A Survey on Efficacy and Safety in Patients With Endometriosis
Study Details
Study Description
Brief Summary
This survey is intended to collect efficacy and safety data of Duphaston® Tablets in patients with endometriosis under actual condition of its use and to obtain data for effectively and safely utilizing this drug.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
Detailed Description
In Japan, Duphaston® Tablets have appeared in 1965 for the treatment of endometriosis and been used at some medical institutions. However, after releasing of danazol in the early 1980's and gonadotropin-releasing hormone (GnRH) agonists in the late 1980's, pseudomenopause therapy became mainstream because of its high efficacy. However, pseudopregnancy therapy was recognized again due to adverse reactions associated with pseudomenopause therapy. After 2000, low-dose estrogen/progestin (LEP) combination drugs (as LEP products, ethinylestradiol/norethisterone combination drug and ethinylestradiol/drospirenone combination drug) and dienogest have been utilized as drugs that are safer and can be administered for a long time. In recent years, Duphaston® Tablets are increasing recognized again from the viewpoints of its efficacy and safety because the drug has no effect to inhibit ovulation or effect on basal body temperature, a diagnosis of ovulation and other conditions may be made by following up basal body temperature, and pregnancy may be achieved even during treatment with Duphaston. As previously mentioned, Duphaston® Tablets are an old drug, and there are only few clinical data from Japanese patients; thus, its latest clinical efficacy and safety data are being demanded again mainly by obstetrician-gynecologists.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
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. |
Drug: Dydrogesterone
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Change in the Volume of Ovarian Chocolate Cyst (If There Are Two or More Cysts, a Total Volume) [Before treatment initiation (baseline), 3 months, and 5 months.]
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."
- Volume of Ovarian Chocolate Cyst Over Time (If There Are Two or More Cysts, a Total Volume) [Before treatment initiation (baseline), 3 months, and 5 months.]
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.
- Volume of Ovarian Chocolate Cyst Over Time (If There Are Two or More Cysts, a Total Volume), Absolute Change From Baseline [Before treatment initiation (baseline), 3 months, and 5 months.]
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.
- Volume of Ovarian Chocolate Cyst Over Time (If There Are Two or More Cysts, a Total Volume), % Change From Baseline [Before treatment initiation (baseline), 3 months, and 5 months.]
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.
Secondary Outcome Measures
- Change Over Time in Dysmenorrhea Score (Total of the Dysmenorrhea Severity Score and the Analgesic Use Score) [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.
- Change Over Time in Visual Analogue Scale (VAS) for Dysmenorrhea [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".
- Change in Serum CA125 [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.
- Change Over Time in Dysmenorrhea Score (Total of the Dysmenorrhea Severity Score and the Analgesic Use Score), Difference From Baseline [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
- Change Over Time in Visual Analogue Scale (VAS) for Dysmenorrhea, Difference From Baseline [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". The difference from baseline were calculated on an individual basis and these were totalled and means ± SD calculated.
- Change Over Time in Visual Analogue Scale (VAS) for Dysmenorrhea, Change Rate From Baseline (%) [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 change rate from baseline were calculated on an individual basis and these were totalled and means ± SD calculated.
- Change in Serum CA125, Difference From Baseline [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.
- Change in Serum CA125, Change Rate From Baseline (%) [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.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Women aged 20 to < 50 years
-
Subjects with a chocolate cyst of the ovary measuring 3 cm in diameter on transvaginal ultrasonography at patient enrollment
-
Subjects with a menstrual cycle of 25 to 38 days who ovulate and are confirmed to have normal menstruation at patient enrollment
Exclusion Criteria:
-
Subjects who used GnRH agonists within 6 months before patient enrollment
-
Subjects who utilized hormone preparations containing corpus luteum hormone or estrogen as an active ingredient, low-dose contraceptive pills, middle-dose contraceptive pills, testosterone derivatives, or herbal products indicated for endometriosis within 3 months before patient enrollment
-
Subjects who received surgical treatment for endometriosis such as transvaginal alcohol fixation, laparotomy or laparoscopic surgery within 2 months before patient enrollment
-
Subjects who are pregnant or may possibly be pregnant at patient enrollment
-
Subjects who are in breast feeding at patient enrollment
-
Subjects who are determined by the investigator/subinvestigator to be not suitable for the subjects of the survey because of other reasons
-
Subjects with liver disorder or liver disease
-
Subjects with known hypersensitivity to the active substance or to any of the excipients
-
Subjects with known or suspected progestogen dependent neoplasms (e.g. meningioma)
-
Subjects with undiagnosed vaginal bleeding
-
Subjects with a past or current history of heart or kidney disease
-
Subjects with porphyria
-
Subjects with depression
-
Subjects with abnormal liver function values caused by acute or chronic liver disease
-
Subjects with rare hereditary problems of galactose intolerance, Lapp lactase deficiency or glucosegalactose malabsorption
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Mylan Investigational Site G | Tokyo | Chiyodaku | Japan | 101-0062 |
2 | Mylan Investigational Site N | Tokyo | Chuouku | Japan | 104-8560 |
3 | Mylan Investigational Site C | Kyoto | Fushimiku | Japan | 612-0064 |
4 | Mylan Investigational Site D | Saitama | Iwatsukiku | Japan | 339-0057 |
5 | Mylan Investigational Site M | Okayama | Kurashikishi | Japan | 710-0824 |
6 | Mylan Investigational Site H | Kyoto | Kyotanabeshi | Japan | 610-0357 |
7 | Mylan Investigational Site A | Kamigyo-ku | Kyoto | Japan | 602-8566 |
8 | Mylan Investigational Site I | Kyoto | Nakagyoku | Japan | 604-0965 |
9 | Mylan Investigational Site K | Kyoto | Nakagyoku | Japan | 604-8381 |
10 | Mylan Investigational Site F | Kyoto | Nakagyoku | Japan | 604-8453 |
11 | Mylan Investigational Site J | Tokyo | Shibuyaku | Japan | 151-0051 |
12 | Mylan Investigational Site B | Bunkyō | Tokyo | Japan | 113-8655 |
13 | Mylan Investigational Site E | Kyoto | Ukyouku | Japan | 615-0883 |
14 | Mylan Investigational Site L | Kyoto | Yosanocho | Japan | 629-2261 |
15 | Mylan Investigational Site O | Tokushima | Japan | 770-8503 |
Sponsors and Collaborators
- Mylan Inc.
Investigators
- Principal Investigator: Jo Kitawaki, MD., PhD., Kyoto Prefectural University of Medicine
Study Documents (Full-Text)
More Information
Publications
None provided.- DUPKST16002
Study Results
Participant Flow
Recruitment Details | |
---|---|
Pre-assignment Detail |
Arm/Group Title | Dydrogesterone |
---|---|
Arm/Group Description | 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 |
Period Title: Overall Study | |
STARTED | 60 |
COMPLETED | 42 |
NOT COMPLETED | 18 |
Baseline Characteristics
Arm/Group Title | Dydrogesterone |
---|---|
Arm/Group Description | 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 Participants | 59 |
Age (years) [Mean (Standard Deviation) ] | |
Mean (Standard Deviation) [years] |
37.1
(7.0)
|
Age, Customized (Count of Participants) | |
>= 20 and < 30 years old |
11
18.6%
|
>= 30 and < 40 years old |
21
35.6%
|
>= 40 and < 50 years old |
27
45.8%
|
Sex: Female, Male (Count of Participants) | |
Female |
59
100%
|
Male |
0
0%
|
Race (NIH/OMB) (Count of Participants) | |
American Indian or Alaska Native |
0
0%
|
Asian |
59
100%
|
Native Hawaiian or Other Pacific Islander |
0
0%
|
Black or African American |
0
0%
|
White |
0
0%
|
More than one race |
0
0%
|
Unknown or Not Reported |
0
0%
|
Region of Enrollment (participants) [Number] | |
Japan |
59
100%
|
Height (cm) [Mean (Standard Deviation) ] | |
Mean (Standard Deviation) [cm] |
159.8
(5.0)
|
Weight (kg) [Mean (Standard Deviation) ] | |
Mean (Standard Deviation) [kg] |
54.4
(9.3)
|
Menstrual cycle (days) [Mean (Standard Deviation) ] | |
Mean (Standard Deviation) [days] |
28.6
(2.3)
|
History of surgical treatment (for endometriosis) (Count of Participants) | |
No |
48
81.4%
|
Yes |
11
18.6%
|
Outcome Measures
Title | Change in the Volume of Ovarian Chocolate Cyst (If There Are Two or More Cysts, a Total Volume) |
---|---|
Description | 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." |
Time Frame | Before treatment initiation (baseline), 3 months, and 5 months. |
Outcome Measure Data
Analysis Population Description |
---|
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. |
Arm/Group Title | Dydrogesterone |
---|---|
Arm/Group Description | 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 |
Measure Participants | 52 |
Decreased |
26
44.1%
|
Unchanged |
13
22%
|
Increased |
13
22%
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Dydrogesterone |
---|---|---|
Comments | For the volume calculated from the major and minor axes of ovarian chocolate cyst, the values before treatment initiation and at last observation were compared, frequency of increase and decrease was summarized and the sign test was performed separately in the "efficacy analysis set" and "study completers." | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | =0.0533 |
Comments | ||
Method | Sign test | |
Comments |
Title | Volume of Ovarian Chocolate Cyst Over Time (If There Are Two or More Cysts, a Total Volume) |
---|---|
Description | 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. |
Time Frame | Before treatment initiation (baseline), 3 months, and 5 months. |
Outcome Measure Data
Analysis Population Description |
---|
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). |
Arm/Group Title | Dydrogesterone |
---|---|
Arm/Group Description | 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 |
Measure Participants | 57 |
Cycle -1 |
45.76
(40.70)
|
Cycle 3 |
51.97
(50.20)
|
Cycle 5 |
60.27
(109.04)
|
Title | Volume of Ovarian Chocolate Cyst Over Time (If There Are Two or More Cysts, a Total Volume), Absolute Change From Baseline |
---|---|
Description | 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. |
Time Frame | Before treatment initiation (baseline), 3 months, and 5 months. |
Outcome Measure Data
Analysis Population Description |
---|
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). |
Arm/Group Title | Cycle 3 | Cycle 5 |
---|---|---|
Arm/Group Description | 2 Cycles of dydrogesterone treatment completed | 4 Cycles of dydrogesterone treatment completed (at the completion of the observation period) |
Measure Participants | 39 | 40 |
Mean (Standard Deviation) [cm^3] |
0.04
(24.91)
|
8.48
(83.69)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Dydrogesterone |
---|---|---|
Comments | For the volume calculated from the major and minor axes of ovarian chocolate cyst (a total volume if there were two or more cysts), the value, difference from the value before treatment and change rate were calculated using the summary statistics at each measurement point and last observation in each analysis set, namely "efficacy analysis set" and "study completers," and the Wilcoxon signed-rank test was performed for the difference and change rate. | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | =0.7328 |
Comments | ||
Method | Wilcoxon (Mann-Whitney) | |
Comments |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | Cycle 5 |
---|---|---|
Comments | For the volume calculated from the major and minor axes of ovarian chocolate cyst (a total volume if there were two or more cysts), the value, difference from the value before treatment and change rate were calculated using the summary statistics at each measurement point and last observation in each analysis set, namely "efficacy analysis set" and "study completers," and the Wilcoxon signed-rank test was performed for the difference and change rate. | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | =0.1193 |
Comments | ||
Method | Wilcoxon (Mann-Whitney) | |
Comments |
Title | Volume of Ovarian Chocolate Cyst Over Time (If There Are Two or More Cysts, a Total Volume), % Change From Baseline |
---|---|
Description | 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. |
Time Frame | Before treatment initiation (baseline), 3 months, and 5 months. |
Outcome Measure Data
Analysis Population Description |
---|
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). |
Arm/Group Title | Cycle 3 | Cycle 5 |
---|---|---|
Arm/Group Description | 2 Cycles of dydrogesterone treatment completed | 4 Cycles of dydrogesterone treatment completed (at the completion of the observation period) |
Measure Participants | 39 | 40 |
Mean (Standard Deviation) [percent change] |
3.97
(46.06)
|
-6.40
(86.88)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Dydrogesterone |
---|---|---|
Comments | For the volume calculated from the major and minor axes of ovarian chocolate cyst (a total volume if there were two or more cysts), the value, difference from the value before treatment and change rate were calculated using the summary statistics at each measurement point and last observation in each analysis set, namely "efficacy analysis set" and "study completers," and the Wilcoxon signed-rank test was performed for the difference and change rate. | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.7221 |
Comments | ||
Method | Wilcoxon (Mann-Whitney) | |
Comments |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | Cycle 5 |
---|---|---|
Comments | For the volume calculated from the major and minor axes of ovarian chocolate cyst (a total volume if there were two or more cysts), the value, difference from the value before treatment and change rate were calculated using the summary statistics at each measurement point and last observation in each analysis set, namely "efficacy analysis set" and "study completers," and the Wilcoxon signed-rank test was performed for the difference and change rate. | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0861 |
Comments | ||
Method | Wilcoxon (Mann-Whitney) | |
Comments |
Title | Change Over Time in Dysmenorrhea Score (Total of the Dysmenorrhea Severity Score and the Analgesic Use Score) |
---|---|
Description | 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. |
Time Frame | Baseline, 1 month, 2 months, 3 months, 4 months, and 5 months. |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Cycle -1 | Cycle 1 | Cycle 2 | Cycle 3 | Cycle 4 | Cycle 5 |
---|---|---|---|---|---|---|
Arm/Group Description | Before treatment initiation (Baseline) | At treatment initiation (the administration could be started during menstruation of cycle 1) | 1 Cycles of dydrogesterone treatment completed | 2 Cycles of dydrogesterone treatment completed | 3 Cycles of dydrogesterone treatment completed | 4 Cycles of dydrogesterone treatment completed (at the completion of the observation period) |
Measure Participants | 57 | 57 | 52 | 50 | 45 | 42 |
Mean (Standard Deviation) [score on a scale] |
2.30
(1.89)
|
1.75
(1.83)
|
1.31
(1.67)
|
1.12
(1.42)
|
1.00
(1.38)
|
1.05
(1.40)
|
Title | Change Over Time in Visual Analogue Scale (VAS) for Dysmenorrhea |
---|---|
Description | 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". |
Time Frame | Baseline, 1 month, 2 months, 3 months, 4 months, and 5 months. |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Cycle -1 | Cycle 1 | Cycle 2 | Cycle 3 | Cycle 4 | Cycle 5 |
---|---|---|---|---|---|---|
Arm/Group Description | Before treatment initiation (Baseline) | At treatment initiation (the administration could be started during menstruation of cycle 1) | 1 Cycles of dydrogesterone treatment completed | 2 Cycles of dydrogesterone treatment completed | 3 Cycles of dydrogesterone treatment completed | 4 Cycles of dydrogesterone treatment completed (at the completion of the observation period) |
Measure Participants | 55 | 53 | 41 | 43 | 39 | 35 |
Mean (Standard Deviation) [cm] |
4.33
(2.92)
|
3.35
(2.66)
|
2.54
(2.36)
|
2.37
(2.41)
|
2.03
(2.39)
|
2.01
(2.26)
|
Title | Change in Serum CA125 |
---|---|
Description | 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. |
Time Frame | Baseline, and 5 months. |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Cycle -1 | Cycle 5 |
---|---|---|
Arm/Group Description | Before treatment initiation (Baseline) | 4 Cycles of dydrogesterone treatment completed (at the completion of the observation period) |
Measure Participants | 56 | 33 |
Mean (Standard Deviation) [U/mL] |
55.66
(70.57)
|
47.52
(47.37)
|
Title | Change Over Time in Dysmenorrhea Score (Total of the Dysmenorrhea Severity Score and the Analgesic Use Score), Difference From Baseline |
---|---|
Description | 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 |
Time Frame | Baseline, 1 month, 2 months, 3 months, 4 months, and 5 months. |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Cycle 1 | Cycle 2 | Cycle 3 | Cycle 4 | Cycle 5 |
---|---|---|---|---|---|
Arm/Group Description | At treatment initiation (the administration could be started during menstruation of cycle 1) | 1 Cycles of dydrogesterone treatment completed | 2 Cycles of dydrogesterone treatment completed | 3 Cycles of dydrogesterone treatment completed | 4 Cycles of dydrogesterone treatment completed (at the completion of the observation period) |
Measure Participants | 57 | 52 | 50 | 45 | 42 |
Mean (Standard Deviation) [score on a scale] |
-0.54
(1.45)
|
-0.90
(1.61)
|
-1.02
(1.30)
|
-0.96
(1.28)
|
-1.00
(1.47)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Dydrogesterone |
---|---|---|
Comments | The score value and difference from the value before treatment were calculated at the same points using the summary statistics, and the Wilcoxon signed-rank test was performed. | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | =0.0020 |
Comments | ||
Method | Wilcoxon (Mann-Whitney) | |
Comments |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | Cycle 5 |
---|---|---|
Comments | The score value and difference from the value before treatment were calculated at the same points using the summary statistics, and the Wilcoxon signed-rank test was performed. | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | =0.0001 |
Comments | ||
Method | Wilcoxon (Mann-Whitney) | |
Comments |
Statistical Analysis 3
Statistical Analysis Overview | Comparison Group Selection | Cycle 2 |
---|---|---|
Comments | The score value and difference from the value before treatment were calculated at the same points using the summary statistics, and the Wilcoxon signed-rank test was performed. | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | <0.0001 |
Comments | ||
Method | Wilcoxon (Mann-Whitney) | |
Comments |
Statistical Analysis 4
Statistical Analysis Overview | Comparison Group Selection | Cycle 3 |
---|---|---|
Comments | The score value and difference from the value before treatment were calculated at the same points using the summary statistics, and the Wilcoxon signed-rank test was performed. | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | <0.0001 |
Comments | ||
Method | Wilcoxon (Mann-Whitney) | |
Comments |
Statistical Analysis 5
Statistical Analysis Overview | Comparison Group Selection | Cycle 4 |
---|---|---|
Comments | The score value and difference from the value before treatment were calculated at the same points using the summary statistics, and the Wilcoxon signed-rank test was performed. | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | <0.0001 |
Comments | ||
Method | Wilcoxon (Mann-Whitney) | |
Comments |
Title | Change Over Time in Visual Analogue Scale (VAS) for Dysmenorrhea, Difference From Baseline |
---|---|
Description | 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. |
Time Frame | Baseline, 1 month, 2 months, 3 months, 4 months, and 5 months. |
Outcome Measure Data
Analysis Population Description |
---|
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 |
Arm/Group Title | Cycle 1 | Cycle 2 | Cycle 3 | Cycle 4 | Cycle 5 |
---|---|---|---|---|---|
Arm/Group Description | At treatment initiation (the administration could be started during menstruation of cycle 1) | 1 Cycles of dydrogesterone treatment completed | 2 Cycles of dydrogesterone treatment completed | 3 Cycles of dydrogesterone treatment completed | 4 Cycles of dydrogesterone treatment completed (at the completion of the observation period) |
Measure Participants | 52 | 41 | 43 | 39 | 35 |
Mean (Standard Deviation) [cm] |
-0.93
(2.24)
|
-1.61
(2.11)
|
-1.98
(2.38)
|
-1.94
(2.82)
|
-1.52
(2.18)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Dydrogesterone |
---|---|---|
Comments | The difference from the value before treatment and change rate were calculated using the summary statistics at each observation point and last observation, and the Wilcoxon signed-rank test was performed for the difference and change rate. | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | =0.0024 |
Comments | ||
Method | Wilcoxon (Mann-Whitney) | |
Comments |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | Cycle 5 |
---|---|---|
Comments | The difference from the value before treatment and change rate were calculated using the summary statistics at each observation point and last observation, and the Wilcoxon signed-rank test was performed for the difference and change rate. | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | <0.0001 |
Comments | ||
Method | Wilcoxon (Mann-Whitney) | |
Comments |
Statistical Analysis 3
Statistical Analysis Overview | Comparison Group Selection | Cycle 2 |
---|---|---|
Comments | The difference from the value before treatment and change rate were calculated using the summary statistics at each observation point and last observation, and the Wilcoxon signed-rank test was performed for the difference and change rate. | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | <0.0001 |
Comments | ||
Method | Wilcoxon (Mann-Whitney) | |
Comments |
Statistical Analysis 4
Statistical Analysis Overview | Comparison Group Selection | Cycle 3 |
---|---|---|
Comments | The difference from the value before treatment and change rate were calculated using the summary statistics at each observation point and last observation, and the Wilcoxon signed-rank test was performed for the difference and change rate. | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | <0.0001 |
Comments | ||
Method | Wilcoxon (Mann-Whitney) | |
Comments |
Statistical Analysis 5
Statistical Analysis Overview | Comparison Group Selection | Cycle 4 |
---|---|---|
Comments | The difference from the value before treatment and change rate were calculated using the summary statistics at each observation point and last observation, and the Wilcoxon signed-rank test was performed for the difference and change rate. | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | <0.0001 |
Comments | ||
Method | Wilcoxon (Mann-Whitney) | |
Comments |
Title | Change Over Time in Visual Analogue Scale (VAS) for Dysmenorrhea, Change Rate From Baseline (%) |
---|---|
Description | 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. |
Time Frame | Baseline, 1 month, 2 months, 3 months, 4 months, and 5 months. |
Outcome Measure Data
Analysis Population Description |
---|
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 |
Arm/Group Title | Cycle 1 | Cycle 2 | Cycle 3 | Cycle 4 | Cycle 5 |
---|---|---|---|---|---|
Arm/Group Description | At treatment initiation (the administration could be started during menstruation of cycle 1) | 1 Cycles of dydrogesterone treatment completed | 2 Cycles of dydrogesterone treatment completed | 3 Cycles of dydrogesterone treatment completed | 4 Cycles of dydrogesterone treatment completed (at the completion of the observation period) |
Measure Participants | 47 | 37 | 39 | 34 | 31 |
Mean (Standard Deviation) [percent change] |
-9.23
(95)
|
-33.97
(65.48)
|
-38.01
(80.00)
|
-41.24
(76.62)
|
-35.75
(79.68)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Dydrogesterone |
---|---|---|
Comments | The difference from the value before treatment and change rate were calculated using the summary statistics at each observation point and last observation, and the Wilcoxon signed-rank test was performed for the difference and change rate. | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | =0.0037 |
Comments | ||
Method | Wilcoxon (Mann-Whitney) | |
Comments |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | Cycle 5 |
---|---|---|
Comments | The difference from the value before treatment and change rate were calculated using the summary statistics at each observation point and last observation, and the Wilcoxon signed-rank test was performed for the difference and change rate. | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | <0.0001 |
Comments | ||
Method | Wilcoxon (Mann-Whitney) | |
Comments |
Statistical Analysis 3
Statistical Analysis Overview | Comparison Group Selection | Cycle 2 |
---|---|---|
Comments | The difference from the value before treatment and change rate were calculated using the summary statistics at each observation point and last observation, and the Wilcoxon signed-rank test was performed for the difference and change rate. | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | <0.0001 |
Comments | ||
Method | Wilcoxon (Mann-Whitney) | |
Comments |
Statistical Analysis 4
Statistical Analysis Overview | Comparison Group Selection | Cycle 3 |
---|---|---|
Comments | The difference from the value before treatment and change rate were calculated using the summary statistics at each observation point and last observation, and the Wilcoxon signed-rank test was performed for the difference and change rate. | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | <0.0001 |
Comments | ||
Method | Wilcoxon (Mann-Whitney) | |
Comments |
Statistical Analysis 5
Statistical Analysis Overview | Comparison Group Selection | Cycle 4 |
---|---|---|
Comments | The difference from the value before treatment and change rate were calculated using the summary statistics at each observation point and last observation, and the Wilcoxon signed-rank test was performed for the difference and change rate. | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | =0.0003 |
Comments | ||
Method | Wilcoxon (Mann-Whitney) | |
Comments |
Title | Change in Serum CA125, Difference From Baseline |
---|---|
Description | 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. |
Time Frame | Baseline, and 5 months. |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Cycle 5 |
---|---|
Arm/Group Description | 4 Cycles of dydrogesterone treatment completed (at the completion of the observation period) |
Measure Participants | 32 |
Mean (Standard Deviation) [U/mL] |
-6.47
(97.38)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Dydrogesterone |
---|---|---|
Comments | Separately in the "efficacy analysis set" and "study completers," the values before treatment initiation and at last observation were compared, the value, difference from the value before treatment and change rate were calculated using the summary statistics, and the Wilcoxon signed-rank test was performed for the difference and change rate. | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | =0.8035 |
Comments | ||
Method | Wilcoxon (Mann-Whitney) | |
Comments |
Title | Change in Serum CA125, Change Rate From Baseline (%) |
---|---|
Description | 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. |
Time Frame | Baseline, and 5 months. |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Cycle 5 |
---|---|
Arm/Group Description | 4 Cycles of dydrogesterone treatment completed (at the completion of the observation period) |
Measure Participants | 32 |
Mean (Standard Deviation) [percent change] |
38
(183.02)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Dydrogesterone |
---|---|---|
Comments | Separately in the "efficacy analysis set" and "study completers," the values before treatment initiation and at last observation were compared, the value, difference from the value before treatment and change rate were calculated using the summary statistics, and the Wilcoxon signed-rank test was performed for the difference and change rate. | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | =0.8185 |
Comments | ||
Method | Wilcoxon (Mann-Whitney) | |
Comments |
Adverse Events
Time Frame | 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) | |
---|---|---|
Adverse Event Reporting Description | 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. | |
Arm/Group Title | Dydrogesterone | |
Arm/Group Description | 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). | |
All Cause Mortality |
||
Dydrogesterone | ||
Affected / at Risk (%) | # Events | |
Total | 0/59 (0%) | |
Serious Adverse Events |
||
Dydrogesterone | ||
Affected / at Risk (%) | # Events | |
Total | 1/59 (1.7%) | |
Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||
Breast cancer | 1/59 (1.7%) | |
Other (Not Including Serious) Adverse Events |
||
Dydrogesterone | ||
Affected / at Risk (%) | # Events | |
Total | 7/59 (11.9%) | |
Gastrointestinal disorders | ||
Constipation | 1/59 (1.7%) | |
Infections and infestations | ||
Nasopharyngitis | 1/59 (1.7%) | |
Nervous system disorders | ||
Headache | 1/59 (1.7%) | |
Somnolence | 1/59 (1.7%) | |
Reproductive system and breast disorders | ||
Menorrhagia | 1/59 (1.7%) | |
Menstruation irregular | 1/59 (1.7%) | |
Metrorrhagia | 3/59 (5.1%) |
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title | Takumi Kanzo |
---|---|
Organization | Mylan EPD G.K. |
Phone | +81-3-5656-0516 |
takumi.kanzo@viatris.com |
- DUPKST16002