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E4 FREEDOM (Female Response Concerning Efficacy and Safety of Estetrol/Drospirenone as Oral Contraceptive in a Multicentric Study) - United States/Canada Study

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ClinicalTrials.gov Identifier: NCT02817841
Recruitment Status : Completed
First Posted : June 29, 2016
Results First Posted : November 6, 2019
Last Update Posted : February 10, 2020
Sponsor:
Collaborator:
PRA Health Sciences
Information provided by (Responsible Party):
Estetra

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Prevention
Condition Contraception
Intervention Drug: 15 mg E4/3 mg DRSP
Enrollment 2148
Recruitment Details  
Pre-assignment Details A total of 2,148 participants aged 16-50 years were enrolled. Of those, 1,864 participants started the investigational product. Two hundred and eighty-four participants did not start the investigational product for the following reasons: lost to follow-up (166), withdrew consent (31), and other reasons (87).
Arm/Group Title 15 mg E4/3 mg DRSP
Hide Arm/Group Description

15 mg estetrol (E4)/3 mg drospirenone (DRSP) combined oral contraceptive

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.
Period Title: Overall Study
Started 1864
Completed 1016
Not Completed 848
Reason Not Completed
Lost to Follow-up             287
Withdrawal by Subject             183
Adverse event not related to bleeding             131
Adverse event related to bleeding             51
Pregnancy             32
Pregnancy wish             17
Other reasons             53
Protocol Violation             94
Arm/Group Title 15 mg E4/3 mg DRSP
Hide Arm/Group Description

15 mg estetrol (E4)/3 mg drospirenone (DRSP) combined oral contraceptive

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.
Overall Number of Baseline Participants 1,864
Hide Baseline Analysis Population Description
All participants aged 16 to 50 years who received at least one dose of 15 mg E4/3 mg DRSP
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1,864 participants
<=18 years
74
   4.0%
Between 18 and 65 years
1,790
  96.0%
>=65 years
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 1,864 participants
27.3  (6.48)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1,864 participants
Female
1,864
 100.0%
Male
0
   0.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1,864 participants
Hispanic or Latino
488
  26.2%
Not Hispanic or Latino
1,376
  73.8%
Unknown or Not Reported
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
 Number Analyzed 1,864 participants
Canada 152
United States 1,712
Body Mass Index (BMI)  
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 1,864 participants
25.89  (4.705)
1.Primary Outcome
Title 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
Hide Description

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)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants aged 16 to 35 years, inclusive, at screening with at least 1 cycle included in the denominator.
Arm/Group Title 15 mg E4/3 mg DRSP
Hide Arm/Group Description:

15 mg estetrol (E4)/3 mg drospirenone (DRSP) combined oral contraceptive

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.
Overall Number of Participants Analyzed 1,524
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Pearl Index
2.65
(1.73 to 3.88)
2.Secondary Outcome
Title 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
Hide Description

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)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants aged 16 to 35 years, inclusive, at screening with at least 1 cycle included in the denominator.
Arm/Group Title 15 mg E4/3 mg DRSP
Hide Arm/Group Description:

15 mg estetrol (E4)/3 mg drospirenone (DRSP) combined oral contraceptive

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.
Overall Number of Participants Analyzed 1,524
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Method failure Pearl Index
1.43
(0.78 to 2.39)
3.Secondary Outcome
Title 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)
Hide Description

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)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants aged 16 to 50 years, inclusive, at screening with at least 1 cycle included in the denominator.
Arm/Group Title 15 mg E4/3 mg DRSP
Hide Arm/Group Description:

15 mg estetrol (E4)/3 mg drospirenone (DRSP) combined oral contraceptive

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.
Overall Number of Participants Analyzed 1,705
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Pearl Index
2.52
(1.68 to 3.64)
4.Secondary Outcome
Title The Number of On-treatment Pregnancies as Assessed by the Method Failure Pearl Index in the Overall Study Population (16-50 Years)
Hide Description

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)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants aged 18 to 50 years, inclusive, at screening with at least 1 cycle included in the denominator.
Arm/Group Title 15 mg E4/3 mg DRSP
Hide Arm/Group Description:

15 mg estetrol (E4)/3 mg drospirenone (DRSP) combined oral contraceptive

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.
Overall Number of Participants Analyzed 1,705
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Method failure Pearl Index
1.44
(0.82 to 2.34)
5.Secondary Outcome
Title Rate of Pregnancy (Life-table Analysis) in Participants Aged 16 to 35 Years
Hide Description

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)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants aged 16 to 35 years, inclusive, at screening, who received at least one dose of investigational product
Arm/Group Title 15 mg E4/3 mg DRSP
Hide Arm/Group Description:

15 mg estetrol (E4)/3 mg drospirenone (DRSP) combined oral contraceptive

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.
Overall Number of Participants Analyzed 901
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
2.06
(1.40 to 3.04)
6.Secondary Outcome
Title Rate of Pregnancy (Life-table Analysis) in Participants Aged 16 to 50 Years
Hide Description

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)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants aged 16 to 50 years, inclusive, at screening, who received at least one dose of investigational product
Arm/Group Title 15 mg E4/3 mg DRSP
Hide Arm/Group Description:

15 mg estetrol (E4)/3 mg drospirenone (DRSP) combined oral contraceptive

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.
Overall Number of Participants Analyzed 1,017
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
2.00
(1.38 to 2.91)
7.Secondary Outcome
Title Number of Subjects With Unscheduled Bleeding/Spotting Episodes
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants aged 16 to 50 years, inclusive, at screening, with evaluable cycle data for the bleeding analysis.
Arm/Group Title 15 mg E4/3 mg DRSP
Hide Arm/Group Description:

15 mg estetrol (E4)/3 mg drospirenone (DRSP) combined oral contraceptive

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.
Overall Number of Participants Analyzed 1,864
Measure Type: Count of Participants
Unit of Measure: Participants
Cycle 1 Number Analyzed 1,758 participants
532
  30.3%
Cycle 2 Number Analyzed 1,579 participants
345
  21.8%
Cycle 3 Number Analyzed 1,526 participants
337
  22.1%
Cycle 4 Number Analyzed 1,420 participants
302
  21.3%
Cycle 5 Number Analyzed 1,352 participants
238
  17.6%
Cycle 6 Number Analyzed 1,319 participants
253
  19.2%
Cycle 7 Number Analyzed 1,235 participants
229
  18.5%
Cycle 8 Number Analyzed 1,208 participants
204
  16.9%
Cycle 9 Number Analyzed 1,162 participants
221
  19.0%
Cycle 10 Number Analyzed 1,053 participants
184
  17.5%
Cycle 11 Number Analyzed 1,028 participants
159
  15.5%
Cycle 12 Number Analyzed 1,006 participants
175
  17.4%
8.Secondary Outcome
Title Number of Unscheduled Bleeding Days Per Cycle
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants aged 16 to 50 years, inclusive, at screening, with evaluable cycle data for the bleeding analysis.
Arm/Group Title 15 mg E4/3 mg DRSP
Hide Arm/Group Description:

15 mg estetrol (E4)/3 mg drospirenone (DRSP) combined oral contraceptive

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.
Overall Number of Participants Analyzed 1,864
Mean (Standard Deviation)
Unit of Measure: Days
Cycle 1 Number Analyzed 1,758 participants
0.4  (1.42)
Cycle 2 Number Analyzed 1,579 participants
0.3  (1.08)
Cycle 3 Number Analyzed 1,526 participants
0.4  (1.20)
Cycle 4 Number Analyzed 1,420 participants
0.3  (1.00)
Cycle 5 Number Analyzed 1,352 participants
0.3  (1.04)
Cycle 6 Number Analyzed 1,319 participants
0.3  (1.04)
Cycle 7 Number Analyzed 1,235 participants
0.3  (1.04)
Cycle 8 Number Analyzed 1,208 participants
0.2  (0.94)
Cycle 9 Number Analyzed 1,162 participants
0.3  (1.01)
Cycle 10 Number Analyzed 1,053 participants
0.3  (1.07)
Cycle 11 Number Analyzed 1,028 participants
0.2  (0.94)
Cycle 12 Number Analyzed 1,006 participants
0.2  (0.98)
9.Secondary Outcome
Title Number of Unscheduled Spotting Days Per Cycle
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants aged 16 to 50 years, inclusive, at screening, with evaluable cycle data for the bleeding analysis.
Arm/Group Title 15 mg E4/3 mg DRSP
Hide Arm/Group Description:

15 mg estetrol (E4)/3 mg drospirenone (DRSP) combined oral contraceptive

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.
Overall Number of Participants Analyzed 1,864
Mean (Standard Deviation)
Unit of Measure: Days
Cycle 1 Number Analyzed 1,758 participants
1.0  (2.21)
Cycle 2 Number Analyzed 1,579 participants
0.6  (1.50)
Cycle 3 Number Analyzed 1,526 participants
0.6  (1.40)
Cycle 4 Number Analyzed 1,420 participants
0.5  (1.31)
Cycle 5 Number Analyzed 1,352 participants
0.5  (1.26)
Cycle 6 Number Analyzed 1,319 participants
0.5  (1.30)
Cycle 7 Number Analyzed 1,235 participants
0.5  (1.31)
Cycle 8 Number Analyzed 1,208 participants
0.4  (1.18)
Cycle 9 Number Analyzed 1,162 participants
0.5  (1.21)
Cycle 10 Number Analyzed 1,053 participants
0.4  (1.20)
Cycle 11 Number Analyzed 1,028 participants
0.4  (1.08)
Cycle 12 Number Analyzed 1,006 participants
0.4  (1.09)
10.Secondary Outcome
Title Number of Subjects With Absence of Scheduled Bleeding and/or Spotting
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants aged 16 to 50 years, inclusive, at screening, with evaluable cycle data for the bleeding analysis
Arm/Group Title 15 mg E4/3 mg DRSP
Hide Arm/Group Description:

15 mg estetrol (E4)/3 mg drospirenone (DRSP) combined oral contraceptive

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.
Overall Number of Participants Analyzed 1,864
Measure Type: Count of Participants
Unit of Measure: Participants
Cycle 1 Number Analyzed 1,758 participants
230
  13.1%
Cycle 2 Number Analyzed 1,579 participants
254
  16.1%
Cycle 3 Number Analyzed 1,526 participants
274
  18.0%
Cycle 4 Number Analyzed 1,420 participants
233
  16.4%
Cycle 5 Number Analyzed 1,352 participants
209
  15.5%
Cycle 6 Number Analyzed 1,319 participants
225
  17.1%
Cycle 7 Number Analyzed 1,235 participants
191
  15.5%
Cycle 8 Number Analyzed 1,208 participants
183
  15.1%
Cycle 9 Number Analyzed 1,162 participants
180
  15.5%
Cycle 10 Number Analyzed 1,053 participants
137
  13.0%
Cycle 11 Number Analyzed 1,028 participants
136
  13.2%
Cycle 12 Number Analyzed 1,006 participants
134
  13.3%
11.Secondary Outcome
Title Number of Scheduled Bleeding and/or Spotting Days Per Cycle
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants aged 16 to 50 years, inclusive, at screening, with evaluable cycle data for the bleeding analysis.
Arm/Group Title 15 mg E4/3 mg DRSP
Hide Arm/Group Description:

15 mg estetrol (E4)/3 mg drospirenone (DRSP) combined oral contraceptive

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.
Overall Number of Participants Analyzed 1,864
Mean (Standard Deviation)
Unit of Measure: Days
Cycle 1 Number Analyzed 1,758 participants
6.1  (10.16)
Cycle 2 Number Analyzed 1,579 participants
4.7  (4.01)
Cycle 3 Number Analyzed 1,526 participants
4.7  (6.72)
Cycle 4 Number Analyzed 1,420 participants
4.8  (6.50)
Cycle 5 Number Analyzed 1,352 participants
4.4  (3.70)
Cycle 6 Number Analyzed 1,319 participants
4.4  (3.39)
Cycle 7 Number Analyzed 1,235 participants
4.5  (5.00)
Cycle 8 Number Analyzed 1,208 participants
4.5  (3.69)
Cycle 9 Number Analyzed 1,162 participants
4.4  (5.64)
Cycle 10 Number Analyzed 1,053 participants
4.3  (3.41)
Cycle 11 Number Analyzed 1,028 participants
4.3  (3.87)
Cycle 12 Number Analyzed 1,006 participants
4.3  (3.07)
12.Secondary Outcome
Title Number of Subjects With Bleeding and/or Spotting Episodes by Reference Period
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants aged 16 to 50 years, inclusive, at screening, with evaluable reference period for the bleeding analysis.
Arm/Group Title 15 mg E4/3 mg DRSP - RP1
Hide Arm/Group Description:

15 mg estetrol (E4)/3 mg drospirenone (DRSP) combined oral contraceptive

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.
Overall Number of Participants Analyzed 1,864
Measure Type: Count of Participants
Unit of Measure: Participants
Reference Period 1 Number Analyzed 1,864 participants
1,249
  67.0%
Reference Period 2 Number Analyzed 1,120 participants
1,098
  98.0%
Reference Period 3 Number Analyzed 1,002 participants
982
  98.0%
Reference Period 4 Number Analyzed 933 participants
914
  98.0%
13.Secondary Outcome
Title Mean Number of Bleeding and Spotting Days by Reference Period
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants aged 16 to 50 years, inclusive, at screening, with evaluable cycle data for the bleeding analysis.
Arm/Group Title 15 mg E4/3 mg DRSP
Hide Arm/Group Description:

15 mg estetrol (E4)/3 mg drospirenone (DRSP) combined oral contraceptive

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.
Overall Number of Participants Analyzed 1,864
Mean (Standard Deviation)
Unit of Measure: Days
Reference Period 1 Number Analyzed 1,864 participants
3.6  (1.23)
Reference Period 2 Number Analyzed 1,120 participants
3.3  (1.27)
Reference Period 3 Number Analyzed 1,002 participants
3.3  (1.25)
Reference Period 4 Number Analyzed 933 participants
3.9  (1.30)
14.Secondary Outcome
Title Number of Subjects With Treatment-emergent Adverse Events as a Measure of Safety and Tolerability.
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants aged 16 to 50 years, inclusive, at screening who received at least one dose of investigational product.
Arm/Group Title 15 mg E4/3 mg DRSP
Hide Arm/Group Description:

15 mg estetrol (E4)/3 mg drospirenone (DRSP) combined oral contraceptive

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.
Overall Number of Participants Analyzed 1,864
Measure Type: Count of Participants
Unit of Measure: Participants
1,002
  53.8%
15.Secondary Outcome
Title Number of Participants With Clinically Significant out-of Range Hematology Results
Hide Description [Not Specified]
Time Frame Up to 12 months (13 cycles with 1 cycle = 28 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants aged 16 to 50 years, inclusive, at screening, who received at least one dose of investigational product.
Arm/Group Title 15 mg E4/3 mg DRSP
Hide Arm/Group Description:

15 mg estetrol (E4)/3 mg drospirenone (DRSP) combined oral contraceptive

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.
Overall Number of Participants Analyzed 1,864
Measure Type: Count of Participants
Unit of Measure: Participants
8
   0.4%
16.Secondary Outcome
Title Number of Participants With Clinically Significant out-of Range Serum Chemistry and Lipid Profile Results
Hide Description [Not Specified]
Time Frame Up to 12 months (13 cycles with 1 cycle = 28 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants aged 16 to 50 years, inclusive, at screening, who received at least one dose of investigational product.
Arm/Group Title 15 mg E4/3 mg DRSP
Hide Arm/Group Description:

15 mg estetrol (E4)/3 mg drospirenone (DRSP) combined oral contraceptive

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.
Overall Number of Participants Analyzed 1,864
Measure Type: Count of Participants
Unit of Measure: Participants
21
   1.1%
17.Secondary Outcome
Title Number of Subjects With Clinically Abnormal Vital Signs
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants aged 16 to 50 years, inclusive, at screening, who received at least one dose of investigational product.
Arm/Group Title 15 mg E4/3 mg DRSP
Hide Arm/Group Description:

15 mg estetrol (E4)/3 mg drospirenone (DRSP) combined oral contraceptive

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.
Overall Number of Participants Analyzed 1,864
Measure Type: Count of Participants
Unit of Measure: Participants
10
   0.5%
18.Secondary Outcome
Title Number of Participants With Clinically Abnormal Physical Examination Results
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants aged 16 to 50 years, inclusive, at screening, who received at least one dose of investigational product with baseline and end of treatment (EOT) data.
Arm/Group Title 15 mg E4/3 mg DRSP
Hide Arm/Group Description:

15 mg estetrol (E4)/3 mg drospirenone (DRSP) combined oral contraceptive

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.
Overall Number of Participants Analyzed 1,864
Measure Type: Count of Participants
Unit of Measure: Participants
Body as a whole -Baseline Number Analyzed 1,864 participants
Normal
1,862
  99.9%
Abnormal
2
   0.1%
Not done
0
   0.0%
Body as a whole - EOT Number Analyzed 1,432 participants
Normal
1,431
  99.9%
Abnormal
0
   0.0%
Not done
1
   0.1%
Skin - Baseline Number Analyzed 1,864 participants
Normal
1,838
  98.6%
Abnormal
25
   1.3%
Not done
1
   0.1%
Skin - EOT Number Analyzed 1,431 participants
Normal
1,412
  98.7%
Abnormal
18
   1.3%
Not done
1
   0.1%
Head, Eyes, Ears, Nose and Throat - Baseline Number Analyzed 1,864 participants
Normal
1,856
  99.6%
Abnormal
7
   0.4%
Not done
1
   0.1%
Head, Eyes, Ears, Nose - EOT Number Analyzed 1,432 participants
Normal
1,424
  99.4%
Abnormal
2
   0.1%
Not done
6
   0.4%
Neck - Baseline Number Analyzed 1,864 participants
Normal
1,852
  99.4%
Abnormal
2
   0.1%
Not done
10
   0.5%
Neck - EOT Number Analyzed 1,432 participants
Normal
1,429
  99.8%
Abnormal
3
   0.2%
Not done
0
   0.0%
Cardiovascular - Baseline Number Analyzed 1,864 participants
Normal
1,862
  99.9%
Abnormal
2
   0.1%
Not done
0
   0.0%
Cardiovascular - EOT Number Analyzed 1,432 participants
Normal
1,429
  99.8%
Abnormal
3
   0.2%
Not done
0
   0.0%
Respiratory - Baseline Number Analyzed 1,864 participants
Normal
1,861
  99.8%
Abnormal
3
   0.2%
Not done
0
   0.0%
Respiratory - EOT Number Analyzed 1,432 participants
Normal
1,428
  99.7%
Abnormal
1
   0.1%
Not done
3
   0.2%
Musculoskeletal - Baseline Number Analyzed 1,864 participants
Normal
1,852
  99.4%
Abnormal
2
   0.1%
Not done
10
   0.5%
Musculoskeletal - EOT Number Analyzed 1,432 participants
Normal
1,423
  99.4%
Abnormal
3
   0.2%
Not done
6
   0.4%
Neurologic - Baseline Number Analyzed 1,864 participants
Normal
1,851
  99.3%
Abnormal
1
   0.1%
Not done
12
   0.6%
Neurologic - EOT Number Analyzed 1,432 participants
Normal
1,423
  99.4%
Abnormal
1
   0.1%
Not done
8
   0.6%
Lymphatic/Thyroid - Baseline Number Analyzed 1,864 participants
Normal
1,860
  99.8%
Abnormal
4
   0.2%
Not done
0
   0.0%
Lymphatic/Thyroid - EOT Number Analyzed 1,432 participants
Normal
1,431
  99.9%
Abnormal
1
   0.1%
Not done
0
   0.0%
Abdomen - Baseline Number Analyzed 1,864 participants
Normal
1,860
  99.8%
Abnormal
3
   0.2%
Not done
1
   0.1%
Abdomen - EOT Number Analyzed 1,432 participants
Normal
1,431
  99.9%
Abnormal
1
   0.1%
Not done
0
   0.0%
Additional findings -Baseline Number Analyzed 25 participants
Normal
3
  12.0%
Abnormal
1
   4.0%
Not done
21
  84.0%
Additional findings - EOT Number Analyzed 34 participants
Normal
3
   8.8%
Abnormal
1
   2.9%
Not done
30
  88.2%
19.Secondary Outcome
Title Number of Participants With Clinically Abnormal Gynecological Examination Results
Hide Description

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)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants aged 16 to 50 years, inclusive, at screening, who received at least one dose of investigational product with baseline and end of treatment (EOT) data.
Arm/Group Title 15 mg E4/3 mg DRSP
Hide Arm/Group Description:

15 mg estetrol (E4)/3 mg drospirenone (DRSP) combined oral contraceptive

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.
Overall Number of Participants Analyzed 1,864
Measure Type: Count of Participants
Unit of Measure: Participants
Breast -Baseline Number Analyzed 1,864 participants
Normal
1,857
  99.6%
Abnormal
6
   0.3%
Not done
1
   0.1%
Breast - EOT Number Analyzed 1,414 participants
Normal
1,387
  98.1%
Abnormal
16
   1.1%
Not done
11
   0.8%
Adnexa - Baseline Number Analyzed 1,864 participants
Normal
1,861
  99.8%
Abnormal
1
   0.1%
Not done
2
   0.1%
Adnexa - EOT Number Analyzed 1,414 participants
Normal
1,404
  99.3%
Abnormal
4
   0.3%
Not done
6
   0.4%
Cervix- Baseline Number Analyzed 1,864 participants
Normal
1,862
  99.9%
Abnormal
2
   0.1%
Not done
0
   0.0%
Cervix - EOT Number Analyzed 1,414 participants
Normal
1,397
  98.8%
Abnormal
5
   0.4%
Not done
12
   0.8%
Uterus - Baseline Number Analyzed 1,864 participants
Normal
1,861
  99.8%
Abnormal
3
   0.2%
Not done
0
   0.0%
Uterus - EOT Number Analyzed 1,414 participants
Normal
1,402
  99.2%
Abnormal
7
   0.5%
Not done
5
   0.4%
Vagina - Baseline Number Analyzed 1,864 participants
Normal
1,841
  98.8%
Abnormal
23
   1.2%
Not done
0
   0.0%
Vagina - EOT Number Analyzed 1,414 participants
Normal
1,386
  98.0%
Abnormal
22
   1.6%
Not done
6
   0.4%
External genitalia - Baseline Number Analyzed 1,864 participants
Normal
1,860
  99.8%
Abnormal
4
   0.2%
Not done
0
   0.0%
External genitalia - EOT Number Analyzed 1,413 participants
Normal
1,398
  98.9%
Abnormal
10
   0.7%
Not done
5
   0.4%
20.Secondary Outcome
Title 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)
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants aged 16 to 50 years, inclusive, at screening with baseline and end of treatment (EOT) Q-LES-Q-SF results.
Arm/Group Title 15 mg E4/3 mg DRSP
Hide Arm/Group Description:

15 mg estetrol (E4)/3 mg drospirenone (DRSP) combined oral contraceptive

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.
Overall Number of Participants Analyzed 1,864
Mean (Standard Deviation)
Unit of Measure: Percentage maximum score on a scale
Baseline Number Analyzed 1,490 participants
75.8  (13.58)
EOT Number Analyzed 1,358 participants
75.4  (14.80)
21.Secondary Outcome
Title 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
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants aged 16 to 50 years, inclusive, at screening with baseline and end of treatment (EOT) Q-LES-Q-SF results.
Arm/Group Title 15 mg E4/3 mg DRSP
Hide Arm/Group Description:

15 mg estetrol (E4)/3 mg drospirenone (DRSP) combined oral contraceptive

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.
Overall Number of Participants Analyzed 1,864
Mean (Standard Deviation)
Unit of Measure: Units on a scale
Satisfaction with medicine - Baseline Number Analyzed 493 participants
4.2  (0.69)
Satisfaction with medicine - EOT Number Analyzed 514 participants
4.1  (0.75)
Overall life satisfaction - Baseline Number Analyzed 1,490 participants
4.1  (0.73)
Overall life satisfaction - EOT Number Analyzed 1,358 participants
4.1  (0.77)
22.Secondary Outcome
Title Change From Baseline to End of Treatment in the Score of the Menstrual Distress Questionnaire (MDQ)
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants aged 16 to 50 years, inclusive, at screening with both baseline and end of treatment (EOT) MDQ results
Arm/Group Title 15 mg E4/3 mg DRSP - Intermenstrual Phase 15 mg E4/3 mg DRSP - Premenstrual Phase 15 mg E4/3 mg DRSP - Menstrual Phase
Hide Arm/Group Description:

15 mg estetrol (E4)/3 mg drospirenone (DRSP) combined oral contraceptive

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.

15 mg estetrol (E4)/3 mg drospirenone (DRSP) combined oral contraceptive

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.

15 mg estetrol (E4)/3 mg drospirenone (DRSP) combined oral contraceptive

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.
Overall Number of Participants Analyzed 1,864 1,864 1,864
Mean (Standard Deviation)
Unit of Measure: units on a scale
Pain Number Analyzed 1,304 participants 1,297 participants 1,302 participants
-0.3  (4.13) -0.1  (4.19) -0.6  (4.68)
Water retention Number Analyzed 1,305 participants 1,298 participants 1,303 participants
-0.1  (2.58) -0.2  (2.91) -0.2  (2.9)
Autonomic reactions Number Analyzed 1,305 participants 1,298 participants 1,303 participants
0.0  (1.56) 0.0  (1.69) 0.1  (1.71)
Negative affect Number Analyzed 1,305 participants 1,298 participants 1,303 participants
-0.1  (5.17) -0.4  (5.94) -0.3  (5.98)
Impaired concentration Number Analyzed 1,305 participants 1,298 participants 1,303 participants
0.0  (3.00) -0.1  (3.19) -0.1  (3.42)
Behaviour change Number Analyzed 1,305 participants 1,298 participants 1,303 participants
-0.0  (2.99) -0.0  (3.19) -0.0  (3.37)
Arousal Number Analyzed 1,305 participants 1,298 participants 1,303 participants
-0.2  (4.66) -0.2  (4.42) -0.2  (4.28)
Control Number Analyzed 1,305 participants 1,298 participants 1,303 participants
0.1  (1.69) 0.1  (1.94) 0.1  (1.92)
Time Frame From screening to end of treatment (13 months)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title 15 mg E4/3 mg DRSP
Hide Arm/Group Description

15 mg estetrol (E4)/3 mg drospirenone (DRSP) combined oral contraceptive

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.
All-Cause Mortality
15 mg E4/3 mg DRSP
Affected / at Risk (%)
Total   1/1,864    
Hide Serious Adverse Events
15 mg E4/3 mg DRSP
Affected / at Risk (%) # Events
Total   25/1,864    
Gastrointestinal disorders   
Pancreatitis acute * 1  1/1864 (0.05%)  1
Hepatobiliary disorders   
Cholecystitis * 1  1/1864 (0.05%)  1
Hepatic haematoma * 1  1/1864 (0.05%)  1
Immune system disorders   
Drug hypersensitivity * 1  1/1864 (0.05%)  1
Infections and infestations   
Gastroenteritis * 1  1/1864 (0.05%)  2
Appendicitis * 1  1/1864 (0.05%)  1
Bacterial pyelonephritis * 1  1/1864 (0.05%)  1
Campylobacter gastroenteritis * 1  1/1864 (0.05%)  1
Infection parasitic * 1  1/1864 (0.05%)  1
Injury, poisoning and procedural complications   
Accidental overdose * 1  1/1864 (0.05%)  1
Rib fracture * 1  1/1864 (0.05%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Acute myeloid leukaemia * 1  1/1864 (0.05%)  1
Thyroid neoplasm * 1  1/1864 (0.05%)  1
Pregnancy, puerperium and perinatal conditions   
Abortion spontaneous * 1  7/1864 (0.38%)  7
Ectopic pregnancy * 1  2/1864 (0.11%)  2
Psychiatric disorders   
Depression * 1  2/1864 (0.11%)  2
Affective disorder * 1  1/1864 (0.05%)  1
Bipolar I disorder * 1  1/1864 (0.05%)  1
Psychotic disorder * 1  1/1864 (0.05%)  1
Suicidal ideation * 1  1/1864 (0.05%)  1
Respiratory, thoracic and mediastinal disorders   
Pneumomediastinum * 1  1/1864 (0.05%)  1
1
Term from vocabulary, MedDRA 20.0
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 1%
15 mg E4/3 mg DRSP
Affected / at Risk (%) # Events
Total   1,002/1,864    
Gastrointestinal disorders   
Nausea * 1  70/1864 (3.76%)  74
Abdominal pain * 1  39/1864 (2.09%)  43
Vomiting * 1  29/1864 (1.56%)  31
Diarrhoea * 1  24/1864 (1.29%)  24
Abdominal distension * 1  20/1864 (1.07%)  20
Abdominal pain lower * 1  18/1864 (0.97%)  18
General disorders   
Fatigue * 1  42/1864 (2.25%)  42
Infections and infestations   
Urinary tract infection * 1  64/1864 (3.43%)  71
Upper respiratory tract infection * 1  62/1864 (3.33%)  65
Viral upper respiratory tract infection * 1  61/1864 (3.27%)  71
Bacterial vaginosis * 1  45/1864 (2.41%)  47
Sinusitis * 1  29/1864 (1.56%)  30
Fungal infection * 1  24/1864 (1.29%)  32
Influenza * 1  24/1864 (1.29%)  27
Vulvovaginal mycotic infection * 1  24/1864 (1.29%)  27
Pharyngitis streptococcal * 1  18/1864 (0.97%)  20
Investigations   
Weight increased * 1  62/1864 (3.33%)  62
Musculoskeletal and connective tissue disorders   
Back pain * 1  29/1864 (1.56%)  33
Nervous system disorders   
Headache * 1  94/1864 (5.04%)  100
Dizziness * 1  22/1864 (1.18%)  23
Psychiatric disorders   
Anxiety * 1  45/1864 (2.41%)  45
Mood swings * 1  38/1864 (2.04%)  40
Depression * 1  35/1864 (1.88%)  38
Libido decreased * 1  25/1864 (1.34%)  25
Insomnia * 1  22/1864 (1.18%)  23
Mood altered * 1  19/1864 (1.02%)  19
Irritability * 1  18/1864 (0.97%)  18
Reproductive system and breast disorders   
Metrorrhagia * 1  86/1864 (4.61%)  88
Dysmenorrhoea * 1  66/1864 (3.54%)  69
Breast tenderness * 1  54/1864 (2.90%)  55
Vaginal haemorrhage * 1  41/1864 (2.20%)  45
Menorrhagia * 1  39/1864 (2.09%)  40
Breast pain * 1  26/1864 (1.39%)  27
Vaginal discharge * 1  20/1864 (1.07%)  20
Respiratory, thoracic and mediastinal disorders   
Cough * 1  18/1864 (0.97%)  18
Skin and subcutaneous tissue disorders   
Acne * 1  63/1864 (3.38%)  69
1
Term from vocabulary, MedDRA 20.0
*
Indicates events were collected by non-systematic assessment
[Not Specified]
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Mithra Pharmaceuticals SA Pharma Department
Organization: Estetra SPRL
Phone: +3243492822
EMail: clinical.trials@mithra.com
Layout table for additonal information
Responsible Party: Estetra
ClinicalTrials.gov Identifier: NCT02817841    
Other Study ID Numbers: MIT-Es0001-C302
First Submitted: June 27, 2016
First Posted: June 29, 2016
Results First Submitted: October 16, 2019
Results First Posted: November 6, 2019
Last Update Posted: February 10, 2020