Trial Outcomes & Findings for A Survey on Efficacy and Safety in Patients With Endometriosis (NCT NCT02921763)

NCT ID: NCT02921763

Last Updated: 2022-07-06

Results Overview

In measurement of ovarian chocolate cyst, on a section visualizing the maximum diameter, two radial directions, namely the maximum diameter (D1) and maximum diameter (D2) orthogonal to D1, will be measured. A chocolate cyst of the ovary will be deemed as a spheroid, and its volume will be calculated using the following formula: \[(D1 + D2) × 1/2\]3 × 0.52 (π = 3.1). If there are two or more chocolate cysts of the ovary, similarly, two radial directions (D1 and D2) of each cyst will be measured. Also, each of their volumes will be calculated in the same manner. The change rate within ±15% from the total volume measured before treatment was defined as "unchanged," and the rate out of this range was defined as "decreased" or "increased."

• Recruitment status: COMPLETED
• Target enrollment: 60 participants
• Primary outcome timeframe: Before treatment initiation (baseline), 3 months, and 5 months.
• Results posted on: 2022-07-06

Participant Flow

Participant milestones

Measure	Dydrogesterone Dydrogesterone 20 mg (4 tablets) per day should be orally administered in 2 divided doses (in the morning and evening). It should be administered for 21 days; dosage starts on the 5th day of each menstrual cycle until 25th day. The administration period will be from the start of Duphaston treatment (cycle 1) to cycle 4. Dydrogesterone
Overall Study STARTED	60
Overall Study COMPLETED	42
Overall Study NOT COMPLETED	18

Reasons for withdrawal

Measure	Dydrogesterone Dydrogesterone 20 mg (4 tablets) per day should be orally administered in 2 divided doses (in the morning and evening). It should be administered for 21 days; dosage starts on the 5th day of each menstrual cycle until 25th day. The administration period will be from the start of Duphaston treatment (cycle 1) to cycle 4. Dydrogesterone
Overall Study Adverse Event	4
Overall Study Lost to Follow-up	4
Overall Study Lack of Efficacy	3
Overall Study Protocol Violation	2
Overall Study Withdrawal by Subject	2
Overall Study Physician Decision	1
Overall Study No data obtained	2

Baseline Characteristics

the corresponding data has not been acquired

Baseline characteristics by cohort

Measure	Dydrogesterone n=59 Participants Dydrogesterone 20 mg (4 tablets) per day should be orally administered in 2 divided doses (in the morning and evening). It should be administered for 21 days; dosage starts on the 5th day of each menstrual cycle until 25th day. The administration period will be from the start of Duphaston treatment (cycle 1) to cycle 4. Dydrogesterone
Age, Continuous	37.1 years STANDARD_DEVIATION 7.0 • n=59 Participants
Age, Customized >= 20 and < 30 years old	11 Participants n=59 Participants
Age, Customized >= 30 and < 40 years old	21 Participants n=59 Participants
Age, Customized >= 40 and < 50 years old	27 Participants n=59 Participants
Sex: Female, Male Female	59 Participants n=59 Participants
Sex: Female, Male Male	0 Participants n=59 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=59 Participants
Race (NIH/OMB) Asian	59 Participants n=59 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=59 Participants
Race (NIH/OMB) Black or African American	0 Participants n=59 Participants
Race (NIH/OMB) White	0 Participants n=59 Participants
Race (NIH/OMB) More than one race	0 Participants n=59 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=59 Participants
Region of Enrollment Japan	59 participants n=59 Participants
Height	159.8 cm STANDARD_DEVIATION 5.0 • n=56 Participants • the corresponding data has not been acquired
Weight	54.4 kg STANDARD_DEVIATION 9.3 • n=56 Participants • the corresponding data has not been acquired
Menstrual cycle	28.6 days STANDARD_DEVIATION 2.3 • n=59 Participants
History of surgical treatment (for endometriosis) No	48 Participants n=59 Participants
History of surgical treatment (for endometriosis) Yes	11 Participants n=59 Participants

PRIMARY outcome

Timeframe: Before treatment initiation (baseline), 3 months, and 5 months.

Population: 57 subjects were included in the efficacy analysis set. Of 57 subjects in the efficacy analysis set, changes in the volume of ovarian chocolate cyst before and after treatment in 52 subjects with values before and after Duphaston treatment.

In measurement of ovarian chocolate cyst, on a section visualizing the maximum diameter, two radial directions, namely the maximum diameter (D1) and maximum diameter (D2) orthogonal to D1, will be measured. A chocolate cyst of the ovary will be deemed as a spheroid, and its volume will be calculated using the following formula: [(D1 + D2) × 1/2]3 × 0.52 (π = 3.1). If there are two or more chocolate cysts of the ovary, similarly, two radial directions (D1 and D2) of each cyst will be measured. Also, each of their volumes will be calculated in the same manner.

The change rate within ±15% from the total volume measured before treatment was defined as "unchanged," and the rate out of this range was defined as "decreased" or "increased."

Outcome measures

Measure	Dydrogesterone n=52 Participants Dydrogesterone 20 mg (4 tablets) per day should be orally administered in 2 divided doses (in the morning and evening). It should be administered for 21 days; dosage starts on the 5th day of each menstrual cycle until 25th day. The administration period will be from the start of Duphaston treatment (cycle 1) to cycle 4. Dydrogesterone	Cycle 5 4 Cycles of dydrogesterone treatment completed (at the completion of the observation period)	Cycle 2 1 Cycles of dydrogesterone treatment completed	Cycle 3 2 Cycles of dydrogesterone treatment completed	Cycle 4 3 Cycles of dydrogesterone treatment completed	Cycle 5 4 Cycles of dydrogesterone treatment completed (at the completion of the observation period)
Change in the Volume of Ovarian Chocolate Cyst (If There Are Two or More Cysts, a Total Volume) Decreased	26 Participants	—	—	—	—	—
Change in the Volume of Ovarian Chocolate Cyst (If There Are Two or More Cysts, a Total Volume) Unchanged	13 Participants	—	—	—	—	—
Change in the Volume of Ovarian Chocolate Cyst (If There Are Two or More Cysts, a Total Volume) Increased	13 Participants	—	—	—	—	—

PRIMARY outcome

Timeframe: Before treatment initiation (baseline), 3 months, and 5 months.

Population: Of the safety analysis set (59 subjects), 57 subjects were included in the "efficacy analysis set," after excluding twe subjects (reason: one subject, use of concomitant medication indicated for endometriosis; one subject, violation of entry criteria).

In measurement of ovarian chocolate cyst, on a section visualizing the maximum diameter, two radial directions, namely the maximum diameter (D1) and maximum diameter (D2) orthogonal to D1, will be measured. A chocolate cyst of the ovary will be deemed as a spheroid, and its volume will be calculated using the following formula: [(D1 + D2) × 1/2]3 × 0.52 (π = 3.1). If there are two or more chocolate cysts of the ovary, similarly, two radial directions (D1 and D2) of each cyst will be measured. Also, each of their volumes will be calculated in the same manner.

Outcome measures

Measure	Dydrogesterone n=57 Participants Dydrogesterone 20 mg (4 tablets) per day should be orally administered in 2 divided doses (in the morning and evening). It should be administered for 21 days; dosage starts on the 5th day of each menstrual cycle until 25th day. The administration period will be from the start of Duphaston treatment (cycle 1) to cycle 4. Dydrogesterone	Cycle 5 4 Cycles of dydrogesterone treatment completed (at the completion of the observation period)	Cycle 2 1 Cycles of dydrogesterone treatment completed	Cycle 3 2 Cycles of dydrogesterone treatment completed	Cycle 4 3 Cycles of dydrogesterone treatment completed	Cycle 5 4 Cycles of dydrogesterone treatment completed (at the completion of the observation period)
Volume of Ovarian Chocolate Cyst Over Time (If There Are Two or More Cysts, a Total Volume) Cycle 3	51.97 cm^3 Standard Deviation 50.20	—	—	—	—	—
Volume of Ovarian Chocolate Cyst Over Time (If There Are Two or More Cysts, a Total Volume) Cycle -1	45.76 cm^3 Standard Deviation 40.70	—	—	—	—	—
Volume of Ovarian Chocolate Cyst Over Time (If There Are Two or More Cysts, a Total Volume) Cycle 5	60.27 cm^3 Standard Deviation 109.04	—	—	—	—	—

PRIMARY outcome

Timeframe: Before treatment initiation (baseline), 3 months, and 5 months.

Population: Of the safety analysis set (59 subjects), 57 subjects were included in the "efficacy analysis set," after excluding twe subjects (reason: one subject, use of concomitant medication indicated for endometriosis; one subject, violation of entry criteria).

The absolute change from baseline were calculated on an individual basis and these were totalled and means ± SD calculated.

For the mean value of the absolute changes shown here, the mean value of the absolute changes of the cases that could be measured at each time point is calculated. In other words, of the 57 cases with the volume value of baseline, Cycle 3 calculates the mean value of the absolute change in 39 cases with the volume value at this time, and Cycle 5 calculates the mean value of the absolute change in 40 cases with the volume value at this time.

The remaining 18 cases are excluded from this calculation because there is no volume value for Cycle 3 and the absolute change from baseline cannot be calculated. The same applies to the 17 cases of Cycle 5.

For this reason, these values cannot be calculated directly from the volume mean value at each time point shown in the result measurement 2.

Outcome measures

Measure	Dydrogesterone n=39 Participants Dydrogesterone 20 mg (4 tablets) per day should be orally administered in 2 divided doses (in the morning and evening). It should be administered for 21 days; dosage starts on the 5th day of each menstrual cycle until 25th day. The administration period will be from the start of Duphaston treatment (cycle 1) to cycle 4. Dydrogesterone	Cycle 5 n=40 Participants 4 Cycles of dydrogesterone treatment completed (at the completion of the observation period)	Cycle 2 1 Cycles of dydrogesterone treatment completed	Cycle 3 2 Cycles of dydrogesterone treatment completed	Cycle 4 3 Cycles of dydrogesterone treatment completed	Cycle 5 4 Cycles of dydrogesterone treatment completed (at the completion of the observation period)
Volume of Ovarian Chocolate Cyst Over Time (If There Are Two or More Cysts, a Total Volume), Absolute Change From Baseline	0.04 cm^3 Standard Deviation 24.91	8.48 cm^3 Standard Deviation 83.69	—	—	—	—

PRIMARY outcome

Timeframe: Before treatment initiation (baseline), 3 months, and 5 months.

Population: Of the safety analysis set (59 subjects), 57 subjects were included in the "efficacy analysis set," after excluding twe subjects (reason: one subject, use of concomitant medication indicated for endometriosis; one subject, violation of entry criteria).

The % change from baseline were calculated on an individual basis and these were totalled and means ± SD calculated.

For the mean value of the % changes shown here, the mean value of the % changes of the cases that could be measured at each time point is calculated. In other words, of the 57 cases with the volume value of baseline, Cycle 3 calculates the mean value of the % change in 39 cases with the volume value at this time, and Cycle 5 calculates the mean value of the % change in 40 cases with the volume value at this time.

The remaining 18 cases are excluded from this calculation because there is no volume value for Cycle 3 and the % change from baseline cannot be calculated. The same applies to the 17 cases of Cycle 5.

For this reason, these values cannot be calculated directly from the volume mean value at each time point shown in the result measurement 2.

Outcome measures

Measure	Dydrogesterone n=39 Participants Dydrogesterone 20 mg (4 tablets) per day should be orally administered in 2 divided doses (in the morning and evening). It should be administered for 21 days; dosage starts on the 5th day of each menstrual cycle until 25th day. The administration period will be from the start of Duphaston treatment (cycle 1) to cycle 4. Dydrogesterone	Cycle 5 n=40 Participants 4 Cycles of dydrogesterone treatment completed (at the completion of the observation period)	Cycle 2 1 Cycles of dydrogesterone treatment completed	Cycle 3 2 Cycles of dydrogesterone treatment completed	Cycle 4 3 Cycles of dydrogesterone treatment completed	Cycle 5 4 Cycles of dydrogesterone treatment completed (at the completion of the observation period)
Volume of Ovarian Chocolate Cyst Over Time (If There Are Two or More Cysts, a Total Volume), % Change From Baseline	3.97 percent change Standard Deviation 46.06	-6.40 percent change Standard Deviation 86.88	—	—	—	—

SECONDARY outcome

Timeframe: Baseline, 1 month, 2 months, 3 months, 4 months, and 5 months.

The dysmenorrhea score is the sum of the dysmenorrhea severity score and the analgesic use score. Shown as the mean value for the number of cases at each time point.

A dysmenorrhea severity score is defined as follows. None: Score 0, Rarely interfering with work (study and house work): Score 1, Interfering with work (study and house work) requiring lying down to rest: Score 2, Being confined to bed for 1 day, being unable to work (study and house work): Score 3.

A analgesic use score is defined as follows. None: Score 0, An analgesic was used for a day during the last (or current) menstruation period: Score 1, An analgesic was used for 2 days during the last (or current) menstruation period: Score 2, An analgesic was used for 3 days during the last (or current) menstruation period: Score 3 The minimum dysmenorrhea score is 0 and the maximum dysmenorrhea score is 6.

Outcome measures

Measure	Dydrogesterone n=57 Participants Dydrogesterone 20 mg (4 tablets) per day should be orally administered in 2 divided doses (in the morning and evening). It should be administered for 21 days; dosage starts on the 5th day of each menstrual cycle until 25th day. The administration period will be from the start of Duphaston treatment (cycle 1) to cycle 4. Dydrogesterone	Cycle 5 n=57 Participants 4 Cycles of dydrogesterone treatment completed (at the completion of the observation period)	Cycle 2 n=52 Participants 1 Cycles of dydrogesterone treatment completed	Cycle 3 n=50 Participants 2 Cycles of dydrogesterone treatment completed	Cycle 4 n=45 Participants 3 Cycles of dydrogesterone treatment completed	Cycle 5 n=42 Participants 4 Cycles of dydrogesterone treatment completed (at the completion of the observation period)
Change Over Time in Dysmenorrhea Score (Total of the Dysmenorrhea Severity Score and the Analgesic Use Score)	2.30 score on a scale Standard Deviation 1.89	1.75 score on a scale Standard Deviation 1.83	1.31 score on a scale Standard Deviation 1.67	1.12 score on a scale Standard Deviation 1.42	1.00 score on a scale Standard Deviation 1.38	1.05 score on a scale Standard Deviation 1.40

SECONDARY outcome

Timeframe: Baseline, 1 month, 2 months, 3 months, 4 months, and 5 months.

A straight line with a total length of 10 cm was prepared. This straight line was defined as "no pain" at the left end and "Worst pain imaginable" at the right end.

The cases marked the degree of pain on this straight line at each time point, and the length (cm) from the left end of the line (0) was measured.

The minimum value of VAS is 0 cm (no pain) and the maximum value is 10 cm (Worst pain imaginable).

The units on a scale is "cm".

Outcome measures

Measure	Dydrogesterone n=55 Participants Dydrogesterone 20 mg (4 tablets) per day should be orally administered in 2 divided doses (in the morning and evening). It should be administered for 21 days; dosage starts on the 5th day of each menstrual cycle until 25th day. The administration period will be from the start of Duphaston treatment (cycle 1) to cycle 4. Dydrogesterone	Cycle 5 n=53 Participants 4 Cycles of dydrogesterone treatment completed (at the completion of the observation period)	Cycle 2 n=41 Participants 1 Cycles of dydrogesterone treatment completed	Cycle 3 n=43 Participants 2 Cycles of dydrogesterone treatment completed	Cycle 4 n=39 Participants 3 Cycles of dydrogesterone treatment completed	Cycle 5 n=35 Participants 4 Cycles of dydrogesterone treatment completed (at the completion of the observation period)
Change Over Time in Visual Analogue Scale (VAS) for Dysmenorrhea	4.33 cm Standard Deviation 2.92	3.35 cm Standard Deviation 2.66	2.54 cm Standard Deviation 2.36	2.37 cm Standard Deviation 2.41	2.03 cm Standard Deviation 2.39	2.01 cm Standard Deviation 2.26

SECONDARY outcome

Timeframe: Baseline, and 5 months.

CA-125 is a glycoprotein antigen recognized by the monoclonal antibody OC125 made against ovarian cancer cell cultures.

Serum CA125 is commonly used as a tumor marker for ovarian cancer, and since it increases at a high rate in endometriosis, it has an aspect of being used as a diagnostic aid for endometriosis.

There are many reports that the normal value of serum CA-125 is 35 U/mL or less.

The test was performed during a non-menstruation period, as serum CA-125 levels are high during the menstrual period.

Outcome measures

Measure	Dydrogesterone n=56 Participants Dydrogesterone 20 mg (4 tablets) per day should be orally administered in 2 divided doses (in the morning and evening). It should be administered for 21 days; dosage starts on the 5th day of each menstrual cycle until 25th day. The administration period will be from the start of Duphaston treatment (cycle 1) to cycle 4. Dydrogesterone	Cycle 5 n=33 Participants 4 Cycles of dydrogesterone treatment completed (at the completion of the observation period)	Cycle 2 1 Cycles of dydrogesterone treatment completed	Cycle 3 2 Cycles of dydrogesterone treatment completed	Cycle 4 3 Cycles of dydrogesterone treatment completed	Cycle 5 4 Cycles of dydrogesterone treatment completed (at the completion of the observation period)
Change in Serum CA125	55.66 U/mL Standard Deviation 70.57	47.52 U/mL Standard Deviation 47.37	—	—	—	—

SECONDARY outcome

Timeframe: Baseline, 1 month, 2 months, 3 months, 4 months, and 5 months.

The dysmenorrhea score is the sum of the dysmenorrhea severity score and the analgesic use score.

The difference from baseline were calculated on an individual basis and these were totalled and means ± SD calculated.

A dysmenorrhea severity score is defined as follows. None: Score 0, Rarely interfering with work (study and house work): Score 1, Interfering with work (study and house work) requiring lying down to rest: Score 2, Being confined to bed for 1 day, being unable to work (study and house work): Score 3.

A score for the use of analgesics is defined as follows. None: Score 0, An analgesic was used for a day during the last (or current) menstruation period: Score 1, An analgesic was used for 2 days during the last (or current) menstruation period: Score 2, An analgesic was used for 3 days during the last (or current) menstruation period: Score 3

Outcome measures

Measure	Dydrogesterone n=57 Participants Dydrogesterone 20 mg (4 tablets) per day should be orally administered in 2 divided doses (in the morning and evening). It should be administered for 21 days; dosage starts on the 5th day of each menstrual cycle until 25th day. The administration period will be from the start of Duphaston treatment (cycle 1) to cycle 4. Dydrogesterone	Cycle 5 n=52 Participants 4 Cycles of dydrogesterone treatment completed (at the completion of the observation period)	Cycle 2 n=50 Participants 1 Cycles of dydrogesterone treatment completed	Cycle 3 n=45 Participants 2 Cycles of dydrogesterone treatment completed	Cycle 4 n=42 Participants 3 Cycles of dydrogesterone treatment completed	Cycle 5 4 Cycles of dydrogesterone treatment completed (at the completion of the observation period)
Change Over Time in Dysmenorrhea Score (Total of the Dysmenorrhea Severity Score and the Analgesic Use Score), Difference From Baseline	-0.54 score on a scale Standard Deviation 1.45	-0.90 score on a scale Standard Deviation 1.61	-1.02 score on a scale Standard Deviation 1.30	-0.96 score on a scale Standard Deviation 1.28	-1.00 score on a scale Standard Deviation 1.47	—

SECONDARY outcome

Timeframe: Baseline, 1 month, 2 months, 3 months, 4 months, and 5 months.

Population: One patient had a pain score at Cycle 1 but did not have a pain score at baseline and the absolute change could not be calculated in this instance

A straight line with a total length of 10 cm was prepared. This straight line was defined as "no pain" at the left end and "Worst pain imaginable" at the right end.

The cases marked the degree of pain on this straight line at each time point, and the length (cm) from the left end of the line (0) was measured.

The minimum value of VAS is 0 cm (no pain) and the maximum value is 10 cm (Worst pain imaginable).

The units on a scale is "cm". The difference from baseline were calculated on an individual basis and these were totalled and means ± SD calculated.

Outcome measures

Measure	Dydrogesterone n=52 Participants Dydrogesterone 20 mg (4 tablets) per day should be orally administered in 2 divided doses (in the morning and evening). It should be administered for 21 days; dosage starts on the 5th day of each menstrual cycle until 25th day. The administration period will be from the start of Duphaston treatment (cycle 1) to cycle 4. Dydrogesterone	Cycle 5 n=41 Participants 4 Cycles of dydrogesterone treatment completed (at the completion of the observation period)	Cycle 2 n=43 Participants 1 Cycles of dydrogesterone treatment completed	Cycle 3 n=39 Participants 2 Cycles of dydrogesterone treatment completed	Cycle 4 n=35 Participants 3 Cycles of dydrogesterone treatment completed	Cycle 5 4 Cycles of dydrogesterone treatment completed (at the completion of the observation period)
Change Over Time in Visual Analogue Scale (VAS) for Dysmenorrhea, Difference From Baseline	-0.93 cm Standard Deviation 2.24	-1.61 cm Standard Deviation 2.11	-1.98 cm Standard Deviation 2.38	-1.94 cm Standard Deviation 2.82	-1.52 cm Standard Deviation 2.18	—

SECONDARY outcome

Timeframe: Baseline, 1 month, 2 months, 3 months, 4 months, and 5 months.

Population: A number of patients at each timepoint had pain scores of "zero" or discontinued treatment and a % change could not be calculated in these instances

A straight line with a total length of 10 cm was prepared. This straight line was defined as "no pain" at the left end and "Worst pain imaginable" at the right end.

The cases marked the degree of pain on this straight line at each time point, and the length (cm) from the left end of the line (0) was measured.

The minimum value of VAS is 0 cm (no pain) and the maximum value is 10 cm (Worst pain imaginable).

The change rate from baseline were calculated on an individual basis and these were totalled and means ± SD calculated.

Outcome measures

Measure	Dydrogesterone n=47 Participants Dydrogesterone 20 mg (4 tablets) per day should be orally administered in 2 divided doses (in the morning and evening). It should be administered for 21 days; dosage starts on the 5th day of each menstrual cycle until 25th day. The administration period will be from the start of Duphaston treatment (cycle 1) to cycle 4. Dydrogesterone	Cycle 5 n=37 Participants 4 Cycles of dydrogesterone treatment completed (at the completion of the observation period)	Cycle 2 n=39 Participants 1 Cycles of dydrogesterone treatment completed	Cycle 3 n=34 Participants 2 Cycles of dydrogesterone treatment completed	Cycle 4 n=31 Participants 3 Cycles of dydrogesterone treatment completed	Cycle 5 4 Cycles of dydrogesterone treatment completed (at the completion of the observation period)
Change Over Time in Visual Analogue Scale (VAS) for Dysmenorrhea, Change Rate From Baseline (%)	-9.23 percent change Standard Deviation 95	-33.97 percent change Standard Deviation 65.48	-38.01 percent change Standard Deviation 80.00	-41.24 percent change Standard Deviation 76.62	-35.75 percent change Standard Deviation 79.68	—

SECONDARY outcome

Timeframe: Baseline, and 5 months.

The difference from baseline were calculated on an individual basis and these were totalled and means ± SD calculated.

For the mean value of the difference shown here, the mean value of the difference of the cases that could be measured at each time point is calculated.

In other words, of the 56 cases with baseline serum CA125, cycle 5 can only calculate the difference in 32 cases with serum CA125 at this point.

The mean difference between cycle 5 and baseline in these 32 cases is shown here.

The remaining 24 cases in Baseline are excluded from this calculation because they do not have serum CA125 measurements in Cycle 5.

For this reason, these values cannot be calculated directly from the serum CA125 mean value at each time point shown in the result measurement 7.

Outcome measures

Measure	Dydrogesterone n=32 Participants Dydrogesterone 20 mg (4 tablets) per day should be orally administered in 2 divided doses (in the morning and evening). It should be administered for 21 days; dosage starts on the 5th day of each menstrual cycle until 25th day. The administration period will be from the start of Duphaston treatment (cycle 1) to cycle 4. Dydrogesterone	Cycle 5 4 Cycles of dydrogesterone treatment completed (at the completion of the observation period)	Cycle 2 1 Cycles of dydrogesterone treatment completed	Cycle 3 2 Cycles of dydrogesterone treatment completed	Cycle 4 3 Cycles of dydrogesterone treatment completed	Cycle 5 4 Cycles of dydrogesterone treatment completed (at the completion of the observation period)
Change in Serum CA125, Difference From Baseline	-6.47 U/mL Standard Deviation 97.38	—	—	—	—	—

SECONDARY outcome

Timeframe: Baseline, and 5 months.

The change rate from baseline were calculated on an individual basis and these were totalled and means ± SD calculated.

For the mean value of the change rate shown here, the mean value of the change rate of the cases that could be measured at each time point is calculated.

In other words, of the 56 cases with baseline serum CA125, cycle 5 can only calculate the change rate in 32 cases with serum CA125 at this point.

The mean change rate between cycle 5 and baseline in these 32 cases is shown here.

The remaining 24 cases in baseline are excluded from this calculation because they do not have serum CA125 measurements in Cycle 5.

For this reason, these values cannot be calculated directly from the serum CA125 mean value at each time point shown in the result measurement 7.

Outcome measures

Measure	Dydrogesterone n=32 Participants Dydrogesterone 20 mg (4 tablets) per day should be orally administered in 2 divided doses (in the morning and evening). It should be administered for 21 days; dosage starts on the 5th day of each menstrual cycle until 25th day. The administration period will be from the start of Duphaston treatment (cycle 1) to cycle 4. Dydrogesterone	Cycle 5 4 Cycles of dydrogesterone treatment completed (at the completion of the observation period)	Cycle 2 1 Cycles of dydrogesterone treatment completed	Cycle 3 2 Cycles of dydrogesterone treatment completed	Cycle 4 3 Cycles of dydrogesterone treatment completed	Cycle 5 4 Cycles of dydrogesterone treatment completed (at the completion of the observation period)
Change in Serum CA125, Change Rate From Baseline (%)	38 percent change Standard Deviation 183.02	—	—	—	—	—

Adverse Events

Dydrogesterone

Serious events: 1 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Measure

Dydrogesterone n=59 participants at risk Dydrogesterone 20 mg (4 tablets) per day should be orally administered in 2 divided doses (in the morning and evening). It should be administered for 21 days; dosage starts on the 5th day of each menstrual cycle until 25th day. The administration period will be from the start of Duphaston treatment (cycle 1) to cycle 4. Of 60 subjects whose case report forms were collected, 59 subjects were included in the "safety analysis set," after excluding one subject (reason: one subject, no data entered).

Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer

1.7% 1/59 • AE information during the survey was collected during a period from the start of Duphaston treatment to the end of the observation period or discontinuation. Approximately 5 months in the study completers.(From date of dosage start, up to 5 months) An adverse event (AE) is any unfavorable and unintended sign (including an abnormal laboratory value), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered causally related to the drug. If an AE was noted, a follow-up investigation was performed until it resolved whenever possible. AE information during the survey was collected during a period from the start of Duphaston treatment to the end of the observation period or discontinuation.

Other adverse events

Measure	Dydrogesterone n=59 participants at risk Dydrogesterone 20 mg (4 tablets) per day should be orally administered in 2 divided doses (in the morning and evening). It should be administered for 21 days; dosage starts on the 5th day of each menstrual cycle until 25th day. The administration period will be from the start of Duphaston treatment (cycle 1) to cycle 4. Of 60 subjects whose case report forms were collected, 59 subjects were included in the "safety analysis set," after excluding one subject (reason: one subject, no data entered).
Gastrointestinal disorders Constipation	1.7% 1/59 • AE information during the survey was collected during a period from the start of Duphaston treatment to the end of the observation period or discontinuation. Approximately 5 months in the study completers.(From date of dosage start, up to 5 months) An adverse event (AE) is any unfavorable and unintended sign (including an abnormal laboratory value), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered causally related to the drug. If an AE was noted, a follow-up investigation was performed until it resolved whenever possible. AE information during the survey was collected during a period from the start of Duphaston treatment to the end of the observation period or discontinuation.
Infections and infestations Nasopharyngitis	1.7% 1/59 • AE information during the survey was collected during a period from the start of Duphaston treatment to the end of the observation period or discontinuation. Approximately 5 months in the study completers.(From date of dosage start, up to 5 months) An adverse event (AE) is any unfavorable and unintended sign (including an abnormal laboratory value), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered causally related to the drug. If an AE was noted, a follow-up investigation was performed until it resolved whenever possible. AE information during the survey was collected during a period from the start of Duphaston treatment to the end of the observation period or discontinuation.
Nervous system disorders Headache	1.7% 1/59 • AE information during the survey was collected during a period from the start of Duphaston treatment to the end of the observation period or discontinuation. Approximately 5 months in the study completers.(From date of dosage start, up to 5 months) An adverse event (AE) is any unfavorable and unintended sign (including an abnormal laboratory value), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered causally related to the drug. If an AE was noted, a follow-up investigation was performed until it resolved whenever possible. AE information during the survey was collected during a period from the start of Duphaston treatment to the end of the observation period or discontinuation.
Nervous system disorders Somnolence	1.7% 1/59 • AE information during the survey was collected during a period from the start of Duphaston treatment to the end of the observation period or discontinuation. Approximately 5 months in the study completers.(From date of dosage start, up to 5 months) An adverse event (AE) is any unfavorable and unintended sign (including an abnormal laboratory value), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered causally related to the drug. If an AE was noted, a follow-up investigation was performed until it resolved whenever possible. AE information during the survey was collected during a period from the start of Duphaston treatment to the end of the observation period or discontinuation.
Reproductive system and breast disorders Menorrhagia	1.7% 1/59 • AE information during the survey was collected during a period from the start of Duphaston treatment to the end of the observation period or discontinuation. Approximately 5 months in the study completers.(From date of dosage start, up to 5 months) An adverse event (AE) is any unfavorable and unintended sign (including an abnormal laboratory value), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered causally related to the drug. If an AE was noted, a follow-up investigation was performed until it resolved whenever possible. AE information during the survey was collected during a period from the start of Duphaston treatment to the end of the observation period or discontinuation.
Reproductive system and breast disorders Menstruation irregular	1.7% 1/59 • AE information during the survey was collected during a period from the start of Duphaston treatment to the end of the observation period or discontinuation. Approximately 5 months in the study completers.(From date of dosage start, up to 5 months) An adverse event (AE) is any unfavorable and unintended sign (including an abnormal laboratory value), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered causally related to the drug. If an AE was noted, a follow-up investigation was performed until it resolved whenever possible. AE information during the survey was collected during a period from the start of Duphaston treatment to the end of the observation period or discontinuation.
Reproductive system and breast disorders Metrorrhagia	5.1% 3/59 • AE information during the survey was collected during a period from the start of Duphaston treatment to the end of the observation period or discontinuation. Approximately 5 months in the study completers.(From date of dosage start, up to 5 months) An adverse event (AE) is any unfavorable and unintended sign (including an abnormal laboratory value), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered causally related to the drug. If an AE was noted, a follow-up investigation was performed until it resolved whenever possible. AE information during the survey was collected during a period from the start of Duphaston treatment to the end of the observation period or discontinuation.

Additional Information

Takumi Kanzo

Mylan EPD G.K.

Phone: +81-3-5656-0516

Email: takumi.kanzo@viatris.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place