A Phase 3 interventional study of 15 mg E4/3 mg DRSP in Contraception, sponsored by Estetra. Completed at 2 sites in 2 countries. Open to female participants aged 16 Years to 50 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2020-02-10.
Sponsored by Estetra · Phase 3, Interventional, and Prevention
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 16 to 50 years.
Estetra is the lead sponsor of 15 studies on the registry; none are open to participants now.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
15 mg estetrol (E4)/3 mg drospirenone (DRSP) combined oral contraceptive
Drug: 15 mg E4/3 mg DRSP
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.
Also known as: 15 mg estetrol and 3 mg drospirenone
The Number of On-treatment Pregnancies (With + 7-day Window) Per 100 Woman-years of Exposure (Pearl Index) in Subjects Aged 16 to 35 Years, Inclusive, at the Time of Screening
On-treatment pregnancies are pregnancies with an estimated date of conception within the in-treatment period i.e. Day 1 to 7 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, unless a conception occurred during a cycle. At-risk-cycle was defined as cycle in which no other methods of birth control (including condoms and emergency contraception) 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)
The Number of On-treatment Pregnancies (With +7-day Window) as Assessed by the Method Failure Pearl Index in Subjects Aged 16 to 35 Years, Inclusive, at the Time of Screening
On-treatment pregnancies are pregnancies with an estimated date of conception within the in-treatment period i.e. Day 1 to 7 days after the last intake of investigational product (whether active or inactive tablet). The method failure Pearl Index, defined as the number of pregnancies as a result of method failure per 100 women-years of treatment, was calculated as follow: (1300\*number of on-treatment pregnancies as a result of method failure)/number of women 28-day equivalent cycles of treatment. Pregnancies due to user failure were excluded from the numerator. User failure pregnancies were pregnancies that occurred when the subject did not take the investigational product correctly. At-risk-cycle was defined as cycle in which no other methods of birth control (including condoms and emergency contraception) were used by the subject and during which the subject confirmed that sexual intercourse had occurred.
Time frame: Up to 12 months (13 cycles with 1 cycle = 28 days)
The Number of On-treatment Pregnancies (With + 7-day Window) Per 100 Woman-years of Exposure (Pearl Index) in the Overall Study Population (16-50 Years)
On-treatment pregnancies are pregnancies with an estimated date of conception within the in-treatment period i.e. Day 1 to 7 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, unless a conception occurred during a cycle. At-risk-cycle was defined as cycle in which no other methods of birth control (including condoms and emergency contraception) 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)
The Number of On-treatment Pregnancies as Assessed by the Method Failure Pearl Index in the Overall Study Population (16-50 Years)
On-treatment pregnancies are pregnancies with an estimated date of conception within the in-treatment period i.e. Day 1 to 7 days after the last intake of investigational product (whether active or inactive tablet). The method failure Pearl Index, defined as the number of pregnancies as a result of method failure per 100 women-years of treatment, was calculated as follow: (1300\*number of on-treatment pregnancies as a result of method failure)/number of women 28-day equivalent cycles of treatment. Pregnancies due to user failure were excluded from the numerator. User failure pregnancies were pregnancies that occurred when the subject did not take the investigational product correctly. At-risk-cycle was defined as cycle in which no other methods of birth control (including condoms and emergency contraception) were used by the subject and during which the subject confirmed that sexual intercourse had occurred.
Time frame: Up to 12 months (13 cycles with 1 cycle = 28 days)
Rate of Pregnancy (Life-table Analysis) in Participants Aged 16 to 35 Years
The life-table analysis evaluates the cumulative probability of pregnancy over 13 cycles. Cumulative Rate and 95% CI are from Kaplan-Meier estimation. Only on-treatment pregnancies are included. On-treatment pregnancy is a pregnancy with an estimated date of conception after the date of the first dose of study medication to 7 days after the last dose of study medication (regardless of whether the last dose is an active or inactive tablet) inclusive.
Time frame: Up to 12 months (13 cycles with 1 cycle = 28 days)
Rate of Pregnancy (Life-table Analysis) in Participants Aged 16 to 50 Years
The life-table analysis evaluates the cumulative probability of pregnancy over 13 cycles. Cumulative Rate and 95% confidence interval (CI) are from Kaplan-Meier estimation. Only on-treatment pregnancies are included. On-treatment pregnancy is a pregnancy with an estimated date of conception after the date of the first dose of study medication to 7 days after the last dose of study medication (regardless of whether the last dose is an active or inactive tablet) inclusive.
Time frame: Up to 12 months (13 cycles with 1 cycle = 28 days)
Number of Subjects With Unscheduled Bleeding/Spotting Episodes
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)
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)
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)
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)
Number of Scheduled Bleeding and/or Spotting Days Per Cycle
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)
Number of Subjects With Bleeding and/or Spotting Episodes by Reference Period
Bleeding data were analysed by 91-day reference period. There were 4 RPs: Reference Period 1 = Day 1 to Day 91; Reference Period 2 = Day 92 to Day 182; Reference Period 3 = Day 183 to Day 273; and Reference Period 4 = Day 274 to Day 364.
Time frame: Up to 12 months (13 cycles with 1 cycle = 28 days)
Mean Number of Bleeding and Spotting Days by Reference Period
Bleeding data were analysed by 91-day reference period (RP). There were 4 RPs: Reference Period 1 = Day 1 to Day 91; Reference Period 2 = Day 92 to Day 182; Reference Period 3 = Day 183 to Day 273; and Reference Period 4 = Day 274 to Day 364.
Time frame: up to 12 months (13 cycles)
Number of Subjects With Treatment-emergent Adverse Events as a Measure of Safety and Tolerability.
A treatment-emergent adverse event (TEAE) was defined as any AE not present prior to the initiation of the treatment or any event already present that worsened in either intensity or frequency following exposure to the treatment. Since the starting point for adverse event (AE) collection was the signing of the informed consent, not the start of the investigational product, the AEs recorded prior to first investigational product administration were designated as AEs while those that occurred or worsened after the initiation of the investigational product were designated as TEAEs.
Time frame: Up to 12 months (13 cycles with 1 cycle = 28 days)
Number of Participants With Clinically Significant out-of Range Hematology Results
Time frame: Up to 12 months (13 cycles with 1 cycle = 28 days)
Number of Participants With Clinically Significant out-of Range Serum Chemistry and Lipid Profile Results
Time frame: Up to 12 months (13 cycles with 1 cycle = 28 days)
Number of Subjects With Clinically Abnormal Vital Signs
Vital signs included sitting systolic and diastolic blood pressures, and heart rate. All abnormal findings in vital signs that were considered by the Investigator to be clinically significant were recorded as adverse events.
Time frame: Up to 12 months (13 cycles with 1 cycle = 28 days)
Number of Participants With Clinically 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: Baseline and end of treatment (Cycle 13 with 1 cycle = 28 days)
Number of Participants With Clinically 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: Baseline and end of treatment (Cycle 13 with 1 cycle = 28 days)
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. 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). The minimum raw is 14 and maximum raw score is 70. Thus the formula for % maximum score can be written as (raw score -14)/56. A higher percentage maximum score indicates a higher life enjoyment and satisfaction.
Time frame: Baseline and end of treatment (Cycle 13 with 1 cycle = 28 days)
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 and Contentment 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. The last two items - item 15 rating "satisfaction with medicine" and item 16 rating "overall life satisfaction over the past week" are two global items that are scored individually. For both items, a higher score is associated with a better outcome.
Time frame: Baseline and end of treatment (Cycle 13 with 1 cycle = 28 days)
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 end of treatment (Cycle 13 with 1 cycle = 28 days)
| Milestone | 15 mg E4/3 mg DRSP |
|---|---|
| Started | 1864 |
| Completed | 1016 |
| Not completed | 848 |
| Withdrew: Lost to follow-up | 287 |
| Withdrew: Withdrawal by subject | 183 |
| Withdrew: Adverse event not related to bleeding | 131 |
| Withdrew: Adverse event related to bleeding | 51 |
| Withdrew: Pregnancy | 32 |
| Withdrew: Pregnancy wish | 17 |
| Withdrew: Other reasons | 53 |
| Withdrew: Protocol violation | 94 |
On-treatment pregnancies are pregnancies with an estimated date of conception within the in-treatment period i.e. Day 1 to 7 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, unless a conception occurred during a cycle. At-risk-cycle was defined as cycle in which no other methods of birth control (including condoms and emergency contraception) were used by the subject as confirmed in the subject diary and during which the subject confirmed that sexual intercourse had occurred.
| Pearl Index | 15 mg E4/3 mg DRSP |
|---|---|
| The Number of On-treatment Pregnancies (With + 7-day Window) Per 100 Woman-years of Exposure (Pearl Index) in Subjects Aged 16 to 35 Years, Inclusive, at the Time of Screening | 2.65 (1.73 to 3.88) |
On-treatment pregnancies are pregnancies with an estimated date of conception within the in-treatment period i.e. Day 1 to 7 days after the last intake of investigational product (whether active or inactive tablet). The method failure Pearl Index, defined as the number of pregnancies as a result of method failure per 100 women-years of treatment, was calculated as follow: (1300\*number of on-treatment pregnancies as a result of method failure)/number of women 28-day equivalent cycles of treatment. Pregnancies due to user failure were excluded from the numerator. User failure pregnancies were pregnancies that occurred when the subject did not take the investigational product correctly. At-risk-cycle was defined as cycle in which no other methods of birth control (including condoms and emergency contraception) were used by the subject and during which the subject confirmed that sexual intercourse had occurred.
| Method failure Pearl Index | 15 mg E4/3 mg DRSP |
|---|---|
| The Number of On-treatment Pregnancies (With +7-day Window) as Assessed by the Method Failure Pearl Index in Subjects Aged 16 to 35 Years, Inclusive, at the Time of Screening | 1.43 (0.78 to 2.39) |
On-treatment pregnancies are pregnancies with an estimated date of conception within the in-treatment period i.e. Day 1 to 7 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, unless a conception occurred during a cycle. At-risk-cycle was defined as cycle in which no other methods of birth control (including condoms and emergency contraception) were used by the subject as confirmed in the subject diary and during which the subject confirmed that sexual intercourse had occurred.
| Pearl Index | 15 mg E4/3 mg DRSP |
|---|---|
| The Number of On-treatment Pregnancies (With + 7-day Window) Per 100 Woman-years of Exposure (Pearl Index) in the Overall Study Population (16-50 Years) | 2.52 (1.68 to 3.64) |
On-treatment pregnancies are pregnancies with an estimated date of conception within the in-treatment period i.e. Day 1 to 7 days after the last intake of investigational product (whether active or inactive tablet). The method failure Pearl Index, defined as the number of pregnancies as a result of method failure per 100 women-years of treatment, was calculated as follow: (1300\*number of on-treatment pregnancies as a result of method failure)/number of women 28-day equivalent cycles of treatment. Pregnancies due to user failure were excluded from the numerator. User failure pregnancies were pregnancies that occurred when the subject did not take the investigational product correctly. At-risk-cycle was defined as cycle in which no other methods of birth control (including condoms and emergency contraception) were used by the subject and during which the subject confirmed that sexual intercourse had occurred.
| Method failure Pearl Index | 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 (16-50 Years) | 1.44 (0.82 to 2.34) |
The life-table analysis evaluates the cumulative probability of pregnancy over 13 cycles. Cumulative Rate and 95% CI are from Kaplan-Meier estimation. Only on-treatment pregnancies are included. On-treatment pregnancy is a pregnancy with an estimated date of conception after the date of the first dose of study medication to 7 days after the last dose of study medication (regardless of whether the last dose is an active or inactive tablet) inclusive.
| percentage of participants | 15 mg E4/3 mg DRSP |
|---|---|
| Rate of Pregnancy (Life-table Analysis) in Participants Aged 16 to 35 Years | 2.06 (1.40 to 3.04) |
The life-table analysis evaluates the cumulative probability of pregnancy over 13 cycles. Cumulative Rate and 95% confidence interval (CI) are from Kaplan-Meier estimation. Only on-treatment pregnancies are included. On-treatment pregnancy is a pregnancy with an estimated date of conception after the date of the first dose of study medication to 7 days after the last dose of study medication (regardless of whether the last dose is an active or inactive tablet) inclusive.
| percentage of participants | 15 mg E4/3 mg DRSP |
|---|---|
| Rate of Pregnancy (Life-table Analysis) in Participants Aged 16 to 50 Years | 2.00 (1.38 to 2.91) |
Unscheduled bleeding/spotting is defined as any bleeding/spotting that occurs while taking active hormones that does not meet the criteria for scheduled bleeding.
| Participants | 15 mg E4/3 mg DRSP |
|---|---|
| Cycle 1 | 532 |
| Cycle 2 | 345 |
| Cycle 3 | 337 |
| Cycle 4 | 302 |
| Cycle 5 | 238 |
| Cycle 6 | 253 |
| Cycle 7 | 229 |
| Cycle 8 | 204 |
| Cycle 9 | 221 |
| Cycle 10 | 184 |
| Cycle 11 | 159 |
| Cycle 12 | 175 |
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.
| Days | 15 mg E4/3 mg DRSP |
|---|---|
| Cycle 1 | 0.4 ± 1.42 |
| Cycle 2 | 0.3 ± 1.08 |
| Cycle 3 | 0.4 ± 1.20 |
| Cycle 4 | 0.3 ± 1.00 |
| Cycle 5 | 0.3 ± 1.04 |
| Cycle 6 | 0.3 ± 1.04 |
| Cycle 7 | 0.3 ± 1.04 |
| Cycle 8 | 0.2 ± 0.94 |
| Cycle 9 | 0.3 ± 1.01 |
| Cycle 10 | 0.3 ± 1.07 |
| Cycle 11 | 0.2 ± 0.94 |
| Cycle 12 | 0.2 ± 0.98 |
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.
| Days | 15 mg E4/3 mg DRSP |
|---|---|
| Cycle 1 | 1.0 ± 2.21 |
| Cycle 2 | 0.6 ± 1.50 |
| Cycle 3 | 0.6 ± 1.40 |
| Cycle 4 | 0.5 ± 1.31 |
| Cycle 5 | 0.5 ± 1.26 |
| Cycle 6 | 0.5 ± 1.30 |
| Cycle 7 | 0.5 ± 1.31 |
| Cycle 8 | 0.4 ± 1.18 |
| Cycle 9 | 0.5 ± 1.21 |
| Cycle 10 | 0.4 ± 1.20 |
| Cycle 11 | 0.4 ± 1.08 |
| Cycle 12 | 0.4 ± 1.09 |
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.
| Participants | 15 mg E4/3 mg DRSP |
|---|---|
| Cycle 1 | 230 |
| Cycle 2 | 254 |
| Cycle 3 | 274 |
| Cycle 4 | 233 |
| Cycle 5 | 209 |
| Cycle 6 | 225 |
| Cycle 7 | 191 |
| Cycle 8 | 183 |
| Cycle 9 | 180 |
| Cycle 10 | 137 |
| Cycle 11 | 136 |
| Cycle 12 | 134 |
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.
| Days | 15 mg E4/3 mg DRSP |
|---|---|
| Cycle 1 | 6.1 ± 10.16 |
| Cycle 2 | 4.7 ± 4.01 |
| Cycle 3 | 4.7 ± 6.72 |
| Cycle 4 | 4.8 ± 6.50 |
| Cycle 5 | 4.4 ± 3.70 |
| Cycle 6 | 4.4 ± 3.39 |
| Cycle 7 | 4.5 ± 5.00 |
| Cycle 8 | 4.5 ± 3.69 |
| Cycle 9 | 4.4 ± 5.64 |
| Cycle 10 | 4.3 ± 3.41 |
| Cycle 11 | 4.3 ± 3.87 |
| Cycle 12 | 4.3 ± 3.07 |
Bleeding data were analysed by 91-day reference period. There were 4 RPs: Reference Period 1 = Day 1 to Day 91; Reference Period 2 = Day 92 to Day 182; Reference Period 3 = Day 183 to Day 273; and Reference Period 4 = Day 274 to Day 364.
| Participants | 15 mg E4/3 mg DRSP - RP1 |
|---|---|
| Reference Period 1 | 1,249 |
| Reference Period 2 | 1,098 |
| Reference Period 3 | 982 |
| Reference Period 4 | 914 |
Bleeding data were analysed by 91-day reference period (RP). There were 4 RPs: Reference Period 1 = Day 1 to Day 91; Reference Period 2 = Day 92 to Day 182; Reference Period 3 = Day 183 to Day 273; and Reference Period 4 = Day 274 to Day 364.
| Days | 15 mg E4/3 mg DRSP |
|---|---|
| Reference Period 1 | 3.6 ± 1.23 |
| Reference Period 2 | 3.3 ± 1.27 |
| Reference Period 3 | 3.3 ± 1.25 |
| Reference Period 4 | 3.9 ± 1.30 |
A treatment-emergent adverse event (TEAE) was defined as any AE not present prior to the initiation of the treatment or any event already present that worsened in either intensity or frequency following exposure to the treatment. Since the starting point for adverse event (AE) collection was the signing of the informed consent, not the start of the investigational product, the AEs recorded prior to first investigational product administration were designated as AEs while those that occurred or worsened after the initiation of the investigational product were designated as TEAEs.
| Participants | 15 mg E4/3 mg DRSP |
|---|---|
| Number of Subjects With Treatment-emergent Adverse Events as a Measure of Safety and Tolerability. | 1,002 |
| Participants | 15 mg E4/3 mg DRSP |
|---|---|
| Number of Participants With Clinically Significant out-of Range Hematology Results | 8 |
| Participants | 15 mg E4/3 mg DRSP |
|---|---|
| Number of Participants With Clinically Significant out-of Range Serum Chemistry and Lipid Profile Results | 21 |
Vital signs included sitting systolic and diastolic blood pressures, and heart rate. All abnormal findings in vital signs that were considered by the Investigator to be clinically significant were recorded as adverse events.
| Participants | 15 mg E4/3 mg DRSP |
|---|---|
| Number of Subjects With Clinically Abnormal Vital Signs | 10 |
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.
| Participants | 15 mg E4/3 mg DRSP |
|---|---|
| Body as a whole -Baseline — Normal | 1,862 |
| Body as a whole -Baseline — Abnormal | 2 |
| Body as a whole -Baseline — Not done | 0 |
| Body as a whole - EOT — Normal | 1,431 |
| Body as a whole - EOT — Abnormal | 0 |
| Body as a whole - EOT — Not done | 1 |
| Skin - Baseline — Normal | 1,838 |
| Skin - Baseline — Abnormal | 25 |
| Skin - Baseline — Not done | 1 |
| Skin - EOT — Normal | 1,412 |
| Skin - EOT — Abnormal | 18 |
| Skin - EOT — Not done | 1 |
| Head, Eyes, Ears, Nose and Throat - Baseline — Normal | 1,856 |
| Head, Eyes, Ears, Nose and Throat - Baseline — Abnormal | 7 |
| Head, Eyes, Ears, Nose and Throat - Baseline — Not done | 1 |
| Head, Eyes, Ears, Nose - EOT — Normal | 1,424 |
| Head, Eyes, Ears, Nose - EOT — Abnormal | 2 |
| Head, Eyes, Ears, Nose - EOT — Not done | 6 |
| Neck - Baseline — Normal | 1,852 |
| Neck - Baseline — Abnormal | 2 |
| Neck - Baseline — Not done | 10 |
| Neck - EOT — Normal | 1,429 |
| Neck - EOT — Abnormal | 3 |
| Neck - EOT — Not done | 0 |
| Cardiovascular - Baseline — Normal | 1,862 |
| Cardiovascular - Baseline — Abnormal | 2 |
| Cardiovascular - Baseline — Not done | 0 |
| Cardiovascular - EOT — Normal | 1,429 |
| Cardiovascular - EOT — Abnormal | 3 |
| Cardiovascular - EOT — Not done | 0 |
| Respiratory - Baseline — Normal | 1,861 |
| Respiratory - Baseline — Abnormal | 3 |
| Respiratory - Baseline — Not done | 0 |
| Respiratory - EOT — Normal | 1,428 |
| Respiratory - EOT — Abnormal | 1 |
| Respiratory - EOT — Not done | 3 |
| Musculoskeletal - Baseline — Normal | 1,852 |
| Musculoskeletal - Baseline — Abnormal | 2 |
| Musculoskeletal - Baseline — Not done | 10 |
| Musculoskeletal - EOT — Normal | 1,423 |
| Musculoskeletal - EOT — Abnormal | 3 |
| Musculoskeletal - EOT — Not done | 6 |
| Neurologic - Baseline — Normal | 1,851 |
| Neurologic - Baseline — Abnormal | 1 |
| Neurologic - Baseline — Not done | 12 |
| Neurologic - EOT — Normal | 1,423 |
| Neurologic - EOT — Abnormal | 1 |
| Neurologic - EOT — Not done | 8 |
| Lymphatic/Thyroid - Baseline — Normal | 1,860 |
| Lymphatic/Thyroid - Baseline — Abnormal | 4 |
| Lymphatic/Thyroid - Baseline — Not done | 0 |
| Lymphatic/Thyroid - EOT — Normal | 1,431 |
| Lymphatic/Thyroid - EOT — Abnormal | 1 |
| Lymphatic/Thyroid - EOT — Not done | 0 |
| Abdomen - Baseline — Normal | 1,860 |
| Abdomen - Baseline — Abnormal | 3 |
| Abdomen - Baseline — Not done | 1 |
| Abdomen - EOT — Normal | 1,431 |
| Abdomen - EOT — Abnormal | 1 |
| Abdomen - EOT — Not done | 0 |
| Additional findings -Baseline — Normal | 3 |
| Additional findings -Baseline — Abnormal | 1 |
| Additional findings -Baseline — Not done | 21 |
| Additional findings - EOT — Normal | 3 |
| Additional findings - EOT — Abnormal | 1 |
| Additional findings - EOT — Not done | 30 |
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.
| Participants | 15 mg E4/3 mg DRSP |
|---|---|
| Breast -Baseline — Normal | 1,857 |
| Breast -Baseline — Abnormal | 6 |
| Breast -Baseline — Not done | 1 |
| Breast - EOT — Normal | 1,387 |
| Breast - EOT — Abnormal | 16 |
| Breast - EOT — Not done | 11 |
| Adnexa - Baseline — Normal | 1,861 |
| Adnexa - Baseline — Abnormal | 1 |
| Adnexa - Baseline — Not done | 2 |
| Adnexa - EOT — Normal | 1,404 |
| Adnexa - EOT — Abnormal | 4 |
| Adnexa - EOT — Not done | 6 |
| Cervix- Baseline — Normal | 1,862 |
| Cervix- Baseline — Abnormal | 2 |
| Cervix- Baseline — Not done | 0 |
| Cervix - EOT — Normal | 1,397 |
| Cervix - EOT — Abnormal | 5 |
| Cervix - EOT — Not done | 12 |
| Uterus - Baseline — Normal | 1,861 |
| Uterus - Baseline — Abnormal | 3 |
| Uterus - Baseline — Not done | 0 |
| Uterus - EOT — Normal | 1,402 |
| Uterus - EOT — Abnormal | 7 |
| Uterus - EOT — Not done | 5 |
| Vagina - Baseline — Normal | 1,841 |
| Vagina - Baseline — Abnormal | 23 |
| Vagina - Baseline — Not done | 0 |
| Vagina - EOT — Normal | 1,386 |
| Vagina - EOT — Abnormal | 22 |
| Vagina - EOT — Not done | 6 |
| External genitalia - Baseline — Normal | 1,860 |
| External genitalia - Baseline — Abnormal | 4 |
| External genitalia - Baseline — Not done | 0 |
| External genitalia - EOT — Normal | 1,398 |
| External genitalia - EOT — Abnormal | 10 |
| External genitalia - EOT — Not done | 5 |
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. 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). The minimum raw is 14 and maximum raw score is 70. Thus the formula for % maximum score can be written as (raw score -14)/56. A higher percentage maximum score indicates a higher life enjoyment and satisfaction.
| Percentage maximum score on a scale | 15 mg E4/3 mg DRSP |
|---|---|
| Baseline | 75.8 ± 13.58 |
| EOT | 75.4 ± 14.80 |
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. The last two items - item 15 rating "satisfaction with medicine" and item 16 rating "overall life satisfaction over the past week" are two global items that are scored individually. For both items, a higher score is associated with a better outcome.
| Units on a scale | 15 mg E4/3 mg DRSP |
|---|---|
| Satisfaction with medicine - Baseline | 4.2 ± 0.69 |
| Satisfaction with medicine - EOT | 4.1 ± 0.75 |
| Overall life satisfaction - Baseline | 4.1 ± 0.73 |
| Overall life satisfaction - EOT | 4.1 ± 0.77 |
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.
| units on a scale | 15 mg E4/3 mg DRSP - Intermenstrual Phase | 15 mg E4/3 mg DRSP - Premenstrual Phase | 15 mg E4/3 mg DRSP - Menstrual Phase |
|---|---|---|---|
| Pain | -0.3 ± 4.13 | -0.1 ± 4.19 | -0.6 ± 4.68 |
| Water retention | -0.1 ± 2.58 | -0.2 ± 2.91 | -0.2 ± 2.9 |
| Autonomic reactions | 0.0 ± 1.56 | 0.0 ± 1.69 | 0.1 ± 1.71 |
| Negative affect | -0.1 ± 5.17 | -0.4 ± 5.94 | -0.3 ± 5.98 |
| Impaired concentration | 0.0 ± 3.00 | -0.1 ± 3.19 | -0.1 ± 3.42 |
| Behaviour change | -0.0 ± 2.99 | -0.0 ± 3.19 | -0.0 ± 3.37 |
| Arousal | -0.2 ± 4.66 | -0.2 ± 4.42 | -0.2 ± 4.28 |
| Control | 0.1 ± 1.69 | 0.1 ± 1.94 | 0.1 ± 1.92 |
Collected over From screening to end of treatment (13 months). Non-serious events are listed at a 1% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| 15 mg E4/3 mg DRSP | 1/1,864 (0.1%) | 25/1,864 (1.3%) | 1,002/1,864 (53.8%) |
| Event | 15 mg E4/3 mg DRSP |
|---|---|
| Abortion spontaneousPregnancy, puerperium and perinatal conditions | 7/1864 |
| Ectopic pregnancyPregnancy, puerperium and perinatal conditions | 2/1864 |
| DepressionPsychiatric disorders | 2/1864 |
| Affective disorderPsychiatric disorders | 1/1864 |
| Bipolar I disorderPsychiatric disorders | 1/1864 |
| Psychotic disorderPsychiatric disorders | 1/1864 |
| Suicidal ideationPsychiatric disorders | 1/1864 |
| GastroenteritisInfections and infestations | 1/1864 |
| AppendicitisInfections and infestations | 1/1864 |
| Bacterial pyelonephritisInfections and infestations | 1/1864 |
| Event | 15 mg E4/3 mg DRSP |
|---|---|
| HeadacheNervous system disorders | 94/1864 |
| MetrorrhagiaReproductive system and breast disorders | 86/1864 |
| NauseaGastrointestinal disorders | 70/1864 |
| DysmenorrhoeaReproductive system and breast disorders | 66/1864 |
| Urinary tract infectionInfections and infestations | 64/1864 |
| AcneSkin and subcutaneous tissue disorders | 63/1864 |
| Upper respiratory tract infectionInfections and infestations | 62/1864 |
| Weight increasedInvestigations | 62/1864 |
| Viral upper respiratory tract infectionInfections and infestations | 61/1864 |
| Breast tendernessReproductive system and breast disorders | 54/1864 |
All participants aged 16 to 50 years who received at least one dose of 15 mg E4/3 mg DRSP
| Age, Categorical(Participants) | 15 mg E4/3 mg DRSP |
|---|---|
| <=18 years | 74 |
| Between 18 and 65 years | 1,790 |
| >=65 years | 0 |
| Age, Continuous(years) | 15 mg E4/3 mg DRSP |
|---|---|
| Mean | 27.3 ± 6.48 |
| Sex: Female, Male(Participants) | 15 mg E4/3 mg DRSP |
|---|---|
| Female | 1,864 |
| Male | 0 |
| Ethnicity (NIH/OMB)(Participants) | 15 mg E4/3 mg DRSP |
|---|---|
| Hispanic or Latino | 488 |
| Not Hispanic or Latino | 1,376 |
| Unknown or Not Reported | 0 |
| Region of Enrollment(participants) | 15 mg E4/3 mg DRSP |
|---|---|
| Canada | 152 |
| United States | 1,712 |
| Body Mass Index (BMI)(Kg/m^2) | 15 mg E4/3 mg DRSP |
|---|---|
| Mean | 25.89 ± 4.705 |
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