estimated Based on the Final 8-year Population Pharmacokinetics (popPK) Model | At the beginning of Year 6 (baseline) | 123 ng/L | Geometric Coefficient of Variation 38.3 |
| Levonorgestrel IUS (Mirena, BAY86-5028) | Total LNG Concentrations in Plasma Estimated Based on the Final 8-year Population Pharmacokinetics (popPK) Model | At the end of Year 6 | 114 ng/L | Geometric Coefficient of Variation 38.7 |
| Levonorgestrel IUS (Mirena, BAY86-5028) | Total LNG Concentrations in Plasma Estimated Based on the Final 8-year Population Pharmacokinetics (popPK) Model | At the end of Year 7 | 106 ng/L | Geometric Coefficient of Variation 39.2 |
| Levonorgestrel IUS (Mirena, BAY86-5028) | Total LNG Concentrations in Plasma Estimated Based on the Final 8-year Population Pharmacokinetics (popPK) Model | At the end of Year 8 | 100 ng/L | Geometric Coefficient of Variation 39.9 |