Trial Outcomes & Findings for Estetrol for the Treatment of Moderate to Severe Vasomotor Symptoms in Postmenopausal Women (E4Comfort II) (NCT NCT04090957)
NCT ID: NCT04090957
Last Updated: 2025-12-26
Results Overview
Weekly frequency of moderate to severe VMS at Baseline = total number (sum) of all recorded moderate to severe VMS experienced during the last 7 consecutive days prior randomization (Week 0). Weekly frequency of moderate to severe VMS at Week X = total number (sum) of all recorded moderate to severe VMS experienced during the week X.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
1015 participants
Primary outcome timeframe
Week 0 (Baseline), Week 4, Week 12.
Results posted on
2025-12-26
Participant Flow
Recruitment process for the overall study involved hysterectomized and non hysterectomized postmenopausal women ≥40 up to ≤65 years of age seeking treatment for the relief of vasomotor symptoms (VMS) associated with menopause; N=3974 were screened by study inclusion and exclusion criteria. * Efficacy Study Part: \>=7 moderate to severe VMS/day or \>=50 moderate to severe VMS/week in the last 7 consecutive days during the screening period. * Safety Study Part: \>=1 moderate to severe VMS/week.
Participant milestones
| Measure |
Estetrol 15 mg - Randomized Set - Efficacy Study Part
Estetrol monohydrate 15 mg (E4 15 mg), equivalent to estetrol 14.2 mg. The study drug was to be taken once a day for up to 53 weeks.
|
Estetrol 20 mg - Randomized Set - Efficacy Study Part
Estetrol monohydrate 20 mg (E4 20 mg), equivalent to estetrol 18.9 mg. The study drug was to be taken once a day for up to 53 weeks.
|
Placebo - Randomized Set - Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks.
|
Estetrol 20 mg - Included Set - Safety Study Part
Estetrol monohydrate 20 mg (E4 20 mg), equivalent to estetrol 18.9 mg. The study drug was to be taken once a day for up to 53 weeks.
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
194
|
194
|
196
|
431
|
|
Overall Study
COMPLETED
|
96
|
85
|
108
|
149
|
|
Overall Study
NOT COMPLETED
|
98
|
109
|
88
|
282
|
Reasons for withdrawal
| Measure |
Estetrol 15 mg - Randomized Set - Efficacy Study Part
Estetrol monohydrate 15 mg (E4 15 mg), equivalent to estetrol 14.2 mg. The study drug was to be taken once a day for up to 53 weeks.
|
Estetrol 20 mg - Randomized Set - Efficacy Study Part
Estetrol monohydrate 20 mg (E4 20 mg), equivalent to estetrol 18.9 mg. The study drug was to be taken once a day for up to 53 weeks.
|
Placebo - Randomized Set - Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks.
|
Estetrol 20 mg - Included Set - Safety Study Part
Estetrol monohydrate 20 mg (E4 20 mg), equivalent to estetrol 18.9 mg. The study drug was to be taken once a day for up to 53 weeks.
|
|---|---|---|---|---|
|
Overall Study
Lost to Follow-up
|
22
|
25
|
25
|
36
|
|
Overall Study
Withdrawal of Consent for Another Reason
|
15
|
17
|
21
|
39
|
|
Overall Study
Adverse Event
|
19
|
25
|
8
|
104
|
|
Overall Study
Other
|
10
|
6
|
5
|
12
|
|
Overall Study
Serious Adverse Event
|
7
|
11
|
1
|
32
|
|
Overall Study
Endometrial Biopsy Showing Proliferative Disorder
|
7
|
9
|
1
|
26
|
|
Overall Study
Lack of Efficacy
|
1
|
1
|
9
|
0
|
|
Overall Study
Protocol Violation
|
3
|
5
|
2
|
1
|
|
Overall Study
Withdrawal of Consent Due to Lack of Efficacy
|
2
|
2
|
6
|
3
|
|
Overall Study
COVID-19
|
2
|
2
|
3
|
7
|
|
Overall Study
Non-Compliance with Trial Protocol: Other
|
2
|
2
|
1
|
4
|
|
Overall Study
Physician Decision
|
2
|
1
|
1
|
5
|
|
Overall Study
Sponsor Decision
|
1
|
1
|
1
|
3
|
|
Overall Study
Endometrial Findings - Physician Decision
|
1
|
1
|
0
|
5
|
|
Overall Study
Non-Compliance to Trial Protocol: Study Drug Intake Compliance
|
1
|
0
|
1
|
4
|
|
Overall Study
Non-Compliance to Trial Protocol: VMS Count Compliance
|
0
|
0
|
1
|
0
|
|
Overall Study
Death
|
1
|
0
|
0
|
0
|
|
Overall Study
No Treatment Administered
|
2
|
1
|
2
|
1
|
Baseline Characteristics
Results shown for subjects with available data.
Baseline characteristics by cohort
| Measure |
Estetrol 15 mg - Efficacy Study Part
n=192 Participants
Estetrol (E4) 15 mg oral tablet, administered once daily for up to 53 weeks
|
Estetrol 20 mg - Efficacy Study Part
n=193 Participants
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks
|
Placebo - Efficacy Study Part
n=194 Participants
Placebo was administered orally once daily for up to 53 weeks.
|
Estetrol 20 mg - Safety Study Part
n=430 Participants
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks
|
Total
n=1009 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
54.7 years
STANDARD_DEVIATION 5.14 • n=192 Participants
|
54.5 years
STANDARD_DEVIATION 4.83 • n=193 Participants
|
54.7 years
STANDARD_DEVIATION 4.68 • n=194 Participants
|
54.4 years
STANDARD_DEVIATION 4.88 • n=430 Participants
|
54.7 years
STANDARD_DEVIATION 4.88 • n=1009 Participants
|
|
Sex: Female, Male
Female
|
192 Participants
n=192 Participants
|
193 Participants
n=193 Participants
|
194 Participants
n=194 Participants
|
430 Participants
n=430 Participants
|
1009 Participants
n=1009 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=192 Participants
|
0 Participants
n=193 Participants
|
0 Participants
n=194 Participants
|
0 Participants
n=430 Participants
|
0 Participants
n=1009 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
74 Participants
n=192 Participants
|
59 Participants
n=193 Participants
|
66 Participants
n=194 Participants
|
83 Participants
n=430 Participants
|
282 Participants
n=1009 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
118 Participants
n=192 Participants
|
134 Participants
n=193 Participants
|
128 Participants
n=194 Participants
|
347 Participants
n=430 Participants
|
727 Participants
n=1009 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=192 Participants
|
0 Participants
n=193 Participants
|
0 Participants
n=194 Participants
|
0 Participants
n=430 Participants
|
0 Participants
n=1009 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=192 Participants
|
1 Participants
n=193 Participants
|
3 Participants
n=194 Participants
|
0 Participants
n=430 Participants
|
4 Participants
n=1009 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=192 Participants
|
3 Participants
n=193 Participants
|
1 Participants
n=194 Participants
|
5 Participants
n=430 Participants
|
10 Participants
n=1009 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=192 Participants
|
0 Participants
n=193 Participants
|
0 Participants
n=194 Participants
|
1 Participants
n=430 Participants
|
1 Participants
n=1009 Participants
|
|
Race (NIH/OMB)
Black or African American
|
54 Participants
n=192 Participants
|
55 Participants
n=193 Participants
|
50 Participants
n=194 Participants
|
95 Participants
n=430 Participants
|
254 Participants
n=1009 Participants
|
|
Race (NIH/OMB)
White
|
136 Participants
n=192 Participants
|
133 Participants
n=193 Participants
|
139 Participants
n=194 Participants
|
325 Participants
n=430 Participants
|
733 Participants
n=1009 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=192 Participants
|
0 Participants
n=193 Participants
|
0 Participants
n=194 Participants
|
0 Participants
n=430 Participants
|
0 Participants
n=1009 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=192 Participants
|
1 Participants
n=193 Participants
|
1 Participants
n=194 Participants
|
4 Participants
n=430 Participants
|
7 Participants
n=1009 Participants
|
|
Body Mass Index (BMI)
|
28.83 kg/m^2
STANDARD_DEVIATION 4.59 • n=192 Participants
|
27.93 kg/m^2
STANDARD_DEVIATION 4.40 • n=193 Participants
|
28.75 kg/m^2
STANDARD_DEVIATION 4.61 • n=194 Participants
|
28.33 kg/m^2
STANDARD_DEVIATION 4.54 • n=430 Participants
|
28.43 kg/m^2
STANDARD_DEVIATION 4.545 • n=1009 Participants
|
|
Education Level
Less than Upper Secondary School
|
5 Participants
n=192 Participants
|
6 Participants
n=193 Participants
|
11 Participants
n=194 Participants
|
6 Participants
n=430 Participants
|
28 Participants
n=1009 Participants
|
|
Education Level
Completed Upper Secondary School
|
57 Participants
n=192 Participants
|
68 Participants
n=193 Participants
|
49 Participants
n=194 Participants
|
126 Participants
n=430 Participants
|
300 Participants
n=1009 Participants
|
|
Education Level
Completed Vocational School
|
32 Participants
n=192 Participants
|
23 Participants
n=193 Participants
|
25 Participants
n=194 Participants
|
42 Participants
n=430 Participants
|
122 Participants
n=1009 Participants
|
|
Education Level
Completed College
|
71 Participants
n=192 Participants
|
73 Participants
n=193 Participants
|
81 Participants
n=194 Participants
|
204 Participants
n=430 Participants
|
429 Participants
n=1009 Participants
|
|
Education Level
Completed Graduate School
|
22 Participants
n=192 Participants
|
19 Participants
n=193 Participants
|
26 Participants
n=194 Participants
|
46 Participants
n=430 Participants
|
113 Participants
n=1009 Participants
|
|
Education Level
Unknown
|
5 Participants
n=192 Participants
|
4 Participants
n=193 Participants
|
2 Participants
n=194 Participants
|
6 Participants
n=430 Participants
|
17 Participants
n=1009 Participants
|
|
Smoking status at screening
YES, Hysterectomized
|
9 Participants
n=99 Participants • Results shown for subjects with available data.
|
8 Participants
n=100 Participants • Results shown for subjects with available data.
|
9 Participants
n=99 Participants • Results shown for subjects with available data.
|
24 Participants
n=201 Participants • Results shown for subjects with available data.
|
50 Participants
n=499 Participants • Results shown for subjects with available data.
|
|
Smoking status at screening
YES, Non-Hysterectomized
|
6 Participants
n=93 Participants • Results shown for subjects with available data.
|
14 Participants
n=93 Participants • Results shown for subjects with available data.
|
9 Participants
n=95 Participants • Results shown for subjects with available data.
|
27 Participants
n=229 Participants • Results shown for subjects with available data.
|
56 Participants
n=510 Participants • Results shown for subjects with available data.
|
|
Smoking status at screening
NO, Hysterectomized
|
90 Participants
n=99 Participants • Results shown for subjects with available data.
|
92 Participants
n=100 Participants • Results shown for subjects with available data.
|
90 Participants
n=99 Participants • Results shown for subjects with available data.
|
177 Participants
n=201 Participants • Results shown for subjects with available data.
|
449 Participants
n=499 Participants • Results shown for subjects with available data.
|
|
Smoking status at screening
NO, Non-Hysterectomized
|
87 Participants
n=93 Participants • Results shown for subjects with available data.
|
79 Participants
n=93 Participants • Results shown for subjects with available data.
|
86 Participants
n=95 Participants • Results shown for subjects with available data.
|
202 Participants
n=229 Participants • Results shown for subjects with available data.
|
454 Participants
n=510 Participants • Results shown for subjects with available data.
|
|
Cigarettes smoked per day
≤5, Hysterectomized
|
7 Participants
n=99 Participants • Results shown for subjects with available data.
|
4 Participants
n=100 Participants • Results shown for subjects with available data.
|
5 Participants
n=99 Participants • Results shown for subjects with available data.
|
11 Participants
n=201 Participants • Results shown for subjects with available data.
|
27 Participants
n=499 Participants • Results shown for subjects with available data.
|
|
Cigarettes smoked per day
>5 - 15, Hysterectomized
|
2 Participants
n=99 Participants • Results shown for subjects with available data.
|
4 Participants
n=100 Participants • Results shown for subjects with available data.
|
4 Participants
n=99 Participants • Results shown for subjects with available data.
|
13 Participants
n=201 Participants • Results shown for subjects with available data.
|
23 Participants
n=499 Participants • Results shown for subjects with available data.
|
|
Cigarettes smoked per day
>15, Hysterectomized
|
0 Participants
n=99 Participants • Results shown for subjects with available data.
|
0 Participants
n=100 Participants • Results shown for subjects with available data.
|
0 Participants
n=99 Participants • Results shown for subjects with available data.
|
0 Participants
n=201 Participants • Results shown for subjects with available data.
|
0 Participants
n=499 Participants • Results shown for subjects with available data.
|
|
Cigarettes smoked per day
≤5, Non-Hysterectomized
|
4 Participants
n=93 Participants • Results shown for subjects with available data.
|
9 Participants
n=93 Participants • Results shown for subjects with available data.
|
5 Participants
n=95 Participants • Results shown for subjects with available data.
|
13 Participants
n=229 Participants • Results shown for subjects with available data.
|
31 Participants
n=510 Participants • Results shown for subjects with available data.
|
|
Cigarettes smoked per day
>5 - 15, Non-Hysterectomized
|
1 Participants
n=93 Participants • Results shown for subjects with available data.
|
5 Participants
n=93 Participants • Results shown for subjects with available data.
|
4 Participants
n=95 Participants • Results shown for subjects with available data.
|
14 Participants
n=229 Participants • Results shown for subjects with available data.
|
24 Participants
n=510 Participants • Results shown for subjects with available data.
|
|
Cigarettes smoked per day
>15, Non-Hysterectomized
|
1 Participants
n=93 Participants • Results shown for subjects with available data.
|
0 Participants
n=93 Participants • Results shown for subjects with available data.
|
0 Participants
n=95 Participants • Results shown for subjects with available data.
|
0 Participants
n=229 Participants • Results shown for subjects with available data.
|
1 Participants
n=510 Participants • Results shown for subjects with available data.
|
|
Hysterectomy
YES
|
99 Participants
n=192 Participants
|
100 Participants
n=193 Participants
|
99 Participants
n=194 Participants
|
201 Participants
n=430 Participants
|
499 Participants
n=1009 Participants
|
|
Hysterectomy
NO
|
93 Participants
n=192 Participants
|
93 Participants
n=193 Participants
|
95 Participants
n=194 Participants
|
229 Participants
n=430 Participants
|
510 Participants
n=1009 Participants
|
|
Hysterectomy Type
Total
|
79 Participants
n=192 Participants
|
67 Participants
n=193 Participants
|
69 Participants
n=194 Participants
|
138 Participants
n=430 Participants
|
353 Participants
n=1009 Participants
|
|
Hysterectomy Type
Subtotal
|
20 Participants
n=192 Participants
|
33 Participants
n=193 Participants
|
30 Participants
n=194 Participants
|
63 Participants
n=430 Participants
|
146 Participants
n=1009 Participants
|
|
Bilateral Oophorectomy
YES, Hysterectomized
|
42 Participants
n=192 Participants
|
31 Participants
n=193 Participants
|
26 Participants
n=194 Participants
|
65 Participants
n=430 Participants
|
164 Participants
n=1009 Participants
|
|
Bilateral Oophorectomy
NO, Hysterectomized
|
57 Participants
n=192 Participants
|
69 Participants
n=193 Participants
|
73 Participants
n=194 Participants
|
136 Participants
n=430 Participants
|
335 Participants
n=1009 Participants
|
|
Bilateral Oophorectomy
YES, Non-Hysterectomized
|
0 Participants
n=192 Participants
|
0 Participants
n=193 Participants
|
0 Participants
n=194 Participants
|
0 Participants
n=430 Participants
|
0 Participants
n=1009 Participants
|
|
Bilateral Oophorectomy
NO, Non-Hysterectomized
|
93 Participants
n=192 Participants
|
93 Participants
n=193 Participants
|
95 Participants
n=194 Participants
|
229 Participants
n=430 Participants
|
510 Participants
n=1009 Participants
|
PRIMARY outcome
Timeframe: Week 0 (Baseline), Week 4, Week 12.Population: Intention-to-treat (ITT) Set: included all subjects who received at least one dose of randomized study medication. The ITT set was the primary analysis set for the efficacy analyses and all analyses on this set were based on the randomized treatment.
Weekly frequency of moderate to severe VMS at Baseline = total number (sum) of all recorded moderate to severe VMS experienced during the last 7 consecutive days prior randomization (Week 0). Weekly frequency of moderate to severe VMS at Week X = total number (sum) of all recorded moderate to severe VMS experienced during the week X.
Outcome measures
| Measure |
Estetrol 15 mg - Efficacy Study Part
n=192 Participants
Estetrol (E4) 15 mg oral tablet, administered once daily for up to 53 weeks
|
Estetrol 20 mg - Efficacy Study Part
n=193 Participants
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks
|
Placebo - Efficacy Study Part
n=194 Participants
Placebo was administered orally once daily for up to 53 weeks
|
Estetrol 20 mg - Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Placebo -- Hysterectomized -- Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks.
|
Placebo -- Non-Hysterectomized -- Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks.
|
Estetrol 20 mg -- Hysterectomized -- Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Estetrol 20 mg -- Non-Hysterectomized -- Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
|---|---|---|---|---|---|---|---|---|
|
Mean Change in Weekly Frequency of Moderate to Severe Vasomotor Symptoms (VMS) From Baseline to Week 4 and Week 12 -- (Efficacy Study Part)
Week 4
|
-39.77 number of moderate to severe VMS
Interval -45.75 to -33.79
|
-40.11 number of moderate to severe VMS
Interval -45.51 to -34.71
|
-31.82 number of moderate to severe VMS
Interval -36.96 to -26.67
|
—
|
—
|
—
|
—
|
—
|
|
Mean Change in Weekly Frequency of Moderate to Severe Vasomotor Symptoms (VMS) From Baseline to Week 4 and Week 12 -- (Efficacy Study Part)
Week 12
|
-55.84 number of moderate to severe VMS
Interval -63.58 to -48.09
|
-59.47 number of moderate to severe VMS
Interval -66.98 to -51.95
|
-43.27 number of moderate to severe VMS
Interval -48.82 to -37.71
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Week 0 (Baseline), Week 4, Week 12.Population: Intention-to-treat (ITT) Set: included all subjects who received at least one dose of randomized study medication. The ITT set was the primary analysis set for the efficacy analyses and all analyses on this set were based on the randomized treatment.
Mean severity score of VMS at Baseline: arithmetic mean of daily severity score values of moderate and severe VMS during the last 7 days prior randomization (Week 0). Mean severity score of VMS at Week 4 or 12: arithmetic mean of daily severity score values of moderate and severe VMS during Week 4 or 12. Daily severity score of VMS at Baseline = \[(2 x number of moderate VMS) + (3 x number of severe VMS)\]/(total number of moderate + severe VMS)\], if at least one moderate to severe VMS was recorded during the day. If documented absence of moderate to severe VMS during the day, daily severity was set to zero. Daily severity score of VMS Post-Baseline = \[(1 x number of mild VMS) + (2 x number of moderate VMS) + (3 x number of severe VMS)\]/(total number of mild + moderate + severe VMS)\], if at least one mild to severe VMS was recorded during the day. If documented absence of VMS during the day, daily severity was set to zero. Severity score: mild=1, moderate=2, severe=3.
Outcome measures
| Measure |
Estetrol 15 mg - Efficacy Study Part
n=192 Participants
Estetrol (E4) 15 mg oral tablet, administered once daily for up to 53 weeks
|
Estetrol 20 mg - Efficacy Study Part
n=193 Participants
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks
|
Placebo - Efficacy Study Part
n=194 Participants
Placebo was administered orally once daily for up to 53 weeks
|
Estetrol 20 mg - Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Placebo -- Hysterectomized -- Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks.
|
Placebo -- Non-Hysterectomized -- Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks.
|
Estetrol 20 mg -- Hysterectomized -- Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Estetrol 20 mg -- Non-Hysterectomized -- Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
|---|---|---|---|---|---|---|---|---|
|
Mean Change in Severity of Moderate to Severe Vasomotor Symptoms (VMS) From Baseline to Week 4 and Week 12 -- (Efficacy Study Part)
Week 4
|
-0.58 score
Interval -0.66 to -0.49
|
-0.63 score
Interval -0.71 to -0.54
|
-0.52 score
Interval -0.6 to -0.44
|
—
|
—
|
—
|
—
|
—
|
|
Mean Change in Severity of Moderate to Severe Vasomotor Symptoms (VMS) From Baseline to Week 4 and Week 12 -- (Efficacy Study Part)
Week 12
|
-0.77 score
Interval -0.87 to -0.66
|
-1.01 score
Interval -1.13 to -0.88
|
-0.73 score
Interval -0.85 to -0.62
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Week 0 (Baseline), Week 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12.Population: Intention-to-treat (ITT) Set: included all subjects who received at least one dose of randomized study medication. The ITT set was the primary analysis set for the efficacy analyses and all analyses on this set were based on the randomized treatment.
Mean change from Baseline to Week 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 in the weekly frequency of moderate to severe vasomotor symptoms (VMS) (Efficacy study part). Weekly frequency of moderate to severe VMS at Baseline = total number (sum) of all recorded moderate to severe VMS experienced during the last 7 consecutive days prior randomization (Week 0). Weekly frequency of moderate to severe VMS at Week X = total number (sum) of all recorded moderate to severe VMS experienced during the week X.
Outcome measures
| Measure |
Estetrol 15 mg - Efficacy Study Part
n=192 Participants
Estetrol (E4) 15 mg oral tablet, administered once daily for up to 53 weeks
|
Estetrol 20 mg - Efficacy Study Part
n=193 Participants
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks
|
Placebo - Efficacy Study Part
n=194 Participants
Placebo was administered orally once daily for up to 53 weeks
|
Estetrol 20 mg - Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Placebo -- Hysterectomized -- Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks.
|
Placebo -- Non-Hysterectomized -- Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks.
|
Estetrol 20 mg -- Hysterectomized -- Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Estetrol 20 mg -- Non-Hysterectomized -- Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
|---|---|---|---|---|---|---|---|---|
|
Mean Change From Baseline to Week 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 in the Weekly Frequency of Moderate to Severe Vasomotor Symptoms (VMS) -- (Efficacy Study Part)
Week 2
|
-26.97 number of moderate to severe VMS
Interval -32.31 to -21.63
|
-27.51 number of moderate to severe VMS
Interval -32.73 to -22.3
|
-25.26 number of moderate to severe VMS
Interval -30.55 to -19.97
|
—
|
—
|
—
|
—
|
—
|
|
Mean Change From Baseline to Week 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 in the Weekly Frequency of Moderate to Severe Vasomotor Symptoms (VMS) -- (Efficacy Study Part)
Week 4
|
-39.77 number of moderate to severe VMS
Interval -45.75 to -33.79
|
-40.11 number of moderate to severe VMS
Interval -45.51 to -34.71
|
-31.82 number of moderate to severe VMS
Interval -36.96 to -26.67
|
—
|
—
|
—
|
—
|
—
|
|
Mean Change From Baseline to Week 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 in the Weekly Frequency of Moderate to Severe Vasomotor Symptoms (VMS) -- (Efficacy Study Part)
Week 5
|
-42.98 number of moderate to severe VMS
Interval -49.18 to -36.78
|
-46.68 number of moderate to severe VMS
Interval -52.82 to -40.55
|
-35.14 number of moderate to severe VMS
Interval -40.8 to -29.49
|
—
|
—
|
—
|
—
|
—
|
|
Mean Change From Baseline to Week 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 in the Weekly Frequency of Moderate to Severe Vasomotor Symptoms (VMS) -- (Efficacy Study Part)
Week 6
|
-46.75 number of moderate to severe VMS
Interval -53.11 to -40.39
|
-50.14 number of moderate to severe VMS
Interval -57.09 to -43.2
|
-37.53 number of moderate to severe VMS
Interval -43.49 to -31.58
|
—
|
—
|
—
|
—
|
—
|
|
Mean Change From Baseline to Week 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 in the Weekly Frequency of Moderate to Severe Vasomotor Symptoms (VMS) -- (Efficacy Study Part)
Week 8
|
-50.39 number of moderate to severe VMS
Interval -57.32 to -43.47
|
-54.08 number of moderate to severe VMS
Interval -61.17 to -46.98
|
-39.53 number of moderate to severe VMS
Interval -45.64 to -33.43
|
—
|
—
|
—
|
—
|
—
|
|
Mean Change From Baseline to Week 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 in the Weekly Frequency of Moderate to Severe Vasomotor Symptoms (VMS) -- (Efficacy Study Part)
Week 9
|
-53.94 number of moderate to severe VMS
Interval -61.77 to -46.11
|
-55.79 number of moderate to severe VMS
Interval -62.57 to -49.01
|
-40.87 number of moderate to severe VMS
Interval -46.41 to -35.33
|
—
|
—
|
—
|
—
|
—
|
|
Mean Change From Baseline to Week 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 in the Weekly Frequency of Moderate to Severe Vasomotor Symptoms (VMS) -- (Efficacy Study Part)
Week 11
|
-55.81 number of moderate to severe VMS
Interval -63.63 to -48.0
|
-58.12 number of moderate to severe VMS
Interval -65.63 to -50.6
|
-41.81 number of moderate to severe VMS
Interval -47.28 to -36.34
|
—
|
—
|
—
|
—
|
—
|
|
Mean Change From Baseline to Week 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 in the Weekly Frequency of Moderate to Severe Vasomotor Symptoms (VMS) -- (Efficacy Study Part)
Week 12
|
-55.84 number of moderate to severe VMS
Interval -63.58 to -48.09
|
-59.47 number of moderate to severe VMS
Interval -66.98 to -51.95
|
-43.27 number of moderate to severe VMS
Interval -48.82 to -37.71
|
—
|
—
|
—
|
—
|
—
|
|
Mean Change From Baseline to Week 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 in the Weekly Frequency of Moderate to Severe Vasomotor Symptoms (VMS) -- (Efficacy Study Part)
Week 3
|
-34.60 number of moderate to severe VMS
Interval -40.05 to -29.14
|
-34.99 number of moderate to severe VMS
Interval -40.58 to -29.4
|
-29.47 number of moderate to severe VMS
Interval -34.81 to -24.13
|
—
|
—
|
—
|
—
|
—
|
|
Mean Change From Baseline to Week 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 in the Weekly Frequency of Moderate to Severe Vasomotor Symptoms (VMS) -- (Efficacy Study Part)
Week 1
|
-16.20 number of moderate to severe VMS
Interval -21.36 to -11.03
|
-18.00 number of moderate to severe VMS
Interval -22.38 to -13.62
|
-15.62 number of moderate to severe VMS
Interval -20.42 to -10.81
|
—
|
—
|
—
|
—
|
—
|
|
Mean Change From Baseline to Week 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 in the Weekly Frequency of Moderate to Severe Vasomotor Symptoms (VMS) -- (Efficacy Study Part)
Week 7
|
-48.78 number of moderate to severe VMS
Interval -55.58 to -41.99
|
-51.95 number of moderate to severe VMS
Interval -59.05 to -44.85
|
-38.39 number of moderate to severe VMS
Interval -44.23 to -32.55
|
—
|
—
|
—
|
—
|
—
|
|
Mean Change From Baseline to Week 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 in the Weekly Frequency of Moderate to Severe Vasomotor Symptoms (VMS) -- (Efficacy Study Part)
Week 10
|
-56.57 number of moderate to severe VMS
Interval -64.37 to -48.76
|
-57.24 number of moderate to severe VMS
Interval -64.55 to -49.92
|
-42.41 number of moderate to severe VMS
Interval -47.77 to -37.04
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Week 0 (Baseline), Week 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12.Population: Intention-to-treat (ITT) Set: included all subjects who received at least one dose of randomized study medication. The ITT set was the primary analysis set for the efficacy analyses and all analyses on this set were based on the randomized treatment.
Mean severity score of VMS at Baseline: arithmetic mean of daily severity score values of moderate and severe VMS during the last 7 days prior randomization (Week 0). Mean severity score of VMS at Week X (post-baseline): arithmetic mean of daily severity score values of moderate and severe VMS during Week X. Daily severity score of VMS at Baseline = \[(2 x number of moderate VMS) + (3 x number of severe VMS)\]/(total number of moderate + severe VMS)\], if at least one moderate to severe VMS was recorded during the day. If documented absence of moderate to severe VMS during the day, daily severity was set to zero. Daily severity score of VMS Post-Baseline = \[(1 x number of mild VMS) + (2 x number of moderate VMS) + (3 x number of severe VMS)\]/(total number of mild + moderate + severe VMS)\], if at least one mild to severe VMS was recorded during the day. If documented absence of VMS during the day, daily severity was set to zero. Severity score: mild=1, moderate=2, severe=3.
Outcome measures
| Measure |
Estetrol 15 mg - Efficacy Study Part
n=192 Participants
Estetrol (E4) 15 mg oral tablet, administered once daily for up to 53 weeks
|
Estetrol 20 mg - Efficacy Study Part
n=193 Participants
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks
|
Placebo - Efficacy Study Part
n=194 Participants
Placebo was administered orally once daily for up to 53 weeks
|
Estetrol 20 mg - Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Placebo -- Hysterectomized -- Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks.
|
Placebo -- Non-Hysterectomized -- Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks.
|
Estetrol 20 mg -- Hysterectomized -- Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Estetrol 20 mg -- Non-Hysterectomized -- Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
|---|---|---|---|---|---|---|---|---|
|
Mean Change in Severity of Moderate and Severe Vasomotor Symptoms (VMS) From Baseline to Week 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 -- (Efficacy Study Part)
Week 1
|
-0.30 score
Interval -0.35 to -0.24
|
-0.31 score
Interval -0.36 to -0.25
|
-0.33 score
Interval -0.37 to -0.28
|
—
|
—
|
—
|
—
|
—
|
|
Mean Change in Severity of Moderate and Severe Vasomotor Symptoms (VMS) From Baseline to Week 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 -- (Efficacy Study Part)
Week 2
|
-0.40 score
Interval -0.47 to -0.33
|
-0.40 score
Interval -0.47 to -0.33
|
-0.43 score
Interval -0.5 to -0.36
|
—
|
—
|
—
|
—
|
—
|
|
Mean Change in Severity of Moderate and Severe Vasomotor Symptoms (VMS) From Baseline to Week 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 -- (Efficacy Study Part)
Week 3
|
-0.51 score
Interval -0.59 to -0.42
|
-0.57 score
Interval -0.65 to -0.48
|
-0.49 score
Interval -0.57 to -0.41
|
—
|
—
|
—
|
—
|
—
|
|
Mean Change in Severity of Moderate and Severe Vasomotor Symptoms (VMS) From Baseline to Week 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 -- (Efficacy Study Part)
Week 4
|
-0.58 score
Interval -0.66 to -0.49
|
-0.63 score
Interval -0.71 to -0.54
|
-0.52 score
Interval -0.6 to -0.44
|
—
|
—
|
—
|
—
|
—
|
|
Mean Change in Severity of Moderate and Severe Vasomotor Symptoms (VMS) From Baseline to Week 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 -- (Efficacy Study Part)
Week 7
|
-0.65 score
Interval -0.75 to -0.56
|
-0.88 score
Interval -0.99 to -0.76
|
-0.64 score
Interval -0.73 to -0.54
|
—
|
—
|
—
|
—
|
—
|
|
Mean Change in Severity of Moderate and Severe Vasomotor Symptoms (VMS) From Baseline to Week 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 -- (Efficacy Study Part)
Week 5
|
-0.63 score
Interval -0.73 to -0.53
|
-0.72 score
Interval -0.82 to -0.62
|
-0.54 score
Interval -0.63 to -0.45
|
—
|
—
|
—
|
—
|
—
|
|
Mean Change in Severity of Moderate and Severe Vasomotor Symptoms (VMS) From Baseline to Week 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 -- (Efficacy Study Part)
Week 6
|
-0.65 score
Interval -0.75 to -0.55
|
-0.78 score
Interval -0.89 to -0.68
|
-0.63 score
Interval -0.72 to -0.53
|
—
|
—
|
—
|
—
|
—
|
|
Mean Change in Severity of Moderate and Severe Vasomotor Symptoms (VMS) From Baseline to Week 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 -- (Efficacy Study Part)
Week 8
|
-0.68 score
Interval -0.78 to -0.58
|
-0.89 score
Interval -1.01 to -0.78
|
-0.69 score
Interval -0.79 to -0.59
|
—
|
—
|
—
|
—
|
—
|
|
Mean Change in Severity of Moderate and Severe Vasomotor Symptoms (VMS) From Baseline to Week 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 -- (Efficacy Study Part)
Week 9
|
-0.76 score
Interval -0.87 to -0.66
|
-0.91 score
Interval -1.02 to -0.79
|
-0.66 score
Interval -0.76 to -0.56
|
—
|
—
|
—
|
—
|
—
|
|
Mean Change in Severity of Moderate and Severe Vasomotor Symptoms (VMS) From Baseline to Week 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 -- (Efficacy Study Part)
Week 10
|
-0.78 score
Interval -0.88 to -0.68
|
-0.96 score
Interval -1.09 to -0.84
|
-0.69 score
Interval -0.8 to -0.58
|
—
|
—
|
—
|
—
|
—
|
|
Mean Change in Severity of Moderate and Severe Vasomotor Symptoms (VMS) From Baseline to Week 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 -- (Efficacy Study Part)
Week 11
|
-0.79 score
Interval -0.89 to -0.68
|
-0.96 score
Interval -1.08 to -0.83
|
-0.68 score
Interval -0.8 to -0.56
|
—
|
—
|
—
|
—
|
—
|
|
Mean Change in Severity of Moderate and Severe Vasomotor Symptoms (VMS) From Baseline to Week 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 -- (Efficacy Study Part)
Week 12
|
-0.77 score
Interval -0.87 to -0.66
|
-1.01 score
Interval -1.13 to -0.88
|
-0.73 score
Interval -0.85 to -0.62
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Week 0 (Baseline), Week 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12.Population: Intention-to-treat (ITT) Set: included all subjects who received at least one dose of randomized study medication. The ITT set was the primary analysis set for the efficacy analyses and all analyses on this set were based on the randomized treatment.
Weekly frequency of mild to severe VMS at Baseline = total number (sum) of all recorded mild to severe VMS experienced during the last 7 consecutive days prior randomization (Week 0). Weekly frequency of mild to severe VMS at Week X = total number (sum) of all recorded mild to severe VMS experienced during the week X.
Outcome measures
| Measure |
Estetrol 15 mg - Efficacy Study Part
n=192 Participants
Estetrol (E4) 15 mg oral tablet, administered once daily for up to 53 weeks
|
Estetrol 20 mg - Efficacy Study Part
n=193 Participants
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks
|
Placebo - Efficacy Study Part
n=194 Participants
Placebo was administered orally once daily for up to 53 weeks
|
Estetrol 20 mg - Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Placebo -- Hysterectomized -- Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks.
|
Placebo -- Non-Hysterectomized -- Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks.
|
Estetrol 20 mg -- Hysterectomized -- Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Estetrol 20 mg -- Non-Hysterectomized -- Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
|---|---|---|---|---|---|---|---|---|
|
Mean Change From Baseline to Week 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 in the Weekly Frequency of Mild to Severe Vasomotor Symptoms (VMS) -- (Efficacy Study Part)
Week 1
|
-17.25 number of mild, moderate to severe VMS
Interval -22.95 to -11.56
|
-19.35 number of mild, moderate to severe VMS
Interval -23.96 to -14.75
|
-16.92 number of mild, moderate to severe VMS
Interval -22.29 to -11.56
|
—
|
—
|
—
|
—
|
—
|
|
Mean Change From Baseline to Week 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 in the Weekly Frequency of Mild to Severe Vasomotor Symptoms (VMS) -- (Efficacy Study Part)
Week 4
|
-40.49 number of mild, moderate to severe VMS
Interval -47.34 to -33.63
|
-43.12 number of mild, moderate to severe VMS
Interval -49.18 to -37.07
|
-35.18 number of mild, moderate to severe VMS
Interval -41.62 to -28.73
|
—
|
—
|
—
|
—
|
—
|
|
Mean Change From Baseline to Week 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 in the Weekly Frequency of Mild to Severe Vasomotor Symptoms (VMS) -- (Efficacy Study Part)
Week 5
|
-44.36 number of mild, moderate to severe VMS
Interval -51.58 to -37.15
|
-49.73 number of mild, moderate to severe VMS
Interval -56.47 to -42.99
|
-40.20 number of mild, moderate to severe VMS
Interval -47.23 to -33.16
|
—
|
—
|
—
|
—
|
—
|
|
Mean Change From Baseline to Week 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 in the Weekly Frequency of Mild to Severe Vasomotor Symptoms (VMS) -- (Efficacy Study Part)
Week 10
|
-59.91 number of mild, moderate to severe VMS
Interval -69.64 to -50.17
|
-61.75 number of mild, moderate to severe VMS
Interval -69.83 to -53.67
|
-48.50 number of mild, moderate to severe VMS
Interval -55.72 to -41.28
|
—
|
—
|
—
|
—
|
—
|
|
Mean Change From Baseline to Week 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 in the Weekly Frequency of Mild to Severe Vasomotor Symptoms (VMS) -- (Efficacy Study Part)
Week 2
|
-28.20 number of mild, moderate to severe VMS
Interval -34.15 to -22.24
|
-28.88 number of mild, moderate to severe VMS
Interval -34.47 to -23.28
|
-28.47 number of mild, moderate to severe VMS
Interval -34.37 to -22.57
|
—
|
—
|
—
|
—
|
—
|
|
Mean Change From Baseline to Week 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 in the Weekly Frequency of Mild to Severe Vasomotor Symptoms (VMS) -- (Efficacy Study Part)
Week 3
|
-34.81 number of mild, moderate to severe VMS
Interval -41.23 to -28.39
|
-36.98 number of mild, moderate to severe VMS
Interval -43.17 to -30.8
|
-32.50 number of mild, moderate to severe VMS
Interval -38.87 to -26.12
|
—
|
—
|
—
|
—
|
—
|
|
Mean Change From Baseline to Week 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 in the Weekly Frequency of Mild to Severe Vasomotor Symptoms (VMS) -- (Efficacy Study Part)
Week 6
|
-48.24 number of mild, moderate to severe VMS
Interval -55.84 to -40.64
|
-53.27 number of mild, moderate to severe VMS
Interval -60.86 to -45.68
|
-42.95 number of mild, moderate to severe VMS
Interval -50.27 to -35.64
|
—
|
—
|
—
|
—
|
—
|
|
Mean Change From Baseline to Week 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 in the Weekly Frequency of Mild to Severe Vasomotor Symptoms (VMS) -- (Efficacy Study Part)
Week 7
|
-50.12 number of mild, moderate to severe VMS
Interval -58.01 to -42.23
|
-55.22 number of mild, moderate to severe VMS
Interval -62.94 to -47.5
|
-43.18 number of mild, moderate to severe VMS
Interval -50.35 to -36.01
|
—
|
—
|
—
|
—
|
—
|
|
Mean Change From Baseline to Week 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 in the Weekly Frequency of Mild to Severe Vasomotor Symptoms (VMS) -- (Efficacy Study Part)
Week 8
|
-52.04 number of mild, moderate to severe VMS
Interval -60.25 to -43.83
|
-57.42 number of mild, moderate to severe VMS
Interval -65.21 to -49.63
|
-44.32 number of mild, moderate to severe VMS
Interval -51.75 to -36.9
|
—
|
—
|
—
|
—
|
—
|
|
Mean Change From Baseline to Week 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 in the Weekly Frequency of Mild to Severe Vasomotor Symptoms (VMS) -- (Efficacy Study Part)
Week 9
|
-57.09 number of mild, moderate to severe VMS
Interval -66.65 to -47.53
|
-59.72 number of mild, moderate to severe VMS
Interval -67.3 to -52.14
|
-46.57 number of mild, moderate to severe VMS
Interval -53.71 to -39.42
|
—
|
—
|
—
|
—
|
—
|
|
Mean Change From Baseline to Week 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 in the Weekly Frequency of Mild to Severe Vasomotor Symptoms (VMS) -- (Efficacy Study Part)
Week 11
|
-59.40 number of mild, moderate to severe VMS
Interval -69.24 to 49.57
|
-62.86 number of mild, moderate to severe VMS
Interval -71.13 to -54.6
|
-48.48 number of mild, moderate to severe VMS
Interval -55.77 to -41.19
|
—
|
—
|
—
|
—
|
—
|
|
Mean Change From Baseline to Week 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 in the Weekly Frequency of Mild to Severe Vasomotor Symptoms (VMS) -- (Efficacy Study Part)
Week 12
|
-59.78 number of mild, moderate to severe VMS
Interval -69.41 to -50.14
|
-64.76 number of mild, moderate to severe VMS
Interval -73.24 to -56.29
|
-49.03 number of mild, moderate to severe VMS
Interval -56.44 to -41.62
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Week 0 (Baseline), Week 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12.Population: Intention-to-treat (ITT) Set: included all subjects who received at least one dose of randomized study medication. The ITT set was the primary analysis set for the efficacy analyses and all analyses on this set were based on the randomized treatment.
Weekly frequency of moderate to severe VMS at Baseline = total number (sum) of all recorded moderate to severe VMS experienced during the last 7 consecutive days prior randomization (Week 0). Weekly frequency of moderate to severe VMS at Week X = Total number (sum) of all recorded moderate to severe VMS experienced during the week X Percentages of participants are based on the number of subjects with a non-missing percent change from Baseline result in each treatment arm by visit in the ITT Set.
Outcome measures
| Measure |
Estetrol 15 mg - Efficacy Study Part
n=192 Participants
Estetrol (E4) 15 mg oral tablet, administered once daily for up to 53 weeks
|
Estetrol 20 mg - Efficacy Study Part
n=193 Participants
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks
|
Placebo - Efficacy Study Part
n=194 Participants
Placebo was administered orally once daily for up to 53 weeks
|
Estetrol 20 mg - Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Placebo -- Hysterectomized -- Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks.
|
Placebo -- Non-Hysterectomized -- Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks.
|
Estetrol 20 mg -- Hysterectomized -- Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Estetrol 20 mg -- Non-Hysterectomized -- Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
|---|---|---|---|---|---|---|---|---|
|
Percentage of Subjects With ≥50% and ≥75% Reduction From Baseline in the Weekly Frequency of Moderate to Severe Vasomotor Symptoms (VMS) at Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 -- (Efficacy Study Part)
Week 1: ≥50% reduction from baseline
|
17.0 percentage of participants
|
20.8 percentage of participants
|
17.1 percentage of participants
|
—
|
—
|
—
|
—
|
—
|
|
Percentage of Subjects With ≥50% and ≥75% Reduction From Baseline in the Weekly Frequency of Moderate to Severe Vasomotor Symptoms (VMS) at Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 -- (Efficacy Study Part)
Week 1: ≥75% reduction from baseline
|
5.8 percentage of participants
|
4.4 percentage of participants
|
5.0 percentage of participants
|
—
|
—
|
—
|
—
|
—
|
|
Percentage of Subjects With ≥50% and ≥75% Reduction From Baseline in the Weekly Frequency of Moderate to Severe Vasomotor Symptoms (VMS) at Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 -- (Efficacy Study Part)
Week 2: ≥50% reduction from baseline
|
31.2 percentage of participants
|
31.7 percentage of participants
|
29.1 percentage of participants
|
—
|
—
|
—
|
—
|
—
|
|
Percentage of Subjects With ≥50% and ≥75% Reduction From Baseline in the Weekly Frequency of Moderate to Severe Vasomotor Symptoms (VMS) at Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 -- (Efficacy Study Part)
Week 2: ≥75% reduction from baseline
|
14.1 percentage of participants
|
13.1 percentage of participants
|
14.3 percentage of participants
|
—
|
—
|
—
|
—
|
—
|
|
Percentage of Subjects With ≥50% and ≥75% Reduction From Baseline in the Weekly Frequency of Moderate to Severe Vasomotor Symptoms (VMS) at Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 -- (Efficacy Study Part)
Week 3: ≥50% reduction from baseline
|
42.7 percentage of participants
|
44.4 percentage of participants
|
37.6 percentage of participants
|
—
|
—
|
—
|
—
|
—
|
|
Percentage of Subjects With ≥50% and ≥75% Reduction From Baseline in the Weekly Frequency of Moderate to Severe Vasomotor Symptoms (VMS) at Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 -- (Efficacy Study Part)
Week 3: ≥75% reduction from baseline
|
18.1 percentage of participants
|
23.9 percentage of participants
|
19.3 percentage of participants
|
—
|
—
|
—
|
—
|
—
|
|
Percentage of Subjects With ≥50% and ≥75% Reduction From Baseline in the Weekly Frequency of Moderate to Severe Vasomotor Symptoms (VMS) at Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 -- (Efficacy Study Part)
Week 4: ≥50% reduction from baseline
|
51.5 percentage of participants
|
53.6 percentage of participants
|
44.1 percentage of participants
|
—
|
—
|
—
|
—
|
—
|
|
Percentage of Subjects With ≥50% and ≥75% Reduction From Baseline in the Weekly Frequency of Moderate to Severe Vasomotor Symptoms (VMS) at Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 -- (Efficacy Study Part)
Week 4: ≥75% reduction from baseline
|
24.6 percentage of participants
|
29.1 percentage of participants
|
17.9 percentage of participants
|
—
|
—
|
—
|
—
|
—
|
|
Percentage of Subjects With ≥50% and ≥75% Reduction From Baseline in the Weekly Frequency of Moderate to Severe Vasomotor Symptoms (VMS) at Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 -- (Efficacy Study Part)
Week 5: ≥50% reduction from baseline
|
57.7 percentage of participants
|
64.4 percentage of participants
|
46.8 percentage of participants
|
—
|
—
|
—
|
—
|
—
|
|
Percentage of Subjects With ≥50% and ≥75% Reduction From Baseline in the Weekly Frequency of Moderate to Severe Vasomotor Symptoms (VMS) at Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 -- (Efficacy Study Part)
Week 5: ≥75% reduction from baseline
|
29.2 percentage of participants
|
39.1 percentage of participants
|
22.5 percentage of participants
|
—
|
—
|
—
|
—
|
—
|
|
Percentage of Subjects With ≥50% and ≥75% Reduction From Baseline in the Weekly Frequency of Moderate to Severe Vasomotor Symptoms (VMS) at Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 -- (Efficacy Study Part)
Week 6: ≥50% reduction from baseline
|
61.7 percentage of participants
|
70.2 percentage of participants
|
51.8 percentage of participants
|
—
|
—
|
—
|
—
|
—
|
|
Percentage of Subjects With ≥50% and ≥75% Reduction From Baseline in the Weekly Frequency of Moderate to Severe Vasomotor Symptoms (VMS) at Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 -- (Efficacy Study Part)
Week 6: ≥75% reduction from baseline
|
31.1 percentage of participants
|
46.4 percentage of participants
|
32.1 percentage of participants
|
—
|
—
|
—
|
—
|
—
|
|
Percentage of Subjects With ≥50% and ≥75% Reduction From Baseline in the Weekly Frequency of Moderate to Severe Vasomotor Symptoms (VMS) at Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 -- (Efficacy Study Part)
Week 7: ≥50% reduction from baseline
|
62.2 percentage of participants
|
70.9 percentage of participants
|
55.1 percentage of participants
|
—
|
—
|
—
|
—
|
—
|
|
Percentage of Subjects With ≥50% and ≥75% Reduction From Baseline in the Weekly Frequency of Moderate to Severe Vasomotor Symptoms (VMS) at Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 -- (Efficacy Study Part)
Week 7: ≥75% reduction from baseline
|
35.4 percentage of participants
|
49.7 percentage of participants
|
31.7 percentage of participants
|
—
|
—
|
—
|
—
|
—
|
|
Percentage of Subjects With ≥50% and ≥75% Reduction From Baseline in the Weekly Frequency of Moderate to Severe Vasomotor Symptoms (VMS) at Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 -- (Efficacy Study Part)
Week 8: ≥50% reduction from baseline
|
64.0 percentage of participants
|
70.4 percentage of participants
|
55.7 percentage of participants
|
—
|
—
|
—
|
—
|
—
|
|
Percentage of Subjects With ≥50% and ≥75% Reduction From Baseline in the Weekly Frequency of Moderate to Severe Vasomotor Symptoms (VMS) at Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 -- (Efficacy Study Part)
Week 8: ≥75% reduction from baseline
|
36.0 percentage of participants
|
52.5 percentage of participants
|
31.7 percentage of participants
|
—
|
—
|
—
|
—
|
—
|
|
Percentage of Subjects With ≥50% and ≥75% Reduction From Baseline in the Weekly Frequency of Moderate to Severe Vasomotor Symptoms (VMS) at Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 -- (Efficacy Study Part)
Week 9: ≥50% reduction from baseline
|
75.5 percentage of participants
|
74.1 percentage of participants
|
58.8 percentage of participants
|
—
|
—
|
—
|
—
|
—
|
|
Percentage of Subjects With ≥50% and ≥75% Reduction From Baseline in the Weekly Frequency of Moderate to Severe Vasomotor Symptoms (VMS) at Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 -- (Efficacy Study Part)
Week 9: ≥75% reduction from baseline
|
40.3 percentage of participants
|
51.9 percentage of participants
|
35.0 percentage of participants
|
—
|
—
|
—
|
—
|
—
|
|
Percentage of Subjects With ≥50% and ≥75% Reduction From Baseline in the Weekly Frequency of Moderate to Severe Vasomotor Symptoms (VMS) at Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 -- (Efficacy Study Part)
Week 10: ≥50% reduction from baseline
|
76.9 percentage of participants
|
78.5 percentage of participants
|
64.3 percentage of participants
|
—
|
—
|
—
|
—
|
—
|
|
Percentage of Subjects With ≥50% and ≥75% Reduction From Baseline in the Weekly Frequency of Moderate to Severe Vasomotor Symptoms (VMS) at Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 -- (Efficacy Study Part)
Week 10: ≥75% reduction from baseline
|
46.8 percentage of participants
|
53.2 percentage of participants
|
39.0 percentage of participants
|
—
|
—
|
—
|
—
|
—
|
|
Percentage of Subjects With ≥50% and ≥75% Reduction From Baseline in the Weekly Frequency of Moderate to Severe Vasomotor Symptoms (VMS) at Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 -- (Efficacy Study Part)
Week 11: ≥50% reduction from baseline
|
78.8 percentage of participants
|
80.0 percentage of participants
|
62.3 percentage of participants
|
—
|
—
|
—
|
—
|
—
|
|
Percentage of Subjects With ≥50% and ≥75% Reduction From Baseline in the Weekly Frequency of Moderate to Severe Vasomotor Symptoms (VMS) at Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 -- (Efficacy Study Part)
Week 11: ≥75% reduction from baseline
|
48.7 percentage of participants
|
52.3 percentage of participants
|
33.8 percentage of participants
|
—
|
—
|
—
|
—
|
—
|
|
Percentage of Subjects With ≥50% and ≥75% Reduction From Baseline in the Weekly Frequency of Moderate to Severe Vasomotor Symptoms (VMS) at Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 -- (Efficacy Study Part)
Week 12: ≥50% reduction from baseline
|
81.3 percentage of participants
|
81.7 percentage of participants
|
61.3 percentage of participants
|
—
|
—
|
—
|
—
|
—
|
|
Percentage of Subjects With ≥50% and ≥75% Reduction From Baseline in the Weekly Frequency of Moderate to Severe Vasomotor Symptoms (VMS) at Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 -- (Efficacy Study Part)
Week 12: ≥75% reduction from baseline
|
49.0 percentage of participants
|
56.9 percentage of participants
|
37.3 percentage of participants
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Week 4, Week 12.Population: Intention-to-treat (ITT) Set: included all subjects who received at least one dose of randomized study medication. The ITT set was the primary analysis set for the efficacy analyses and all analyses on this set were based on the randomized treatment.
Percentage of subjects with a clinically important difference (CID) compared with baseline in the weekly frequency of moderate to severe VMS after Week 4 and Week 12, using the Clinical Global Impression (CGI) questionnaire (Efficacy Study Part). CGI questionnaire: questionnaire in which subjects were to answer the question "Rate the total improvement, whether or not in your judgement it is due entirely to drug treatment. Compared to your condition at administration to the study, how much has it changed?". The options were: very much improved, much improved, minimally improved, no change, minimally worse, much worse, and very much worse. CID (=Clinically Important Difference) = much improved + very much improved; MCID (=Minimally Clinically Important Difference) = minimally improved.
Outcome measures
| Measure |
Estetrol 15 mg - Efficacy Study Part
n=192 Participants
Estetrol (E4) 15 mg oral tablet, administered once daily for up to 53 weeks
|
Estetrol 20 mg - Efficacy Study Part
n=193 Participants
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks
|
Placebo - Efficacy Study Part
n=194 Participants
Placebo was administered orally once daily for up to 53 weeks
|
Estetrol 20 mg - Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Placebo -- Hysterectomized -- Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks.
|
Placebo -- Non-Hysterectomized -- Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks.
|
Estetrol 20 mg -- Hysterectomized -- Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Estetrol 20 mg -- Non-Hysterectomized -- Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
|---|---|---|---|---|---|---|---|---|
|
Percentage of Subjects With a Clinically Important Difference (CID) Compared With Baseline in the Weekly Frequency of Moderate to Severe VMS -- Week 4 and Week 12 -- Clinical Global Impression (CGI) Questionnaire -- (Efficacy Study Part)
Week 4, CID
|
37.6 percentage of participants
|
52.6 percentage of participants
|
35.8 percentage of participants
|
—
|
—
|
—
|
—
|
—
|
|
Percentage of Subjects With a Clinically Important Difference (CID) Compared With Baseline in the Weekly Frequency of Moderate to Severe VMS -- Week 4 and Week 12 -- Clinical Global Impression (CGI) Questionnaire -- (Efficacy Study Part)
Week 4, MCID
|
46.5 percentage of participants
|
29.7 percentage of participants
|
37.6 percentage of participants
|
—
|
—
|
—
|
—
|
—
|
|
Percentage of Subjects With a Clinically Important Difference (CID) Compared With Baseline in the Weekly Frequency of Moderate to Severe VMS -- Week 4 and Week 12 -- Clinical Global Impression (CGI) Questionnaire -- (Efficacy Study Part)
Week 4, Worsen/No Change
|
15.9 percentage of participants
|
17.7 percentage of participants
|
26.6 percentage of participants
|
—
|
—
|
—
|
—
|
—
|
|
Percentage of Subjects With a Clinically Important Difference (CID) Compared With Baseline in the Weekly Frequency of Moderate to Severe VMS -- Week 4 and Week 12 -- Clinical Global Impression (CGI) Questionnaire -- (Efficacy Study Part)
Week 12, CID
|
63.5 percentage of participants
|
71.3 percentage of participants
|
52.8 percentage of participants
|
—
|
—
|
—
|
—
|
—
|
|
Percentage of Subjects With a Clinically Important Difference (CID) Compared With Baseline in the Weekly Frequency of Moderate to Severe VMS -- Week 4 and Week 12 -- Clinical Global Impression (CGI) Questionnaire -- (Efficacy Study Part)
Week 12, MCID
|
26.4 percentage of participants
|
18.2 percentage of participants
|
31.3 percentage of participants
|
—
|
—
|
—
|
—
|
—
|
|
Percentage of Subjects With a Clinically Important Difference (CID) Compared With Baseline in the Weekly Frequency of Moderate to Severe VMS -- Week 4 and Week 12 -- Clinical Global Impression (CGI) Questionnaire -- (Efficacy Study Part)
Week 12, Worsen/No Change
|
10.1 percentage of participants
|
10.5 percentage of participants
|
16.0 percentage of participants
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 (Baseline), Weeks 12 and 52.Population: Intention-to-treat (ITT) Set: included all subjects who received at least one dose of randomized study medication. All analyses on this set were based on the randomized treatment.
Serum concentration of total cholesterol (Efficacy study part). Lipid Metabolism: Change from Baseline to Week 12 and Week 52.
Outcome measures
| Measure |
Estetrol 15 mg - Efficacy Study Part
n=192 Participants
Estetrol (E4) 15 mg oral tablet, administered once daily for up to 53 weeks
|
Estetrol 20 mg - Efficacy Study Part
n=193 Participants
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks
|
Placebo - Efficacy Study Part
n=194 Participants
Placebo was administered orally once daily for up to 53 weeks
|
Estetrol 20 mg - Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Placebo -- Hysterectomized -- Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks.
|
Placebo -- Non-Hysterectomized -- Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks.
|
Estetrol 20 mg -- Hysterectomized -- Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Estetrol 20 mg -- Non-Hysterectomized -- Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
|---|---|---|---|---|---|---|---|---|
|
Total Cholesterol -- (Efficacy Study Part)
Week 12
|
-0.08 mmol/L
Interval -0.2 to 0.04
|
-0.07 mmol/L
Interval -0.2 to 0.05
|
0.06 mmol/L
Interval -0.06 to 0.19
|
—
|
—
|
—
|
—
|
—
|
|
Total Cholesterol -- (Efficacy Study Part)
Week 52
|
-0.25 mmol/L
Interval -0.4 to -0.1
|
-0.26 mmol/L
Interval -0.41 to -0.1
|
-0.02 mmol/L
Interval -0.16 to 0.13
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 (Baseline), Weeks 12 and 52.Population: Safety analysis set (SAF): included all subjects who received at least one dose of study medication. The SAF was used for all analyses of safety and background characteristics.
Serum concentration of total cholesterol (Safety study part). Lipid Metabolism: Change from Baseline to Week 12 and Week 52.
Outcome measures
| Measure |
Estetrol 15 mg - Efficacy Study Part
n=430 Participants
Estetrol (E4) 15 mg oral tablet, administered once daily for up to 53 weeks
|
Estetrol 20 mg - Efficacy Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks
|
Placebo - Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks
|
Estetrol 20 mg - Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Placebo -- Hysterectomized -- Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks.
|
Placebo -- Non-Hysterectomized -- Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks.
|
Estetrol 20 mg -- Hysterectomized -- Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Estetrol 20 mg -- Non-Hysterectomized -- Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
|---|---|---|---|---|---|---|---|---|
|
Total Cholesterol -- (Safety Study Part)
Week 12
|
-0.139 mmol/L
Interval -0.22 to -0.06
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Total Cholesterol -- (Safety Study Part)
Week 52
|
-0.317 mmol/L
Interval -0.43 to -0.2
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 (Baseline), Weeks 12 and 52.Population: Intention-to-treat (ITT) Set: included all subjects who received at least one dose of randomized study medication. All analyses on this set were based on the randomized treatment.
Cholesterol/High-density lipoprotein (HDL) Ratio (Efficacy study part). Lipid Metabolism: Change from Baseline to Week 12 and Week 52.
Outcome measures
| Measure |
Estetrol 15 mg - Efficacy Study Part
n=192 Participants
Estetrol (E4) 15 mg oral tablet, administered once daily for up to 53 weeks
|
Estetrol 20 mg - Efficacy Study Part
n=193 Participants
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks
|
Placebo - Efficacy Study Part
n=194 Participants
Placebo was administered orally once daily for up to 53 weeks
|
Estetrol 20 mg - Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Placebo -- Hysterectomized -- Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks.
|
Placebo -- Non-Hysterectomized -- Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks.
|
Estetrol 20 mg -- Hysterectomized -- Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Estetrol 20 mg -- Non-Hysterectomized -- Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
|---|---|---|---|---|---|---|---|---|
|
Cholesterol/High-density Lipoprotein (HDL) Ratio -- (Efficacy Study Part)
Week 52
|
-0.11 Cholesterol/HDL Ratio
Interval -0.24 to 0.02
|
-0.08 Cholesterol/HDL Ratio
Interval -0.22 to 0.05
|
0.01 Cholesterol/HDL Ratio
Interval -0.11 to 0.13
|
—
|
—
|
—
|
—
|
—
|
|
Cholesterol/High-density Lipoprotein (HDL) Ratio -- (Efficacy Study Part)
Week 12
|
-0.06 Cholesterol/HDL Ratio
Interval -0.16 to 0.05
|
-0.18 Cholesterol/HDL Ratio
Interval -0.29 to -0.07
|
0.02 Cholesterol/HDL Ratio
Interval -0.08 to 0.13
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 (Baseline), Weeks 12 and 52.Population: Safety analysis set (SAF): included all subjects who received at least one dose of study medication. The SAF was used for all analyses of safety and background characteristics.
Cholesterol/High-density lipoprotein (HDL) Ratio (Safety study part). Lipid Metabolism: Change from Baseline to Week 12 and Week 52.
Outcome measures
| Measure |
Estetrol 15 mg - Efficacy Study Part
n=430 Participants
Estetrol (E4) 15 mg oral tablet, administered once daily for up to 53 weeks
|
Estetrol 20 mg - Efficacy Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks
|
Placebo - Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks
|
Estetrol 20 mg - Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Placebo -- Hysterectomized -- Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks.
|
Placebo -- Non-Hysterectomized -- Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks.
|
Estetrol 20 mg -- Hysterectomized -- Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Estetrol 20 mg -- Non-Hysterectomized -- Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
|---|---|---|---|---|---|---|---|---|
|
Cholesterol/High-density Lipoprotein (HDL) Ratio -- (Safety Study Part).
Week 12
|
-0.158 Cholesterol/HDL Ratio
Interval -0.23 to -0.09
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Cholesterol/High-density Lipoprotein (HDL) Ratio -- (Safety Study Part).
Week 52
|
-0.146 Cholesterol/HDL Ratio
Interval -0.24 to -0.05
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 (Baseline), Weeks 12 and 52.Population: Intention-to-treat (ITT) Set: included all subjects who received at least one dose of randomized study medication. All analyses on this set were based on the randomized treatment.
Serum concentration of high-density lipoprotein (HDL)-cholesterol (Efficacy study part). Lipid Metabolism: Change from Baseline to Week 12 and Week 52.
Outcome measures
| Measure |
Estetrol 15 mg - Efficacy Study Part
n=192 Participants
Estetrol (E4) 15 mg oral tablet, administered once daily for up to 53 weeks
|
Estetrol 20 mg - Efficacy Study Part
n=193 Participants
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks
|
Placebo - Efficacy Study Part
n=194 Participants
Placebo was administered orally once daily for up to 53 weeks
|
Estetrol 20 mg - Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Placebo -- Hysterectomized -- Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks.
|
Placebo -- Non-Hysterectomized -- Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks.
|
Estetrol 20 mg -- Hysterectomized -- Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Estetrol 20 mg -- Non-Hysterectomized -- Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
|---|---|---|---|---|---|---|---|---|
|
High-density Lipoprotein (HDL)-Cholesterol -- (Efficacy Study Part)
Week 52
|
-0.02 mmol/L
Interval -0.07 to 0.03
|
-0.03 mmol/L
Interval -0.08 to 0.02
|
-0.01 mmol/L
Interval -0.06 to 0.04
|
—
|
—
|
—
|
—
|
—
|
|
High-density Lipoprotein (HDL)-Cholesterol -- (Efficacy Study Part)
Week 12
|
0.00 mmol/L
Interval -0.04 to 0.04
|
0.05 mmol/L
Interval 0.01 to 0.09
|
0.02 mmol/L
Interval -0.02 to 0.06
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 (Baseline), Weeks 12 and 52.Population: Safety analysis set (SAF): included all subjects who received at least one dose of study medication. The SAF was used for all analyses of safety and background characteristics.
Serum concentration of total HDL cholesterol (Safety study part). Lipid Metabolism: Change from Baseline to Week 12 and Week 52.
Outcome measures
| Measure |
Estetrol 15 mg - Efficacy Study Part
n=430 Participants
Estetrol (E4) 15 mg oral tablet, administered once daily for up to 53 weeks
|
Estetrol 20 mg - Efficacy Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks
|
Placebo - Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks
|
Estetrol 20 mg - Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Placebo -- Hysterectomized -- Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks.
|
Placebo -- Non-Hysterectomized -- Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks.
|
Estetrol 20 mg -- Hysterectomized -- Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Estetrol 20 mg -- Non-Hysterectomized -- Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
|---|---|---|---|---|---|---|---|---|
|
High-density Lipoprotein (HDL)-Cholesterol -- (Safety Study Part)
Week 12
|
0.037 mmol/L
Interval 0.01 to 0.06
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
High-density Lipoprotein (HDL)-Cholesterol -- (Safety Study Part)
Week 52
|
-0.024 mmol/L
Interval -0.06 to 0.01
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 (Baseline), Weeks 12 and 52Population: Intention-to-treat (ITT) Set: included all subjects who received at least one dose of randomized study medication. All analyses on this set were based on the randomized treatment.
Serum concentration of low-density lipoprotein (LDL)-cholesterol (Efficacy study part) Lipid Metabolism: Change from Baseline to Week 12 and Week 52.
Outcome measures
| Measure |
Estetrol 15 mg - Efficacy Study Part
n=192 Participants
Estetrol (E4) 15 mg oral tablet, administered once daily for up to 53 weeks
|
Estetrol 20 mg - Efficacy Study Part
n=193 Participants
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks
|
Placebo - Efficacy Study Part
n=194 Participants
Placebo was administered orally once daily for up to 53 weeks
|
Estetrol 20 mg - Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Placebo -- Hysterectomized -- Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks.
|
Placebo -- Non-Hysterectomized -- Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks.
|
Estetrol 20 mg -- Hysterectomized -- Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Estetrol 20 mg -- Non-Hysterectomized -- Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
|---|---|---|---|---|---|---|---|---|
|
Low-density Lipoprotein (LDL)-Cholesterol -- (Efficacy Study Part)
Week 12
|
-0.12 mmol/L
Interval -0.23 to -0.01
|
-0.10 mmol/L
Interval -0.22 to 0.01
|
0.11 mmol/L
Interval -0.01 to 0.22
|
—
|
—
|
—
|
—
|
—
|
|
Low-density Lipoprotein (LDL)-Cholesterol -- (Efficacy Study Part)
Week 52
|
-0.21 mmol/L
Interval -0.35 to -0.07
|
-0.20 mmol/L
Interval -0.35 to -0.05
|
0.10 mmol/L
Interval -0.04 to 0.23
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 (Baseline), Weeks 12 and 52.Population: Safety analysis set (SAF): included all subjects who received at least one dose of study medication. The SAF was used for all analyses of safety and background characteristics.
Serum Concentration of LDL-cholesterol (Safety study part). Lipid Metabolism: Change from Baseline to Week 12 and Week 52.
Outcome measures
| Measure |
Estetrol 15 mg - Efficacy Study Part
n=430 Participants
Estetrol (E4) 15 mg oral tablet, administered once daily for up to 53 weeks
|
Estetrol 20 mg - Efficacy Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks
|
Placebo - Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks
|
Estetrol 20 mg - Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Placebo -- Hysterectomized -- Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks.
|
Placebo -- Non-Hysterectomized -- Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks.
|
Estetrol 20 mg -- Hysterectomized -- Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Estetrol 20 mg -- Non-Hysterectomized -- Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
|---|---|---|---|---|---|---|---|---|
|
Low-density Lipoprotein (LDL)-Cholesterol -- (Safety Study Part)
Week 12
|
-0.175 mmol/L
Interval -0.25 to -0.1
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Low-density Lipoprotein (LDL)-Cholesterol -- (Safety Study Part)
Week 52
|
-0.286 mmol/L
Interval -0.4 to -0.18
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 (Baseline), Weeks 12 and 52.Population: Intention-to-treat (ITT) Set: included all subjects who received at least one dose of randomized study medication. All analyses on this set were based on the randomized treatment.
Serum concentration of lipoprotein(a) (Efficacy study part). Lipid Metabolism: Change from Baseline to Week 12 and Week 52.
Outcome measures
| Measure |
Estetrol 15 mg - Efficacy Study Part
n=192 Participants
Estetrol (E4) 15 mg oral tablet, administered once daily for up to 53 weeks
|
Estetrol 20 mg - Efficacy Study Part
n=193 Participants
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks
|
Placebo - Efficacy Study Part
n=194 Participants
Placebo was administered orally once daily for up to 53 weeks
|
Estetrol 20 mg - Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Placebo -- Hysterectomized -- Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks.
|
Placebo -- Non-Hysterectomized -- Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks.
|
Estetrol 20 mg -- Hysterectomized -- Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Estetrol 20 mg -- Non-Hysterectomized -- Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
|---|---|---|---|---|---|---|---|---|
|
Lipoprotein(a) -- (Efficacy Study Part)
Week 12
|
-3.35 mg/dL
Interval -4.84 to -1.85
|
-4.04 mg/dL
Interval -5.54 to -2.53
|
-0.01 mg/dL
Interval -1.48 to 1.47
|
—
|
—
|
—
|
—
|
—
|
|
Lipoprotein(a) -- (Efficacy Study Part)
Week 52
|
-2.38 mg/dL
Interval -4.2 to -0.56
|
-2.11 mg/dL
Interval -4.02 to -0.21
|
0.62 mg/dL
Interval -1.11 to 2.35
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 (Baseline), Weeks 12 and 52.Population: Safety analysis set (SAF): included all subjects who received at least one dose of study medication. The SAF was used for all analyses of safety and background characteristics.
Serum Concentration of Lipoprotein(a) (Safety study part). Lipid Metabolism: Change from Baseline to Week 12 and Week 52.
Outcome measures
| Measure |
Estetrol 15 mg - Efficacy Study Part
n=430 Participants
Estetrol (E4) 15 mg oral tablet, administered once daily for up to 53 weeks
|
Estetrol 20 mg - Efficacy Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks
|
Placebo - Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks
|
Estetrol 20 mg - Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Placebo -- Hysterectomized -- Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks.
|
Placebo -- Non-Hysterectomized -- Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks.
|
Estetrol 20 mg -- Hysterectomized -- Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Estetrol 20 mg -- Non-Hysterectomized -- Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
|---|---|---|---|---|---|---|---|---|
|
Lipoprotein(a) -- (Safety Study Part)
Week 12
|
-2.20 mg/dL
Interval -3.66 to -0.73
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Lipoprotein(a) -- (Safety Study Part)
Week 52
|
-0.81 mg/dL
Interval -3.08 to 1.46
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 (Baseline), Weeks 12 and 52.Population: Intention-to-treat (ITT) Set: included all subjects who received at least one dose of randomized study medication. All analyses on this set were based on the randomized treatment.
Serum concentration of triglycerides (Efficacy study part). Lipid Metabolism: Change from Baseline to Week 12 and Week 52.
Outcome measures
| Measure |
Estetrol 15 mg - Efficacy Study Part
n=192 Participants
Estetrol (E4) 15 mg oral tablet, administered once daily for up to 53 weeks
|
Estetrol 20 mg - Efficacy Study Part
n=193 Participants
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks
|
Placebo - Efficacy Study Part
n=194 Participants
Placebo was administered orally once daily for up to 53 weeks
|
Estetrol 20 mg - Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Placebo -- Hysterectomized -- Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks.
|
Placebo -- Non-Hysterectomized -- Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks.
|
Estetrol 20 mg -- Hysterectomized -- Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Estetrol 20 mg -- Non-Hysterectomized -- Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
|---|---|---|---|---|---|---|---|---|
|
Triglycerides -- (Efficacy Study Part)
Week 12
|
0.17 mmol/L
Interval 0.05 to 0.28
|
0.14 mmol/L
Interval 0.03 to 0.26
|
-0.07 mmol/L
Interval -0.19 to 0.04
|
—
|
—
|
—
|
—
|
—
|
|
Triglycerides -- (Efficacy Study Part)
Week 52
|
0.14 mmol/L
Interval 0.0 to 0.28
|
0.21 mmol/L
Interval 0.06 to 0.35
|
0.00 mmol/L
Interval -0.13 to 0.13
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 (Baseline), Weeks 12 and 52.Population: Safety analysis set (SAF): included all subjects who received at least one dose of study drug. The SAF was used for all analyses of safety and background characteristics.
Serum concentration of triglycerides (Safety study part). Lipid Metabolism: Change from Baseline to Week 12 and Week 52.
Outcome measures
| Measure |
Estetrol 15 mg - Efficacy Study Part
n=430 Participants
Estetrol (E4) 15 mg oral tablet, administered once daily for up to 53 weeks
|
Estetrol 20 mg - Efficacy Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks
|
Placebo - Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks
|
Estetrol 20 mg - Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Placebo -- Hysterectomized -- Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks.
|
Placebo -- Non-Hysterectomized -- Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks.
|
Estetrol 20 mg -- Hysterectomized -- Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Estetrol 20 mg -- Non-Hysterectomized -- Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
|---|---|---|---|---|---|---|---|---|
|
Triglycerides -- (Safety Study Part)
Week 12
|
0.195 mmol/L
Interval 0.12 to 0.27
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Triglycerides -- (Safety Study Part)
Week 52
|
0.202 mmol/L
Interval 0.07 to 0.34
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 (Baseline), Weeks 12 and 52.Population: Intention-to-treat (ITT) Set: included all subjects who received at least one dose of randomized study medication. All analyses on this set were based on the randomized treatment.
Hemoglobin A1c (Efficacy study part). Glucose metabolism parameters: Change from Baseline to Week 12 and Week 52. Hemoglobin A1c = Glycated hemoglobin
Outcome measures
| Measure |
Estetrol 15 mg - Efficacy Study Part
n=192 Participants
Estetrol (E4) 15 mg oral tablet, administered once daily for up to 53 weeks
|
Estetrol 20 mg - Efficacy Study Part
n=193 Participants
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks
|
Placebo - Efficacy Study Part
n=194 Participants
Placebo was administered orally once daily for up to 53 weeks
|
Estetrol 20 mg - Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Placebo -- Hysterectomized -- Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks.
|
Placebo -- Non-Hysterectomized -- Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks.
|
Estetrol 20 mg -- Hysterectomized -- Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Estetrol 20 mg -- Non-Hysterectomized -- Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
|---|---|---|---|---|---|---|---|---|
|
Hemoglobin A1c -- (Efficacy Study Part)
Week 12
|
-0.02 percentage of glycated hemoglobin
Interval -0.07 to 0.04
|
-0.09 percentage of glycated hemoglobin
Interval -0.14 to -0.03
|
0.02 percentage of glycated hemoglobin
Interval -0.03 to 0.07
|
—
|
—
|
—
|
—
|
—
|
|
Hemoglobin A1c -- (Efficacy Study Part)
Week 52
|
-0.08 percentage of glycated hemoglobin
Interval -0.15 to -0.02
|
-0.15 percentage of glycated hemoglobin
Interval -0.22 to -0.08
|
-0.08 percentage of glycated hemoglobin
Interval -0.15 to -0.02
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 (Baseline), Weeks 12 and 52.Population: Safety analysis set (SAF): included all subjects who received at least one dose of study medication. The SAF was used for all analyses of safety and background characteristics.
Hemoglobin A1c (Safety study part). Glucose metabolism parameters: Change from Baseline to Week 12 and Week 52. Hemoglobin A1c = Glycated hemoglobin
Outcome measures
| Measure |
Estetrol 15 mg - Efficacy Study Part
n=430 Participants
Estetrol (E4) 15 mg oral tablet, administered once daily for up to 53 weeks
|
Estetrol 20 mg - Efficacy Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks
|
Placebo - Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks
|
Estetrol 20 mg - Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Placebo -- Hysterectomized -- Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks.
|
Placebo -- Non-Hysterectomized -- Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks.
|
Estetrol 20 mg -- Hysterectomized -- Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Estetrol 20 mg -- Non-Hysterectomized -- Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
|---|---|---|---|---|---|---|---|---|
|
Hemoglobin A1c -- (Safety Study Part)
Week 12
|
-0.05 percentage of glycated hemoglobin
Interval -0.07 to -0.02
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Hemoglobin A1c -- (Safety Study Part)
Week 52
|
-0.02 percentage of glycated hemoglobin
Interval -0.08 to 0.04
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 (Baseline), Weeks 12 and 52.Population: Intention-to-treat (ITT) Set: included all subjects who received at least one dose of randomized study medication. All analyses on this set were based on the randomized treatment.
Concentration of fasting glucose in plasma. Glucose metabolism parameters: Change from Baseline to Week 12 and Week 52.
Outcome measures
| Measure |
Estetrol 15 mg - Efficacy Study Part
n=192 Participants
Estetrol (E4) 15 mg oral tablet, administered once daily for up to 53 weeks
|
Estetrol 20 mg - Efficacy Study Part
n=193 Participants
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks
|
Placebo - Efficacy Study Part
n=194 Participants
Placebo was administered orally once daily for up to 53 weeks
|
Estetrol 20 mg - Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Placebo -- Hysterectomized -- Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks.
|
Placebo -- Non-Hysterectomized -- Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks.
|
Estetrol 20 mg -- Hysterectomized -- Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Estetrol 20 mg -- Non-Hysterectomized -- Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
|---|---|---|---|---|---|---|---|---|
|
Fasting Glucose -- (Efficacy Study Part)
Week 52
|
-0.04 mmol/L
Interval -0.19 to 0.1
|
0.00 mmol/L
Interval -0.15 to 0.15
|
-0.04 mmol/L
Interval -0.17 to 0.1
|
—
|
—
|
—
|
—
|
—
|
|
Fasting Glucose -- (Efficacy Study Part)
Week 12
|
0.01 mmol/L
Interval -0.11 to 0.12
|
-0.04 mmol/L
Interval -0.15 to 0.08
|
0.06 mmol/L
Interval -0.05 to 0.18
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 (Baseline), Weeks 12 and 52.Population: Safety analysis set (SAF): included all subjects who received at least one dose of study medication. The SAF was used for all analyses of safety and background characteristics.
Concentration of fasting glucose in plasma. Glucose metabolism parameters: Change from Baseline to Week 12 and Week 52.
Outcome measures
| Measure |
Estetrol 15 mg - Efficacy Study Part
n=430 Participants
Estetrol (E4) 15 mg oral tablet, administered once daily for up to 53 weeks
|
Estetrol 20 mg - Efficacy Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks
|
Placebo - Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks
|
Estetrol 20 mg - Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Placebo -- Hysterectomized -- Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks.
|
Placebo -- Non-Hysterectomized -- Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks.
|
Estetrol 20 mg -- Hysterectomized -- Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Estetrol 20 mg -- Non-Hysterectomized -- Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
|---|---|---|---|---|---|---|---|---|
|
Fasting Glucose -- (Safety Study Part)
Week 12
|
0.074 mmol/L
Interval -0.02 to 0.17
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Fasting Glucose -- (Safety Study Part)
Week 52
|
0.092 mmol/L
Interval -0.08 to 0.27
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 (Baseline), Weeks 12 and 52.Population: Intention-to-treat (ITT) Set: included all subjects who received at least one dose of randomized study medication. All analyses on this set were based on the randomized treatment.
Insulin resistance (HOMA-IR) -- Homeostasis model assessment (Efficacy study part). Glucose Metabolism parameters: Change from Baseline to Week 12 and Week 52. HOMA-IR is a mathematical homeostasis model assessment (HOMA) that evaluates systemic insulin resistance (IR). The HOMA-IR score is calculated as the product of fasting insulin and fasting glucose values divided by a constant. Low HOMA-IR means that a small amount of the hormone insulin is sufficient to keep blood sugars in good balance. HOMA-IR values less than 1.0 mean insulin-sensitivity which is optimal. Values ≥1.9 are indicative of early insulin resistance, and ≥2.9 indicate significant insulin resistance.
Outcome measures
| Measure |
Estetrol 15 mg - Efficacy Study Part
n=192 Participants
Estetrol (E4) 15 mg oral tablet, administered once daily for up to 53 weeks
|
Estetrol 20 mg - Efficacy Study Part
n=193 Participants
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks
|
Placebo - Efficacy Study Part
n=194 Participants
Placebo was administered orally once daily for up to 53 weeks
|
Estetrol 20 mg - Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Placebo -- Hysterectomized -- Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks.
|
Placebo -- Non-Hysterectomized -- Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks.
|
Estetrol 20 mg -- Hysterectomized -- Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Estetrol 20 mg -- Non-Hysterectomized -- Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
|---|---|---|---|---|---|---|---|---|
|
Insulin Resistance (HOMA-IR) -- Homeostasis Model Assessment -- (Efficacy Study Part)
Week 12
|
-0.09 index
Interval -0.66 to 0.49
|
-0.02 index
Interval -0.62 to 0.57
|
0.07 index
Interval -0.51 to 0.65
|
—
|
—
|
—
|
—
|
—
|
|
Insulin Resistance (HOMA-IR) -- Homeostasis Model Assessment -- (Efficacy Study Part)
Week 52
|
-0.66 index
Interval -1.42 to 0.09
|
0.27 index
Interval -0.53 to 1.07
|
-0.46 index
Interval -1.16 to 0.24
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 (Baseline), Weeks 12 and 52.Population: Safety analysis set (SAF): included all subjects who received at least one dose of study drug. The SAF was used for all analyses of safety and background characteristics.
Insulin resistance (HOMA-IR) -- Homeostasis model assessment (Safety study part). Glucose Metabolism parameters: Change from Baseline to Week 12 and Week 52. HOMA-IR is a mathematical homeostasis model assessment (HOMA) that evaluates systemic insulin resistance (IR). The HOMA-IR score is calculated as the product of fasting insulin and fasting glucose values divided by a constant. Low HOMA-IR means that a small amount of the hormone insulin is sufficient to keep blood sugars in good balance. HOMA-IR values less than 1.0 mean insulin-sensitivity which is optimal. Values ≥1.9 are indicative of early insulin resistance, and ≥2.9 indicate significant insulin resistance.
Outcome measures
| Measure |
Estetrol 15 mg - Efficacy Study Part
n=430 Participants
Estetrol (E4) 15 mg oral tablet, administered once daily for up to 53 weeks
|
Estetrol 20 mg - Efficacy Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks
|
Placebo - Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks
|
Estetrol 20 mg - Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Placebo -- Hysterectomized -- Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks.
|
Placebo -- Non-Hysterectomized -- Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks.
|
Estetrol 20 mg -- Hysterectomized -- Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Estetrol 20 mg -- Non-Hysterectomized -- Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
|---|---|---|---|---|---|---|---|---|
|
Insulin Resistance (HOMA-IR) -- Homeostasis Model Assessment -- (Safety Study Part)
Week 12
|
0.124 index
Interval -0.33 to 0.58
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Insulin Resistance (HOMA-IR) -- Homeostasis Model Assessment -- (Safety Study Part)
Week 52
|
-0.156 index
Interval -0.76 to 0.45
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 (Baseline), Weeks 12 and 52.Population: Intention-to-treat (ITT) Set: included all subjects who received at least one dose of randomized study medication. All analyses on this set were based on the randomized treatment.
Serum concentration of insulin (Efficacy study part). Glucose metabolism parameters: Change from Baseline to Week 12 and Week 52.
Outcome measures
| Measure |
Estetrol 15 mg - Efficacy Study Part
n=192 Participants
Estetrol (E4) 15 mg oral tablet, administered once daily for up to 53 weeks
|
Estetrol 20 mg - Efficacy Study Part
n=193 Participants
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks
|
Placebo - Efficacy Study Part
n=194 Participants
Placebo was administered orally once daily for up to 53 weeks
|
Estetrol 20 mg - Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Placebo -- Hysterectomized -- Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks.
|
Placebo -- Non-Hysterectomized -- Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks.
|
Estetrol 20 mg -- Hysterectomized -- Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Estetrol 20 mg -- Non-Hysterectomized -- Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
|---|---|---|---|---|---|---|---|---|
|
Insulin -- (Efficacy Study Part)
Week 12
|
-4.28 pmol/L
Interval -19.18 to 10.62
|
-2.66 pmol/L
Interval -17.67 to 12.36
|
-0.41 pmol/L
Interval -15.18 to 14.36
|
—
|
—
|
—
|
—
|
—
|
|
Insulin -- (Efficacy Study Part)
Week 52
|
-16.40 pmol/L
Interval -35.57 to 2.78
|
6.48 pmol/L
Interval -13.92 to 26.89
|
-10.67 pmol/L
Interval -28.54 to 7.21
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 (Baseline), Weeks 12 and 52.Population: Safety analysis set (SAF): included all subjects who received at least one dose of study drug. The SAF was used for all analyses of safety and background characteristics.
Serum concentration of insulin (Safety study part). Glucose metabolism parameters: Change from Baseline to Week 12 and Week 52.
Outcome measures
| Measure |
Estetrol 15 mg - Efficacy Study Part
n=430 Participants
Estetrol (E4) 15 mg oral tablet, administered once daily for up to 53 weeks
|
Estetrol 20 mg - Efficacy Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks
|
Placebo - Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks
|
Estetrol 20 mg - Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Placebo -- Hysterectomized -- Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks.
|
Placebo -- Non-Hysterectomized -- Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks.
|
Estetrol 20 mg -- Hysterectomized -- Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Estetrol 20 mg -- Non-Hysterectomized -- Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
|---|---|---|---|---|---|---|---|---|
|
Insulin -- (Safety Study Part)
Week 12
|
1.2 pmol/L
Interval -9.44 to 11.89
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Insulin -- (Safety Study Part)
Week 52
|
-5.2 pmol/L
Interval -19.98 to 9.65
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 (Baseline), Weeks 12 and 52.Population: Intention-to-treat (ITT) Set: included all subjects who received at least one dose of randomized study medication. All analyses on this set were based on the randomized treatment.
Angiotensinogen (Efficacy study part). Change from Baseline to Week 12 and Week 52.
Outcome measures
| Measure |
Estetrol 15 mg - Efficacy Study Part
n=192 Participants
Estetrol (E4) 15 mg oral tablet, administered once daily for up to 53 weeks
|
Estetrol 20 mg - Efficacy Study Part
n=193 Participants
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks
|
Placebo - Efficacy Study Part
n=194 Participants
Placebo was administered orally once daily for up to 53 weeks
|
Estetrol 20 mg - Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Placebo -- Hysterectomized -- Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks.
|
Placebo -- Non-Hysterectomized -- Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks.
|
Estetrol 20 mg -- Hysterectomized -- Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Estetrol 20 mg -- Non-Hysterectomized -- Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
|---|---|---|---|---|---|---|---|---|
|
Angiotensinogen -- (Efficacy Study Part)
Week 12
|
16.86 µg/mL
Interval 13.93 to 19.8
|
18.90 µg/mL
Interval 15.95 to 21.84
|
-0.50 µg/mL
Interval -3.31 to 2.31
|
—
|
—
|
—
|
—
|
—
|
|
Angiotensinogen -- (Efficacy Study Part)
Week 52
|
18.47 µg/mL
Interval 15.01 to 21.93
|
21.22 µg/mL
Interval 17.39 to 25.04
|
1.03 µg/mL
Interval -2.25 to 4.3
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 (Baseline), Weeks 12 and 52.Population: Intention-to-treat (ITT) Set: included all subjects who received at least one dose of randomized study medication. All analyses on this set were based on the randomized treatment.
Antithrombin Activity (AT III) -- (Efficacy study part) Hemostasis parameters: Change from Baseline to Week 12 and Week 52. Antithrombin Activity (AT III) is a key biomarker that measures how effectively antithrombin, a natural anticoagulant protein, functions in the blood. The functional AT III assay is based on the principle of inhibition of Factor Xa by antithrombin in the presence of heparin. Antithrombin Activity results are expressed as a percentage, with normal levels ranging between 80% and 120%. Lower than normal levels may indicate an increased risk of blood clotting disorders, while elevated levels can occur during inflammation or certain physiological conditions.
Outcome measures
| Measure |
Estetrol 15 mg - Efficacy Study Part
n=192 Participants
Estetrol (E4) 15 mg oral tablet, administered once daily for up to 53 weeks
|
Estetrol 20 mg - Efficacy Study Part
n=193 Participants
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks
|
Placebo - Efficacy Study Part
n=194 Participants
Placebo was administered orally once daily for up to 53 weeks
|
Estetrol 20 mg - Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Placebo -- Hysterectomized -- Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks.
|
Placebo -- Non-Hysterectomized -- Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks.
|
Estetrol 20 mg -- Hysterectomized -- Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Estetrol 20 mg -- Non-Hysterectomized -- Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
|---|---|---|---|---|---|---|---|---|
|
Antithrombin Activity (AT III) -- (Efficacy Study Part)
Week 12
|
-8.99 percentage of activity
Interval -11.23 to -6.75
|
-8.97 percentage of activity
Interval -11.28 to -6.65
|
-0.71 percentage of activity
Interval -2.96 to 1.52
|
—
|
—
|
—
|
—
|
—
|
|
Antithrombin Activity (AT III) -- (Efficacy Study Part)
Week 52
|
-7.66 percentage of activity
Interval -10.43 to -4.88
|
-5.49 percentage of activity
Interval -8.63 to -2.35
|
0.02 percentage of activity
Interval -2.69 to 2.73
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 (Baseline), Weeks 12 and 52.Population: Intention-to-treat (ITT) Set: included all subjects who received at least one dose of randomized study medication. All analyses on this set were based on the randomized treatment.
Activated partial thromboplastin time (aPTT) based activated Protein-C resistance (APCr) (APCR-V ratio) (Efficacy study part). Hemostasis parameters: Change from Baseline to Week 12 and Week 52.
Outcome measures
| Measure |
Estetrol 15 mg - Efficacy Study Part
n=192 Participants
Estetrol (E4) 15 mg oral tablet, administered once daily for up to 53 weeks
|
Estetrol 20 mg - Efficacy Study Part
n=193 Participants
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks
|
Placebo - Efficacy Study Part
n=194 Participants
Placebo was administered orally once daily for up to 53 weeks
|
Estetrol 20 mg - Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Placebo -- Hysterectomized -- Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks.
|
Placebo -- Non-Hysterectomized -- Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks.
|
Estetrol 20 mg -- Hysterectomized -- Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Estetrol 20 mg -- Non-Hysterectomized -- Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
|---|---|---|---|---|---|---|---|---|
|
Activated Partial Thromboplastin Time (aPTT) Based Activated Protein-C Resistance (APCr) (APCR-V Ratio) -- (Efficacy Study Part)
Week 52
|
0.08 APCR-V ratio
Interval 0.03 to 0.13
|
0.05 APCR-V ratio
Interval 0.0 to 0.11
|
0.09 APCR-V ratio
Interval 0.04 to 0.13
|
—
|
—
|
—
|
—
|
—
|
|
Activated Partial Thromboplastin Time (aPTT) Based Activated Protein-C Resistance (APCr) (APCR-V Ratio) -- (Efficacy Study Part)
Week 12
|
0.04 APCR-V ratio
Interval 0.0 to 0.08
|
0.02 APCR-V ratio
Interval -0.02 to 0.07
|
0.05 APCR-V ratio
Interval 0.01 to 0.09
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 (Baseline), Weeks 12 and 52.Population: Intention-to-treat (ITT) Set: included all subjects who received at least one dose of randomized study medication. All analyses on this set were based on the randomized treatment.
Prothrombin fragment 1 + 2 (Efficacy study part). Hemostasis parameters: Change from Baseline to Week 12 and Week 52.
Outcome measures
| Measure |
Estetrol 15 mg - Efficacy Study Part
n=192 Participants
Estetrol (E4) 15 mg oral tablet, administered once daily for up to 53 weeks
|
Estetrol 20 mg - Efficacy Study Part
n=193 Participants
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks
|
Placebo - Efficacy Study Part
n=194 Participants
Placebo was administered orally once daily for up to 53 weeks
|
Estetrol 20 mg - Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Placebo -- Hysterectomized -- Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks.
|
Placebo -- Non-Hysterectomized -- Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks.
|
Estetrol 20 mg -- Hysterectomized -- Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Estetrol 20 mg -- Non-Hysterectomized -- Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
|---|---|---|---|---|---|---|---|---|
|
Prothrombin Fragment 1 + 2 -- (Efficacy Study Part)
Week 12
|
-44.61 pmol/L
Interval -104.5 to 15.27
|
-57.53 pmol/L
Interval -120.31 to 5.25
|
-50.48 pmol/L
Interval -110.13 to 9.18
|
—
|
—
|
—
|
—
|
—
|
|
Prothrombin Fragment 1 + 2 -- (Efficacy Study Part)
Week 52
|
-69.85 pmol/L
Interval -146.81 to 7.11
|
-95.03 pmol/L
Interval -183.39 to 6.66
|
-23.39 pmol/L
Interval -97.76 to 50.99
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 (Baseline), Weeks 12 and 52.Population: Intention-to-treat (ITT) Set: included all subjects who received at least one dose of randomized study medication. All analyses on this set were based on the randomized treatment.
Factor VIII (Efficacy study part). Hemostasis parameters: Change from Baseline to Week 12 and Week 52. This test measures the activity of Factor VIII which is an essential protein for effective formation of a blood clot. Factor VIII activity results are expressed as a percentage, with normal levels ranging from 50% to 150%. Lower than normal levels can indicate bleeding disorders such as hemophilia A or acquired Factor VIII deficiency.
Outcome measures
| Measure |
Estetrol 15 mg - Efficacy Study Part
n=192 Participants
Estetrol (E4) 15 mg oral tablet, administered once daily for up to 53 weeks
|
Estetrol 20 mg - Efficacy Study Part
n=193 Participants
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks
|
Placebo - Efficacy Study Part
n=194 Participants
Placebo was administered orally once daily for up to 53 weeks
|
Estetrol 20 mg - Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Placebo -- Hysterectomized -- Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks.
|
Placebo -- Non-Hysterectomized -- Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks.
|
Estetrol 20 mg -- Hysterectomized -- Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Estetrol 20 mg -- Non-Hysterectomized -- Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
|---|---|---|---|---|---|---|---|---|
|
Factor VIII -- (Efficacy Study Part)
Week 12
|
-0.52 percentage of activity
Interval -6.07 to 5.02
|
3.21 percentage of activity
Interval -2.49 to 8.92
|
-2.45 percentage of activity
Interval -7.94 to 3.04
|
—
|
—
|
—
|
—
|
—
|
|
Factor VIII -- (Efficacy Study Part)
Week 52
|
-2.39 percentage of activity
Interval -9.13 to 4.35
|
6.99 percentage of activity
Interval -0.57 to 14.55
|
1.47 percentage of activity
Interval -5.13 to 8.07
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 (Baseline), Weeks 12 and 52.Population: Intention-to-treat (ITT) Set: included all subjects who received at least one dose of randomized study medication. All analyses on this set were based on the randomized treatment.
Endogenous thrombin potential (ETP)-based activated Protein-C sensitivity ratio (APCsr ETP) (Efficacy study part). Hemostasis parameters: Change from Baseline to Week 12 and Week 52.
Outcome measures
| Measure |
Estetrol 15 mg - Efficacy Study Part
n=192 Participants
Estetrol (E4) 15 mg oral tablet, administered once daily for up to 53 weeks
|
Estetrol 20 mg - Efficacy Study Part
n=193 Participants
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks
|
Placebo - Efficacy Study Part
n=194 Participants
Placebo was administered orally once daily for up to 53 weeks
|
Estetrol 20 mg - Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Placebo -- Hysterectomized -- Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks.
|
Placebo -- Non-Hysterectomized -- Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks.
|
Estetrol 20 mg -- Hysterectomized -- Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Estetrol 20 mg -- Non-Hysterectomized -- Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
|---|---|---|---|---|---|---|---|---|
|
Endogenous Thrombin Potential (ETP)-Based Activated Protein-C Sensitivity Ratio (APCsr ETP) -- (Efficacy Study Part)
Week 12
|
0.65 APCsr ETP ratio
Interval 0.36 to 0.94
|
0.84 APCsr ETP ratio
Interval 0.57 to 1.12
|
0.08 APCsr ETP ratio
Interval -0.19 to 0.35
|
—
|
—
|
—
|
—
|
—
|
|
Endogenous Thrombin Potential (ETP)-Based Activated Protein-C Sensitivity Ratio (APCsr ETP) -- (Efficacy Study Part)
Week 52
|
0.66 APCsr ETP ratio
Interval 0.32 to 1.0
|
0.90 APCsr ETP ratio
Interval 0.55 to 1.26
|
0.47 APCsr ETP ratio
Interval 0.15 to 0.78
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 (Baseline), Weeks 12 and 52.Population: Intention-to-treat (ITT) Set: included all subjects who received at least one dose of randomized study medication. All analyses on this set were based on the randomized treatment.
Protein-C (Efficacy study part). Hemostasis parameters: Change from Baseline to Week 12 and Week 52.
Outcome measures
| Measure |
Estetrol 15 mg - Efficacy Study Part
n=192 Participants
Estetrol (E4) 15 mg oral tablet, administered once daily for up to 53 weeks
|
Estetrol 20 mg - Efficacy Study Part
n=193 Participants
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks
|
Placebo - Efficacy Study Part
n=194 Participants
Placebo was administered orally once daily for up to 53 weeks
|
Estetrol 20 mg - Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Placebo -- Hysterectomized -- Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks.
|
Placebo -- Non-Hysterectomized -- Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks.
|
Estetrol 20 mg -- Hysterectomized -- Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Estetrol 20 mg -- Non-Hysterectomized -- Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
|---|---|---|---|---|---|---|---|---|
|
Protein-C -- (Efficacy Study Part)
Week 52
|
-6.13 percentage of activity
Interval -9.38 to -2.89
|
-3.93 percentage of activity
Interval -7.55 to -0.32
|
-3.76 percentage of activity
Interval -6.93 to -0.59
|
—
|
—
|
—
|
—
|
—
|
|
Protein-C -- (Efficacy Study Part)
Week 12
|
-4.82 percentage of activity
Interval -7.53 to -2.11
|
-2.34 percentage of activity
Interval -5.12 to 0.44
|
-2.37 percentage of activity
Interval -5.05 to 0.31
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 (Baseline), Weeks 12 and 52.Population: Intention-to-treat (ITT) Set: included all subjects who received at least one dose of randomized study medication. All analyses on this set were based on the randomized treatment.
Free Protein-S (Efficacy study part). Hemostasis parameters: Change from Baseline to Week 12 and Week 52.
Outcome measures
| Measure |
Estetrol 15 mg - Efficacy Study Part
n=192 Participants
Estetrol (E4) 15 mg oral tablet, administered once daily for up to 53 weeks
|
Estetrol 20 mg - Efficacy Study Part
n=193 Participants
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks
|
Placebo - Efficacy Study Part
n=194 Participants
Placebo was administered orally once daily for up to 53 weeks
|
Estetrol 20 mg - Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Placebo -- Hysterectomized -- Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks.
|
Placebo -- Non-Hysterectomized -- Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks.
|
Estetrol 20 mg -- Hysterectomized -- Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Estetrol 20 mg -- Non-Hysterectomized -- Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
|---|---|---|---|---|---|---|---|---|
|
Free Protein-S -- (Efficacy Study Part)
Week 12
|
-4.96 percent free protein S
Interval -7.04 to -2.87
|
-5.79 percent free protein S
Interval -7.86 to -3.71
|
-1.01 percent free protein S
Interval -3.05 to 1.02
|
—
|
—
|
—
|
—
|
—
|
|
Free Protein-S -- (Efficacy Study Part)
Week 52
|
-4.84 percent free protein S
Interval -7.41 to -2.26
|
-4.06 percent free protein S
Interval -6.84 to -1.28
|
-0.28 percent free protein S
Interval -2.74 to 2.19
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 (Baseline), Weeks 12 and 52.Population: Intention-to-treat (ITT) Set: included all subjects who received at least one dose of randomized study medication. All analyses on this set were based on the randomized treatment.
Sex Hormone Binding Globulin (SHBG) (Efficacy study part). Change from Baseline to Week 12 and Week 52.
Outcome measures
| Measure |
Estetrol 15 mg - Efficacy Study Part
n=192 Participants
Estetrol (E4) 15 mg oral tablet, administered once daily for up to 53 weeks
|
Estetrol 20 mg - Efficacy Study Part
n=193 Participants
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks
|
Placebo - Efficacy Study Part
n=194 Participants
Placebo was administered orally once daily for up to 53 weeks
|
Estetrol 20 mg - Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Placebo -- Hysterectomized -- Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks.
|
Placebo -- Non-Hysterectomized -- Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks.
|
Estetrol 20 mg -- Hysterectomized -- Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Estetrol 20 mg -- Non-Hysterectomized -- Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
|---|---|---|---|---|---|---|---|---|
|
Sex Hormone Binding Globulin (SHBG) -- (Efficacy Study Part)
Week 12
|
26.76 nmol/L
Interval 19.37 to 34.15
|
43.85 nmol/L
Interval 36.53 to 51.17
|
-1.14 nmol/L
Interval -8.15 to 5.87
|
—
|
—
|
—
|
—
|
—
|
|
Sex Hormone Binding Globulin (SHBG) -- (Efficacy Study Part)
Week 52
|
31.47 nmol/L
Interval 23.26 to 39.69
|
50.70 nmol/L
Interval 41.99 to 59.42
|
1.55 nmol/L
Interval -6.23 to 9.34
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 (Baseline), Weeks 12 and 52.Population: Intention-to-treat (ITT) Set: included all subjects who received at least one dose of randomized study medication. All analyses on this set were based on the randomized treatment.
Calcium (Efficacy study part). Bone turnover markers: Change from Baseline to Week 12 and Week 52.
Outcome measures
| Measure |
Estetrol 15 mg - Efficacy Study Part
n=192 Participants
Estetrol (E4) 15 mg oral tablet, administered once daily for up to 53 weeks
|
Estetrol 20 mg - Efficacy Study Part
n=193 Participants
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks
|
Placebo - Efficacy Study Part
n=194 Participants
Placebo was administered orally once daily for up to 53 weeks
|
Estetrol 20 mg - Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Placebo -- Hysterectomized -- Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks.
|
Placebo -- Non-Hysterectomized -- Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks.
|
Estetrol 20 mg -- Hysterectomized -- Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Estetrol 20 mg -- Non-Hysterectomized -- Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
|---|---|---|---|---|---|---|---|---|
|
Calcium -- (Efficacy Study Part)
Week 12
|
-0.04 mmol/L
Interval -0.06 to -0.03
|
-0.08 mmol/L
Interval -0.09 to -0.06
|
0.00 mmol/L
Interval -0.02 to 0.02
|
—
|
—
|
—
|
—
|
—
|
|
Calcium -- (Efficacy Study Part)
Week 52
|
-0.07 mmol/L
Interval -0.09 to -0.04
|
-0.11 mmol/L
Interval -0.13 to -0.08
|
-0.04 mmol/L
Interval -0.06 to -0.02
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 (Baseline), Weeks 12 and 52.Population: Intention-to-treat (ITT) Set: included all subjects who received at least one dose of randomized study medication. All analyses on this set were based on the randomized treatment.
C-terminal telopeptide type 1 (CTX-1) (Efficacy study part). Bone turnover markers: Change from Baseline to Week 12 and Week 52.
Outcome measures
| Measure |
Estetrol 15 mg - Efficacy Study Part
n=192 Participants
Estetrol (E4) 15 mg oral tablet, administered once daily for up to 53 weeks
|
Estetrol 20 mg - Efficacy Study Part
n=193 Participants
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks
|
Placebo - Efficacy Study Part
n=194 Participants
Placebo was administered orally once daily for up to 53 weeks
|
Estetrol 20 mg - Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Placebo -- Hysterectomized -- Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks.
|
Placebo -- Non-Hysterectomized -- Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks.
|
Estetrol 20 mg -- Hysterectomized -- Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Estetrol 20 mg -- Non-Hysterectomized -- Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
|---|---|---|---|---|---|---|---|---|
|
C-Terminal Telopeptide Type 1 (CTX-1) -- (Efficacy Study Part)
Week 12
|
-0.15 µg/L
Interval -0.18 to -0.12
|
-0.15 µg/L
Interval -0.19 to -0.12
|
-0.02 µg/L
Interval -0.05 to 0.01
|
—
|
—
|
—
|
—
|
—
|
|
C-Terminal Telopeptide Type 1 (CTX-1) -- (Efficacy Study Part)
Week 52
|
-0.19 µg/L
Interval -0.22 to -0.15
|
-0.16 µg/L
Interval -0.2 to -0.12
|
-0.02 µg/L
Interval -0.05 to 0.02
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 (Baseline), Weeks 12 and 52.Population: Intention-to-treat (ITT) Set: included all subjects who received at least one dose of randomized study medication. All analyses on this set were based on the randomized treatment.
Procollagen I N-Terminal Propeptide (PINP) (Efficacy study part). Bone turnover markers: Change from Baseline to Week 12 and Week 52.
Outcome measures
| Measure |
Estetrol 15 mg - Efficacy Study Part
n=192 Participants
Estetrol (E4) 15 mg oral tablet, administered once daily for up to 53 weeks
|
Estetrol 20 mg - Efficacy Study Part
n=193 Participants
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks
|
Placebo - Efficacy Study Part
n=194 Participants
Placebo was administered orally once daily for up to 53 weeks
|
Estetrol 20 mg - Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Placebo -- Hysterectomized -- Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks.
|
Placebo -- Non-Hysterectomized -- Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks.
|
Estetrol 20 mg -- Hysterectomized -- Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Estetrol 20 mg -- Non-Hysterectomized -- Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
|---|---|---|---|---|---|---|---|---|
|
Procollagen I N-Terminal Propeptide (PINP) -- (Efficacy Study Part)
Week 12
|
-8.45 µg/L
Interval -11.99 to -4.91
|
-13.84 µg/L
Interval -17.4 to -10.27
|
-2.22 µg/L
Interval -5.71 to 1.26
|
—
|
—
|
—
|
—
|
—
|
|
Procollagen I N-Terminal Propeptide (PINP) -- (Efficacy Study Part)
Week 52
|
-16.08 µg/L
Interval -20.57 to -11.59
|
-13.83 µg/L
Interval -18.63 to -9.03
|
-0.15 µg/L
Interval -4.34 to 4.04
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 (Baseline), Weeks 12 and 52.Population: Intention-to-treat (ITT) Set: included all subjects who received at least one dose of randomized study medication. All analyses on this set were based on the randomized treatment.
25-Hydroxyvitamin D (Efficacy study part). Bone turnover markers: Change from Baseline to Week 12 and Week 52.
Outcome measures
| Measure |
Estetrol 15 mg - Efficacy Study Part
n=192 Participants
Estetrol (E4) 15 mg oral tablet, administered once daily for up to 53 weeks
|
Estetrol 20 mg - Efficacy Study Part
n=193 Participants
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks
|
Placebo - Efficacy Study Part
n=194 Participants
Placebo was administered orally once daily for up to 53 weeks
|
Estetrol 20 mg - Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Placebo -- Hysterectomized -- Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks.
|
Placebo -- Non-Hysterectomized -- Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks.
|
Estetrol 20 mg -- Hysterectomized -- Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Estetrol 20 mg -- Non-Hysterectomized -- Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
|---|---|---|---|---|---|---|---|---|
|
25-Hydroxyvitamin D -- (Efficacy Study Part)
Week 12
|
2.37 nmol/L
Interval -1.92 to 6.66
|
-2.19 nmol/L
Interval -6.46 to 2.07
|
0.51 nmol/L
Interval -3.66 to 4.67
|
—
|
—
|
—
|
—
|
—
|
|
25-Hydroxyvitamin D -- (Efficacy Study Part)
Week 52
|
13.89 nmol/L
Interval 8.44 to 19.33
|
5.52 nmol/L
Interval -0.29 to 11.34
|
7.07 nmol/L
Interval 1.97 to 12.17
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 (Baseline), Week 12, and 52.Population: Intention-to-treat (ITT) Set: included all subjects who received at least one dose of randomized study medication. The ITT set was the primary analysis set for the efficacy analyses and all analyses on this set were based on the randomized treatment.
Change from Baseline to W12 and W52 in HRQoL using the MENQOL questionnaire. MENQOL questionnaire=29-item assessment of QoL to capture self-reported information on the presence and bother of symptoms and feelings in the domains of vasomotor, psychosocial, physical and sexual functioning, among midlife women in the immediate post-menopause time. For each item, women are asked if they experience that symptom or feeling, and if yes, to rate bother on a scale of 0-6 corresponding to "not at all bothered" to "extremely bothered". Non-endorsement of an item is scored a "1" and endorsement a "2", plus the number of the particular rating, so that the possible score on any item ranges from 1 (not experiencing symptom or feeling) to 8 (extremely bothered). Domain score=mean of the item scores in that domain. Total MENQOL=mean of the domain-specific scores. Administered at Day 1 (=day of randomization) for baseline, W12 and W52. It refers to the symptoms experienced over the past month.
Outcome measures
| Measure |
Estetrol 15 mg - Efficacy Study Part
n=192 Participants
Estetrol (E4) 15 mg oral tablet, administered once daily for up to 53 weeks
|
Estetrol 20 mg - Efficacy Study Part
n=193 Participants
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks
|
Placebo - Efficacy Study Part
n=194 Participants
Placebo was administered orally once daily for up to 53 weeks
|
Estetrol 20 mg - Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Placebo -- Hysterectomized -- Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks.
|
Placebo -- Non-Hysterectomized -- Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks.
|
Estetrol 20 mg -- Hysterectomized -- Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Estetrol 20 mg -- Non-Hysterectomized -- Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
|---|---|---|---|---|---|---|---|---|
|
Health-related Quality of Life (HRQoL) Assessment, Change From Baseline -- Menopause-specific Quality of Life (MENQOL) Questionnaire -- (Efficacy Study Part)
Week 52 -- Vasomotor Domain
|
-3.75 scores on a scale
Interval -4.14 to -3.36
|
-3.74 scores on a scale
Interval -4.16 to -3.32
|
-2.99 scores on a scale
Interval -3.36 to -2.63
|
—
|
—
|
—
|
—
|
—
|
|
Health-related Quality of Life (HRQoL) Assessment, Change From Baseline -- Menopause-specific Quality of Life (MENQOL) Questionnaire -- (Efficacy Study Part)
Week 12 -- Vasomotor Domain
|
-2.83 scores on a scale
Interval -3.15 to -2.51
|
-3.15 scores on a scale
Interval -3.48 to -2.83
|
-2.38 scores on a scale
Interval -2.7 to -2.06
|
—
|
—
|
—
|
—
|
—
|
|
Health-related Quality of Life (HRQoL) Assessment, Change From Baseline -- Menopause-specific Quality of Life (MENQOL) Questionnaire -- (Efficacy Study Part)
Week 12 -- Psychosocial Domain
|
-1.27 scores on a scale
Interval -1.49 to -1.05
|
-1.31 scores on a scale
Interval -1.53 to -1.09
|
-1.15 scores on a scale
Interval -1.36 to -0.93
|
—
|
—
|
—
|
—
|
—
|
|
Health-related Quality of Life (HRQoL) Assessment, Change From Baseline -- Menopause-specific Quality of Life (MENQOL) Questionnaire -- (Efficacy Study Part)
Week 52 -- Psychosocial Domain
|
-1.57 scores on a scale
Interval -1.83 to -1.3
|
-1.17 scores on a scale
Interval -1.45 to -0.89
|
-1.25 scores on a scale
Interval -1.5 to -1.0
|
—
|
—
|
—
|
—
|
—
|
|
Health-related Quality of Life (HRQoL) Assessment, Change From Baseline -- Menopause-specific Quality of Life (MENQOL) Questionnaire -- (Efficacy Study Part)
Week 12 -- Physical Domain
|
-1.23 scores on a scale
Interval -1.44 to -1.02
|
-1.03 scores on a scale
Interval -1.24 to -0.82
|
-1.15 scores on a scale
Interval -1.36 to -0.94
|
—
|
—
|
—
|
—
|
—
|
|
Health-related Quality of Life (HRQoL) Assessment, Change From Baseline -- Menopause-specific Quality of Life (MENQOL) Questionnaire -- (Efficacy Study Part)
Week 52 -- Physical Domain
|
-1.39 scores on a scale
Interval -1.64 to -1.14
|
-1.05 scores on a scale
Interval -1.32 to -0.78
|
-1.14 scores on a scale
Interval -1.38 to -0.9
|
—
|
—
|
—
|
—
|
—
|
|
Health-related Quality of Life (HRQoL) Assessment, Change From Baseline -- Menopause-specific Quality of Life (MENQOL) Questionnaire -- (Efficacy Study Part)
Week 12 -- Sexual functioning Domain
|
-1.42 scores on a scale
Interval -1.73 to -1.12
|
-1.37 scores on a scale
Interval -1.68 to -1.06
|
-1.15 scores on a scale
Interval -1.45 to -0.84
|
—
|
—
|
—
|
—
|
—
|
|
Health-related Quality of Life (HRQoL) Assessment, Change From Baseline -- Menopause-specific Quality of Life (MENQOL) Questionnaire -- (Efficacy Study Part)
Week 52 -- Sexual functioning Domain
|
-1.65 scores on a scale
Interval -2.02 to -1.27
|
-1.11 scores on a scale
Interval -1.51 to -0.71
|
-1.25 scores on a scale
Interval -1.61 to -0.9
|
—
|
—
|
—
|
—
|
—
|
|
Health-related Quality of Life (HRQoL) Assessment, Change From Baseline -- Menopause-specific Quality of Life (MENQOL) Questionnaire -- (Efficacy Study Part)
Week 12 -- Total MENQOL
|
-1.69 scores on a scale
Interval -1.89 to -1.49
|
-1.72 scores on a scale
Interval -1.93 to -1.52
|
-1.47 scores on a scale
Interval -1.67 to -1.27
|
—
|
—
|
—
|
—
|
—
|
|
Health-related Quality of Life (HRQoL) Assessment, Change From Baseline -- Menopause-specific Quality of Life (MENQOL) Questionnaire -- (Efficacy Study Part)
Week 52 -- Total MENQOL
|
-2.08 scores on a scale
Interval -2.32 to -1.85
|
-1.78 scores on a scale
Interval -2.04 to -1.53
|
-1.66 scores on a scale
Interval -1.89 to -1.43
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 (Baseline), Week 12 and 52.Population: Safety analysis set (SAF): included all subjects who received at least one dose of study medication.
Change from Baseline to W12 and W52 in HRQoL using the MENQOL questionnaire. MENQOL questionnaire=29-item assessment of QoL to capture self-reported information on the presence and bother of symptoms and feelings in the domains of vasomotor, psychosocial, physical and sexual functioning, among midlife women in the immediate post-menopause time. For each item, women are asked if they experience that symptom or feeling, and if yes, to rate bother on a scale of 0-6 corresponding to "not at all bothered" to "extremely bothered". Non-endorsement of an item is scored a "1" and endorsement a "2", plus the number of the particular rating, so that the possible score on any item ranges from 1 (not experiencing symptom or feeling) to 8 (extremely bothered). Domain score=mean of the item scores in that domain. Total MENQOL=mean of the domain-specific scores. Administered at Day 1 (=day of randomization) for baseline, W12 and W52. It refers to the symptoms experienced over the past month.
Outcome measures
| Measure |
Estetrol 15 mg - Efficacy Study Part
n=430 Participants
Estetrol (E4) 15 mg oral tablet, administered once daily for up to 53 weeks
|
Estetrol 20 mg - Efficacy Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks
|
Placebo - Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks
|
Estetrol 20 mg - Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Placebo -- Hysterectomized -- Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks.
|
Placebo -- Non-Hysterectomized -- Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks.
|
Estetrol 20 mg -- Hysterectomized -- Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Estetrol 20 mg -- Non-Hysterectomized -- Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
|---|---|---|---|---|---|---|---|---|
|
Health-related Quality of Life (HRQoL) Assessment, Change From Baseline -- Menopause-specific Quality of Life (MENQOL) Questionnaire -- (Safety Study Part)
Week 52 -- Physical Domain
|
-1.11 scores on a scale
Interval -1.37 to -0.86
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Health-related Quality of Life (HRQoL) Assessment, Change From Baseline -- Menopause-specific Quality of Life (MENQOL) Questionnaire -- (Safety Study Part)
Week 12 -- Vasomotor Domain
|
-3.34 scores on a scale
Interval -3.58 to -3.11
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Health-related Quality of Life (HRQoL) Assessment, Change From Baseline -- Menopause-specific Quality of Life (MENQOL) Questionnaire -- (Safety Study Part)
Week 52 -- Vasomotor Domain
|
-3.19 scores on a scale
Interval -3.56 to -2.83
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Health-related Quality of Life (HRQoL) Assessment, Change From Baseline -- Menopause-specific Quality of Life (MENQOL) Questionnaire -- (Safety Study Part)
Week 12 -- Psychosocial Domain
|
-1.20 scores on a scale
Interval -1.4 to -1.01
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Health-related Quality of Life (HRQoL) Assessment, Change From Baseline -- Menopause-specific Quality of Life (MENQOL) Questionnaire -- (Safety Study Part)
Week 52 -- Psychosocial Domain
|
-1.25 scores on a scale
Interval -1.52 to -0.97
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Health-related Quality of Life (HRQoL) Assessment, Change From Baseline -- Menopause-specific Quality of Life (MENQOL) Questionnaire -- (Safety Study Part)
Week 12 -- Physical Domain
|
-1.27 scores on a scale
Interval -1.44 to -1.09
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Health-related Quality of Life (HRQoL) Assessment, Change From Baseline -- Menopause-specific Quality of Life (MENQOL) Questionnaire -- (Safety Study Part)
Week 12 -- Sexual functioning Domain
|
-1.63 scores on a scale
Interval -1.88 to -1.39
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Health-related Quality of Life (HRQoL) Assessment, Change From Baseline -- Menopause-specific Quality of Life (MENQOL) Questionnaire -- (Safety Study Part)
Week 52 -- Sexual functioning Domain
|
-1.55 scores on a scale
Interval -1.94 to -1.17
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Health-related Quality of Life (HRQoL) Assessment, Change From Baseline -- Menopause-specific Quality of Life (MENQOL) Questionnaire -- (Safety Study Part)
Week 12 -- Total MENQOL
|
-1.86 scores on a scale
Interval -2.01 to -1.71
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Health-related Quality of Life (HRQoL) Assessment, Change From Baseline -- Menopause-specific Quality of Life (MENQOL) Questionnaire -- (Safety Study Part)
Week 52 -- Total MENQOL
|
-1.78 scores on a scale
Interval -2.02 to -1.53
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Weeks 4, 12, and 52.Population: Intention-to-treat (ITT) Set for Efficacy Study Part: included all subjects who received at least one dose of randomized study medication. The ITT set was the primary analysis set for the efficacy analyses and all analyses on this set were based on the randomized treatment. Safety analysis set (SAF) for Safety Study Part: included all subjects who received at least one dose of study drug.
Total score in treatment satisfaction (TS) using the Clinical Global Impression (CGI) questionnaire (Efficacy study part and Safety study part). CGI questionnaire: questionnaire in which subjects were to answer the question "Rate the total improvement, whether or not in your judgement it is due entirely to drug treatment. Compared to your condition at administration to the study, how much has it changed?". The options were: very much improved, much improved, minimally improved, no change, minimally worse, much worse, and very much worse. Results are shown as percentage of participants. TS=Treatment satisfaction
Outcome measures
| Measure |
Estetrol 15 mg - Efficacy Study Part
n=192 Participants
Estetrol (E4) 15 mg oral tablet, administered once daily for up to 53 weeks
|
Estetrol 20 mg - Efficacy Study Part
n=193 Participants
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks
|
Placebo - Efficacy Study Part
n=194 Participants
Placebo was administered orally once daily for up to 53 weeks
|
Estetrol 20 mg - Safety Study Part
n=430 Participants
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Placebo -- Hysterectomized -- Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks.
|
Placebo -- Non-Hysterectomized -- Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks.
|
Estetrol 20 mg -- Hysterectomized -- Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Estetrol 20 mg -- Non-Hysterectomized -- Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
|---|---|---|---|---|---|---|---|---|
|
Total Score in Treatment Satisfaction (TS) Using the Clinical Global Impression (CGI) Questionnaire -- (Efficacy Study Part, Safety Study Part)
5_Week 4 - Minimally worse
|
0.6 percentage of participants
|
0.6 percentage of participants
|
1.7 percentage of participants
|
1.6 percentage of participants
|
—
|
—
|
—
|
—
|
|
Total Score in Treatment Satisfaction (TS) Using the Clinical Global Impression (CGI) Questionnaire -- (Efficacy Study Part, Safety Study Part)
6_Week 4 - Much worse
|
0.6 percentage of participants
|
1.1 percentage of participants
|
0.6 percentage of participants
|
0.5 percentage of participants
|
—
|
—
|
—
|
—
|
|
Total Score in Treatment Satisfaction (TS) Using the Clinical Global Impression (CGI) Questionnaire -- (Efficacy Study Part, Safety Study Part)
1_Week 4 - Very Much Improved
|
11.6 percentage of participants
|
17.5 percentage of participants
|
10.3 percentage of participants
|
22.5 percentage of participants
|
—
|
—
|
—
|
—
|
|
Total Score in Treatment Satisfaction (TS) Using the Clinical Global Impression (CGI) Questionnaire -- (Efficacy Study Part, Safety Study Part)
2_Week 4 - Much Improved
|
25.4 percentage of participants
|
34.5 percentage of participants
|
25.1 percentage of participants
|
36.6 percentage of participants
|
—
|
—
|
—
|
—
|
|
Total Score in Treatment Satisfaction (TS) Using the Clinical Global Impression (CGI) Questionnaire -- (Efficacy Study Part, Safety Study Part)
3_Week 4 - Minimally Improved
|
46.8 percentage of participants
|
29.9 percentage of participants
|
37.7 percentage of participants
|
28.6 percentage of participants
|
—
|
—
|
—
|
—
|
|
Total Score in Treatment Satisfaction (TS) Using the Clinical Global Impression (CGI) Questionnaire -- (Efficacy Study Part, Safety Study Part)
4_Week 4 - No change
|
14.5 percentage of participants
|
16.4 percentage of participants
|
24.6 percentage of participants
|
10.2 percentage of participants
|
—
|
—
|
—
|
—
|
|
Total Score in Treatment Satisfaction (TS) Using the Clinical Global Impression (CGI) Questionnaire -- (Efficacy Study Part, Safety Study Part)
7_Week 4 - Very Much Worse
|
0.6 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0.0 percentage of participants
|
—
|
—
|
—
|
—
|
|
Total Score in Treatment Satisfaction (TS) Using the Clinical Global Impression (CGI) Questionnaire -- (Efficacy Study Part, Safety Study Part)
1_Week 12 - Very Much Improved
|
19.9 percentage of participants
|
26.4 percentage of participants
|
15.9 percentage of participants
|
29.8 percentage of participants
|
—
|
—
|
—
|
—
|
|
Total Score in Treatment Satisfaction (TS) Using the Clinical Global Impression (CGI) Questionnaire -- (Efficacy Study Part, Safety Study Part)
2_Week 12 - Much Improved
|
43.7 percentage of participants
|
45.1 percentage of participants
|
37.1 percentage of participants
|
44.6 percentage of participants
|
—
|
—
|
—
|
—
|
|
Total Score in Treatment Satisfaction (TS) Using the Clinical Global Impression (CGI) Questionnaire -- (Efficacy Study Part, Safety Study Part)
3_Week 12 - Minimally Improved
|
26.5 percentage of participants
|
18.1 percentage of participants
|
31.8 percentage of participants
|
18.6 percentage of participants
|
—
|
—
|
—
|
—
|
|
Total Score in Treatment Satisfaction (TS) Using the Clinical Global Impression (CGI) Questionnaire -- (Efficacy Study Part, Safety Study Part)
4_Week 12 - No change
|
6.0 percentage of participants
|
5.6 percentage of participants
|
14.6 percentage of participants
|
4.6 percentage of participants
|
—
|
—
|
—
|
—
|
|
Total Score in Treatment Satisfaction (TS) Using the Clinical Global Impression (CGI) Questionnaire -- (Efficacy Study Part, Safety Study Part)
5_Week 12 - Minimally worse
|
2.6 percentage of participants
|
4.2 percentage of participants
|
0.7 percentage of participants
|
1.4 percentage of participants
|
—
|
—
|
—
|
—
|
|
Total Score in Treatment Satisfaction (TS) Using the Clinical Global Impression (CGI) Questionnaire -- (Efficacy Study Part, Safety Study Part)
6_Week 12 - Much worse
|
0.7 percentage of participants
|
0.7 percentage of participants
|
0.0 percentage of participants
|
0.4 percentage of participants
|
—
|
—
|
—
|
—
|
|
Total Score in Treatment Satisfaction (TS) Using the Clinical Global Impression (CGI) Questionnaire -- (Efficacy Study Part, Safety Study Part)
7_Week 12 - Very Much Worse
|
0.7 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
0.7 percentage of participants
|
—
|
—
|
—
|
—
|
|
Total Score in Treatment Satisfaction (TS) Using the Clinical Global Impression (CGI) Questionnaire -- (Efficacy Study Part, Safety Study Part)
1_Week 52 - Very Much Improved
|
34.4 percentage of participants
|
35.8 percentage of participants
|
24.8 percentage of participants
|
37.0 percentage of participants
|
—
|
—
|
—
|
—
|
|
Total Score in Treatment Satisfaction (TS) Using the Clinical Global Impression (CGI) Questionnaire -- (Efficacy Study Part, Safety Study Part)
2_Week 52- Much Improved
|
41.9 percentage of participants
|
46.9 percentage of participants
|
38.1 percentage of participants
|
37.7 percentage of participants
|
—
|
—
|
—
|
—
|
|
Total Score in Treatment Satisfaction (TS) Using the Clinical Global Impression (CGI) Questionnaire -- (Efficacy Study Part, Safety Study Part)
3_Week 52 - Minimally Improved
|
17.2 percentage of participants
|
13.6 percentage of participants
|
22.9 percentage of participants
|
21.7 percentage of participants
|
—
|
—
|
—
|
—
|
|
Total Score in Treatment Satisfaction (TS) Using the Clinical Global Impression (CGI) Questionnaire -- (Efficacy Study Part, Safety Study Part)
4_Week 52 - No change
|
4.3 percentage of participants
|
2.5 percentage of participants
|
12.4 percentage of participants
|
2.2 percentage of participants
|
—
|
—
|
—
|
—
|
|
Total Score in Treatment Satisfaction (TS) Using the Clinical Global Impression (CGI) Questionnaire -- (Efficacy Study Part, Safety Study Part)
5_Week 52 - Minimally worse
|
1.1 percentage of participants
|
0.0 percentage of participants
|
1.9 percentage of participants
|
0.7 percentage of participants
|
—
|
—
|
—
|
—
|
|
Total Score in Treatment Satisfaction (TS) Using the Clinical Global Impression (CGI) Questionnaire -- (Efficacy Study Part, Safety Study Part)
6_Week 52 - Much worse
|
1.1 percentage of participants
|
1.2 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
—
|
—
|
—
|
—
|
|
Total Score in Treatment Satisfaction (TS) Using the Clinical Global Impression (CGI) Questionnaire -- (Efficacy Study Part, Safety Study Part)
7_Week 52 - Very Much Worse
|
0.0 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
0.7 percentage of participants
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Screening, Week 13, 29, 41, 53, Follow-up (Week 55/56), and early discontinuation (up to Week 53 for hysterectomized subjects and Week 55/56 for non-hysterectomized subjects)Population: Safety Analysis Set (SAF) for Efficacy study part: included all subjects who received at least one dose of randomized study medication. The SAF was used for all safety analyses and background characteristics and all analyses on this set were based on the treatment received. Safety Analysis Set (SAF) for Safety study part: included all subjects who received at least one dose of study medication. The SAF was used for all safety analyses and background characteristics.
Change from baseline for non-hysterectomized subjects by visit (Efficacy Study Part and Safety Study Part). Endometrial thickness was assessed by transvaginal ultrasound (TVUS).
Outcome measures
| Measure |
Estetrol 15 mg - Efficacy Study Part
n=93 Participants
Estetrol (E4) 15 mg oral tablet, administered once daily for up to 53 weeks
|
Estetrol 20 mg - Efficacy Study Part
n=93 Participants
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks
|
Placebo - Efficacy Study Part
n=95 Participants
Placebo was administered orally once daily for up to 53 weeks
|
Estetrol 20 mg - Safety Study Part
n=229 Participants
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Placebo -- Hysterectomized -- Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks.
|
Placebo -- Non-Hysterectomized -- Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks.
|
Estetrol 20 mg -- Hysterectomized -- Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Estetrol 20 mg -- Non-Hysterectomized -- Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Mean Endometrial Thickness -- (Efficacy Study Part, Safety Study Part)
Week 55/56 (Follow-up)
|
0.84 millimeter
Interval 0.36 to 1.32
|
1.31 millimeter
Interval 0.72 to 1.91
|
0.05 millimeter
Interval -0.27 to 0.37
|
1.13 millimeter
Interval 0.76 to 1.51
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Mean Endometrial Thickness -- (Efficacy Study Part, Safety Study Part)
Early Discontinuation
|
5.21 millimeter
Interval 1.26 to 9.16
|
5.56 millimeter
Interval 3.55 to 7.58
|
-0.23 millimeter
Interval -1.06 to 0.6
|
4.96 millimeter
Interval 3.8 to 6.12
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Mean Endometrial Thickness -- (Efficacy Study Part, Safety Study Part)
Week 29
|
2.65 millimeter
Interval 0.88 to 4.43
|
3.62 millimeter
Interval 1.52 to 5.71
|
0.32 millimeter
Interval -0.05 to 0.69
|
4.34 millimeter
Interval 3.0 to 5.69
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Mean Endometrial Thickness -- (Efficacy Study Part, Safety Study Part)
Week 41
|
1.74 millimeter
Interval 0.77 to 2.72
|
2.08 millimeter
Interval 0.32 to 3.83
|
0.52 millimeter
Interval -0.05 to 1.09
|
3.08 millimeter
Interval 1.75 to 4.41
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Mean Endometrial Thickness -- (Efficacy Study Part, Safety Study Part)
Week 53
|
1.93 millimeter
Interval 0.4 to 3.45
|
1.66 millimeter
Interval 0.63 to 2.69
|
0.63 millimeter
Interval 0.13 to 1.14
|
3.19 millimeter
Interval 1.7 to 4.68
|
—
|
—
|
—
|
—
|
|
Change From Baseline in Mean Endometrial Thickness -- (Efficacy Study Part, Safety Study Part)
Week 13
|
4.20 millimeter
Interval 2.66 to 5.74
|
3.90 millimeter
Interval 2.44 to 5.36
|
0.23 millimeter
Interval -0.08 to 0.54
|
6.91 millimeter
Interval 5.76 to 8.07
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Screening and Week 53.Population: Safety Analysis Set (SAF) for Efficacy study part: included all subjects who received at least one dose of randomized study medication. All analyses on this set were based on the treatment received. Safety Analysis Set (SAF) for Safety study part: included all subjects who received at least one dose of study medication.
A summary of the Final/Consensus diagnosis of endometrial biopsies across all post-baseline visits is provided. An endometrial biopsy was obtained during the Screening period and at the EOT/Early Discontinuation visit. An additional unscheduled biopsy could have been taken if a subject presented with endometrial thickness \>10 mm on TVUS, or persistent and/or recurrent bleeding. Biopsies were read by 3 independent expert pathologists as per regulatory requirements. The Final/Consensus diagnosis was defined as the concurrence of at least 2 diagnoses from the 3 pathologists, and if there was no agreement among at least 2 pathologists, the most severe pathologic diagnosis was used. The World Health Organization (WHO) classification which separates endometrial diagnoses into 6 categories (benign endometrium, simple hyperplasia, complex hyperplasia, simple atypical hyperplasia, complex atypical hyperplasia, carcinoma) was applied for the assessment of the Final/Consensus diagnosis.
Outcome measures
| Measure |
Estetrol 15 mg - Efficacy Study Part
n=93 Participants
Estetrol (E4) 15 mg oral tablet, administered once daily for up to 53 weeks
|
Estetrol 20 mg - Efficacy Study Part
n=93 Participants
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks
|
Placebo - Efficacy Study Part
n=95 Participants
Placebo was administered orally once daily for up to 53 weeks
|
Estetrol 20 mg - Safety Study Part
n=229 Participants
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Placebo -- Hysterectomized -- Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks.
|
Placebo -- Non-Hysterectomized -- Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks.
|
Estetrol 20 mg -- Hysterectomized -- Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Estetrol 20 mg -- Non-Hysterectomized -- Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
|---|---|---|---|---|---|---|---|---|
|
Number of Subjects in the Different Endometrial Categories -- (Efficacy Study Part, Safety Study Part)
Subjects with performed biopsy
|
46 Participants
|
48 Participants
|
28 Participants
|
142 Participants
|
—
|
—
|
—
|
—
|
|
Number of Subjects in the Different Endometrial Categories -- (Efficacy Study Part, Safety Study Part)
Subjects with evaluable biopsy
|
44 Participants
|
45 Participants
|
20 Participants
|
132 Participants
|
—
|
—
|
—
|
—
|
|
Number of Subjects in the Different Endometrial Categories -- (Efficacy Study Part, Safety Study Part)
Benign Endometrium
|
41 Participants
|
40 Participants
|
20 Participants
|
125 Participants
|
—
|
—
|
—
|
—
|
|
Number of Subjects in the Different Endometrial Categories -- (Efficacy Study Part, Safety Study Part)
Simple Hyperplasia Without Atypia
|
1 Participants
|
3 Participants
|
0 Participants
|
7 Participants
|
—
|
—
|
—
|
—
|
|
Number of Subjects in the Different Endometrial Categories -- (Efficacy Study Part, Safety Study Part)
Simple Hyperplasia With Atypia
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
|
Number of Subjects in the Different Endometrial Categories -- (Efficacy Study Part, Safety Study Part)
Complex Hyperplasia Without Atypia
|
1 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
|
Number of Subjects in the Different Endometrial Categories -- (Efficacy Study Part, Safety Study Part)
Complex Hyperplasia With Atypia
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
|
Number of Subjects in the Different Endometrial Categories -- (Efficacy Study Part, Safety Study Part)
Carcinoma
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Cycle 1,2,3,4,5,6,7,8,9,10,11,12,13Population: Safety Analysis Set (SAF) for Efficacy study part: included all subjects who received at least one dose of randomized study medication. All analyses on this set were based on the treatment received. Safety Analysis Set (SAF) for Safety study part: included all subjects who received at least one dose of study medication.
Frequency (percentage) of non-hysterectomized participants with vaginal bleeding and/or spotting during each 28-day cycle of treatment with E4, based on the subject diary (Efficacy study part and Safety study part). Vaginal bleeding was daily recorded by the participant in the diary. Absence or occurrence of vaginal bleeding/ spotting was assessed using the scale below: 0=Absence of vaginal bleeding or spotting; 1=Spotting: evidence of minimal blood loss requiring none or at most one pad, tampon or panty liner per day; 2=Bleeding: evidence of blood loss requiring more than one pad, tampon or panty liner per day.
Outcome measures
| Measure |
Estetrol 15 mg - Efficacy Study Part
n=93 Participants
Estetrol (E4) 15 mg oral tablet, administered once daily for up to 53 weeks
|
Estetrol 20 mg - Efficacy Study Part
n=93 Participants
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks
|
Placebo - Efficacy Study Part
n=95 Participants
Placebo was administered orally once daily for up to 53 weeks
|
Estetrol 20 mg - Safety Study Part
n=229 Participants
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Placebo -- Hysterectomized -- Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks.
|
Placebo -- Non-Hysterectomized -- Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks.
|
Estetrol 20 mg -- Hysterectomized -- Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Estetrol 20 mg -- Non-Hysterectomized -- Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
|---|---|---|---|---|---|---|---|---|
|
Vaginal Bleeding and/or Spotting During Each 28-day Cycle of Treatment With E4 -- (Efficacy Study Part, Safety Study Part)
1_Cycle 13 Subjects with any bleeding and/or spotting during the cycle
|
6.5 percentage of participants
|
16.7 percentage of participants
|
2.4 percentage of participants
|
23.8 percentage of participants
|
—
|
—
|
—
|
—
|
|
Vaginal Bleeding and/or Spotting During Each 28-day Cycle of Treatment With E4 -- (Efficacy Study Part, Safety Study Part)
1_Cycle 1 Subjects with any bleeding and/or spotting during the cycle
|
9.4 percentage of participants
|
13.6 percentage of participants
|
5.6 percentage of participants
|
12.3 percentage of participants
|
—
|
—
|
—
|
—
|
|
Vaginal Bleeding and/or Spotting During Each 28-day Cycle of Treatment With E4 -- (Efficacy Study Part, Safety Study Part)
2_Cycle 1 Subjects with spotting only during the cycle
|
5.9 percentage of participants
|
13.6 percentage of participants
|
4.5 percentage of participants
|
8.4 percentage of participants
|
—
|
—
|
—
|
—
|
|
Vaginal Bleeding and/or Spotting During Each 28-day Cycle of Treatment With E4 -- (Efficacy Study Part, Safety Study Part)
1_Cycle 2 Subjects with any bleeding and/or spotting during the cycle
|
23.8 percentage of participants
|
37.3 percentage of participants
|
7.2 percentage of participants
|
42.3 percentage of participants
|
—
|
—
|
—
|
—
|
|
Vaginal Bleeding and/or Spotting During Each 28-day Cycle of Treatment With E4 -- (Efficacy Study Part, Safety Study Part)
2_Cycle 2 Subjects with spotting only during the cycle
|
13.1 percentage of participants
|
25.3 percentage of participants
|
4.8 percentage of participants
|
11.4 percentage of participants
|
—
|
—
|
—
|
—
|
|
Vaginal Bleeding and/or Spotting During Each 28-day Cycle of Treatment With E4 -- (Efficacy Study Part, Safety Study Part)
1_Cycle 3 Subjects with any bleeding and/or spotting during the cycle
|
36.7 percentage of participants
|
50.6 percentage of participants
|
1.3 percentage of participants
|
59.2 percentage of participants
|
—
|
—
|
—
|
—
|
|
Vaginal Bleeding and/or Spotting During Each 28-day Cycle of Treatment With E4 -- (Efficacy Study Part, Safety Study Part)
2_Cycle 3 Subjects with spotting only during the cycle
|
10.1 percentage of participants
|
19.5 percentage of participants
|
0.0 percentage of participants
|
19.7 percentage of participants
|
—
|
—
|
—
|
—
|
|
Vaginal Bleeding and/or Spotting During Each 28-day Cycle of Treatment With E4 -- (Efficacy Study Part, Safety Study Part)
1_Cycle 4 Subjects with any bleeding and/or spotting during the cycle
|
31.0 percentage of participants
|
46.3 percentage of participants
|
2.9 percentage of participants
|
55.6 percentage of participants
|
—
|
—
|
—
|
—
|
|
Vaginal Bleeding and/or Spotting During Each 28-day Cycle of Treatment With E4 -- (Efficacy Study Part, Safety Study Part)
2_Cycle 4 Subjects with spotting only during the cycle
|
8.5 percentage of participants
|
16.4 percentage of participants
|
2.9 percentage of participants
|
15.4 percentage of participants
|
—
|
—
|
—
|
—
|
|
Vaginal Bleeding and/or Spotting During Each 28-day Cycle of Treatment With E4 -- (Efficacy Study Part, Safety Study Part)
1_Cycle 5 Subjects with any bleeding and/or spotting during the cycle
|
20.8 percentage of participants
|
40.4 percentage of participants
|
7.1 percentage of participants
|
48.1 percentage of participants
|
—
|
—
|
—
|
—
|
|
Vaginal Bleeding and/or Spotting During Each 28-day Cycle of Treatment With E4 -- (Efficacy Study Part, Safety Study Part)
2_Cycle 5 Subjects with spotting only during the cycle
|
6.3 percentage of participants
|
10.6 percentage of participants
|
7.1 percentage of participants
|
19.5 percentage of participants
|
—
|
—
|
—
|
—
|
|
Vaginal Bleeding and/or Spotting During Each 28-day Cycle of Treatment With E4 -- (Efficacy Study Part, Safety Study Part)
1_Cycle 6 Subjects with any bleeding and/or spotting during the cycle
|
15.9 percentage of participants
|
46.2 percentage of participants
|
1.8 percentage of participants
|
36.1 percentage of participants
|
—
|
—
|
—
|
—
|
|
Vaginal Bleeding and/or Spotting During Each 28-day Cycle of Treatment With E4 -- (Efficacy Study Part, Safety Study Part)
2_Cycle 6 Subjects with spotting only during the cycle
|
4.5 percentage of participants
|
20.5 percentage of participants
|
0.0 percentage of participants
|
19.7 percentage of participants
|
—
|
—
|
—
|
—
|
|
Vaginal Bleeding and/or Spotting During Each 28-day Cycle of Treatment With E4 -- (Efficacy Study Part, Safety Study Part)
1_Cycle 7 Subjects with any bleeding and/or spotting during the cycle
|
11.9 percentage of participants
|
25.7 percentage of participants
|
3.8 percentage of participants
|
37.7 percentage of participants
|
—
|
—
|
—
|
—
|
|
Vaginal Bleeding and/or Spotting During Each 28-day Cycle of Treatment With E4 -- (Efficacy Study Part, Safety Study Part)
2_Cycle 7 Subjects with spotting only during the cycle
|
4.8 percentage of participants
|
8.6 percentage of participants
|
3.8 percentage of participants
|
15.1 percentage of participants
|
—
|
—
|
—
|
—
|
|
Vaginal Bleeding and/or Spotting During Each 28-day Cycle of Treatment With E4 -- (Efficacy Study Part, Safety Study Part)
1_Cycle 8 Subjects with any bleeding and/or spotting during the cycle
|
17.5 percentage of participants
|
24.2 percentage of participants
|
1.9 percentage of participants
|
33.3 percentage of participants
|
—
|
—
|
—
|
—
|
|
Vaginal Bleeding and/or Spotting During Each 28-day Cycle of Treatment With E4 -- (Efficacy Study Part, Safety Study Part)
2_Cycle 8 Subjects with spotting only during the cycle
|
5.0 percentage of participants
|
3.0 percentage of participants
|
1.9 percentage of participants
|
7.1 percentage of participants
|
—
|
—
|
—
|
—
|
|
Vaginal Bleeding and/or Spotting During Each 28-day Cycle of Treatment With E4 -- (Efficacy Study Part, Safety Study Part)
1_Cycle 9 Subjects with any bleeding and/or spotting during the cycle
|
13.9 percentage of participants
|
17.2 percentage of participants
|
0.0 percentage of participants
|
31.6 percentage of participants
|
—
|
—
|
—
|
—
|
|
Vaginal Bleeding and/or Spotting During Each 28-day Cycle of Treatment With E4 -- (Efficacy Study Part, Safety Study Part)
2_Cycle 9 Subjects with spotting only during the cycle
|
2.8 percentage of participants
|
6.9 percentage of participants
|
0.0 percentage of participants
|
15.8 percentage of participants
|
—
|
—
|
—
|
—
|
|
Vaginal Bleeding and/or Spotting During Each 28-day Cycle of Treatment With E4 -- (Efficacy Study Part, Safety Study Part)
1_Cycle 10 Subjects with any bleeding and/or spotting during the cycle
|
11.4 percentage of participants
|
11.1 percentage of participants
|
0.0 percentage of participants
|
36.7 percentage of participants
|
—
|
—
|
—
|
—
|
|
Vaginal Bleeding and/or Spotting During Each 28-day Cycle of Treatment With E4 -- (Efficacy Study Part, Safety Study Part)
2_Cycle 10 Subjects with spotting only during the cycle
|
0.0 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
23.3 percentage of participants
|
—
|
—
|
—
|
—
|
|
Vaginal Bleeding and/or Spotting During Each 28-day Cycle of Treatment With E4 -- (Efficacy Study Part, Safety Study Part)
1_Cycle 11 Subjects with any bleeding and/or spotting during the cycle
|
11.1 percentage of participants
|
11.5 percentage of participants
|
2.5 percentage of participants
|
25.0 percentage of participants
|
—
|
—
|
—
|
—
|
|
Vaginal Bleeding and/or Spotting During Each 28-day Cycle of Treatment With E4 -- (Efficacy Study Part, Safety Study Part)
2_Cycle 11 Subjects with spotting only during the cycle
|
5.6 percentage of participants
|
3.8 percentage of participants
|
0.0 percentage of participants
|
17.9 percentage of participants
|
—
|
—
|
—
|
—
|
|
Vaginal Bleeding and/or Spotting During Each 28-day Cycle of Treatment With E4 -- (Efficacy Study Part, Safety Study Part)
1_Cycle 12 Subjects with any bleeding and/or spotting during the cycle
|
5.7 percentage of participants
|
16.7 percentage of participants
|
2.5 percentage of participants
|
29.6 percentage of participants
|
—
|
—
|
—
|
—
|
|
Vaginal Bleeding and/or Spotting During Each 28-day Cycle of Treatment With E4 -- (Efficacy Study Part, Safety Study Part)
2_Cycle 12 Subjects with spotting only during the cycle
|
2.9 percentage of participants
|
12.5 percentage of participants
|
2.5 percentage of participants
|
18.5 percentage of participants
|
—
|
—
|
—
|
—
|
|
Vaginal Bleeding and/or Spotting During Each 28-day Cycle of Treatment With E4 -- (Efficacy Study Part, Safety Study Part)
2_Cycle 13 Subjects with spotting only during the cycle
|
6.5 percentage of participants
|
4.2 percentage of participants
|
2.4 percentage of participants
|
19.0 percentage of participants
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Cycle 1,2,3,4,5,6,7,8,9,10,11,12,13.Population: Safety Analysis Set (SAF) for Efficacy study part: included all subjects who received at least one dose of randomized study medication. All analyses on this set based on the treatment received. Outcome assessed only in the non-hysterectomized (NH) women of SAF: n=93, 93, 95 in E4 15 mg, E4 20 mg, Placebo, respectively. Safety Analysis Set (SAF) for Safety study part: included all subjects who received at least one dose of study medication. Outcome assessed only in the NH women of SAF: n=229.
Number of days with bleeding or spotting during each 28-day cycle of treatment for non-hysterectomized (NH) subjects (Efficacy study part, Safety study part). The Overall Number of Participants Analyzed corresponds to the total number of NH participants in each study arm in the SAF. For each cycle, the number analyzed corresponds to the number of NH subjects with corresponding bleeding/spotting information available in the diary for that cycle. Women with bleeding and spotting during a cycle are counted in both the Bleeding Days and Spotting Days categories for that cycle. Vaginal bleeding was recorded daily by the participants in the diary. Absence or occurrence of vaginal bleeding/spotting was assessed using the scale below: 0=Absence of vaginal bleeding or spotting; 1=Spotting: evidence of minimal blood loss requiring none or at most one pad, tampon or panty liner per day; 2=Bleeding: evidence of blood loss requiring more than one pad, tampon or panty liner per day.
Outcome measures
| Measure |
Estetrol 15 mg - Efficacy Study Part
n=93 Participants
Estetrol (E4) 15 mg oral tablet, administered once daily for up to 53 weeks
|
Estetrol 20 mg - Efficacy Study Part
n=93 Participants
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks
|
Placebo - Efficacy Study Part
n=95 Participants
Placebo was administered orally once daily for up to 53 weeks
|
Estetrol 20 mg - Safety Study Part
n=229 Participants
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Placebo -- Hysterectomized -- Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks.
|
Placebo -- Non-Hysterectomized -- Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks.
|
Estetrol 20 mg -- Hysterectomized -- Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Estetrol 20 mg -- Non-Hysterectomized -- Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
|---|---|---|---|---|---|---|---|---|
|
Number of Days With Bleeding or Spotting by Cycle for Non-Hysterectomized Subjects (Efficacy Study Part, Safety Study Part)
Cycle 3 - Bleeding Days
|
6.0 days
Standard Deviation 4.79
|
8.8 days
Standard Deviation 6.48
|
5.0 days
Standard Deviation NA
Data available from only 1 subject.
|
1.1 days
Standard Deviation 0.34
|
—
|
—
|
—
|
—
|
|
Number of Days With Bleeding or Spotting by Cycle for Non-Hysterectomized Subjects (Efficacy Study Part, Safety Study Part)
Cycle 3 - Spotting Days
|
6.8 days
Standard Deviation 6.39
|
5.1 days
Standard Deviation 3.49
|
1.0 days
Standard Deviation NA
Data available from only 1 subject.
|
1.1 days
Standard Deviation 0.31
|
—
|
—
|
—
|
—
|
|
Number of Days With Bleeding or Spotting by Cycle for Non-Hysterectomized Subjects (Efficacy Study Part, Safety Study Part)
Cycle 4 - No Bleeding, No Spotting
|
0 days
Standard Deviation 0
|
0 days
Standard Deviation 0
|
0 days
Standard Deviation 0
|
0 days
Standard Deviation 0
|
—
|
—
|
—
|
—
|
|
Number of Days With Bleeding or Spotting by Cycle for Non-Hysterectomized Subjects (Efficacy Study Part, Safety Study Part)
Cycle 12 - No Bleeding, No Spotting
|
0 days
Standard Deviation 0
|
0 days
Standard Deviation 0
|
0 days
Standard Deviation 0
|
0 days
Standard Deviation 0
|
—
|
—
|
—
|
—
|
|
Number of Days With Bleeding or Spotting by Cycle for Non-Hysterectomized Subjects (Efficacy Study Part, Safety Study Part)
Cycle 4 - Bleeding Days
|
2.6 days
Standard Deviation 2.19
|
2.7 days
Standard Deviation 2.85
|
—
|
1.2 days
Standard Deviation 0.38
|
—
|
—
|
—
|
—
|
|
Number of Days With Bleeding or Spotting by Cycle for Non-Hysterectomized Subjects (Efficacy Study Part, Safety Study Part)
Cycle 4 - Spotting Days
|
1.9 days
Standard Deviation 1.59
|
2.1 days
Standard Deviation 1.59
|
1.0 days
Standard Deviation 0.00
|
1.2 days
Standard Deviation 0.47
|
—
|
—
|
—
|
—
|
|
Number of Days With Bleeding or Spotting by Cycle for Non-Hysterectomized Subjects (Efficacy Study Part, Safety Study Part)
Cycle 5 - No Bleeding, No Spotting
|
0 days
Standard Deviation 0
|
0 days
Standard Deviation 0
|
0 days
Standard Deviation 0
|
0 days
Standard Deviation 0
|
—
|
—
|
—
|
—
|
|
Number of Days With Bleeding or Spotting by Cycle for Non-Hysterectomized Subjects (Efficacy Study Part, Safety Study Part)
Cycle 5 - Bleeding Days
|
1.0 days
Standard Deviation 0.00
|
1.0 days
Standard Deviation 0.00
|
—
|
1.1 days
Standard Deviation 0.35
|
—
|
—
|
—
|
—
|
|
Number of Days With Bleeding or Spotting by Cycle for Non-Hysterectomized Subjects (Efficacy Study Part, Safety Study Part)
Cycle 5 - Spotting Days
|
1.0 days
Standard Deviation 0.00
|
1.0 days
Standard Deviation 0.00
|
1.0 days
Standard Deviation 0.00
|
1.1 days
Standard Deviation 0.36
|
—
|
—
|
—
|
—
|
|
Number of Days With Bleeding or Spotting by Cycle for Non-Hysterectomized Subjects (Efficacy Study Part, Safety Study Part)
Cycle 6 - No Bleeding, No Spotting
|
0 days
Standard Deviation 0
|
0 days
Standard Deviation 0
|
0 days
Standard Deviation 0
|
0 days
Standard Deviation 0
|
—
|
—
|
—
|
—
|
|
Number of Days With Bleeding or Spotting by Cycle for Non-Hysterectomized Subjects (Efficacy Study Part, Safety Study Part)
Cycle 6 - Bleeding Days
|
1.0 days
Standard Deviation 0.00
|
1.1 days
Standard Deviation 0.32
|
1.0 days
Standard Deviation NA
Data available from only 1 subject.
|
1.1 days
Standard Deviation 0.32
|
—
|
—
|
—
|
—
|
|
Number of Days With Bleeding or Spotting by Cycle for Non-Hysterectomized Subjects (Efficacy Study Part, Safety Study Part)
Cycle 6 - Spotting Days
|
1.0 days
Standard Deviation 0.00
|
1.1 days
Standard Deviation 0.24
|
1.0 days
Standard Deviation NA
Data available from only 1 subject.
|
1.1 days
Standard Deviation 0.23
|
—
|
—
|
—
|
—
|
|
Number of Days With Bleeding or Spotting by Cycle for Non-Hysterectomized Subjects (Efficacy Study Part, Safety Study Part)
Cycle 7 - No Bleeding, No Spotting
|
0 days
Standard Deviation 0
|
0 days
Standard Deviation 0
|
0 days
Standard Deviation 0
|
0 days
Standard Deviation 0
|
—
|
—
|
—
|
—
|
|
Number of Days With Bleeding or Spotting by Cycle for Non-Hysterectomized Subjects (Efficacy Study Part, Safety Study Part)
Cycle 7 - Bleeding Days
|
1.0 days
Standard Deviation 0.00
|
1.2 days
Standard Deviation 0.41
|
—
|
1.2 days
Standard Deviation 0.39
|
—
|
—
|
—
|
—
|
|
Number of Days With Bleeding or Spotting by Cycle for Non-Hysterectomized Subjects (Efficacy Study Part, Safety Study Part)
Cycle 7 - Spotting Days
|
1.0 days
Standard Deviation 0.00
|
1.1 days
Standard Deviation 0.33
|
1.0 days
Standard Deviation 0.00
|
1.2 days
Standard Deviation 0.38
|
—
|
—
|
—
|
—
|
|
Number of Days With Bleeding or Spotting by Cycle for Non-Hysterectomized Subjects (Efficacy Study Part, Safety Study Part)
Cycle 8 - No Bleeding, No Spotting
|
0 days
Standard Deviation 0
|
0 days
Standard Deviation 0
|
0 days
Standard Deviation 0
|
0 days
Standard Deviation 0
|
—
|
—
|
—
|
—
|
|
Number of Days With Bleeding or Spotting by Cycle for Non-Hysterectomized Subjects (Efficacy Study Part, Safety Study Part)
Cycle 8 - Bleeding Days
|
1.2 days
Standard Deviation 0.45
|
1.3 days
Standard Deviation 0.49
|
—
|
1.1 days
Standard Deviation 0.30
|
—
|
—
|
—
|
—
|
|
Number of Days With Bleeding or Spotting by Cycle for Non-Hysterectomized Subjects (Efficacy Study Part, Safety Study Part)
Cycle 8 - Spotting Days
|
1.2 days
Standard Deviation 0.41
|
1.4 days
Standard Deviation 0.53
|
1.0 days
Standard Deviation NA
Data available from only 1 subject.
|
1.1 days
Standard Deviation 0.28
|
—
|
—
|
—
|
—
|
|
Number of Days With Bleeding or Spotting by Cycle for Non-Hysterectomized Subjects (Efficacy Study Part, Safety Study Part)
Cycle 9 - No Bleeding, No Spotting
|
0 days
Standard Deviation 0
|
0 days
Standard Deviation 0
|
0 days
Standard Deviation 0
|
0 days
Standard Deviation 0
|
—
|
—
|
—
|
—
|
|
Number of Days With Bleeding or Spotting by Cycle for Non-Hysterectomized Subjects (Efficacy Study Part, Safety Study Part)
Cycle 9 - Bleeding Days
|
1.0 days
Standard Deviation 0.00
|
1.0 days
Standard Deviation 0.00
|
—
|
1.2 days
Standard Deviation 0.41
|
—
|
—
|
—
|
—
|
|
Number of Days With Bleeding or Spotting by Cycle for Non-Hysterectomized Subjects (Efficacy Study Part, Safety Study Part)
Cycle 9 - Spotting Days
|
1.0 days
Standard Deviation 0.00
|
1.0 days
Standard Deviation 0.00
|
—
|
1.0 days
Standard Deviation 0.00
|
—
|
—
|
—
|
—
|
|
Number of Days With Bleeding or Spotting by Cycle for Non-Hysterectomized Subjects (Efficacy Study Part, Safety Study Part)
Cycle 10 - No Bleeding, No Spotting
|
0 days
Standard Deviation 0
|
0 days
Standard Deviation 0
|
0 days
Standard Deviation 0
|
0 days
Standard Deviation 0
|
—
|
—
|
—
|
—
|
|
Number of Days With Bleeding or Spotting by Cycle for Non-Hysterectomized Subjects (Efficacy Study Part, Safety Study Part)
Cycle 10 - Bleeding Days
|
1.0 days
Standard Deviation 0.00
|
1.0 days
Standard Deviation 0.00
|
—
|
1.3 days
Standard Deviation 0.50
|
—
|
—
|
—
|
—
|
|
Number of Days With Bleeding or Spotting by Cycle for Non-Hysterectomized Subjects (Efficacy Study Part, Safety Study Part)
Cycle 10 - Spotting Days
|
1.0 days
Standard Deviation 0.00
|
1.0 days
Standard Deviation 0.00
|
—
|
1.0 days
Standard Deviation 0.00
|
—
|
—
|
—
|
—
|
|
Number of Days With Bleeding or Spotting by Cycle for Non-Hysterectomized Subjects (Efficacy Study Part, Safety Study Part)
Cycle 11 - No Bleeding, No Spotting
|
0 days
Standard Deviation 0
|
0 days
Standard Deviation 0
|
0 days
Standard Deviation 0
|
0 days
Standard Deviation 0
|
—
|
—
|
—
|
—
|
|
Number of Days With Bleeding or Spotting by Cycle for Non-Hysterectomized Subjects (Efficacy Study Part, Safety Study Part)
Cycle 11 - Bleeding Days
|
1.0 days
Standard Deviation 0.00
|
1.0 days
Standard Deviation 0.00
|
1.0 days
|
1.5 days
Standard Deviation 0.71
|
—
|
—
|
—
|
—
|
|
Number of Days With Bleeding or Spotting by Cycle for Non-Hysterectomized Subjects (Efficacy Study Part, Safety Study Part)
Cycle 11 - Spotting Days
|
1.0 days
Standard Deviation 0.00
|
1.0 days
Standard Deviation 0.00
|
1.0 days
Standard Deviation NA
Data available from only 1 subject.
|
1.1 days
Standard Deviation 0.38
|
—
|
—
|
—
|
—
|
|
Number of Days With Bleeding or Spotting by Cycle for Non-Hysterectomized Subjects (Efficacy Study Part, Safety Study Part)
Cycle 12 - Bleeding Days
|
1.0 days
Standard Deviation NA
Data available from only 1 subject.
|
1.0 days
Standard Deviation NA
Data available from only 1 subject.
|
—
|
1.3 days
Standard Deviation 0.58
|
—
|
—
|
—
|
—
|
|
Number of Days With Bleeding or Spotting by Cycle for Non-Hysterectomized Subjects (Efficacy Study Part, Safety Study Part)
Cycle 12 - Spotting Days
|
1.0 days
Standard Deviation 0.00
|
1.0 days
Standard Deviation 0.00
|
1.0 days
Standard Deviation NA
Data available from only 1 subject.
|
1.1 days
Standard Deviation 0.35
|
—
|
—
|
—
|
—
|
|
Number of Days With Bleeding or Spotting by Cycle for Non-Hysterectomized Subjects (Efficacy Study Part, Safety Study Part)
Cycle 1 - No Bleeding, No Spotting
|
0 days
Standard Deviation 0
|
0 days
Standard Deviation 0
|
0 days
Standard Deviation 0
|
0 days
Standard Deviation 0
|
—
|
—
|
—
|
—
|
|
Number of Days With Bleeding or Spotting by Cycle for Non-Hysterectomized Subjects (Efficacy Study Part, Safety Study Part)
Cycle 1 - Bleeding Days
|
3.7 days
Standard Deviation 2.08
|
—
|
4.0 days
Standard Deviation NA
Data available from only 1 subject.
|
1.0 days
Standard Deviation 0.00
|
—
|
—
|
—
|
—
|
|
Number of Days With Bleeding or Spotting by Cycle for Non-Hysterectomized Subjects (Efficacy Study Part, Safety Study Part)
Cycle 1 - Spotting Days
|
3.3 days
Standard Deviation 2.36
|
1.8 days
Standard Deviation 1.03
|
4.2 days
Standard Deviation 2.68
|
1.0 days
Standard Deviation 0.00
|
—
|
—
|
—
|
—
|
|
Number of Days With Bleeding or Spotting by Cycle for Non-Hysterectomized Subjects (Efficacy Study Part, Safety Study Part)
Cycle 2 - No Bleeding, No Spotting
|
0 days
Standard Deviation 0
|
0 days
Standard Deviation 0
|
0 days
Standard Deviation 0
|
0 days
Standard Deviation 0
|
—
|
—
|
—
|
—
|
|
Number of Days With Bleeding or Spotting by Cycle for Non-Hysterectomized Subjects (Efficacy Study Part, Safety Study Part)
Cycle 2 - Bleeding Days
|
5.3 days
Standard Deviation 4.58
|
4.2 days
Standard Deviation 1.87
|
2.0 days
Standard Deviation 1.41
|
1.1 days
Standard Deviation 0.29
|
—
|
—
|
—
|
—
|
|
Number of Days With Bleeding or Spotting by Cycle for Non-Hysterectomized Subjects (Efficacy Study Part, Safety Study Part)
Cycle 2 - Spotting Days
|
3.8 days
Standard Deviation 3.56
|
4.1 days
Standard Deviation 3.73
|
3.8 days
Standard Deviation 2.14
|
1.1 days
Standard Deviation 0.35
|
—
|
—
|
—
|
—
|
|
Number of Days With Bleeding or Spotting by Cycle for Non-Hysterectomized Subjects (Efficacy Study Part, Safety Study Part)
Cycle 3 - No Bleeding, No Spotting
|
0 days
Standard Deviation 0
|
0 days
Standard Deviation 0
|
0 days
Standard Deviation 0
|
0 days
Standard Deviation 0
|
—
|
—
|
—
|
—
|
|
Number of Days With Bleeding or Spotting by Cycle for Non-Hysterectomized Subjects (Efficacy Study Part, Safety Study Part)
Cycle 13 - No Bleeding, No Spotting
|
0 days
Standard Deviation 0
|
0 days
Standard Deviation 0
|
0 days
Standard Deviation 0
|
0 days
Standard Deviation 0
|
—
|
—
|
—
|
—
|
|
Number of Days With Bleeding or Spotting by Cycle for Non-Hysterectomized Subjects (Efficacy Study Part, Safety Study Part)
Cycle 13 - Bleeding Days
|
—
|
1.0 days
Standard Deviation 0.00
|
—
|
1.0 days
Standard Deviation NA
Data available from only 1 subject.
|
—
|
—
|
—
|
—
|
|
Number of Days With Bleeding or Spotting by Cycle for Non-Hysterectomized Subjects (Efficacy Study Part, Safety Study Part)
Cycle 13 - Spotting Days
|
1.0 days
Standard Deviation 0.00
|
1.0 days
Standard Deviation 0.00
|
1.0 days
Standard Deviation NA
Data available from only 1 subject.
|
1.2 days
Standard Deviation 0.45
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Cycle 1,2,3,4,5,6,7,8,9,10,11,12,13.Population: Safety Analysis Set (SAF) for Efficacy study part: included all subjects who received at least one dose of randomized study medication. All analyses on this set were based on the treatment received. Safety Analysis Set (SAF) for Safety study part: included all subjects who received at least one dose of study medication.
Cumulative rates of amenorrhea defined as the percentage of women who reported consecutive cycles of amenorrhea (absence of any bleeding or spotting) for a given cycle of time (Efficacy study part and Safety study part). Percentages (%) are based on the number of non-hysterectomized subjects with amenorrhea diary data available through cycle 13 in the Safety Analysis Set in each treatment arm.
Outcome measures
| Measure |
Estetrol 15 mg - Efficacy Study Part
n=82 Participants
Estetrol (E4) 15 mg oral tablet, administered once daily for up to 53 weeks
|
Estetrol 20 mg - Efficacy Study Part
n=83 Participants
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks
|
Placebo - Efficacy Study Part
n=88 Participants
Placebo was administered orally once daily for up to 53 weeks
|
Estetrol 20 mg - Safety Study Part
n=229 Participants
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Placebo -- Hysterectomized -- Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks.
|
Placebo -- Non-Hysterectomized -- Efficacy Study Part
Placebo was administered orally once daily for up to 53 weeks.
|
Estetrol 20 mg -- Hysterectomized -- Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Estetrol 20 mg -- Non-Hysterectomized -- Safety Study Part
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
|---|---|---|---|---|---|---|---|---|
|
Cumulative Rate of Amenorrhea (Absence of Any Bleeding or Spotting) During Each 28-day Cycle of Treatment With E4 -- (Efficacy Study Part, Safety Study Part)
Cycle 1-13
|
34.4 percentage of participants
|
25.8 percentage of participants
|
66.3 percentage of participants
|
18.8 percentage of participants
|
—
|
—
|
—
|
—
|
|
Cumulative Rate of Amenorrhea (Absence of Any Bleeding or Spotting) During Each 28-day Cycle of Treatment With E4 -- (Efficacy Study Part, Safety Study Part)
Cycle 2-13
|
35.5 percentage of participants
|
28.0 percentage of participants
|
66.3 percentage of participants
|
20.5 percentage of participants
|
—
|
—
|
—
|
—
|
|
Cumulative Rate of Amenorrhea (Absence of Any Bleeding or Spotting) During Each 28-day Cycle of Treatment With E4 -- (Efficacy Study Part, Safety Study Part)
Cycle 3-13
|
37.6 percentage of participants
|
31.2 percentage of participants
|
69.5 percentage of participants
|
25.3 percentage of participants
|
—
|
—
|
—
|
—
|
|
Cumulative Rate of Amenorrhea (Absence of Any Bleeding or Spotting) During Each 28-day Cycle of Treatment With E4 -- (Efficacy Study Part, Safety Study Part)
Cycle 4-13
|
40.9 percentage of participants
|
36.6 percentage of participants
|
69.5 percentage of participants
|
30.6 percentage of participants
|
—
|
—
|
—
|
—
|
|
Cumulative Rate of Amenorrhea (Absence of Any Bleeding or Spotting) During Each 28-day Cycle of Treatment With E4 -- (Efficacy Study Part, Safety Study Part)
Cycle 5-13
|
44.1 percentage of participants
|
37.6 percentage of participants
|
70.5 percentage of participants
|
32.3 percentage of participants
|
—
|
—
|
—
|
—
|
|
Cumulative Rate of Amenorrhea (Absence of Any Bleeding or Spotting) During Each 28-day Cycle of Treatment With E4 -- (Efficacy Study Part, Safety Study Part)
Cycle 6-13
|
45.2 percentage of participants
|
37.6 percentage of participants
|
71.6 percentage of participants
|
33.6 percentage of participants
|
—
|
—
|
—
|
—
|
|
Cumulative Rate of Amenorrhea (Absence of Any Bleeding or Spotting) During Each 28-day Cycle of Treatment With E4 -- (Efficacy Study Part, Safety Study Part)
Cycle 7-13
|
46.2 percentage of participants
|
41.9 percentage of participants
|
71.6 percentage of participants
|
33.6 percentage of participants
|
—
|
—
|
—
|
—
|
|
Cumulative Rate of Amenorrhea (Absence of Any Bleeding or Spotting) During Each 28-day Cycle of Treatment With E4 -- (Efficacy Study Part, Safety Study Part)
Cycle 8-13
|
46.2 percentage of participants
|
44.1 percentage of participants
|
74.7 percentage of participants
|
34.9 percentage of participants
|
—
|
—
|
—
|
—
|
|
Cumulative Rate of Amenorrhea (Absence of Any Bleeding or Spotting) During Each 28-day Cycle of Treatment With E4 -- (Efficacy Study Part, Safety Study Part)
Cycle 9-13
|
46.2 percentage of participants
|
45.2 percentage of participants
|
77.9 percentage of participants
|
35.4 percentage of participants
|
—
|
—
|
—
|
—
|
|
Cumulative Rate of Amenorrhea (Absence of Any Bleeding or Spotting) During Each 28-day Cycle of Treatment With E4 -- (Efficacy Study Part, Safety Study Part)
Cycle 10-13
|
49.5 percentage of participants
|
46.2 percentage of participants
|
77.9 percentage of participants
|
35.8 percentage of participants
|
—
|
—
|
—
|
—
|
|
Cumulative Rate of Amenorrhea (Absence of Any Bleeding or Spotting) During Each 28-day Cycle of Treatment With E4 -- (Efficacy Study Part, Safety Study Part)
Cycle 11-13
|
52.7 percentage of participants
|
46.2 percentage of participants
|
77.9 percentage of participants
|
36.7 percentage of participants
|
—
|
—
|
—
|
—
|
|
Cumulative Rate of Amenorrhea (Absence of Any Bleeding or Spotting) During Each 28-day Cycle of Treatment With E4 -- (Efficacy Study Part, Safety Study Part)
Cycle 12-13
|
53.8 percentage of participants
|
46.2 percentage of participants
|
81.1 percentage of participants
|
36.7 percentage of participants
|
—
|
—
|
—
|
—
|
|
Cumulative Rate of Amenorrhea (Absence of Any Bleeding or Spotting) During Each 28-day Cycle of Treatment With E4 -- (Efficacy Study Part, Safety Study Part)
Cycle 13
|
53.8 percentage of participants
|
46.2 percentage of participants
|
83.2 percentage of participants
|
37.1 percentage of participants
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants).Population: Safety Analysis Set (SAF) for Efficacy study part: included all randomized subjects who received at least one dose of randomized study medication. All analyses on this set were based on the treatment received. Safety Analysis Set (SAF) for Safety study part: included all subjects who received at least one dose of study medication.
Number of participants with SAEs belonging to the system organ class (SOC) 'Reproductive system and breast disorders' or with preferred term (PT) 'Abdominal Pain', by hysterectomy status (hysterectomized and non-hysterectomized); Efficacy Study Part and Safety Study Part. Adverse events (AEs) are defined as occurring from time of first IMP intake until last visit or any event already present that worsens (in either intensity or frequency) after exposure to the treatment. AEs in SOC 'Reproductive System and Breast Disorders' or with PT 'Abdominal Pain' were reported separately for non-hysterectomized (NH) and hysterectomized women. For endometrial protection, NH women received commercially available P4 200 mg once daily for 14 consecutive days, after completing the E4/placebo treatment. All AEs were collected until the last visit, including the period of P4 intake, and reported grouped by arm (ESP: E4 15 mg/E4 20 mg/Placebo; SSP: E4 20 mg).
Outcome measures
| Measure |
Estetrol 15 mg - Efficacy Study Part
n=99 Participants
Estetrol (E4) 15 mg oral tablet, administered once daily for up to 53 weeks
|
Estetrol 20 mg - Efficacy Study Part
n=93 Participants
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks
|
Placebo - Efficacy Study Part
n=100 Participants
Placebo was administered orally once daily for up to 53 weeks
|
Estetrol 20 mg - Safety Study Part
n=93 Participants
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Placebo -- Hysterectomized -- Efficacy Study Part
n=99 Participants
Placebo was administered orally once daily for up to 53 weeks.
|
Placebo -- Non-Hysterectomized -- Efficacy Study Part
n=95 Participants
Placebo was administered orally once daily for up to 53 weeks.
|
Estetrol 20 mg -- Hysterectomized -- Safety Study Part
n=201 Participants
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Estetrol 20 mg -- Non-Hysterectomized -- Safety Study Part
n=229 Participants
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
|---|---|---|---|---|---|---|---|---|
|
Number of Participants With Serious Adverse Events (SAE) in SOC 'Reproductive System and Breast Disorders' or With PT 'Abdominal Pain' by Hysterectomy Status (Hysterectomized and Non-Hysterectomized) -- (Efficacy Study Part, Safety Study Part)
Reproductive System and Breast Disorders
|
0 Participants
|
15 Participants
|
0 Participants
|
20 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
53 Participants
|
|
Number of Participants With Serious Adverse Events (SAE) in SOC 'Reproductive System and Breast Disorders' or With PT 'Abdominal Pain' by Hysterectomy Status (Hysterectomized and Non-Hysterectomized) -- (Efficacy Study Part, Safety Study Part)
Ovarian vein thrombosis
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Serious Adverse Events (SAE) in SOC 'Reproductive System and Breast Disorders' or With PT 'Abdominal Pain' by Hysterectomy Status (Hysterectomized and Non-Hysterectomized) -- (Efficacy Study Part, Safety Study Part)
Endometrial disorder
|
0 Participants
|
12 Participants
|
0 Participants
|
12 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
45 Participants
|
|
Number of Participants With Serious Adverse Events (SAE) in SOC 'Reproductive System and Breast Disorders' or With PT 'Abdominal Pain' by Hysterectomy Status (Hysterectomized and Non-Hysterectomized) -- (Efficacy Study Part, Safety Study Part)
Endometrial hyperplasia
|
0 Participants
|
3 Participants
|
0 Participants
|
8 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
6 Participants
|
|
Number of Participants With Serious Adverse Events (SAE) in SOC 'Reproductive System and Breast Disorders' or With PT 'Abdominal Pain' by Hysterectomy Status (Hysterectomized and Non-Hysterectomized) -- (Efficacy Study Part, Safety Study Part)
Vaginal haemorrhage
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
3 Participants
|
SECONDARY outcome
Timeframe: Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants).Population: Safety Analysis Set (SAF) for Efficacy study part: included all randomized subjects who received at least one dose of randomized study medication. All analyses on this set were based on the treatment received. Safety Analysis Set (SAF) for Safety study part: included all subjects who received at least one dose of study medication.
Number of participants with non-serious AEs at 2% threshold in any treatment group in the system organ class (SOC) 'Reproductive system and breast disorders' or with preferred term (PT) 'Abdominal Pain', during the Efficacy Study Part and the Safety Study Part. Adverse events (AEs) are defined as occurring from time of first IMP intake until last visit or any event already present that worsens (in either intensity or frequency) after exposure to the treatment. AEs in SOC 'Reproductive System and Breast Disorders' or with PT 'Abdominal Pain' were reported separately for non-hysterectomized (NH) and hysterectomized women. For endometrial protection, NH women received commercially available P4 200 mg once daily for 14 consecutive days, after completing the E4/placebo treatment. All AEs were collected until the last visit, including the period of P4 intake, and reported grouped by arm (ESP: E4 15 mg/E4 20 mg/Placebo; SSP: E4 20 mg).
Outcome measures
| Measure |
Estetrol 15 mg - Efficacy Study Part
n=93 Participants
Estetrol (E4) 15 mg oral tablet, administered once daily for up to 53 weeks
|
Estetrol 20 mg - Efficacy Study Part
n=99 Participants
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks
|
Placebo - Efficacy Study Part
n=93 Participants
Placebo was administered orally once daily for up to 53 weeks
|
Estetrol 20 mg - Safety Study Part
n=100 Participants
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Placebo -- Hysterectomized -- Efficacy Study Part
n=95 Participants
Placebo was administered orally once daily for up to 53 weeks.
|
Placebo -- Non-Hysterectomized -- Efficacy Study Part
n=99 Participants
Placebo was administered orally once daily for up to 53 weeks.
|
Estetrol 20 mg -- Hysterectomized -- Safety Study Part
n=229 Participants
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Estetrol 20 mg -- Non-Hysterectomized -- Safety Study Part
n=201 Participants
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
|---|---|---|---|---|---|---|---|---|
|
Number of Participants With Non-serious Adverse Events (AEs) in SOC 'Reproductive System and Breast Disorders' or With PT 'Abdominal Pain' by Hysterectomy Status -- (Efficacy Study Part, Safety Study Part)
Reproductive system and breast disorders
|
43 Participants
|
25 Participants
|
52 Participants
|
22 Participants
|
12 Participants
|
9 Participants
|
166 Participants
|
57 Participants
|
|
Number of Participants With Non-serious Adverse Events (AEs) in SOC 'Reproductive System and Breast Disorders' or With PT 'Abdominal Pain' by Hysterectomy Status -- (Efficacy Study Part, Safety Study Part)
Vaginal haemorrhage
|
28 Participants
|
0 Participants
|
35 Participants
|
0 Participants
|
5 Participants
|
0 Participants
|
103 Participants
|
1 Participants
|
|
Number of Participants With Non-serious Adverse Events (AEs) in SOC 'Reproductive System and Breast Disorders' or With PT 'Abdominal Pain' by Hysterectomy Status -- (Efficacy Study Part, Safety Study Part)
Endometrial thickening
|
15 Participants
|
0 Participants
|
18 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
59 Participants
|
0 Participants
|
|
Number of Participants With Non-serious Adverse Events (AEs) in SOC 'Reproductive System and Breast Disorders' or With PT 'Abdominal Pain' by Hysterectomy Status -- (Efficacy Study Part, Safety Study Part)
Endometrial disorder
|
9 Participants
|
0 Participants
|
11 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
40 Participants
|
0 Participants
|
|
Number of Participants With Non-serious Adverse Events (AEs) in SOC 'Reproductive System and Breast Disorders' or With PT 'Abdominal Pain' by Hysterectomy Status -- (Efficacy Study Part, Safety Study Part)
Breast tenderness
|
7 Participants
|
15 Participants
|
10 Participants
|
14 Participants
|
0 Participants
|
6 Participants
|
34 Participants
|
28 Participants
|
|
Number of Participants With Non-serious Adverse Events (AEs) in SOC 'Reproductive System and Breast Disorders' or With PT 'Abdominal Pain' by Hysterectomy Status -- (Efficacy Study Part, Safety Study Part)
Vaginal discharge
|
7 Participants
|
2 Participants
|
1 Participants
|
2 Participants
|
1 Participants
|
0 Participants
|
14 Participants
|
5 Participants
|
|
Number of Participants With Non-serious Adverse Events (AEs) in SOC 'Reproductive System and Breast Disorders' or With PT 'Abdominal Pain' by Hysterectomy Status -- (Efficacy Study Part, Safety Study Part)
Uterine haemorrhage
|
4 Participants
|
0 Participants
|
4 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
11 Participants
|
0 Participants
|
|
Number of Participants With Non-serious Adverse Events (AEs) in SOC 'Reproductive System and Breast Disorders' or With PT 'Abdominal Pain' by Hysterectomy Status -- (Efficacy Study Part, Safety Study Part)
Uterine spasm
|
2 Participants
|
0 Participants
|
4 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
15 Participants
|
0 Participants
|
|
Number of Participants With Non-serious Adverse Events (AEs) in SOC 'Reproductive System and Breast Disorders' or With PT 'Abdominal Pain' by Hysterectomy Status -- (Efficacy Study Part, Safety Study Part)
Ovarian cyst
|
0 Participants
|
1 Participants
|
2 Participants
|
1 Participants
|
3 Participants
|
1 Participants
|
0 Participants
|
2 Participants
|
|
Number of Participants With Non-serious Adverse Events (AEs) in SOC 'Reproductive System and Breast Disorders' or With PT 'Abdominal Pain' by Hysterectomy Status -- (Efficacy Study Part, Safety Study Part)
Endometrial hyperplasia
|
1 Participants
|
0 Participants
|
3 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
4 Participants
|
0 Participants
|
|
Number of Participants With Non-serious Adverse Events (AEs) in SOC 'Reproductive System and Breast Disorders' or With PT 'Abdominal Pain' by Hysterectomy Status -- (Efficacy Study Part, Safety Study Part)
Nipple pain
|
2 Participants
|
3 Participants
|
2 Participants
|
4 Participants
|
0 Participants
|
2 Participants
|
14 Participants
|
14 Participants
|
|
Number of Participants With Non-serious Adverse Events (AEs) in SOC 'Reproductive System and Breast Disorders' or With PT 'Abdominal Pain' by Hysterectomy Status -- (Efficacy Study Part, Safety Study Part)
Menopausal symptoms
|
2 Participants
|
1 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
4 Participants
|
3 Participants
|
|
Number of Participants With Non-serious Adverse Events (AEs) in SOC 'Reproductive System and Breast Disorders' or With PT 'Abdominal Pain' by Hysterectomy Status -- (Efficacy Study Part, Safety Study Part)
Vulvovaginal discomfort
|
2 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Non-serious Adverse Events (AEs) in SOC 'Reproductive System and Breast Disorders' or With PT 'Abdominal Pain' by Hysterectomy Status -- (Efficacy Study Part, Safety Study Part)
Breast pain
|
0 Participants
|
2 Participants
|
1 Participants
|
2 Participants
|
0 Participants
|
1 Participants
|
2 Participants
|
7 Participants
|
|
Number of Participants With Non-serious Adverse Events (AEs) in SOC 'Reproductive System and Breast Disorders' or With PT 'Abdominal Pain' by Hysterectomy Status -- (Efficacy Study Part, Safety Study Part)
Breast discomfort
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
2 Participants
|
5 Participants
|
|
Number of Participants With Non-serious Adverse Events (AEs) in SOC 'Reproductive System and Breast Disorders' or With PT 'Abdominal Pain' by Hysterectomy Status -- (Efficacy Study Part, Safety Study Part)
Gastrointestinal disorders / PT Abdominal pain lower
|
0 Participants
|
1 Participants
|
0 Participants
|
3 Participants
|
0 Participants
|
1 Participants
|
4 Participants
|
0 Participants
|
|
Number of Participants With Non-serious Adverse Events (AEs) in SOC 'Reproductive System and Breast Disorders' or With PT 'Abdominal Pain' by Hysterectomy Status -- (Efficacy Study Part, Safety Study Part)
Gastrointestinal disorders / PT Abdominal pain
|
2 Participants
|
2 Participants
|
3 Participants
|
2 Participants
|
2 Participants
|
0 Participants
|
17 Participants
|
3 Participants
|
|
Number of Participants With Non-serious Adverse Events (AEs) in SOC 'Reproductive System and Breast Disorders' or With PT 'Abdominal Pain' by Hysterectomy Status -- (Efficacy Study Part, Safety Study Part)
Gastrointestinal disorders / PT Abdominal pain upper
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
2 Participants
|
0 Participants
|
0 Participants
|
Adverse Events
Estetrol 15 mg - Efficacy Part
Serious events: 21 serious events
Other events: 125 other events
Deaths: 1 deaths
Estetrol 20 mg - Efficacy Part
Serious events: 21 serious events
Other events: 126 other events
Deaths: 0 deaths
Placebo - Efficacy Part
Serious events: 3 serious events
Other events: 98 other events
Deaths: 0 deaths
Estetrol 20 mg - Safety Part
Serious events: 60 serious events
Other events: 309 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Estetrol 15 mg - Efficacy Part
n=192 participants at risk
Estetrol (E4) 15 mg oral tablet, administered once daily for up to 53 weeks.
|
Estetrol 20 mg - Efficacy Part
n=193 participants at risk
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Placebo - Efficacy Part
n=194 participants at risk
Placebo was administered orally once daily for up to 53 weeks.
|
Estetrol 20 mg - Safety Part
n=430 participants at risk
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
|---|---|---|---|---|
|
Reproductive system and breast disorders
Endometrial disorder
|
6.2%
12/192 • Number of events 12 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
6.2%
12/193 • Number of events 12 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
0.00%
0/194 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
10.5%
45/430 • Number of events 46 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
|
Reproductive system and breast disorders
Endometrial hyperplasia
|
1.6%
3/192 • Number of events 3 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
4.1%
8/193 • Number of events 8 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
0.00%
0/194 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
1.4%
6/430 • Number of events 6 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
|
Reproductive system and breast disorders
Vaginal haemorrhage
|
0.00%
0/192 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
0.00%
0/193 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
0.00%
0/194 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
0.70%
3/430 • Number of events 3 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
|
Reproductive system and breast disorders
Ovarian vein thrombosis
|
0.00%
0/192 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
0.00%
0/193 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
0.00%
0/194 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
0.23%
1/430 • Number of events 1 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
|
Cardiac disorders
Angina pectoris
|
0.52%
1/192 • Number of events 1 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
0.00%
0/193 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
0.00%
0/194 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
0.00%
0/430 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
|
Cardiac disorders
Palpitations
|
0.52%
1/192 • Number of events 1 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
0.00%
0/193 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
0.00%
0/194 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
0.00%
0/430 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
|
Cardiac disorders
Acute myocardial infarction
|
0.00%
0/192 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
0.00%
0/193 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
0.00%
0/194 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
0.23%
1/430 • Number of events 1 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
|
Gastrointestinal disorders
Abdominal discomfort
|
0.52%
1/192 • Number of events 1 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
0.00%
0/193 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
0.00%
0/194 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
0.00%
0/430 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
|
Gastrointestinal disorders
Large intestine perforation
|
0.00%
0/192 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
0.00%
0/193 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
0.52%
1/194 • Number of events 1 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
0.00%
0/430 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
|
Infections and infestations
COVID-19
|
0.52%
1/192 • Number of events 1 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
0.00%
0/193 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
0.00%
0/194 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
0.00%
0/430 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
|
Infections and infestations
Gastroenteritis
|
0.52%
1/192 • Number of events 1 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
0.00%
0/193 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
0.00%
0/194 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
0.00%
0/430 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
|
Infections and infestations
Kidney infection
|
0.00%
0/192 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
0.00%
0/193 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
0.00%
0/194 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
0.23%
1/430 • Number of events 1 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
|
Infections and infestations
Pneumonia
|
0.00%
0/192 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
0.00%
0/193 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
0.00%
0/194 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
0.23%
1/430 • Number of events 1 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
|
Injury, poisoning and procedural complications
Limb injury
|
0.52%
1/192 • Number of events 1 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
0.00%
0/193 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
0.00%
0/194 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
0.00%
0/430 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
|
Injury, poisoning and procedural complications
Road traffic accident
|
0.52%
1/192 • Number of events 1 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
0.00%
0/193 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
0.00%
0/194 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
0.00%
0/430 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma gastric
|
0.52%
1/192 • Number of events 1 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
0.00%
0/193 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
0.00%
0/194 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
0.00%
0/430 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Intraductal proliferative breast lesion
|
0.00%
0/192 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
0.52%
1/193 • Number of events 1 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
0.00%
0/194 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
0.00%
0/430 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Papillary thyroid cancer
|
0.00%
0/192 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
0.00%
0/193 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
0.00%
0/194 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
0.23%
1/430 • Number of events 1 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
|
Hepatobiliary disorders
Cholecystitis acute
|
0.00%
0/192 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
0.00%
0/193 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
0.52%
1/194 • Number of events 1 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
0.00%
0/430 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
|
Immune system disorders
Drug hypersensitivity
|
0.52%
1/192 • Number of events 1 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
0.00%
0/193 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
0.00%
0/194 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
0.00%
0/430 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/192 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
0.00%
0/193 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
0.52%
1/194 • Number of events 1 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
0.00%
0/430 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
0.00%
0/192 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
0.00%
0/193 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
0.00%
0/194 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
0.23%
1/430 • Number of events 2 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
|
Vascular disorders
Deep vein thrombosis
|
0.00%
0/192 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
0.00%
0/193 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
0.00%
0/194 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
0.23%
1/430 • Number of events 1 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
|
Vascular disorders
Superficial vein thrombosis
|
0.00%
0/192 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
0.00%
0/193 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
0.00%
0/194 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
0.23%
1/430 • Number of events 1 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/192 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
0.00%
0/193 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
0.00%
0/194 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
0.23%
1/430 • Number of events 1 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
|
General disorders
Non-cardiac chest pain
|
0.00%
0/192 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
0.00%
0/193 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
0.00%
0/194 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
0.23%
1/430 • Number of events 1 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
Other adverse events
| Measure |
Estetrol 15 mg - Efficacy Part
n=192 participants at risk
Estetrol (E4) 15 mg oral tablet, administered once daily for up to 53 weeks.
|
Estetrol 20 mg - Efficacy Part
n=193 participants at risk
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
Placebo - Efficacy Part
n=194 participants at risk
Placebo was administered orally once daily for up to 53 weeks.
|
Estetrol 20 mg - Safety Part
n=430 participants at risk
Estetrol (E4) 20 mg oral tablet, administered once daily for up to 53 weeks.
|
|---|---|---|---|---|
|
Reproductive system and breast disorders
Vaginal haemorrhage
|
14.6%
28/192 • Number of events 47 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
18.1%
35/193 • Number of events 56 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
2.6%
5/194 • Number of events 7 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
24.2%
104/430 • Number of events 175 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
|
Reproductive system and breast disorders
Breast tenderness
|
11.5%
22/192 • Number of events 23 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
12.4%
24/193 • Number of events 24 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
3.1%
6/194 • Number of events 6 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
14.4%
62/430 • Number of events 62 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
|
Reproductive system and breast disorders
Endometrial thickening
|
7.8%
15/192 • Number of events 16 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
9.3%
18/193 • Number of events 19 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
0.52%
1/194 • Number of events 1 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
13.7%
59/430 • Number of events 59 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
|
Reproductive system and breast disorders
Endometrial disorder
|
4.7%
9/192 • Number of events 9 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
5.7%
11/193 • Number of events 11 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
0.52%
1/194 • Number of events 1 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
9.3%
40/430 • Number of events 40 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
|
Reproductive system and breast disorders
Nipple pain
|
2.6%
5/192 • Number of events 5 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
3.1%
6/193 • Number of events 6 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
1.0%
2/194 • Number of events 3 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
6.5%
28/430 • Number of events 29 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
|
Reproductive system and breast disorders
Vaginal discharge
|
4.7%
9/192 • Number of events 9 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
1.6%
3/193 • Number of events 3 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
0.52%
1/194 • Number of events 1 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
4.4%
19/430 • Number of events 19 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
|
Reproductive system and breast disorders
Ovarian cyst
|
0.52%
1/192 • Number of events 1 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
1.6%
3/193 • Number of events 3 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
2.1%
4/194 • Number of events 4 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
1.2%
5/430 • Number of events 5 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
|
Reproductive system and breast disorders
Uterine haemorrhage
|
2.1%
4/192 • Number of events 4 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
2.1%
4/193 • Number of events 4 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
0.00%
0/194 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
2.6%
11/430 • Number of events 12 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
|
Reproductive system and breast disorders
Uterine spasm
|
1.0%
2/192 • Number of events 2 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
2.1%
4/193 • Number of events 4 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
0.52%
1/194 • Number of events 1 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
3.5%
15/430 • Number of events 17 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
|
Reproductive system and breast disorders
Breast pain
|
1.0%
2/192 • Number of events 2 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
1.6%
3/193 • Number of events 3 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
0.52%
1/194 • Number of events 1 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
2.1%
9/430 • Number of events 10 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
|
Infections and infestations
COVID-19
|
1.6%
3/192 • Number of events 3 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
3.1%
6/193 • Number of events 6 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
2.6%
5/194 • Number of events 5 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
3.5%
15/430 • Number of events 15 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
|
Infections and infestations
Urinary tract infection
|
2.1%
4/192 • Number of events 6 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
2.6%
5/193 • Number of events 5 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
1.5%
3/194 • Number of events 3 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
1.4%
6/430 • Number of events 7 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
|
Infections and infestations
Sinusitis
|
2.6%
5/192 • Number of events 5 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
1.0%
2/193 • Number of events 2 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
1.5%
3/194 • Number of events 3 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
2.3%
10/430 • Number of events 10 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
|
Gastrointestinal disorders
Diarrhoea
|
2.6%
5/192 • Number of events 5 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
2.1%
4/193 • Number of events 4 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
2.1%
4/194 • Number of events 4 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
1.9%
8/430 • Number of events 8 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
|
Gastrointestinal disorders
Nausea
|
3.6%
7/192 • Number of events 8 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
2.1%
4/193 • Number of events 4 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
1.0%
2/194 • Number of events 2 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
3.5%
15/430 • Number of events 15 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
|
Gastrointestinal disorders
Abdominal pain
|
2.1%
4/192 • Number of events 4 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
2.6%
5/193 • Number of events 5 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
1.0%
2/194 • Number of events 2 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
4.7%
20/430 • Number of events 20 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
|
Gastrointestinal disorders
Constipation
|
2.1%
4/192 • Number of events 4 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
2.1%
4/193 • Number of events 5 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
1.5%
3/194 • Number of events 3 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
0.47%
2/430 • Number of events 2 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
|
Gastrointestinal disorders
Abdominal distension
|
2.1%
4/192 • Number of events 4 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
1.0%
2/193 • Number of events 2 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
1.5%
3/194 • Number of events 3 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
1.9%
8/430 • Number of events 9 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
|
Nervous system disorders
Headache
|
4.7%
9/192 • Number of events 10 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
5.2%
10/193 • Number of events 11 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
9.8%
19/194 • Number of events 21 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
5.1%
22/430 • Number of events 26 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
|
Nervous system disorders
Dizziness
|
2.6%
5/192 • Number of events 5 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
0.52%
1/193 • Number of events 1 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
1.0%
2/194 • Number of events 2 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
2.1%
9/430 • Number of events 10 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
|
Psychiatric disorders
Anxiety
|
3.1%
6/192 • Number of events 6 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
4.1%
8/193 • Number of events 8 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
4.6%
9/194 • Number of events 9 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
1.2%
5/430 • Number of events 6 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
|
Psychiatric disorders
Insomnia
|
2.6%
5/192 • Number of events 5 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
1.0%
2/193 • Number of events 2 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
0.52%
1/194 • Number of events 1 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
2.3%
10/430 • Number of events 10 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
1.6%
3/192 • Number of events 3 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
1.6%
3/193 • Number of events 3 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
3.6%
7/194 • Number of events 7 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
2.1%
9/430 • Number of events 11 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
2.1%
4/192 • Number of events 4 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
1.0%
2/193 • Number of events 2 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
1.5%
3/194 • Number of events 3 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
0.70%
3/430 • Number of events 4 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
0.52%
1/192 • Number of events 1 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
0.52%
1/193 • Number of events 1 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
1.0%
2/194 • Number of events 3 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
2.1%
9/430 • Number of events 9 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
|
Skin and subcutaneous tissue disorders
Rash
|
1.6%
3/192 • Number of events 3 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
1.6%
3/193 • Number of events 4 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
3.6%
7/194 • Number of events 7 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
0.93%
4/430 • Number of events 5 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
|
Investigations
Weight increased
|
2.6%
5/192 • Number of events 5 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
1.0%
2/193 • Number of events 2 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
3.1%
6/194 • Number of events 6 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
3.7%
16/430 • Number of events 16 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
|
Metabolism and nutrition disorders
Vitamin D deficiency
|
2.6%
5/192 • Number of events 5 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
3.1%
6/193 • Number of events 6 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
2.6%
5/194 • Number of events 5 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
0.00%
0/430 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
|
General disorders
Fatigue
|
0.00%
0/192 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
2.1%
4/193 • Number of events 5 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
3.1%
6/194 • Number of events 6 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
2.3%
10/430 • Number of events 10 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Uterine leiomyoma
|
2.1%
4/192 • Number of events 4 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
0.52%
1/193 • Number of events 1 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
0.00%
0/194 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
1.2%
5/430 • Number of events 5 • Day 1 (allocation to treatment) until Week 53 (hysterectomized participants) or Week 55/56 (non-hysterectomized participants)
AEs were reported by arm (ESP:E4 15 mg;E4 20 mg;placebo, and SSP:E4 20 mg); AEs in the SOC Reproductive System and Breast Disorders or PT Abdominal Pain were analyzed by hysterectomy status (see Secondary Outcomes 49-50). NH participants took P4 200 mg for 14 days after completion of E4/placebo treatment, for endometrial protection. AEs collected during P4 treatment were included in the E4 or placebo arm to which the participant was allocated; a separate analysis of these AEs was not performed.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60