Contraception
Conditions
Keywords
Estetrol
Brief summary
The objectives of this study are to evaluate the contraceptive efficacy, vaginal bleeding pattern (cycle control), and the general safety and acceptability of the 15 mg estetrol (E4)/3 mg drospirenone (DRSP) combination in healthy women aged 18 to 50 years.
Interventions
15 mg estetrol and 3 mg drospirenone tablets administered once daily for 13 consecutive cycles following a 24/4-day regimen, i.e. one 15 mg E4/3 mg DRSP active tablet per day for 24 consecutive days followed by one placebo tablet per day for 4 consecutive days.
Sponsors
PRA Health Sciences
Estetra
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
* Heterosexually active female at risk for pregnancy and requesting contraception. * Negative serum pregnancy test at subject enrollment. * Willing to use the investigational product as the primary method of contraception for 13 consecutive cycles. * Good physical and mental health on the basis of medical, surgical and gynecological history, physical examination, gynecological examination, clinical laboratory, and vital signs. * Body mass index (BMI) below or equal to (≤) 35.0 kg/m2. * Able to fulfill the requirements of the protocol and have indicated a willingness to participate in the study by providing written informed consent (IC). * Willing and able to complete the diaries and questionnaires.
Exclusion criteria
* Known hypersensitivity to any of the investigational product ingredients. * Smoking if ≥ 35 years old, at screening. * Any condition associated with decrease fertility. * Dyslipoproteinemia requiring active treatment with antilipidemic agent. * Diabetes mellitus with vascular involvement (nephropathy, retinopathy, neuropathy, other) or diabetes mellitus of more than 20-year duration. * Arterial hypertension. * Any condition associated with an increased risk of venous thromboembolism and/or arterial thromboembolism. * Any condition associated with abnormal uterine/vaginal bleeding. * Abnormal Pap test based on current international recommendations. * Presence of an undiagnosed breast mass. * Current symptomatic gallbladder disease. * History of COC related cholestasis. * Presence or history of severe hepatic disease. * Presence or history of pancreatitis if associated with hypertriglyceridemia. * Porphyria. * Presence or history of hepatocellular adenoma or malignant liver tumors. * Renal impairment. * Hyperkaliemia or presence of conditions that predispose to hyperkaliemia. * Presence or history of hormone-related malignancy. * History of non-hormone-related malignancy within 5 years before screening. Subjects with a non-melanoma skin cancer are allowed in the study. * Use of drugs potentially triggering interactions with COCs. * History of alcohol or drug abuse (including laxatives) within 12 months prior to screening. * Any condition that could result in altered absorption, excessive accumulation, impaired metabolism, or altered excretion of the investigational product. * Uncontrolled thyroid disorders. * Participation in another investigational drug clinical study within 1 month (30 days) or have received an investigational drug within the last 3 months (90 days) prior to study entry. Subjects who participated in an oral contraceptive clinical study, using FDA/EU approved active ingredients, may be enrolled 2 months (60 days) after completing the preceding study. * Sponsor, CRO or Investigator's site personnel directly affiliated with this study. * Is judged by the Investigator to be unsuitable for any reason.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Number of On-treatment Pregnancies (With + 2-day Window) Per 100 Woman-years of Exposure (Pearl Index) in Subjects Aged 18 to 35 Years, Inclusive, at the Time of Screening | Up to 12 months (13 cycles with 1 cycle = 28 days) | On-treatment pregnancies are defined as pregnancies with an estimated date of conception within the in-treatment period i.e. Day 1 to 2 days after the last intake of investigational product (whether active or inactive tablet). The Pearl Index, defined as the number of pregnancies per 100 women-years of treatment was calculated as: Pearl Index = (1300\*number of on-treatment pregnancies)/number of women 28-day equivalent cycles of treatment.Only at-risk cycles were included in the denominator of the Pearl Index calculation. At-risk-cycles were defined as cycles in which no other methods of birth control (including condoms) were used by the subject as confirmed in the subject diary and during which the subject confirmed that sexual intercourse had occurred. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Number of On-treatment Pregnancies (With + 2-day Window) Per 100 Woman-years of Exposure (Pearl Index) in the Overall Study Population (18-50 Years) | Up to 12 months (13 cycles with 1 cycle = 28 days) | On-treatment pregnancies are defined as pregnancies with an estimated date of conception within the in-treatment period i.e. Day 1 to 2 days after the last intake of investigational product (whether active or inactive tablet). The Pearl Index, defined as the number of pregnancies per 100 women-years of treatment was calculated as: Pearl Index = (1300\*number of on-treatment pregnancies)/number of women 28-day equivalent cycles of treatment.Only at-risk cycles were included in the denominator of the Pearl Index calculation. At-risk-cycles were defined as cycles in which no other methods of birth control (including condoms) were used by the subject as confirmed in the subject diary and during which the subject confirmed that sexual intercourse had occurred. |
| The Number of On-Treatment Pregnancies as Assessed by the Method Failure Pearl Index in the Overall Study Population (18-50 Years) | Up to 12 months (13 cycles with 1 cycle = 28 days) | On-treatment pregnancies are defined as pregnancies with an estimated date of conception within the in-treatment period i.e. Day 1 to 2 days after the last intake of investigational product (whether active or inactive tablet). The Pearl Index, defined as the number of pregnancies per 100 women-years of treatment was calculated as: Pearl Index = (1300\*number of on-treatment pregnancies)/number of women 28-day equivalent cycles of treatment. The method failure Pearl Index includes only those pregnancies that were classified as method failure and not the pregnancies due to user failure, i.e. incorrect intake of the contraceptive method. Only at-risk cycles were included in the denominator of the Pearl Index calculation. At-risk-cycles were defined as cycles in which no other methods of birth control (including condoms) were used by the subject as confirmed in the subject diary and during which the subject confirmed that sexual intercourse had occurred. |
| Number of Subjects With Unscheduled Bleeding/Spotting | Up to 11 months (12 cycles with 1 cycle = 28 days) | Unscheduled bleeding/spotting is defined as any bleeding/spotting that occurs while taking active hormones that does not meet the criteria for scheduled bleeding. |
| Number of Unscheduled Bleeding Days Per Cycle | Up to 11 months (12 cycles with 1 cycle = 28 days) | Unscheduled bleeding is defined as any bleeding that occurs while taking active hormones that does not meet the criteria for scheduled bleeding and/or spotting. |
| Number of Unscheduled Spotting Days Per Cycle | Up to 11 months (12 cycles with 1 cycle = 28 days) | Unscheduled spotting is defined as any spotting that occurs while taking active hormones that does not meet the criteria for scheduled bleeding and/or spotting. |
| Number of Subjects With Absence of Scheduled Bleeding and/or Spotting | Up to 11 months (12 cycles with 1 cycle = 28 days) | Scheduled bleeding/spotting is defined as any bleeding/spotting that occurs during the hormone-free interval (i.e. Days 25 - 28) and continues through Days 1-3 of the subsequent active cycle. |
| Number of Scheduled Bleeding and/or Spotting Days Per Cycle | Up to 11 months (12 cycles with 1 cycle = 28 days) | Scheduled bleeding and /or spotting is defined as any bleeding and/or spotting that occurs during the hormone-free interval (i.e. Days 25 - 28) and continues through Days 1-3 of the subsequent active cycle. |
| The Number of On-treatment Pregnancies (With 2-day Window) as Assessed by the Method Failure Pearl Index in Subjects Aged 18 to 35 Years, Inclusive, at the Time of Screening | Up to 12 months (13 cycles with 1 cycle = 28 days) | On-treatment pregnancies are defined as pregnancies with an estimated date of conception within the in-treatment period i.e. Day 1 to 2 days after the last intake of investigational product (whether active or inactive tablet). The Pearl Index, defined as the number of pregnancies per 100 women-years of treatment was calculated as: Pearl Index = (1300\*number of on-treatment pregnancies)/number of women 28-day equivalent cycles of treatment. The method failure Pearl Index includes only those pregnancies that were classified as method failure and not the pregnancies due to user failure, i.e. incorrect intake of the contraceptive method. Only at-risk cycles were included in the denominator of the Pearl Index calculation. At-risk-cycles were defined as cycles in which no other methods of birth control (including condoms) were used by the subject as confirmed in the subject diary and during which the subject confirmed that sexual intercourse had occurred. |
| Number of Subjects With Abnormal Laboratory Assessment Results | From screening to end of treatment (12 months) | Laboratory assessment included blood hematology, biochemistry, and lipids |
| Number of Subjects With Abnormal Physical Examination Results | From screening to end of treatment (12 months) | Physical examinations included an evaluation of body as a whole, skin, head, eyes, ears, nose, and throat, neck, cardiovascular, respiratory, musculoskeletal, neurologic, lymphatic/thyroid, abdomen. When reporting the results of the physical examination, the use of the Abnormal category was reserved for findings that were considered clinically significant, in the opinion of the Investigator; the Normal category included Abnormal results that were not clinically significant, as well as no findings. |
| Number of Subjects With Abnormal Gynecological Examination Results | From screening to end of treatment (12 months) | Gynecological examinations included breast examination (performed by palpation) and assessment of the adnexa, cervix, uterus, vagina, and external genitalia. When reporting the results, the use of the Abnormal category was reserved for findings that were considered clinically significant, in the opinion of the Investigator; the Normal category included Abnormal results that were not clinically significant, as well as no findings. |
| Endometrial Biopsy Histology at Screening and End of Treatment | Baseline and end of treatment (up to 13 cycles with 1 cycle = 28 days) | Endometrial biopsies was obtained from a subset of subjects included in the endometrial safety substudy at the screening visit and at the end of treatment visit if the subject has completed at least 10 cycles. |
| Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) Results at Baseline and End of Treatment - Percentage Maximum (Sum of First 14 Items) | Baseline and Cycle 13 (1 cycle = 28 days) | The Q-LES-Q-SF is a self-report measure designed to assess the degree of enjoyment and satisfaction in daily functioning. Participants were asked to rate 16 different items on a 5-point scale where score 1 = very poor and score 5 = very good. A raw total score is calculated by summing the first 14 items and ranges from 14 to 70 with a higher scores indicating higher life enjoyment and satisfaction. The raw total score is then transformed into a percentage maximum score using the following formula: (raw total score-minimum score)/(maximum possible raw score-minimum score). In addition, the last two items (15 and 16) are two global items that are scored individually. These items rate satisfaction with medicine and overall life satisfaction over the past week. |
| Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) Results at Baseline and End of Treatment - Satisfaction With Medicine and Overall Life Satisfaction Over the Past Week | Baseline and Cycle 13 (1 cycle = 28 days) | The Q-LES-Q-SF is a self-report measure designed to assess the degree of enjoyment and satisfaction in daily functioning. Participants were asked to rate 16 different items on a 5-point scale where score 1 = very poor and score 5 = very good. A raw total score is calculated by summing the first 14 items and ranges from 14 to 70 with a higher scores indicating higher life enjoyment and satisfaction. The raw total score is then transformed into a percentage maximum score using the following formula: (raw total score-minimum score)/(maximum possible raw score-minimum score). In addition, the last two items (15 and 16) are two global items that are scored individually. These items rate satisfaction with medicine and overall life satisfaction over the past week. |
| Change From Baseline to End of Treatment in the Score of the Menstrual Distress Questionnaire (MDQ) | Baseline and Cycle 13 (1 cycle = 28 days) | The MDQ is a standard method for measuring cyclical perimenstrual symptoms. The participants rated common symptoms and feelings associated with menstruation using the following scale: 0 (no experience of symptom), 1 (present, mild), 2 (present, moderate), 3 (present, strong),and 4 (present, severe) observed during pre-menstrual (4 days before menstruation), menstrual (most recent flow) and intermenstrual (remainder of the cycle) phases. Reported values are values at Cycle 13 minus values at Baseline. An overall positive change from baseline represents an increase in symptom or feeling severity. |
| Number of Subjects With Abnormal Vital Signs | From screening to end of treatment (12 months) | Vital signs included sitting systolic and diastolic blood pressures, and heart rate. |
Countries
Belgium
Participant flow
Pre-assignment details
A total of 1,577 participants aged 18-50 years were enrolled. Of those, 1,553 started the study treatment. Twenty-four participants did not start the treatment for the following reasons: consent withdrawn (8), unspecified reason (5), protocol deviation (3), pregnancy (4), lost to follow-up (3), and adverse event not related to bleeding (1).
Participants by arm
| Arm | Count |
|---|---|
| 15 mg E4/3 mg DRSP 15 mg E4/3 mg DRSP tablet
15 mg E4/3 mg DRSP: 15 mg estetrol and 3 mg drospirenone tablets administered orally once daily for 13 consecutive cycles following a 24/4-day regimen, i.e. one 15 mg E4/3 mg DRSP active tablet per day for 24 consecutive days followed by one placebo tablet per day for 4 consecutive days. | 1 |
| Total | 1 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse event not related to bleeding | 104 |
| Overall Study | Adverse event related to bleeding | 53 |
| Overall Study | Lost to Follow-up | 41 |
| Overall Study | Other | 26 |
| Overall Study | Pregnancy | 7 |
| Overall Study | Pregnancy wish | 15 |
| Overall Study | Protocol Violation | 11 |
| Overall Study | Withdrawal by Subject | 78 |
Baseline characteristics
| Characteristic | 15 mg E4/3 mg DRSP |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 1,553 Participants |
| Age, Continuous | 27.1 years STANDARD_DEVIATION 6.86 |
| Body mass index | 23.0 Kg/m^2 STANDARD_DEVIATION 3.469 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 13 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1540 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Region of Enrollment Belgium | 87 Participants |
| Region of Enrollment Czechia | 335 Participants |
| Region of Enrollment Finland | 181 Participants |
| Region of Enrollment Germany | 141 Participants |
| Region of Enrollment Hungary | 190 Participants |
| Region of Enrollment Norway | 108 Participants |
| Region of Enrollment Poland | 221 Participants |
| Region of Enrollment Russia | 280 Participants |
| Region of Enrollment Sweden | 10 Participants |
| Sex: Female, Male Female | 1,553 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 1,553 |
| other Total, other adverse events | 784 / 1,553 |
| serious Total, serious adverse events | 13 / 1,553 |
Outcome results
Primary
The Number of On-treatment Pregnancies (With + 2-day Window) Per 100 Woman-years of Exposure (Pearl Index) in Subjects Aged 18 to 35 Years, Inclusive, at the Time of Screening
On-treatment pregnancies are defined as pregnancies with an estimated date of conception within the in-treatment period i.e. Day 1 to 2 days after the last intake of investigational product (whether active or inactive tablet). The Pearl Index, defined as the number of pregnancies per 100 women-years of treatment was calculated as: Pearl Index = (1300\*number of on-treatment pregnancies)/number of women 28-day equivalent cycles of treatment.Only at-risk cycles were included in the denominator of the Pearl Index calculation. At-risk-cycles were defined as cycles in which no other methods of birth control (including condoms) were used by the subject as confirmed in the subject diary and during which the subject confirmed that sexual intercourse had occurred.
Time frame: Up to 12 months (13 cycles with 1 cycle = 28 days)
Population: Participants aged 18 to 35 years, inclusive, at screening with at least 1 cycle included in the denominator.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 15 mg E4/3 mg DRSP | The Number of On-treatment Pregnancies (With + 2-day Window) Per 100 Woman-years of Exposure (Pearl Index) in Subjects Aged 18 to 35 Years, Inclusive, at the Time of Screening | 0.47 Pearl Index |
Secondary
Change From Baseline to End of Treatment in the Score of the Menstrual Distress Questionnaire (MDQ)
The MDQ is a standard method for measuring cyclical perimenstrual symptoms. The participants rated common symptoms and feelings associated with menstruation using the following scale: 0 (no experience of symptom), 1 (present, mild), 2 (present, moderate), 3 (present, strong),and 4 (present, severe) observed during pre-menstrual (4 days before menstruation), menstrual (most recent flow) and intermenstrual (remainder of the cycle) phases. Reported values are values at Cycle 13 minus values at Baseline. An overall positive change from baseline represents an increase in symptom or feeling severity.
Time frame: Baseline and Cycle 13 (1 cycle = 28 days)
Population: Participants aged 18 to 50 years, inclusive, at screening with both baseline and end of treatment MDQ results.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 15 mg E4/3 mg DRSP | Change From Baseline to End of Treatment in the Score of the Menstrual Distress Questionnaire (MDQ) | Pain | -0.4 units on a scale | Standard Deviation 3.6 |
| 15 mg E4/3 mg DRSP | Change From Baseline to End of Treatment in the Score of the Menstrual Distress Questionnaire (MDQ) | Water retention | -0.1 units on a scale | Standard Deviation 2.61 |
| 15 mg E4/3 mg DRSP | Change From Baseline to End of Treatment in the Score of the Menstrual Distress Questionnaire (MDQ) | Autonomic reactions | -0.1 units on a scale | Standard Deviation 1.42 |
| 15 mg E4/3 mg DRSP | Change From Baseline to End of Treatment in the Score of the Menstrual Distress Questionnaire (MDQ) | Negative affect | -0.4 units on a scale | Standard Deviation 4.9 |
| 15 mg E4/3 mg DRSP | Change From Baseline to End of Treatment in the Score of the Menstrual Distress Questionnaire (MDQ) | Impaired concentration | 0.0 units on a scale | Standard Deviation 2.67 |
| 15 mg E4/3 mg DRSP | Change From Baseline to End of Treatment in the Score of the Menstrual Distress Questionnaire (MDQ) | Behaviour change | -0.1 units on a scale | Standard Deviation 2.86 |
| 15 mg E4/3 mg DRSP | Change From Baseline to End of Treatment in the Score of the Menstrual Distress Questionnaire (MDQ) | Arousal | -0.3 units on a scale | Standard Deviation 3.46 |
| 15 mg E4/3 mg DRSP | Change From Baseline to End of Treatment in the Score of the Menstrual Distress Questionnaire (MDQ) | Control | 0.0 units on a scale | Standard Deviation 1.52 |
| 15 mg E4/3 mg DRSP - End of Treatment Results | Change From Baseline to End of Treatment in the Score of the Menstrual Distress Questionnaire (MDQ) | Autonomic reactions | -0.0 units on a scale | Standard Deviation 1.3 |
| 15 mg E4/3 mg DRSP - End of Treatment Results | Change From Baseline to End of Treatment in the Score of the Menstrual Distress Questionnaire (MDQ) | Arousal | -0.3 units on a scale | Standard Deviation 3.62 |
| 15 mg E4/3 mg DRSP - End of Treatment Results | Change From Baseline to End of Treatment in the Score of the Menstrual Distress Questionnaire (MDQ) | Negative affect | -0.3 units on a scale | Standard Deviation 4.7 |
| 15 mg E4/3 mg DRSP - End of Treatment Results | Change From Baseline to End of Treatment in the Score of the Menstrual Distress Questionnaire (MDQ) | Impaired concentration | -0.0 units on a scale | Standard Deviation 2.55 |
| 15 mg E4/3 mg DRSP - End of Treatment Results | Change From Baseline to End of Treatment in the Score of the Menstrual Distress Questionnaire (MDQ) | Behaviour change | -0.1 units on a scale | Standard Deviation 2.55 |
| 15 mg E4/3 mg DRSP - End of Treatment Results | Change From Baseline to End of Treatment in the Score of the Menstrual Distress Questionnaire (MDQ) | Pain | -0.1 units on a scale | Standard Deviation 2.96 |
| 15 mg E4/3 mg DRSP - End of Treatment Results | Change From Baseline to End of Treatment in the Score of the Menstrual Distress Questionnaire (MDQ) | Water retention | -0.1 units on a scale | Standard Deviation 2.57 |
| 15 mg E4/3 mg DRSP - End of Treatment Results | Change From Baseline to End of Treatment in the Score of the Menstrual Distress Questionnaire (MDQ) | Control | 0.0 units on a scale | Standard Deviation 1.57 |
| 15 mg E4/3 mg DRSP Tablet - Intermenstrual Phase | Change From Baseline to End of Treatment in the Score of the Menstrual Distress Questionnaire (MDQ) | Autonomic reactions | -0.0 units on a scale | Standard Deviation 1.22 |
| 15 mg E4/3 mg DRSP Tablet - Intermenstrual Phase | Change From Baseline to End of Treatment in the Score of the Menstrual Distress Questionnaire (MDQ) | Water retention | 0.0 units on a scale | Standard Deviation 2.09 |
| 15 mg E4/3 mg DRSP Tablet - Intermenstrual Phase | Change From Baseline to End of Treatment in the Score of the Menstrual Distress Questionnaire (MDQ) | Pain | -0.1 units on a scale | Standard Deviation 2.67 |
| 15 mg E4/3 mg DRSP Tablet - Intermenstrual Phase | Change From Baseline to End of Treatment in the Score of the Menstrual Distress Questionnaire (MDQ) | Negative affect | -0.1 units on a scale | Standard Deviation 3.93 |
| 15 mg E4/3 mg DRSP Tablet - Intermenstrual Phase | Change From Baseline to End of Treatment in the Score of the Menstrual Distress Questionnaire (MDQ) | Arousal | -0.3 units on a scale | Standard Deviation 3.91 |
| 15 mg E4/3 mg DRSP Tablet - Intermenstrual Phase | Change From Baseline to End of Treatment in the Score of the Menstrual Distress Questionnaire (MDQ) | Behaviour change | -0.0 units on a scale | Standard Deviation 1.99 |
| 15 mg E4/3 mg DRSP Tablet - Intermenstrual Phase | Change From Baseline to End of Treatment in the Score of the Menstrual Distress Questionnaire (MDQ) | Impaired concentration | 0.0 units on a scale | Standard Deviation 2.23 |
| 15 mg E4/3 mg DRSP Tablet - Intermenstrual Phase | Change From Baseline to End of Treatment in the Score of the Menstrual Distress Questionnaire (MDQ) | Control | 0.0 units on a scale | Standard Deviation 1.63 |
Secondary
Endometrial Biopsy Histology at Screening and End of Treatment
Endometrial biopsies was obtained from a subset of subjects included in the endometrial safety substudy at the screening visit and at the end of treatment visit if the subject has completed at least 10 cycles.
Time frame: Baseline and end of treatment (up to 13 cycles with 1 cycle = 28 days)
Population: Participants aged 18 to 50 years, inclusive, at screening with an evaluable endometrial biopsies both at screening and end of treatment.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| 15 mg E4/3 mg DRSP | Endometrial Biopsy Histology at Screening and End of Treatment | Baseline | Complex hyperplasia without atypia | 0 Participants |
| 15 mg E4/3 mg DRSP | Endometrial Biopsy Histology at Screening and End of Treatment | Baseline | No tissue | 0 Participants |
| 15 mg E4/3 mg DRSP | Endometrial Biopsy Histology at Screening and End of Treatment | Baseline | Tissue insufficient for diagnosis | 1 Participants |
| 15 mg E4/3 mg DRSP | Endometrial Biopsy Histology at Screening and End of Treatment | Baseline | Benign histology:Atrophic | 2 Participants |
| 15 mg E4/3 mg DRSP | Endometrial Biopsy Histology at Screening and End of Treatment | Baseline | Benign histology: Inactive | 7 Participants |
| 15 mg E4/3 mg DRSP | Endometrial Biopsy Histology at Screening and End of Treatment | Baseline | Benign histology:Proliferative | 76 Participants |
| 15 mg E4/3 mg DRSP | Endometrial Biopsy Histology at Screening and End of Treatment | Baseline | Secretory | 22 Participants |
| 15 mg E4/3 mg DRSP | Endometrial Biopsy Histology at Screening and End of Treatment | Baseline | Menstrual type | 0 Participants |
| 15 mg E4/3 mg DRSP | Endometrial Biopsy Histology at Screening and End of Treatment | Baseline | Simple hyperplasia without atypia | 0 Participants |
| 15 mg E4/3 mg DRSP | Endometrial Biopsy Histology at Screening and End of Treatment | Baseline | Pre-malignant/Malignant histology | 0 Participants |
| 15 mg E4/3 mg DRSP | Endometrial Biopsy Histology at Screening and End of Treatment | End of Treatment | No tissue | 0 Participants |
| 15 mg E4/3 mg DRSP | Endometrial Biopsy Histology at Screening and End of Treatment | End of Treatment | Tissue insufficient for diagnosis | 9 Participants |
| 15 mg E4/3 mg DRSP | Endometrial Biopsy Histology at Screening and End of Treatment | End of Treatment | Benign histology:Atrophic | 11 Participants |
| 15 mg E4/3 mg DRSP | Endometrial Biopsy Histology at Screening and End of Treatment | End of Treatment | Benign histology: Inactive | 61 Participants |
| 15 mg E4/3 mg DRSP | Endometrial Biopsy Histology at Screening and End of Treatment | End of Treatment | Benign histology:Proliferative | 22 Participants |
| 15 mg E4/3 mg DRSP | Endometrial Biopsy Histology at Screening and End of Treatment | End of Treatment | Secretory | 5 Participants |
| 15 mg E4/3 mg DRSP | Endometrial Biopsy Histology at Screening and End of Treatment | End of Treatment | Menstrual type | 0 Participants |
| 15 mg E4/3 mg DRSP | Endometrial Biopsy Histology at Screening and End of Treatment | End of Treatment | Simple hyperplasia without atypia | 0 Participants |
| 15 mg E4/3 mg DRSP | Endometrial Biopsy Histology at Screening and End of Treatment | End of Treatment | Complex hyperplasia without atypia | 0 Participants |
| 15 mg E4/3 mg DRSP | Endometrial Biopsy Histology at Screening and End of Treatment | End of Treatment | Pre-malignant/Malignant histology | 0 Participants |
Secondary
Number of Scheduled Bleeding and/or Spotting Days Per Cycle
Scheduled bleeding and /or spotting is defined as any bleeding and/or spotting that occurs during the hormone-free interval (i.e. Days 25 - 28) and continues through Days 1-3 of the subsequent active cycle.
Time frame: Up to 11 months (12 cycles with 1 cycle = 28 days)
Population: Participants aged 18 to 50 years, inclusive, at screening, with evaluable cycle data for the bleeding analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 15 mg E4/3 mg DRSP | Number of Scheduled Bleeding and/or Spotting Days Per Cycle | Cycle 1 | 6.1 Days | Standard Deviation 4.95 |
| 15 mg E4/3 mg DRSP | Number of Scheduled Bleeding and/or Spotting Days Per Cycle | Cycle 2 | 5.3 Days | Standard Deviation 3.62 |
| 15 mg E4/3 mg DRSP | Number of Scheduled Bleeding and/or Spotting Days Per Cycle | Cycle 3 | 5.2 Days | Standard Deviation 3.99 |
| 15 mg E4/3 mg DRSP | Number of Scheduled Bleeding and/or Spotting Days Per Cycle | Cycle 4 | 5.0 Days | Standard Deviation 3.14 |
| 15 mg E4/3 mg DRSP | Number of Scheduled Bleeding and/or Spotting Days Per Cycle | Cycle 5 | 4.9 Days | Standard Deviation 3.43 |
| 15 mg E4/3 mg DRSP | Number of Scheduled Bleeding and/or Spotting Days Per Cycle | Cycle 6 | 4.9 Days | Standard Deviation 3.34 |
| 15 mg E4/3 mg DRSP | Number of Scheduled Bleeding and/or Spotting Days Per Cycle | Cycle 7 | 4.7 Days | Standard Deviation 2.8 |
| 15 mg E4/3 mg DRSP | Number of Scheduled Bleeding and/or Spotting Days Per Cycle | Cycle 8 | 4.8 Days | Standard Deviation 3.85 |
| 15 mg E4/3 mg DRSP | Number of Scheduled Bleeding and/or Spotting Days Per Cycle | Cycle 9 | 4.7 Days | Standard Deviation 2.87 |
| 15 mg E4/3 mg DRSP | Number of Scheduled Bleeding and/or Spotting Days Per Cycle | Cycle 10 | 4.6 Days | Standard Deviation 2.69 |
| 15 mg E4/3 mg DRSP | Number of Scheduled Bleeding and/or Spotting Days Per Cycle | Cycle 11 | 4.7 Days | Standard Deviation 3.16 |
| 15 mg E4/3 mg DRSP | Number of Scheduled Bleeding and/or Spotting Days Per Cycle | Cycle 12 | 4.6 Days | Standard Deviation 2.97 |
Secondary
Number of Subjects With Abnormal Gynecological Examination Results
Gynecological examinations included breast examination (performed by palpation) and assessment of the adnexa, cervix, uterus, vagina, and external genitalia. When reporting the results, the use of the Abnormal category was reserved for findings that were considered clinically significant, in the opinion of the Investigator; the Normal category included Abnormal results that were not clinically significant, as well as no findings.
Time frame: From screening to end of treatment (12 months)
Population: Participants aged 18 to 50 years, inclusive, at screening, who received at least one dose of investigational product with baseline and end of treatment (EOT) gynecological results.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| 15 mg E4/3 mg DRSP | Number of Subjects With Abnormal Gynecological Examination Results | Breast - Baseline | Normal | 1,545 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Abnormal Gynecological Examination Results | Breast - Baseline | Abnormal | 8 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Abnormal Gynecological Examination Results | Breast - Baseline | Not done | 0 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Abnormal Gynecological Examination Results | Breast - EOT | Normal | 1,485 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Abnormal Gynecological Examination Results | Breast - EOT | Abnormal | 13 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Abnormal Gynecological Examination Results | Breast - EOT | Not done | 1 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Abnormal Gynecological Examination Results | Adnexa - Baseline | Normal | 1,549 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Abnormal Gynecological Examination Results | Adnexa - Baseline | Abnormal | 4 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Abnormal Gynecological Examination Results | Adnexa - Baseline | Not done | 0 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Abnormal Gynecological Examination Results | Adnexa - EOT | Normal | 1,496 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Abnormal Gynecological Examination Results | Adnexa - EOT | Abnormal | 2 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Abnormal Gynecological Examination Results | Adnexa - EOT | Not done | 1 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Abnormal Gynecological Examination Results | Cervix - Baseline | Normal | 1,532 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Abnormal Gynecological Examination Results | Cervix - Baseline | Abnormal | 21 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Abnormal Gynecological Examination Results | Cervix - Baseline | Not done | 0 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Abnormal Gynecological Examination Results | Cervix - EOT | Normal | 1,485 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Abnormal Gynecological Examination Results | Cervix - EOT | Abnormal | 13 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Abnormal Gynecological Examination Results | Cervix - EOT | Not done | 1 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Abnormal Gynecological Examination Results | Uterus - Baseline | Normal | 1,542 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Abnormal Gynecological Examination Results | Uterus - Baseline | Abnormal | 11 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Abnormal Gynecological Examination Results | Uterus - Baseline | Not done | 0 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Abnormal Gynecological Examination Results | Uterus - EOT | Normal | 1,492 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Abnormal Gynecological Examination Results | Uterus - EOT | Abnormal | 6 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Abnormal Gynecological Examination Results | Uterus - EOT | Not done | 1 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Abnormal Gynecological Examination Results | Vagina - Baseline | Normal | 1,545 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Abnormal Gynecological Examination Results | Vagina - Baseline | Abnormal | 8 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Abnormal Gynecological Examination Results | Vagina - Baseline | Not done | 0 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Abnormal Gynecological Examination Results | Vagina - EOT | Normal | 1,489 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Abnormal Gynecological Examination Results | Vagina - EOT | Abnormal | 8 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Abnormal Gynecological Examination Results | Vagina - EOT | Not done | 2 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Abnormal Gynecological Examination Results | External genitalia - Baseline | Normal | 1,552 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Abnormal Gynecological Examination Results | External genitalia - Baseline | Abnormal | 1 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Abnormal Gynecological Examination Results | External genitalia - Baseline | Not done | 0 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Abnormal Gynecological Examination Results | External genitalia - EOT | Normal | 1,497 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Abnormal Gynecological Examination Results | External genitalia - EOT | Abnormal | 1 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Abnormal Gynecological Examination Results | External genitalia - EOT | Not done | 1 Participants |
Secondary
Number of Subjects With Abnormal Laboratory Assessment Results
Laboratory assessment included blood hematology, biochemistry, and lipids
Time frame: From screening to end of treatment (12 months)
Population: Participants aged 18 to 50 years, inclusive, at screening, who received at least one dose of investigational product.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 15 mg E4/3 mg DRSP | Number of Subjects With Abnormal Laboratory Assessment Results | 55 Participants |
Secondary
Number of Subjects With Abnormal Physical Examination Results
Physical examinations included an evaluation of body as a whole, skin, head, eyes, ears, nose, and throat, neck, cardiovascular, respiratory, musculoskeletal, neurologic, lymphatic/thyroid, abdomen. When reporting the results of the physical examination, the use of the Abnormal category was reserved for findings that were considered clinically significant, in the opinion of the Investigator; the Normal category included Abnormal results that were not clinically significant, as well as no findings.
Time frame: From screening to end of treatment (12 months)
Population: Participants aged 18 to 50 years, inclusive, at screening, who received at least one dose of investigational product with baseline and end of treatment (EOT) results.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| 15 mg E4/3 mg DRSP | Number of Subjects With Abnormal Physical Examination Results | Body as a whole - Baseline | Normal | 1548 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Abnormal Physical Examination Results | Body as a whole - Baseline | Abnormal | 5 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Abnormal Physical Examination Results | Body as a whole - Baseline | Not done | 0 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Abnormal Physical Examination Results | Body as a whole - EOT | Normal | 1493 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Abnormal Physical Examination Results | Body as a whole - EOT | Abnormal | 5 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Abnormal Physical Examination Results | Body as a whole - EOT | Not done | 0 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Abnormal Physical Examination Results | Skin - Baseline | Normal | 1537 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Abnormal Physical Examination Results | Skin - Baseline | Abnormal | 16 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Abnormal Physical Examination Results | Skin - Baseline | Not done | 0 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Abnormal Physical Examination Results | Skin - EOT | Normal | 1,476 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Abnormal Physical Examination Results | Skin - EOT | Abnormal | 22 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Abnormal Physical Examination Results | Skin - EOT | Not done | 0 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Abnormal Physical Examination Results | Head, Eyes, Ears, Nose and Throat - Baseline | Normal | 1,543 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Abnormal Physical Examination Results | Head, Eyes, Ears, Nose and Throat - Baseline | Abnormal | 10 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Abnormal Physical Examination Results | Head, Eyes, Ears, Nose and Throat - Baseline | Not done | 0 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Abnormal Physical Examination Results | Head, Eyes, Ears, Nose and Throat - EOT | Normal | 1,492 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Abnormal Physical Examination Results | Head, Eyes, Ears, Nose and Throat - EOT | Abnormal | 3 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Abnormal Physical Examination Results | Head, Eyes, Ears, Nose and Throat - EOT | Not done | 3 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Abnormal Physical Examination Results | Neck - Baseline | Normal | 1,552 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Abnormal Physical Examination Results | Neck - Baseline | Abnormal | 1 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Abnormal Physical Examination Results | Neck - Baseline | Not done | 0 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Abnormal Physical Examination Results | Neck - EOT | Normal | 1,495 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Abnormal Physical Examination Results | Neck - EOT | Abnormal | 1 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Abnormal Physical Examination Results | Neck - EOT | Not done | 2 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Abnormal Physical Examination Results | Cardiovascular - Baseline | Normal | 1,553 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Abnormal Physical Examination Results | Cardiovascular - Baseline | Abnormal | 0 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Abnormal Physical Examination Results | Cardiovascular - Baseline | Not done | 0 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Abnormal Physical Examination Results | Cardiovascular - EOT | Normal | 1,496 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Abnormal Physical Examination Results | Cardiovascular - EOT | Abnormal | 1 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Abnormal Physical Examination Results | Cardiovascular - EOT | Not done | 1 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Abnormal Physical Examination Results | Respiratory - Baseline | Normal | 1,551 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Abnormal Physical Examination Results | Respiratory - Baseline | Abnormal | 2 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Abnormal Physical Examination Results | Respiratory - Baseline | Not done | 0 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Abnormal Physical Examination Results | Respiratory - EOT | Normal | 1,496 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Abnormal Physical Examination Results | Respiratory - EOT | Abnormal | 1 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Abnormal Physical Examination Results | Respiratory - EOT | Not done | 1 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Abnormal Physical Examination Results | Musculoskeletal - Baseline | Normal | 1,553 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Abnormal Physical Examination Results | Musculoskeletal - Baseline | Abnormal | 0 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Abnormal Physical Examination Results | Musculoskeletal - Baseline | Not done | 0 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Abnormal Physical Examination Results | Musculoskeletal - EOT | Normal | 1,495 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Abnormal Physical Examination Results | Musculoskeletal - EOT | Abnormal | 1 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Abnormal Physical Examination Results | Musculoskeletal - EOT | Not done | 2 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Abnormal Physical Examination Results | Neurologic - Baseline | Normal | 1,553 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Abnormal Physical Examination Results | Neurologic - Baseline | Abnormal | 0 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Abnormal Physical Examination Results | Neurologic - Baseline | Not done | 0 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Abnormal Physical Examination Results | Neurologic - EOT | Normal | 1,494 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Abnormal Physical Examination Results | Neurologic - EOT | Abnormal | 2 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Abnormal Physical Examination Results | Neurologic - EOT | Not done | 2 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Abnormal Physical Examination Results | Lymphatic/Thyroid - Baseline | Normal | 1,549 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Abnormal Physical Examination Results | Lymphatic/Thyroid - Baseline | Abnormal | 2 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Abnormal Physical Examination Results | Lymphatic/Thyroid - Baseline | Not done | 2 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Abnormal Physical Examination Results | Lymphatic/Thyroid - EOT | Normal | 1,494 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Abnormal Physical Examination Results | Lymphatic/Thyroid - EOT | Abnormal | 1 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Abnormal Physical Examination Results | Lymphatic/Thyroid - EOT | Not done | 3 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Abnormal Physical Examination Results | Abdomen - Baseline | Normal | 1,553 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Abnormal Physical Examination Results | Abdomen - Baseline | Abnormal | 0 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Abnormal Physical Examination Results | Abdomen - Baseline | Not done | 0 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Abnormal Physical Examination Results | Abdomen - EOT | Normal | 1,496 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Abnormal Physical Examination Results | Abdomen - EOT | Abnormal | 1 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Abnormal Physical Examination Results | Abdomen - EOT | Not done | 1 Participants |
Secondary
Number of Subjects With Abnormal Vital Signs
Vital signs included sitting systolic and diastolic blood pressures, and heart rate.
Time frame: From screening to end of treatment (12 months)
Population: Participants aged 18 to 50 years, inclusive, at screening, who received at least one dose of investigational product.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 15 mg E4/3 mg DRSP | Number of Subjects With Abnormal Vital Signs | 15 Participants |
Secondary
Number of Subjects With Absence of Scheduled Bleeding and/or Spotting
Scheduled bleeding/spotting is defined as any bleeding/spotting that occurs during the hormone-free interval (i.e. Days 25 - 28) and continues through Days 1-3 of the subsequent active cycle.
Time frame: Up to 11 months (12 cycles with 1 cycle = 28 days)
Population: Participants aged 18 to 50 years, inclusive, at screening, with evaluable cycle data for the bleeding analysis.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 15 mg E4/3 mg DRSP | Number of Subjects With Absence of Scheduled Bleeding and/or Spotting | Cycle 1 | 84 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Absence of Scheduled Bleeding and/or Spotting | Cycle 2 | 90 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Absence of Scheduled Bleeding and/or Spotting | Cycle 3 | 105 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Absence of Scheduled Bleeding and/or Spotting | Cycle 4 | 83 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Absence of Scheduled Bleeding and/or Spotting | Cycle 5 | 91 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Absence of Scheduled Bleeding and/or Spotting | Cycle 6 | 91 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Absence of Scheduled Bleeding and/or Spotting | Cycle 7 | 90 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Absence of Scheduled Bleeding and/or Spotting | Cycle 8 | 103 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Absence of Scheduled Bleeding and/or Spotting | Cycle 9 | 92 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Absence of Scheduled Bleeding and/or Spotting | Cycle 10 | 89 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Absence of Scheduled Bleeding and/or Spotting | Cycle 11 | 80 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Absence of Scheduled Bleeding and/or Spotting | Cycle 12 | 94 Participants |
Secondary
Number of Subjects With Unscheduled Bleeding/Spotting
Unscheduled bleeding/spotting is defined as any bleeding/spotting that occurs while taking active hormones that does not meet the criteria for scheduled bleeding.
Time frame: Up to 11 months (12 cycles with 1 cycle = 28 days)
Population: Participants aged 18 to 50 years, inclusive, at screening, with evaluable cycle data for the bleeding analysis.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 15 mg E4/3 mg DRSP | Number of Subjects With Unscheduled Bleeding/Spotting | Cycle 1 | 354 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Unscheduled Bleeding/Spotting | Cycle 2 | 282 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Unscheduled Bleeding/Spotting | Cycle 3 | 250 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Unscheduled Bleeding/Spotting | Cycle 4 | 249 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Unscheduled Bleeding/Spotting | Cycle 5 | 238 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Unscheduled Bleeding/Spotting | Cycle 6 | 207 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Unscheduled Bleeding/Spotting | Cycle 7 | 170 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Unscheduled Bleeding/Spotting | Cycle 8 | 202 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Unscheduled Bleeding/Spotting | Cycle 9 | 182 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Unscheduled Bleeding/Spotting | Cycle 10 | 168 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Unscheduled Bleeding/Spotting | Cycle 11 | 155 Participants |
| 15 mg E4/3 mg DRSP | Number of Subjects With Unscheduled Bleeding/Spotting | Cycle 12 | 154 Participants |
Secondary
Number of Unscheduled Bleeding Days Per Cycle
Unscheduled bleeding is defined as any bleeding that occurs while taking active hormones that does not meet the criteria for scheduled bleeding and/or spotting.
Time frame: Up to 11 months (12 cycles with 1 cycle = 28 days)
Population: Participants aged 18 to 50 years, inclusive, at screening, with evaluable cycle data for the bleeding analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 15 mg E4/3 mg DRSP | Number of Unscheduled Bleeding Days Per Cycle | Cycle 1 | 0.2 Days | Standard Deviation 0.89 |
| 15 mg E4/3 mg DRSP | Number of Unscheduled Bleeding Days Per Cycle | Cycle 2 | 0.1 Days | Standard Deviation 0.66 |
| 15 mg E4/3 mg DRSP | Number of Unscheduled Bleeding Days Per Cycle | Cycle 3 | 0.1 Days | Standard Deviation 0.67 |
| 15 mg E4/3 mg DRSP | Number of Unscheduled Bleeding Days Per Cycle | Cycle 4 | 0.2 Days | Standard Deviation 0.79 |
| 15 mg E4/3 mg DRSP | Number of Unscheduled Bleeding Days Per Cycle | Cycle 5 | 0.1 Days | Standard Deviation 0.7 |
| 15 mg E4/3 mg DRSP | Number of Unscheduled Bleeding Days Per Cycle | Cycle 6 | 0.1 Days | Standard Deviation 0.8 |
| 15 mg E4/3 mg DRSP | Number of Unscheduled Bleeding Days Per Cycle | Cycle 7 | 0.1 Days | Standard Deviation 0.68 |
| 15 mg E4/3 mg DRSP | Number of Unscheduled Bleeding Days Per Cycle | Cycle 8 | 0.1 Days | Standard Deviation 0.72 |
| 15 mg E4/3 mg DRSP | Number of Unscheduled Bleeding Days Per Cycle | Cycle 9 | 0.1 Days | Standard Deviation 0.7 |
| 15 mg E4/3 mg DRSP | Number of Unscheduled Bleeding Days Per Cycle | Cycle 10 | 0.1 Days | Standard Deviation 0.61 |
| 15 mg E4/3 mg DRSP | Number of Unscheduled Bleeding Days Per Cycle | Cycle 11 | 0.1 Days | Standard Deviation 0.72 |
| 15 mg E4/3 mg DRSP | Number of Unscheduled Bleeding Days Per Cycle | Cycle 12 | 0.1 Days | Standard Deviation 0.68 |
Secondary
Number of Unscheduled Spotting Days Per Cycle
Unscheduled spotting is defined as any spotting that occurs while taking active hormones that does not meet the criteria for scheduled bleeding and/or spotting.
Time frame: Up to 11 months (12 cycles with 1 cycle = 28 days)
Population: Participants aged 18 to 50 years, inclusive, at screening, with evaluable cycle data for the bleeding analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 15 mg E4/3 mg DRSP | Number of Unscheduled Spotting Days Per Cycle | Cycle 9 | 0.4 Days | Standard Deviation 0.13 |
| 15 mg E4/3 mg DRSP | Number of Unscheduled Spotting Days Per Cycle | Cycle 1 | 0.8 Days | Standard Deviation 1.99 |
| 15 mg E4/3 mg DRSP | Number of Unscheduled Spotting Days Per Cycle | Cycle 2 | 0.5 Days | Standard Deviation 1.5 |
| 15 mg E4/3 mg DRSP | Number of Unscheduled Spotting Days Per Cycle | Cycle 3 | 0.5 Days | Standard Deviation 1.46 |
| 15 mg E4/3 mg DRSP | Number of Unscheduled Spotting Days Per Cycle | Cycle 4 | 0.5 Days | Standard Deviation 1.55 |
| 15 mg E4/3 mg DRSP | Number of Unscheduled Spotting Days Per Cycle | Cycle 5 | 0.5 Days | Standard Deviation 1.35 |
| 15 mg E4/3 mg DRSP | Number of Unscheduled Spotting Days Per Cycle | Cycle 6 | 0.4 Days | Standard Deviation 1.24 |
| 15 mg E4/3 mg DRSP | Number of Unscheduled Spotting Days Per Cycle | Cycle 7 | 0.4 Days | Standard Deviation 1.17 |
| 15 mg E4/3 mg DRSP | Number of Unscheduled Spotting Days Per Cycle | Cycle 8 | 0.4 Days | Standard Deviation 1.19 |
| 15 mg E4/3 mg DRSP | Number of Unscheduled Spotting Days Per Cycle | Cycle 10 | 0.4 Days | Standard Deviation 1.25 |
| 15 mg E4/3 mg DRSP | Number of Unscheduled Spotting Days Per Cycle | Cycle 11 | 0.3 Days | Standard Deviation 1.18 |
| 15 mg E4/3 mg DRSP | Number of Unscheduled Spotting Days Per Cycle | Cycle 12 | 0.4 Days | Standard Deviation 1.23 |
Secondary
Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) Results at Baseline and End of Treatment - Percentage Maximum (Sum of First 14 Items)
The Q-LES-Q-SF is a self-report measure designed to assess the degree of enjoyment and satisfaction in daily functioning. Participants were asked to rate 16 different items on a 5-point scale where score 1 = very poor and score 5 = very good. A raw total score is calculated by summing the first 14 items and ranges from 14 to 70 with a higher scores indicating higher life enjoyment and satisfaction. The raw total score is then transformed into a percentage maximum score using the following formula: (raw total score-minimum score)/(maximum possible raw score-minimum score). In addition, the last two items (15 and 16) are two global items that are scored individually. These items rate satisfaction with medicine and overall life satisfaction over the past week.
Time frame: Baseline and Cycle 13 (1 cycle = 28 days)
Population: Participants aged 18 to 50 years, inclusive, at screening with baseline and end of treatment Q-LES-Q-SF results.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 15 mg E4/3 mg DRSP | Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) Results at Baseline and End of Treatment - Percentage Maximum (Sum of First 14 Items) | 73.4 Percentage maximum score on a scale | Standard Deviation 12.77 |
| 15 mg E4/3 mg DRSP - End of Treatment Results | Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) Results at Baseline and End of Treatment - Percentage Maximum (Sum of First 14 Items) | 73.8 Percentage maximum score on a scale | Standard Deviation 12.82 |
Secondary
Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) Results at Baseline and End of Treatment - Satisfaction With Medicine and Overall Life Satisfaction Over the Past Week
The Q-LES-Q-SF is a self-report measure designed to assess the degree of enjoyment and satisfaction in daily functioning. Participants were asked to rate 16 different items on a 5-point scale where score 1 = very poor and score 5 = very good. A raw total score is calculated by summing the first 14 items and ranges from 14 to 70 with a higher scores indicating higher life enjoyment and satisfaction. The raw total score is then transformed into a percentage maximum score using the following formula: (raw total score-minimum score)/(maximum possible raw score-minimum score). In addition, the last two items (15 and 16) are two global items that are scored individually. These items rate satisfaction with medicine and overall life satisfaction over the past week.
Time frame: Baseline and Cycle 13 (1 cycle = 28 days)
Population: Participants aged 18 to 50 years, inclusive, at screening with baseline and end of treatment Q-LES-Q-SF results.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 15 mg E4/3 mg DRSP | Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) Results at Baseline and End of Treatment - Satisfaction With Medicine and Overall Life Satisfaction Over the Past Week | Satisfaction with medicine | 4.0 Units on a scale | Standard Deviation 0.78 |
| 15 mg E4/3 mg DRSP | Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) Results at Baseline and End of Treatment - Satisfaction With Medicine and Overall Life Satisfaction Over the Past Week | Overall life statisfaction over the past week | 4.0 Units on a scale | Standard Deviation 0.68 |
| 15 mg E4/3 mg DRSP - End of Treatment Results | Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) Results at Baseline and End of Treatment - Satisfaction With Medicine and Overall Life Satisfaction Over the Past Week | Satisfaction with medicine | 4.0 Units on a scale | Standard Deviation 0.77 |
| 15 mg E4/3 mg DRSP - End of Treatment Results | Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) Results at Baseline and End of Treatment - Satisfaction With Medicine and Overall Life Satisfaction Over the Past Week | Overall life statisfaction over the past week | 4.0 Units on a scale | Standard Deviation 0.7 |
Secondary
The Number of On-Treatment Pregnancies as Assessed by the Method Failure Pearl Index in the Overall Study Population (18-50 Years)
On-treatment pregnancies are defined as pregnancies with an estimated date of conception within the in-treatment period i.e. Day 1 to 2 days after the last intake of investigational product (whether active or inactive tablet). The Pearl Index, defined as the number of pregnancies per 100 women-years of treatment was calculated as: Pearl Index = (1300\*number of on-treatment pregnancies)/number of women 28-day equivalent cycles of treatment. The method failure Pearl Index includes only those pregnancies that were classified as method failure and not the pregnancies due to user failure, i.e. incorrect intake of the contraceptive method. Only at-risk cycles were included in the denominator of the Pearl Index calculation. At-risk-cycles were defined as cycles in which no other methods of birth control (including condoms) were used by the subject as confirmed in the subject diary and during which the subject confirmed that sexual intercourse had occurred.
Time frame: Up to 12 months (13 cycles with 1 cycle = 28 days)
Population: Participants aged 18 to 50 years, inclusive, at screening with at least 1 cycle included in the denominator.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 15 mg E4/3 mg DRSP | The Number of On-Treatment Pregnancies as Assessed by the Method Failure Pearl Index in the Overall Study Population (18-50 Years) | 0.25 Method Failure Pearl Index |
Secondary
The Number of On-treatment Pregnancies (With 2-day Window) as Assessed by the Method Failure Pearl Index in Subjects Aged 18 to 35 Years, Inclusive, at the Time of Screening
On-treatment pregnancies are defined as pregnancies with an estimated date of conception within the in-treatment period i.e. Day 1 to 2 days after the last intake of investigational product (whether active or inactive tablet). The Pearl Index, defined as the number of pregnancies per 100 women-years of treatment was calculated as: Pearl Index = (1300\*number of on-treatment pregnancies)/number of women 28-day equivalent cycles of treatment. The method failure Pearl Index includes only those pregnancies that were classified as method failure and not the pregnancies due to user failure, i.e. incorrect intake of the contraceptive method. Only at-risk cycles were included in the denominator of the Pearl Index calculation. At-risk-cycles were defined as cycles in which no other methods of birth control (including condoms) were used by the subject as confirmed in the subject diary and during which the subject confirmed that sexual intercourse had occurred.
Time frame: Up to 12 months (13 cycles with 1 cycle = 28 days)
Population: Participants aged 18 to 35 years, inclusive, at screening with at least 1 cycle included in the denominator.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 15 mg E4/3 mg DRSP | The Number of On-treatment Pregnancies (With 2-day Window) as Assessed by the Method Failure Pearl Index in Subjects Aged 18 to 35 Years, Inclusive, at the Time of Screening | 0.29 Method failure Pearl Index |
Secondary
The Number of On-treatment Pregnancies (With + 2-day Window) Per 100 Woman-years of Exposure (Pearl Index) in the Overall Study Population (18-50 Years)
On-treatment pregnancies are defined as pregnancies with an estimated date of conception within the in-treatment period i.e. Day 1 to 2 days after the last intake of investigational product (whether active or inactive tablet). The Pearl Index, defined as the number of pregnancies per 100 women-years of treatment was calculated as: Pearl Index = (1300\*number of on-treatment pregnancies)/number of women 28-day equivalent cycles of treatment.Only at-risk cycles were included in the denominator of the Pearl Index calculation. At-risk-cycles were defined as cycles in which no other methods of birth control (including condoms) were used by the subject as confirmed in the subject diary and during which the subject confirmed that sexual intercourse had occurred.
Time frame: Up to 12 months (13 cycles with 1 cycle = 28 days)
Population: Participants aged 18 to 50 years, inclusive, at screening with at least 1 cycle included in the denominator.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 15 mg E4/3 mg DRSP | The Number of On-treatment Pregnancies (With + 2-day Window) Per 100 Woman-years of Exposure (Pearl Index) in the Overall Study Population (18-50 Years) | 0.41 Pearl Index |