Dysmenorrhea
Conditions
Keywords
Dysmenorrhea, Dysmenorrheal score, Drospirenone, DRSP, Ethinylestradiol
Brief summary
The purpose of this study is to investigate efficacy of drospirenone for dysmenorrhea.
Interventions
DRUGSH T04740B
Drospirenone 1mg/EE 20µg (ß-CDC)
DRUGSH T00186DF
Drospirenone 3 mg/EE 20µg (ß-CDC)
DRUGSH T04740F
Drospirenone 2 mg/EE 20µg (ß-CDC)
DRUGPlacebo
Placebo
Sponsors
Bayer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients aged 20 years or older at obtaining informed consent * Patients having the normal menstrual cycle (28+/-3 days) in the latest two menses before the final enrollment * Patients having a total dysmenorrhea score of at least 3 points in two menstrual cycles before the final enrollment
Exclusion criteria
* Patients with ovarian chocolate cysts and symptomatic uterine fibroids (as defined in greater detail in the study protocol) * Patients with estrogen-dependent tumors (e.g. breast cancer, cancer of the uterine body or breast fibrocystic, etc.), and patients with cervical cancer or suspected cervical cancer (e.g. class III or greater in the cervical smear or endometrial smear examination.) * Patients with undiagnosed abnormal vaginal bleeding * Patients with thrombophlebitis, pulmonary embolism, cerebrovascular disease(including transient ischemic attack, etc.), or coronary artery disease(e.g. myocardial infarction and angina pectoris, etc.), or a history of those diseases * Patients aged 35 years or older who smoke at least 15 cigarettes per day * Patients with migraine accompanied by prodrome (e.g. scintillating scotoma or star-shaped scintillation) * Patients with pulmonary hypertension or valvular heart disease complicated by atrial fibrillation, and patients with a history of subacute bacterial endocarditis * Patients who are regularly taking nutritional products that contain St. John's Wort * Patients who underwent surgical treatment for endometriosis by laparotomy, or laparoscopy within 2 months prior to screening * Patients who need to use analgesics regularly for therapeutic objectives other than relief from the pain of dysmenorrhea during this study (occasional use permitted)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Total Dysmenorrheal Score at Final Evaluation | Baseline and up to 4 Cycles (28 days per cycle) | Total dysmenorrheal score was defined as sum of 2 sub-scores: severity of dysmenorrhea (none: 0, mild: 1, moderate: 2, severe: 3) and use of analgesics (none: 0, mild: 1, moderate: 2, severe: 3). Total possible best is 0, and total possible worst is 6. Note: used with permission of Nobelpharma Co., Ltd. from the phase 3 clinical study protocol (Prog Med 2005:25 (3):739-758) of IKH-01 in dysmenorrhea (associated with endometriosis) (Nobelpharma Co., Ltd.) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Severity of Lower Abdominal Pain During Menstruation at Cycle 4 | Cycle 4 (28 days per cycle) | Severity of lower abdominal pain during menstruation was rated as none (none), mild (can be easily tolerated), moderate (noticeable, but does not interfere with daily activities), or severe (interferes with daily activities). |
| Number of Participants With Severity of Low Back Pain During Menstruation at Cycle 4 | Cycle 4 (28 days per cycle) | Severity of low back pain during menstruation was rated as none (none), mild (can be easily tolerated), moderate (noticeable, but does not interfere with daily activities), or severe (interferes with daily activities). |
| Number of Participants With Severity of Headache During Menstruation at Cycle 4 | Cycle 4 (28 days per cycle) | Severity of headache during menstruation was rated as none (none), mild (can be easily tolerated), moderate (noticeable, but does not interfere with daily activities), or severe (interferes with daily activities). |
| Number of Participants With Severity of Nausea or Vomiting During Menstruation at Cycle 4 | Cycle 4 (28 days per cycle) | Severity of nausea or vomiting during menstruation was rated as none (none), mild (can be easily tolerated), moderate (noticeable, but does not interfere with daily activities), or severe (interferes with daily activities). |
| Number of Participants With Total Pelvic Pain Score at Times Other Than During Menstruation at Cycle 4 | Cycle 4 (28 days per cycle) | Total pelvic pain score was defined as sum of 2 sub-scores: severity of dysmenorrhea and use of analgesics. Higher score means it is more severe. 0=None, 6=Severest. |
| Change From Baseline in Visual Analogue Scale (VAS) for Dysmenorrhea at Times Other Than During Menstruation at Cycle 4 | From baseline up to Cycle 4 (28 days per cycle) | VAS is an unmarked scale on a line 100 mm in length, indicating from 0 mm (no pain) to 100 mm (worst pain a participant has ever experienced). |
| Visual Analogue Scale (VAS) for Pelvic Pain at Times Other Than During Menstruation at Cycle 4 | Cycle 4 (28 days per cycle) | VAS is an unmarked scale on a line 100 mm in length, indicating from 0 mm (no pain) to 100 mm (worst pain a participant has ever experienced). |
| Change From Baseline in Endometrial Thickness After 4-cycle Treatment | From baseline to Cycle 4 (28 days per cycle) | Endometrial thickness was measured via transvaginal ultrasound examination. The endometrium is the inner membrane of the uterus. During the menstrual cycle, the endometrium grows to a thick, blood vessel-rich, glandular tissue layer. |
| Number of Bleeding / Spotting Episodes | For the first 90 days | Bleeding data were captured from the diary a participant recorded by herself. Bleeding is a genital bleeding. Spotting is a slight genital bleeding with participant's experience. An episode means a series of bleeding and/or spotting. The bleeding /spotting analyses are by intensity. |
| Change From Baseline in Total Dysmenorrheal Score at Cycle 1 up to Cycle 4 | Baseline and up to 4 Cycles (28 days per cycle) | Total dysmenorrheal score was defined as sum of 2 sub-scores: severity of dysmenorrhea (none: 0, mild: 1, moderate: 2, severe: 3) and use of analgesics (none: 0, mild: 1, moderate: 2, severe: 3). Total possible best is 0, and total possible worst is 6. |
| Participants With Withdrawal Bleeding | At Cycle 4 (28 days per cycle) | Withdrawal bleedings were defined as bleedings while a participant takes placebo tablets. |
| Participants With Intracyclic Bleeding | At Cycle 4 (28 days per cycle) | Intracyclic bleedings were defined as bleedings while a participant takes active drugs. |
| Participants With Non-heavy Intracyclic Bleeding | At Cycle 4 (28 days per cycle) | Non-heavy bleedings were defined as those other than heavy bleeding (less or normal bleeding). |
| Participants With Non-heavy Withdrawal Bleeding | At Cycle 4 (28 dyas per cycle) | Non-heavy bleedings were defined as those other than heavy bleeding (less or normal bleeding). |
| Change From Baseline in Serum Carbohydrate Antigen-125 (CA125) After 4-cycle Treatment | From baseline to Cycle 4 (28 days per cycle) | CA125 is a laboratory parameter giving an indication of having tumor, whose elevated levels that were defined by a lab suggest a potential tumor. |
| Change From Baseline in Serum C-reactive Protein (CRP) After 4-cycle Treatment | From baseline to Cycle 4 (28 days per cycle) | CRP is a laboratory parameter giving an indication of inflammation, whose elevated levels that were defined by a lab suggest a potential inflammation. |
| Change From Baseline in Serum Estradiol Level After 4-cycle Treatment | From baseline to Cycle 4 (28 days per cycle) | Estradiol is a predominant sex hormone that presents in female. |
| Change From Baseline in Serum Progesterone Level at Cycle 4 | From baseline to Cycle 4 (28 days per cycle) | Progesterone is a steroid hormone involving in the female menstrual cycle, pregnancy, etc. |
| Number of Bleeding / Spotting Days | For the first 90 days | Bleeding data were captured from the diary a participant recorded by herself. Bleeding is a genital bleeding. Spotting is a slight genital bleeding with participant's experience. The bleeding /spotting analyses are by intensity. |
Countries
Japan
Participant flow
Pre-assignment details
Full Analysis Set (FAS) consisted of all patients who received at least one dose of study drug. Patients were analyzed as treated. FAS was the primary analysis set for all efficacy endpoints and safety analyses. Per Protocol Set (PPS) was a subgroup of the FAS. The PPS consisted of patients in the FAS who did not have major protocol deviations.
Participants by arm
| Arm | Count |
|---|---|
| DRSP 1 mg/EE 20 μg 1 tablet per day Drospirenone (DRSP) 1 mg/Ethinylestradiol (EE) 20 μg for 24 days and 1 tablet per day placebo for 4 days in each 28-day cycle | 61 |
| DRSP 2 mg/EE 20 μg 1 tablet per day Drospirenone (DRSP) 2 mg/Ethinylestradiol (EE) 20 μg for 24 days and 1 tablet per day placebo for 4 days in each 28-day cycle | 62 |
| DRSP 3 mg/EE 20 μg 1 tablet per day Drospirenone (DRSP) 3 mg/Ethinylestradiol (EE) 20 μg for 24 days and 1 tablet per day placebo for 4 days in each 28-day cycle | 61 |
| Placebo 1 tablet per day placebo for 28 days in each 28-day cycle | 58 |
| Total | 242 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 2 | 2 | 2 |
| Overall Study | Lost to Follow-up | 1 | 0 | 0 | 1 |
| Overall Study | Never dispensed | 1 | 0 | 1 | 3 |
| Overall Study | Other (moving etc) | 1 | 0 | 1 | 2 |
| Overall Study | Partially missing diary | 0 | 0 | 1 | 0 |
| Overall Study | Pregnancy | 0 | 0 | 0 | 1 |
| Overall Study | Protocol Violation | 0 | 2 | 2 | 3 |
| Overall Study | Study drug not taken | 0 | 1 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 3 | 3 | 4 | 2 |
Baseline characteristics
| Characteristic | DRSP 2 mg/EE 20 μg | DRSP 3 mg/EE 20 μg | Placebo | DRSP 1 mg/EE 20 μg | Total |
|---|---|---|---|---|---|
| Age, Continuous | 30.6 years | 30.9 years | 30.8 years | 31.0 years | 30.8 years |
| Average length of menstrual cycle | 28.7 days | 28.3 days | 28.7 days | 28.6 days | 28.6 days |
| Body mass index (BMI) | 20.41 kg/m^2 | 20.67 kg/m^2 | 21.19 kg/m^2 | 21.05 kg/m^2 | 20.82 kg/m^2 |
| Details of organic dysmenorrhea Bicornuate uterus | 0 participants | 0 participants | 0 participants | 2 participants | 2 participants |
| Details of organic dysmenorrhea Endometriosis | 3 participants | 4 participants | 5 participants | 1 participants | 13 participants |
| Details of organic dysmenorrhea Uterine adenomyosis | 7 participants | 11 participants | 8 participants | 6 participants | 32 participants |
| Details of organic dysmenorrhea Uterine fibroids | 7 participants | 10 participants | 9 participants | 9 participants | 35 participants |
| Diagnosis type Functional dysmenorrhea | 48 participants | 42 participants | 41 participants | 47 participants | 178 participants |
| Diagnosis type Organic dysmenorrhea | 14 participants | 19 participants | 17 participants | 14 participants | 64 participants |
| Gender Female | 62 Participants | 61 Participants | 58 Participants | 61 Participants | 242 Participants |
| Gender Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 56 / 62 | 58 / 63 | 60 / 62 | 53 / 62 |
| serious Total, serious adverse events | 1 / 62 | 2 / 63 | 0 / 62 | 1 / 62 |
Outcome results
Primary
Change From Baseline in Total Dysmenorrheal Score at Final Evaluation
Total dysmenorrheal score was defined as sum of 2 sub-scores: severity of dysmenorrhea (none: 0, mild: 1, moderate: 2, severe: 3) and use of analgesics (none: 0, mild: 1, moderate: 2, severe: 3). Total possible best is 0, and total possible worst is 6. Note: used with permission of Nobelpharma Co., Ltd. from the phase 3 clinical study protocol (Prog Med 2005:25 (3):739-758) of IKH-01 in dysmenorrhea (associated with endometriosis) (Nobelpharma Co., Ltd.)
Time frame: Baseline and up to 4 Cycles (28 days per cycle)
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DRSP 1 mg/EE 20 μg | Change From Baseline in Total Dysmenorrheal Score at Final Evaluation | -2.5 scores on a scale | Standard Deviation 1.52 |
| DRSP 2 mg/EE 20 μg | Change From Baseline in Total Dysmenorrheal Score at Final Evaluation | -2.1 scores on a scale | Standard Deviation 1.51 |
| DRSP 3 mg/EE 20 μg | Change From Baseline in Total Dysmenorrheal Score at Final Evaluation | -1.9 scores on a scale | Standard Deviation 1.63 |
| Placebo | Change From Baseline in Total Dysmenorrheal Score at Final Evaluation | -1.0 scores on a scale | Standard Deviation 1.53 |
Comparison: Three null hypotheses were sequentially tested. H01: DRSP 3 mg \>= Placebo (Active is equal or less in decrease of score) vs H11: DRSP 3 mg \< Placebo (Active is greater in decrease of score), H02: DRSP 2 mg \>= Placebo vs H12: DRSP 2 mg \< Placebo, H03: DRSP 1 mg \>= Placebo vs H13: DRSP 1 mg \< Placebo.p-value: <0.00195% CI: [-1.49, -0.34]t-test, 1 sided
Comparison: Second null hypothesis was tested. H02: DRSP 2 mg \>= Placebo vs H12: DRSP 2 mg \< Placebo.p-value: <0.00195% CI: [-1.64, -0.55]t-test, 1 sided
Comparison: Third null hypotheses was tested. H03: DRSP 1 mg \>= Placebo vs H13: DRSP 1 mg \< Placebo.p-value: <0.00195% CI: [-2, -0.89]t-test, 1 sided
Secondary
Change From Baseline in Endometrial Thickness After 4-cycle Treatment
Endometrial thickness was measured via transvaginal ultrasound examination. The endometrium is the inner membrane of the uterus. During the menstrual cycle, the endometrium grows to a thick, blood vessel-rich, glandular tissue layer.
Time frame: From baseline to Cycle 4 (28 days per cycle)
Population: FAS (Participants with data at Cycle 4)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DRSP 1 mg/EE 20 μg | Change From Baseline in Endometrial Thickness After 4-cycle Treatment | -5.5 mm | Standard Deviation 4.11 |
| DRSP 2 mg/EE 20 μg | Change From Baseline in Endometrial Thickness After 4-cycle Treatment | -7.1 mm | Standard Deviation 3.25 |
| DRSP 3 mg/EE 20 μg | Change From Baseline in Endometrial Thickness After 4-cycle Treatment | -6.3 mm | Standard Deviation 4.07 |
| Placebo | Change From Baseline in Endometrial Thickness After 4-cycle Treatment | -0.1 mm | Standard Deviation 2.79 |
Secondary
Change From Baseline in Serum Carbohydrate Antigen-125 (CA125) After 4-cycle Treatment
CA125 is a laboratory parameter giving an indication of having tumor, whose elevated levels that were defined by a lab suggest a potential tumor.
Time frame: From baseline to Cycle 4 (28 days per cycle)
Population: FAS (Participants with data at Cycle 4)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| DRSP 1 mg/EE 20 μg | Change From Baseline in Serum Carbohydrate Antigen-125 (CA125) After 4-cycle Treatment | -2.78 Units/L |
| DRSP 2 mg/EE 20 μg | Change From Baseline in Serum Carbohydrate Antigen-125 (CA125) After 4-cycle Treatment | 0.53 Units/L |
| DRSP 3 mg/EE 20 μg | Change From Baseline in Serum Carbohydrate Antigen-125 (CA125) After 4-cycle Treatment | -3.79 Units/L |
| Placebo | Change From Baseline in Serum Carbohydrate Antigen-125 (CA125) After 4-cycle Treatment | 0.89 Units/L |
Secondary
Change From Baseline in Serum C-reactive Protein (CRP) After 4-cycle Treatment
CRP is a laboratory parameter giving an indication of inflammation, whose elevated levels that were defined by a lab suggest a potential inflammation.
Time frame: From baseline to Cycle 4 (28 days per cycle)
Population: FAS (Participants with data at Cycle 4)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| DRSP 1 mg/EE 20 μg | Change From Baseline in Serum C-reactive Protein (CRP) After 4-cycle Treatment | 0.015 mg/dL |
| DRSP 2 mg/EE 20 μg | Change From Baseline in Serum C-reactive Protein (CRP) After 4-cycle Treatment | 0.042 mg/dL |
| DRSP 3 mg/EE 20 μg | Change From Baseline in Serum C-reactive Protein (CRP) After 4-cycle Treatment | -0.014 mg/dL |
| Placebo | Change From Baseline in Serum C-reactive Protein (CRP) After 4-cycle Treatment | -0.175 mg/dL |
Secondary
Change From Baseline in Serum Estradiol Level After 4-cycle Treatment
Estradiol is a predominant sex hormone that presents in female.
Time frame: From baseline to Cycle 4 (28 days per cycle)
Population: FAS (Participants with data at Cycle 4)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| DRSP 1 mg/EE 20 μg | Change From Baseline in Serum Estradiol Level After 4-cycle Treatment | -18.32 pg/mL |
| DRSP 2 mg/EE 20 μg | Change From Baseline in Serum Estradiol Level After 4-cycle Treatment | -42.23 pg/mL |
| DRSP 3 mg/EE 20 μg | Change From Baseline in Serum Estradiol Level After 4-cycle Treatment | -98.02 pg/mL |
| Placebo | Change From Baseline in Serum Estradiol Level After 4-cycle Treatment | 49.20 pg/mL |
Secondary
Change From Baseline in Serum Progesterone Level at Cycle 4
Progesterone is a steroid hormone involving in the female menstrual cycle, pregnancy, etc.
Time frame: From baseline to Cycle 4 (28 days per cycle)
Population: FAS (Participants with data at Cycle 4)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| DRSP 1 mg/EE 20 μg | Change From Baseline in Serum Progesterone Level at Cycle 4 | -7.93 ng/mL |
| DRSP 2 mg/EE 20 μg | Change From Baseline in Serum Progesterone Level at Cycle 4 | -8.23 ng/mL |
| DRSP 3 mg/EE 20 μg | Change From Baseline in Serum Progesterone Level at Cycle 4 | -9.37 ng/mL |
| Placebo | Change From Baseline in Serum Progesterone Level at Cycle 4 | -0.27 ng/mL |
Secondary
Change From Baseline in Total Dysmenorrheal Score at Cycle 1 up to Cycle 4
Total dysmenorrheal score was defined as sum of 2 sub-scores: severity of dysmenorrhea (none: 0, mild: 1, moderate: 2, severe: 3) and use of analgesics (none: 0, mild: 1, moderate: 2, severe: 3). Total possible best is 0, and total possible worst is 6.
Time frame: Baseline and up to 4 Cycles (28 days per cycle)
Population: FAS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| DRSP 1 mg/EE 20 μg | Change From Baseline in Total Dysmenorrheal Score at Cycle 1 up to Cycle 4 | Cycle 1 | -2.4 scores on a scale | Standard Deviation 1.4 |
| DRSP 1 mg/EE 20 μg | Change From Baseline in Total Dysmenorrheal Score at Cycle 1 up to Cycle 4 | Cycle 2 | -2.1 scores on a scale | Standard Deviation 1.4 |
| DRSP 1 mg/EE 20 μg | Change From Baseline in Total Dysmenorrheal Score at Cycle 1 up to Cycle 4 | Cycle 3 | -2.5 scores on a scale | Standard Deviation 1.34 |
| DRSP 1 mg/EE 20 μg | Change From Baseline in Total Dysmenorrheal Score at Cycle 1 up to Cycle 4 | Cycle 4 | -2.5 scores on a scale | Standard Deviation 1.55 |
| DRSP 2 mg/EE 20 μg | Change From Baseline in Total Dysmenorrheal Score at Cycle 1 up to Cycle 4 | Cycle 2 | -2.3 scores on a scale | Standard Deviation 1.57 |
| DRSP 2 mg/EE 20 μg | Change From Baseline in Total Dysmenorrheal Score at Cycle 1 up to Cycle 4 | Cycle 3 | -2.3 scores on a scale | Standard Deviation 1.52 |
| DRSP 2 mg/EE 20 μg | Change From Baseline in Total Dysmenorrheal Score at Cycle 1 up to Cycle 4 | Cycle 4 | -2.3 scores on a scale | Standard Deviation 1.41 |
| DRSP 2 mg/EE 20 μg | Change From Baseline in Total Dysmenorrheal Score at Cycle 1 up to Cycle 4 | Cycle 1 | -2.1 scores on a scale | Standard Deviation 1.49 |
| DRSP 3 mg/EE 20 μg | Change From Baseline in Total Dysmenorrheal Score at Cycle 1 up to Cycle 4 | Cycle 3 | -2.1 scores on a scale | Standard Deviation 1.34 |
| DRSP 3 mg/EE 20 μg | Change From Baseline in Total Dysmenorrheal Score at Cycle 1 up to Cycle 4 | Cycle 2 | -1.9 scores on a scale | Standard Deviation 1.5 |
| DRSP 3 mg/EE 20 μg | Change From Baseline in Total Dysmenorrheal Score at Cycle 1 up to Cycle 4 | Cycle 4 | -2.1 scores on a scale | Standard Deviation 1.54 |
| DRSP 3 mg/EE 20 μg | Change From Baseline in Total Dysmenorrheal Score at Cycle 1 up to Cycle 4 | Cycle 1 | -1.8 scores on a scale | Standard Deviation 1.67 |
| Placebo | Change From Baseline in Total Dysmenorrheal Score at Cycle 1 up to Cycle 4 | Cycle 4 | -1.0 scores on a scale | Standard Deviation 1.63 |
| Placebo | Change From Baseline in Total Dysmenorrheal Score at Cycle 1 up to Cycle 4 | Cycle 2 | -1.1 scores on a scale | Standard Deviation 1.59 |
| Placebo | Change From Baseline in Total Dysmenorrheal Score at Cycle 1 up to Cycle 4 | Cycle 1 | -0.8 scores on a scale | Standard Deviation 1.5 |
| Placebo | Change From Baseline in Total Dysmenorrheal Score at Cycle 1 up to Cycle 4 | Cycle 3 | -1.0 scores on a scale | Standard Deviation 1.59 |
Comparison: Test results of 3 mg DRSP and placebo at Cycle 4 are shown. 2-sided 95% confidence intervals were calculated. To keep consistency with 2-sided 95% confidence intervals, 2.5% 1-sided significance levels were used for the statistical tests.p-value: <0.00195% CI: [-1.74, -0.46]t-test, 1 sided
p-value: <0.00195% CI: [-1.95, -0.73]t-test, 1 sided
p-value: <0.00195% CI: [-2.16, -0.9]t-test, 1 sided
Secondary
Change From Baseline in Visual Analogue Scale (VAS) for Dysmenorrhea at Times Other Than During Menstruation at Cycle 4
VAS is an unmarked scale on a line 100 mm in length, indicating from 0 mm (no pain) to 100 mm (worst pain a participant has ever experienced).
Time frame: From baseline up to Cycle 4 (28 days per cycle)
Population: FAS (Participants with data at Cycle 4)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DRSP 1 mg/EE 20 μg | Change From Baseline in Visual Analogue Scale (VAS) for Dysmenorrhea at Times Other Than During Menstruation at Cycle 4 | -43.0 scores on a scale | Standard Deviation 23.44 |
| DRSP 2 mg/EE 20 μg | Change From Baseline in Visual Analogue Scale (VAS) for Dysmenorrhea at Times Other Than During Menstruation at Cycle 4 | -39.5 scores on a scale | Standard Deviation 22.12 |
| DRSP 3 mg/EE 20 μg | Change From Baseline in Visual Analogue Scale (VAS) for Dysmenorrhea at Times Other Than During Menstruation at Cycle 4 | -31.8 scores on a scale | Standard Deviation 23.55 |
| Placebo | Change From Baseline in Visual Analogue Scale (VAS) for Dysmenorrhea at Times Other Than During Menstruation at Cycle 4 | -10.3 scores on a scale | Standard Deviation 24.53 |
Secondary
Number of Bleeding / Spotting Days
Bleeding data were captured from the diary a participant recorded by herself. Bleeding is a genital bleeding. Spotting is a slight genital bleeding with participant's experience. The bleeding /spotting analyses are by intensity.
Time frame: For the first 90 days
Population: FAS (Participants with the defined data)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| DRSP 1 mg/EE 20 μg | Number of Bleeding / Spotting Days | bleeding / spotting | 32.3 days | Standard Deviation 8.7 |
| DRSP 1 mg/EE 20 μg | Number of Bleeding / Spotting Days | spotting only | 11.1 days | Standard Deviation 7 |
| DRSP 1 mg/EE 20 μg | Number of Bleeding / Spotting Days | bleeding only | 21.3 days | Standard Deviation 5.9 |
| DRSP 2 mg/EE 20 μg | Number of Bleeding / Spotting Days | bleeding / spotting | 31.2 days | Standard Deviation 11.4 |
| DRSP 2 mg/EE 20 μg | Number of Bleeding / Spotting Days | spotting only | 11.9 days | Standard Deviation 7.6 |
| DRSP 2 mg/EE 20 μg | Number of Bleeding / Spotting Days | bleeding only | 19.3 days | Standard Deviation 8.8 |
| DRSP 3 mg/EE 20 μg | Number of Bleeding / Spotting Days | bleeding only | 18.6 days | Standard Deviation 6.5 |
| DRSP 3 mg/EE 20 μg | Number of Bleeding / Spotting Days | bleeding / spotting | 29.2 days | Standard Deviation 11 |
| DRSP 3 mg/EE 20 μg | Number of Bleeding / Spotting Days | spotting only | 10.5 days | Standard Deviation 8.2 |
| Placebo | Number of Bleeding / Spotting Days | bleeding / spotting | 22.6 days | Standard Deviation 5.5 |
| Placebo | Number of Bleeding / Spotting Days | spotting only | 5.2 days | Standard Deviation 2.5 |
| Placebo | Number of Bleeding / Spotting Days | bleeding only | 17.4 days | Standard Deviation 4.9 |
Secondary
Number of Bleeding / Spotting Episodes
Bleeding data were captured from the diary a participant recorded by herself. Bleeding is a genital bleeding. Spotting is a slight genital bleeding with participant's experience. An episode means a series of bleeding and/or spotting. The bleeding /spotting analyses are by intensity.
Time frame: For the first 90 days
Population: FAS (Participants with the defined data)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| DRSP 1 mg/EE 20 μg | Number of Bleeding / Spotting Episodes | bleeding / spotting | 3.3 number of episodes | Standard Deviation 0.9 |
| DRSP 1 mg/EE 20 μg | Number of Bleeding / Spotting Episodes | spotting only | 0.3 number of episodes | Standard Deviation 0.6 |
| DRSP 1 mg/EE 20 μg | Number of Bleeding / Spotting Episodes | bleeding only | 0.5 number of episodes | Standard Deviation 0.9 |
| DRSP 2 mg/EE 20 μg | Number of Bleeding / Spotting Episodes | bleeding / spotting | 3.3 number of episodes | Standard Deviation 1.3 |
| DRSP 2 mg/EE 20 μg | Number of Bleeding / Spotting Episodes | spotting only | 0.4 number of episodes | Standard Deviation 1.1 |
| DRSP 2 mg/EE 20 μg | Number of Bleeding / Spotting Episodes | bleeding only | 0.4 number of episodes | Standard Deviation 0.8 |
| DRSP 3 mg/EE 20 μg | Number of Bleeding / Spotting Episodes | bleeding only | 0.3 number of episodes | Standard Deviation 0.5 |
| DRSP 3 mg/EE 20 μg | Number of Bleeding / Spotting Episodes | bleeding / spotting | 3.4 number of episodes | Standard Deviation 0.9 |
| DRSP 3 mg/EE 20 μg | Number of Bleeding / Spotting Episodes | spotting only | 0.4 number of episodes | Standard Deviation 0.8 |
| Placebo | Number of Bleeding / Spotting Episodes | bleeding / spotting | 2.9 number of episodes | Standard Deviation 0.9 |
| Placebo | Number of Bleeding / Spotting Episodes | spotting only | 0.2 number of episodes | Standard Deviation 0.6 |
| Placebo | Number of Bleeding / Spotting Episodes | bleeding only | 0.4 number of episodes | Standard Deviation 0.8 |
Secondary
Number of Participants With Severity of Headache During Menstruation at Cycle 4
Severity of headache during menstruation was rated as none (none), mild (can be easily tolerated), moderate (noticeable, but does not interfere with daily activities), or severe (interferes with daily activities).
Time frame: Cycle 4 (28 days per cycle)
Population: FAS (Participants with data at Cycle 4)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| DRSP 1 mg/EE 20 μg | Number of Participants With Severity of Headache During Menstruation at Cycle 4 | none | 47 participants |
| DRSP 1 mg/EE 20 μg | Number of Participants With Severity of Headache During Menstruation at Cycle 4 | mild | 5 participants |
| DRSP 1 mg/EE 20 μg | Number of Participants With Severity of Headache During Menstruation at Cycle 4 | moderate | 1 participants |
| DRSP 1 mg/EE 20 μg | Number of Participants With Severity of Headache During Menstruation at Cycle 4 | severe | 2 participants |
| DRSP 2 mg/EE 20 μg | Number of Participants With Severity of Headache During Menstruation at Cycle 4 | mild | 10 participants |
| DRSP 2 mg/EE 20 μg | Number of Participants With Severity of Headache During Menstruation at Cycle 4 | moderate | 6 participants |
| DRSP 2 mg/EE 20 μg | Number of Participants With Severity of Headache During Menstruation at Cycle 4 | severe | 2 participants |
| DRSP 2 mg/EE 20 μg | Number of Participants With Severity of Headache During Menstruation at Cycle 4 | none | 35 participants |
| DRSP 3 mg/EE 20 μg | Number of Participants With Severity of Headache During Menstruation at Cycle 4 | moderate | 3 participants |
| DRSP 3 mg/EE 20 μg | Number of Participants With Severity of Headache During Menstruation at Cycle 4 | mild | 5 participants |
| DRSP 3 mg/EE 20 μg | Number of Participants With Severity of Headache During Menstruation at Cycle 4 | severe | 4 participants |
| DRSP 3 mg/EE 20 μg | Number of Participants With Severity of Headache During Menstruation at Cycle 4 | none | 39 participants |
| Placebo | Number of Participants With Severity of Headache During Menstruation at Cycle 4 | severe | 5 participants |
| Placebo | Number of Participants With Severity of Headache During Menstruation at Cycle 4 | mild | 6 participants |
| Placebo | Number of Participants With Severity of Headache During Menstruation at Cycle 4 | none | 29 participants |
| Placebo | Number of Participants With Severity of Headache During Menstruation at Cycle 4 | moderate | 6 participants |
Secondary
Number of Participants With Severity of Low Back Pain During Menstruation at Cycle 4
Severity of low back pain during menstruation was rated as none (none), mild (can be easily tolerated), moderate (noticeable, but does not interfere with daily activities), or severe (interferes with daily activities).
Time frame: Cycle 4 (28 days per cycle)
Population: FAS (Participants with data at Cycle 4)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| DRSP 1 mg/EE 20 μg | Number of Participants With Severity of Low Back Pain During Menstruation at Cycle 4 | mild | 15 participants |
| DRSP 1 mg/EE 20 μg | Number of Participants With Severity of Low Back Pain During Menstruation at Cycle 4 | severe | 1 participants |
| DRSP 1 mg/EE 20 μg | Number of Participants With Severity of Low Back Pain During Menstruation at Cycle 4 | none | 34 participants |
| DRSP 1 mg/EE 20 μg | Number of Participants With Severity of Low Back Pain During Menstruation at Cycle 4 | moderate | 5 participants |
| DRSP 2 mg/EE 20 μg | Number of Participants With Severity of Low Back Pain During Menstruation at Cycle 4 | none | 36 participants |
| DRSP 2 mg/EE 20 μg | Number of Participants With Severity of Low Back Pain During Menstruation at Cycle 4 | mild | 12 participants |
| DRSP 2 mg/EE 20 μg | Number of Participants With Severity of Low Back Pain During Menstruation at Cycle 4 | moderate | 4 participants |
| DRSP 2 mg/EE 20 μg | Number of Participants With Severity of Low Back Pain During Menstruation at Cycle 4 | severe | 1 participants |
| DRSP 3 mg/EE 20 μg | Number of Participants With Severity of Low Back Pain During Menstruation at Cycle 4 | none | 30 participants |
| DRSP 3 mg/EE 20 μg | Number of Participants With Severity of Low Back Pain During Menstruation at Cycle 4 | moderate | 2 participants |
| DRSP 3 mg/EE 20 μg | Number of Participants With Severity of Low Back Pain During Menstruation at Cycle 4 | mild | 18 participants |
| DRSP 3 mg/EE 20 μg | Number of Participants With Severity of Low Back Pain During Menstruation at Cycle 4 | severe | 1 participants |
| Placebo | Number of Participants With Severity of Low Back Pain During Menstruation at Cycle 4 | mild | 14 participants |
| Placebo | Number of Participants With Severity of Low Back Pain During Menstruation at Cycle 4 | moderate | 9 participants |
| Placebo | Number of Participants With Severity of Low Back Pain During Menstruation at Cycle 4 | severe | 5 participants |
| Placebo | Number of Participants With Severity of Low Back Pain During Menstruation at Cycle 4 | none | 18 participants |
Secondary
Number of Participants With Severity of Lower Abdominal Pain During Menstruation at Cycle 4
Severity of lower abdominal pain during menstruation was rated as none (none), mild (can be easily tolerated), moderate (noticeable, but does not interfere with daily activities), or severe (interferes with daily activities).
Time frame: Cycle 4 (28 days per cycle)
Population: FAS (Participants with data at Cycle 4)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| DRSP 1 mg/EE 20 μg | Number of Participants With Severity of Lower Abdominal Pain During Menstruation at Cycle 4 | none | 15 participants |
| DRSP 1 mg/EE 20 μg | Number of Participants With Severity of Lower Abdominal Pain During Menstruation at Cycle 4 | mild | 28 participants |
| DRSP 1 mg/EE 20 μg | Number of Participants With Severity of Lower Abdominal Pain During Menstruation at Cycle 4 | moderate | 9 participants |
| DRSP 1 mg/EE 20 μg | Number of Participants With Severity of Lower Abdominal Pain During Menstruation at Cycle 4 | severe | 3 participants |
| DRSP 2 mg/EE 20 μg | Number of Participants With Severity of Lower Abdominal Pain During Menstruation at Cycle 4 | mild | 27 participants |
| DRSP 2 mg/EE 20 μg | Number of Participants With Severity of Lower Abdominal Pain During Menstruation at Cycle 4 | moderate | 7 participants |
| DRSP 2 mg/EE 20 μg | Number of Participants With Severity of Lower Abdominal Pain During Menstruation at Cycle 4 | severe | 2 participants |
| DRSP 2 mg/EE 20 μg | Number of Participants With Severity of Lower Abdominal Pain During Menstruation at Cycle 4 | none | 17 participants |
| DRSP 3 mg/EE 20 μg | Number of Participants With Severity of Lower Abdominal Pain During Menstruation at Cycle 4 | moderate | 14 participants |
| DRSP 3 mg/EE 20 μg | Number of Participants With Severity of Lower Abdominal Pain During Menstruation at Cycle 4 | mild | 19 participants |
| DRSP 3 mg/EE 20 μg | Number of Participants With Severity of Lower Abdominal Pain During Menstruation at Cycle 4 | severe | 7 participants |
| DRSP 3 mg/EE 20 μg | Number of Participants With Severity of Lower Abdominal Pain During Menstruation at Cycle 4 | none | 11 participants |
| Placebo | Number of Participants With Severity of Lower Abdominal Pain During Menstruation at Cycle 4 | severe | 11 participants |
| Placebo | Number of Participants With Severity of Lower Abdominal Pain During Menstruation at Cycle 4 | mild | 11 participants |
| Placebo | Number of Participants With Severity of Lower Abdominal Pain During Menstruation at Cycle 4 | none | 3 participants |
| Placebo | Number of Participants With Severity of Lower Abdominal Pain During Menstruation at Cycle 4 | moderate | 21 participants |
Secondary
Number of Participants With Severity of Nausea or Vomiting During Menstruation at Cycle 4
Severity of nausea or vomiting during menstruation was rated as none (none), mild (can be easily tolerated), moderate (noticeable, but does not interfere with daily activities), or severe (interferes with daily activities).
Time frame: Cycle 4 (28 days per cycle)
Population: FAS (Participants with data at Cycle 4)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| DRSP 1 mg/EE 20 μg | Number of Participants With Severity of Nausea or Vomiting During Menstruation at Cycle 4 | none | 51 participants |
| DRSP 1 mg/EE 20 μg | Number of Participants With Severity of Nausea or Vomiting During Menstruation at Cycle 4 | mild | 2 participants |
| DRSP 1 mg/EE 20 μg | Number of Participants With Severity of Nausea or Vomiting During Menstruation at Cycle 4 | moderate | 2 participants |
| DRSP 1 mg/EE 20 μg | Number of Participants With Severity of Nausea or Vomiting During Menstruation at Cycle 4 | severe | 0 participants |
| DRSP 2 mg/EE 20 μg | Number of Participants With Severity of Nausea or Vomiting During Menstruation at Cycle 4 | mild | 4 participants |
| DRSP 2 mg/EE 20 μg | Number of Participants With Severity of Nausea or Vomiting During Menstruation at Cycle 4 | moderate | 1 participants |
| DRSP 2 mg/EE 20 μg | Number of Participants With Severity of Nausea or Vomiting During Menstruation at Cycle 4 | severe | 1 participants |
| DRSP 2 mg/EE 20 μg | Number of Participants With Severity of Nausea or Vomiting During Menstruation at Cycle 4 | none | 47 participants |
| DRSP 3 mg/EE 20 μg | Number of Participants With Severity of Nausea or Vomiting During Menstruation at Cycle 4 | moderate | 0 participants |
| DRSP 3 mg/EE 20 μg | Number of Participants With Severity of Nausea or Vomiting During Menstruation at Cycle 4 | mild | 4 participants |
| DRSP 3 mg/EE 20 μg | Number of Participants With Severity of Nausea or Vomiting During Menstruation at Cycle 4 | severe | 0 participants |
| DRSP 3 mg/EE 20 μg | Number of Participants With Severity of Nausea or Vomiting During Menstruation at Cycle 4 | none | 47 participants |
| Placebo | Number of Participants With Severity of Nausea or Vomiting During Menstruation at Cycle 4 | severe | 0 participants |
| Placebo | Number of Participants With Severity of Nausea or Vomiting During Menstruation at Cycle 4 | mild | 4 participants |
| Placebo | Number of Participants With Severity of Nausea or Vomiting During Menstruation at Cycle 4 | none | 40 participants |
| Placebo | Number of Participants With Severity of Nausea or Vomiting During Menstruation at Cycle 4 | moderate | 2 participants |
Secondary
Number of Participants With Total Pelvic Pain Score at Times Other Than During Menstruation at Cycle 4
Total pelvic pain score was defined as sum of 2 sub-scores: severity of dysmenorrhea and use of analgesics. Higher score means it is more severe. 0=None, 6=Severest.
Time frame: Cycle 4 (28 days per cycle)
Population: FAS (Participants with data at Cycle 4)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| DRSP 1 mg/EE 20 μg | Number of Participants With Total Pelvic Pain Score at Times Other Than During Menstruation at Cycle 4 | 0 | 40 participants |
| DRSP 1 mg/EE 20 μg | Number of Participants With Total Pelvic Pain Score at Times Other Than During Menstruation at Cycle 4 | 5 | 1 participants |
| DRSP 1 mg/EE 20 μg | Number of Participants With Total Pelvic Pain Score at Times Other Than During Menstruation at Cycle 4 | 4 | 0 participants |
| DRSP 1 mg/EE 20 μg | Number of Participants With Total Pelvic Pain Score at Times Other Than During Menstruation at Cycle 4 | 1 | 11 participants |
| DRSP 1 mg/EE 20 μg | Number of Participants With Total Pelvic Pain Score at Times Other Than During Menstruation at Cycle 4 | 6 | 0 participants |
| DRSP 1 mg/EE 20 μg | Number of Participants With Total Pelvic Pain Score at Times Other Than During Menstruation at Cycle 4 | 2 | 3 participants |
| DRSP 1 mg/EE 20 μg | Number of Participants With Total Pelvic Pain Score at Times Other Than During Menstruation at Cycle 4 | 3 | 0 participants |
| DRSP 2 mg/EE 20 μg | Number of Participants With Total Pelvic Pain Score at Times Other Than During Menstruation at Cycle 4 | 5 | 0 participants |
| DRSP 2 mg/EE 20 μg | Number of Participants With Total Pelvic Pain Score at Times Other Than During Menstruation at Cycle 4 | 3 | 0 participants |
| DRSP 2 mg/EE 20 μg | Number of Participants With Total Pelvic Pain Score at Times Other Than During Menstruation at Cycle 4 | 2 | 2 participants |
| DRSP 2 mg/EE 20 μg | Number of Participants With Total Pelvic Pain Score at Times Other Than During Menstruation at Cycle 4 | 4 | 0 participants |
| DRSP 2 mg/EE 20 μg | Number of Participants With Total Pelvic Pain Score at Times Other Than During Menstruation at Cycle 4 | 6 | 0 participants |
| DRSP 2 mg/EE 20 μg | Number of Participants With Total Pelvic Pain Score at Times Other Than During Menstruation at Cycle 4 | 1 | 10 participants |
| DRSP 2 mg/EE 20 μg | Number of Participants With Total Pelvic Pain Score at Times Other Than During Menstruation at Cycle 4 | 0 | 41 participants |
| DRSP 3 mg/EE 20 μg | Number of Participants With Total Pelvic Pain Score at Times Other Than During Menstruation at Cycle 4 | 3 | 0 participants |
| DRSP 3 mg/EE 20 μg | Number of Participants With Total Pelvic Pain Score at Times Other Than During Menstruation at Cycle 4 | 0 | 42 participants |
| DRSP 3 mg/EE 20 μg | Number of Participants With Total Pelvic Pain Score at Times Other Than During Menstruation at Cycle 4 | 1 | 7 participants |
| DRSP 3 mg/EE 20 μg | Number of Participants With Total Pelvic Pain Score at Times Other Than During Menstruation at Cycle 4 | 2 | 1 participants |
| DRSP 3 mg/EE 20 μg | Number of Participants With Total Pelvic Pain Score at Times Other Than During Menstruation at Cycle 4 | 4 | 0 participants |
| DRSP 3 mg/EE 20 μg | Number of Participants With Total Pelvic Pain Score at Times Other Than During Menstruation at Cycle 4 | 5 | 1 participants |
| DRSP 3 mg/EE 20 μg | Number of Participants With Total Pelvic Pain Score at Times Other Than During Menstruation at Cycle 4 | 6 | 0 participants |
| Placebo | Number of Participants With Total Pelvic Pain Score at Times Other Than During Menstruation at Cycle 4 | 2 | 5 participants |
| Placebo | Number of Participants With Total Pelvic Pain Score at Times Other Than During Menstruation at Cycle 4 | 6 | 0 participants |
| Placebo | Number of Participants With Total Pelvic Pain Score at Times Other Than During Menstruation at Cycle 4 | 5 | 1 participants |
| Placebo | Number of Participants With Total Pelvic Pain Score at Times Other Than During Menstruation at Cycle 4 | 1 | 6 participants |
| Placebo | Number of Participants With Total Pelvic Pain Score at Times Other Than During Menstruation at Cycle 4 | 0 | 30 participants |
| Placebo | Number of Participants With Total Pelvic Pain Score at Times Other Than During Menstruation at Cycle 4 | 4 | 1 participants |
| Placebo | Number of Participants With Total Pelvic Pain Score at Times Other Than During Menstruation at Cycle 4 | 3 | 3 participants |
Secondary
Participants With Intracyclic Bleeding
Intracyclic bleedings were defined as bleedings while a participant takes active drugs.
Time frame: At Cycle 4 (28 days per cycle)
Population: FAS (Participants with data at Cycle 4)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| DRSP 1 mg/EE 20 μg | Participants With Intracyclic Bleeding | 14 participants |
| DRSP 2 mg/EE 20 μg | Participants With Intracyclic Bleeding | 8 participants |
| DRSP 3 mg/EE 20 μg | Participants With Intracyclic Bleeding | 8 participants |
| Placebo | Participants With Intracyclic Bleeding | 4 participants |
Secondary
Participants With Non-heavy Intracyclic Bleeding
Non-heavy bleedings were defined as those other than heavy bleeding (less or normal bleeding).
Time frame: At Cycle 4 (28 days per cycle)
Population: FAS (Participants with data at Cycle 4)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| DRSP 1 mg/EE 20 μg | Participants With Non-heavy Intracyclic Bleeding | 14 participants |
| DRSP 2 mg/EE 20 μg | Participants With Non-heavy Intracyclic Bleeding | 8 participants |
| DRSP 3 mg/EE 20 μg | Participants With Non-heavy Intracyclic Bleeding | 7 participants |
| Placebo | Participants With Non-heavy Intracyclic Bleeding | 2 participants |
Secondary
Participants With Non-heavy Withdrawal Bleeding
Non-heavy bleedings were defined as those other than heavy bleeding (less or normal bleeding).
Time frame: At Cycle 4 (28 dyas per cycle)
Population: FAS (Participants with data at Cycle 4)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| DRSP 1 mg/EE 20 μg | Participants With Non-heavy Withdrawal Bleeding | 45 participants |
| DRSP 2 mg/EE 20 μg | Participants With Non-heavy Withdrawal Bleeding | 44 participants |
| DRSP 3 mg/EE 20 μg | Participants With Non-heavy Withdrawal Bleeding | 42 participants |
| Placebo | Participants With Non-heavy Withdrawal Bleeding | 38 participants |
Secondary
Participants With Withdrawal Bleeding
Withdrawal bleedings were defined as bleedings while a participant takes placebo tablets.
Time frame: At Cycle 4 (28 days per cycle)
Population: FAS (Participants with data at Cycle 4)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| DRSP 1 mg/EE 20 μg | Participants With Withdrawal Bleeding | 50 participants |
| DRSP 2 mg/EE 20 μg | Participants With Withdrawal Bleeding | 50 participants |
| DRSP 3 mg/EE 20 μg | Participants With Withdrawal Bleeding | 49 participants |
| Placebo | Participants With Withdrawal Bleeding | 47 participants |
Secondary
Visual Analogue Scale (VAS) for Pelvic Pain at Times Other Than During Menstruation at Cycle 4
VAS is an unmarked scale on a line 100 mm in length, indicating from 0 mm (no pain) to 100 mm (worst pain a participant has ever experienced).
Time frame: Cycle 4 (28 days per cycle)
Population: FAS (Participants with data at Cycle 4)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DRSP 1 mg/EE 20 μg | Visual Analogue Scale (VAS) for Pelvic Pain at Times Other Than During Menstruation at Cycle 4 | 5.9 scores on a scale | Standard Deviation 11.52 |
| DRSP 2 mg/EE 20 μg | Visual Analogue Scale (VAS) for Pelvic Pain at Times Other Than During Menstruation at Cycle 4 | 5.4 scores on a scale | Standard Deviation 11.78 |
| DRSP 3 mg/EE 20 μg | Visual Analogue Scale (VAS) for Pelvic Pain at Times Other Than During Menstruation at Cycle 4 | 4.0 scores on a scale | Standard Deviation 14.26 |
| Placebo | Visual Analogue Scale (VAS) for Pelvic Pain at Times Other Than During Menstruation at Cycle 4 | 11.5 scores on a scale | Standard Deviation 20.22 |
Post Hoc
Change From Baseline for Total Pelvic Pain Score at Times Other Than During Menstruation at Cycle 4
Total pelvic pain score was defined as sum of 2 sub-scores: severity of dysmenorrhea (none: 0, mild: 1, moderate: 2, severe: 3) and use of analgesics (none: 0, mild: 1, moderate: 2, severe: 3). Total possible best is 0, and total possible worst is 6.
Time frame: From baseline to Cycle 4(28 days per cycle)
Population: FAS (Participants with data at Cycle 4)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DRSP 1 mg/EE 20 μg | Change From Baseline for Total Pelvic Pain Score at Times Other Than During Menstruation at Cycle 4 | -0.1 scores on a scale | Standard Deviation 1.19 |
| DRSP 2 mg/EE 20 μg | Change From Baseline for Total Pelvic Pain Score at Times Other Than During Menstruation at Cycle 4 | -0.3 scores on a scale | Standard Deviation 1.12 |
| DRSP 3 mg/EE 20 μg | Change From Baseline for Total Pelvic Pain Score at Times Other Than During Menstruation at Cycle 4 | -0.1 scores on a scale | Standard Deviation 1.06 |
| Placebo | Change From Baseline for Total Pelvic Pain Score at Times Other Than During Menstruation at Cycle 4 | 0.1 scores on a scale | Standard Deviation 1.22 |
Post Hoc
Change From Baseline in Total Dysmenorrheal Score at Final Evaluation in Patients Without Previous Medication
Total dysmenorrheal score was defined as sum of 2 sub-scores: severity of dysmenorrhea (none: 0, mild: 1, moderate: 2, severe: 3) and use of analgesics (none: 0, mild: 1, moderate: 2, severe: 3). Total possible best is 0, and total possible worst is 6. Note: used with permission of Nobelpharma Co., Ltd. from the phase 3 clinical study protocol (Prog Med 2005:25 (3):739-758) of IKH-01 in dysmenorrhea (associated with endometriosis) (Nobelpharma Co., Ltd.)
Time frame: Baseline and up to 4 Cycles (28 days per cycle)
Population: The number of subjects without previous medication in DRSP 1 mg/EE 20 μg group was 1, so the standard deviation was not measurable. The number of subjects without previous medication in the other three groups were 0, so the data were not applicable.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| DRSP 1 mg/EE 20 μg | Change From Baseline in Total Dysmenorrheal Score at Final Evaluation in Patients Without Previous Medication | -2.0 scores on a scale |
Post Hoc
Change From Baseline in Total Dysmenorrheal Score at Final Evaluation in Subgroups (1)
Total dysmenorrheal score was defined as sum of 2 sub-scores: severity of dysmenorrhea (none: 0, mild: 1, moderate: 2, severe: 3) and use of analgesics (none: 0, mild: 1, moderate: 2, severe: 3). Total possible best is 0, and total possible worst is 6. Note: used with permission of Nobelpharma Co., Ltd. from the phase 3 clinical study protocol (Prog Med 2005:25 (3):739-758) of IKH-01 in dysmenorrhea (associated with endometriosis) (Nobelpharma Co., Ltd.)
Time frame: Baseline and up to Cycle 4 (28 days per cycle)
Population: FAS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| DRSP 1 mg/EE 20 μg | Change From Baseline in Total Dysmenorrheal Score at Final Evaluation in Subgroups (1) | age: < 30 years | -2.2 scores on a scale | Standard Deviation 1.46 |
| DRSP 1 mg/EE 20 μg | Change From Baseline in Total Dysmenorrheal Score at Final Evaluation in Subgroups (1) | age: >= 30 years | -2.8 scores on a scale | Standard Deviation 1.54 |
| DRSP 1 mg/EE 20 μg | Change From Baseline in Total Dysmenorrheal Score at Final Evaluation in Subgroups (1) | weight: < 50 kg | -3.0 scores on a scale | Standard Deviation 1.3 |
| DRSP 1 mg/EE 20 μg | Change From Baseline in Total Dysmenorrheal Score at Final Evaluation in Subgroups (1) | weight: >= 50kg | -2.1 scores on a scale | Standard Deviation 1.57 |
| DRSP 1 mg/EE 20 μg | Change From Baseline in Total Dysmenorrheal Score at Final Evaluation in Subgroups (1) | functional dysmenorrhea | -2.3 scores on a scale | Standard Deviation 1.63 |
| DRSP 1 mg/EE 20 μg | Change From Baseline in Total Dysmenorrheal Score at Final Evaluation in Subgroups (1) | organic dysmenorrhea | -2.9 scores on a scale | Standard Deviation 1 |
| DRSP 1 mg/EE 20 μg | Change From Baseline in Total Dysmenorrheal Score at Final Evaluation in Subgroups (1) | with medical surgical history | -2.3 scores on a scale | Standard Deviation 1.62 |
| DRSP 1 mg/EE 20 μg | Change From Baseline in Total Dysmenorrheal Score at Final Evaluation in Subgroups (1) | without medical surgical history | -2.6 scores on a scale | Standard Deviation 1.42 |
| DRSP 2 mg/EE 20 μg | Change From Baseline in Total Dysmenorrheal Score at Final Evaluation in Subgroups (1) | organic dysmenorrhea | -2.1 scores on a scale | Standard Deviation 1.49 |
| DRSP 2 mg/EE 20 μg | Change From Baseline in Total Dysmenorrheal Score at Final Evaluation in Subgroups (1) | functional dysmenorrhea | -2.1 scores on a scale | Standard Deviation 1.52 |
| DRSP 2 mg/EE 20 μg | Change From Baseline in Total Dysmenorrheal Score at Final Evaluation in Subgroups (1) | age: >= 30 years | -1.9 scores on a scale | Standard Deviation 1.49 |
| DRSP 2 mg/EE 20 μg | Change From Baseline in Total Dysmenorrheal Score at Final Evaluation in Subgroups (1) | without medical surgical history | -2.3 scores on a scale | Standard Deviation 1.53 |
| DRSP 2 mg/EE 20 μg | Change From Baseline in Total Dysmenorrheal Score at Final Evaluation in Subgroups (1) | with medical surgical history | -2.0 scores on a scale | Standard Deviation 1.5 |
| DRSP 2 mg/EE 20 μg | Change From Baseline in Total Dysmenorrheal Score at Final Evaluation in Subgroups (1) | weight: >= 50kg | -2.0 scores on a scale | Standard Deviation 1.64 |
| DRSP 2 mg/EE 20 μg | Change From Baseline in Total Dysmenorrheal Score at Final Evaluation in Subgroups (1) | weight: < 50 kg | -2.4 scores on a scale | Standard Deviation 0.99 |
| DRSP 2 mg/EE 20 μg | Change From Baseline in Total Dysmenorrheal Score at Final Evaluation in Subgroups (1) | age: < 30 years | -2.4 scores on a scale | Standard Deviation 1.5 |
| DRSP 3 mg/EE 20 μg | Change From Baseline in Total Dysmenorrheal Score at Final Evaluation in Subgroups (1) | with medical surgical history | -2.1 scores on a scale | Standard Deviation 1.61 |
| DRSP 3 mg/EE 20 μg | Change From Baseline in Total Dysmenorrheal Score at Final Evaluation in Subgroups (1) | weight: < 50 kg | -1.5 scores on a scale | Standard Deviation 1.39 |
| DRSP 3 mg/EE 20 μg | Change From Baseline in Total Dysmenorrheal Score at Final Evaluation in Subgroups (1) | weight: >= 50kg | -2.2 scores on a scale | Standard Deviation 1.74 |
| DRSP 3 mg/EE 20 μg | Change From Baseline in Total Dysmenorrheal Score at Final Evaluation in Subgroups (1) | functional dysmenorrhea | -1.8 scores on a scale | Standard Deviation 1.73 |
| DRSP 3 mg/EE 20 μg | Change From Baseline in Total Dysmenorrheal Score at Final Evaluation in Subgroups (1) | organic dysmenorrhea | -2.3 scores on a scale | Standard Deviation 1.37 |
| DRSP 3 mg/EE 20 μg | Change From Baseline in Total Dysmenorrheal Score at Final Evaluation in Subgroups (1) | without medical surgical history | -1.8 scores on a scale | Standard Deviation 1.66 |
| DRSP 3 mg/EE 20 μg | Change From Baseline in Total Dysmenorrheal Score at Final Evaluation in Subgroups (1) | age: < 30 years | -1.9 scores on a scale | Standard Deviation 1.49 |
| DRSP 3 mg/EE 20 μg | Change From Baseline in Total Dysmenorrheal Score at Final Evaluation in Subgroups (1) | age: >= 30 years | -1.9 scores on a scale | Standard Deviation 1.75 |
| Placebo | Change From Baseline in Total Dysmenorrheal Score at Final Evaluation in Subgroups (1) | weight: < 50 kg | -0.7 scores on a scale | Standard Deviation 1.65 |
| Placebo | Change From Baseline in Total Dysmenorrheal Score at Final Evaluation in Subgroups (1) | weight: >= 50kg | -1.1 scores on a scale | Standard Deviation 1.5 |
| Placebo | Change From Baseline in Total Dysmenorrheal Score at Final Evaluation in Subgroups (1) | age: >= 30 years | -0.8 scores on a scale | Standard Deviation 1.6 |
| Placebo | Change From Baseline in Total Dysmenorrheal Score at Final Evaluation in Subgroups (1) | age: < 30 years | -1.2 scores on a scale | Standard Deviation 1.45 |
| Placebo | Change From Baseline in Total Dysmenorrheal Score at Final Evaluation in Subgroups (1) | functional dysmenorrhea | -1.0 scores on a scale | Standard Deviation 1.47 |
| Placebo | Change From Baseline in Total Dysmenorrheal Score at Final Evaluation in Subgroups (1) | without medical surgical history | -0.8 scores on a scale | Standard Deviation 1.27 |
| Placebo | Change From Baseline in Total Dysmenorrheal Score at Final Evaluation in Subgroups (1) | with medical surgical history | -1.1 scores on a scale | Standard Deviation 1.68 |
| Placebo | Change From Baseline in Total Dysmenorrheal Score at Final Evaluation in Subgroups (1) | organic dysmenorrhea | -1.0 scores on a scale | Standard Deviation 1.7 |
Post Hoc
Change From Baseline in Total Dysmenorrheal Score at Final Evaluation in Subgroups (2)
Total dysmenorrheal score was defined as sum of 2 sub-scores: severity of dysmenorrhea (none: 0, mild: 1, moderate: 2, severe: 3) and use of analgesics (none: 0, mild: 1, moderate: 2, severe: 3). Total possible best is 0, and total possible worst is 6. Note: used with permission of Nobelpharma Co., Ltd. from the phase 3 clinical study protocol (Prog Med 2005:25 (3):739-758) of IKH-01 in dysmenorrhea (associated with endometriosis) (Nobelpharma Co., Ltd.)
Time frame: Baseline and up to 4 Cycles (28 days per cycle)
Population: FAS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| DRSP 1 mg/EE 20 μg | Change From Baseline in Total Dysmenorrheal Score at Final Evaluation in Subgroups (2) | with previous medication | -2.5 scores on a scale | Standard Deviation 1.53 |
| DRSP 1 mg/EE 20 μg | Change From Baseline in Total Dysmenorrheal Score at Final Evaluation in Subgroups (2) | total dysmenorrheal score at baseline: 3 or 4 | -2.1 scores on a scale | Standard Deviation 1.28 |
| DRSP 1 mg/EE 20 μg | Change From Baseline in Total Dysmenorrheal Score at Final Evaluation in Subgroups (2) | without birth history | -2.3 scores on a scale | Standard Deviation 1.49 |
| DRSP 1 mg/EE 20 μg | Change From Baseline in Total Dysmenorrheal Score at Final Evaluation in Subgroups (2) | total dysmenorrheal score at baseline: 5 or 6 | -3.4 scores on a scale | Standard Deviation 1.75 |
| DRSP 1 mg/EE 20 μg | Change From Baseline in Total Dysmenorrheal Score at Final Evaluation in Subgroups (2) | with pregnancy history | -2.7 scores on a scale | Standard Deviation 1.62 |
| DRSP 1 mg/EE 20 μg | Change From Baseline in Total Dysmenorrheal Score at Final Evaluation in Subgroups (2) | with birth history | -2.9 scores on a scale | Standard Deviation 1.59 |
| DRSP 1 mg/EE 20 μg | Change From Baseline in Total Dysmenorrheal Score at Final Evaluation in Subgroups (2) | without pregnancy history | -2.3 scores on a scale | Standard Deviation 1.47 |
| DRSP 2 mg/EE 20 μg | Change From Baseline in Total Dysmenorrheal Score at Final Evaluation in Subgroups (2) | total dysmenorrheal score at baseline: 3 or 4 | -1.9 scores on a scale | Standard Deviation 1.36 |
| DRSP 2 mg/EE 20 μg | Change From Baseline in Total Dysmenorrheal Score at Final Evaluation in Subgroups (2) | with previous medication | -2.1 scores on a scale | Standard Deviation 1.51 |
| DRSP 2 mg/EE 20 μg | Change From Baseline in Total Dysmenorrheal Score at Final Evaluation in Subgroups (2) | with birth history | -2.1 scores on a scale | Standard Deviation 1.28 |
| DRSP 2 mg/EE 20 μg | Change From Baseline in Total Dysmenorrheal Score at Final Evaluation in Subgroups (2) | without birth history | -2.1 scores on a scale | Standard Deviation 1.62 |
| DRSP 2 mg/EE 20 μg | Change From Baseline in Total Dysmenorrheal Score at Final Evaluation in Subgroups (2) | total dysmenorrheal score at baseline: 5 or 6 | -2.6 scores on a scale | Standard Deviation 1.77 |
| DRSP 2 mg/EE 20 μg | Change From Baseline in Total Dysmenorrheal Score at Final Evaluation in Subgroups (2) | with pregnancy history | -1.9 scores on a scale | Standard Deviation 1.32 |
| DRSP 2 mg/EE 20 μg | Change From Baseline in Total Dysmenorrheal Score at Final Evaluation in Subgroups (2) | without pregnancy history | -2.2 scores on a scale | Standard Deviation 1.62 |
| DRSP 3 mg/EE 20 μg | Change From Baseline in Total Dysmenorrheal Score at Final Evaluation in Subgroups (2) | with birth history | -2.3 scores on a scale | Standard Deviation 1.96 |
| DRSP 3 mg/EE 20 μg | Change From Baseline in Total Dysmenorrheal Score at Final Evaluation in Subgroups (2) | total dysmenorrheal score at baseline: 3 or 4 | -1.8 scores on a scale | Standard Deviation 1.44 |
| DRSP 3 mg/EE 20 μg | Change From Baseline in Total Dysmenorrheal Score at Final Evaluation in Subgroups (2) | total dysmenorrheal score at baseline: 5 or 6 | -2.4 scores on a scale | Standard Deviation 2.06 |
| DRSP 3 mg/EE 20 μg | Change From Baseline in Total Dysmenorrheal Score at Final Evaluation in Subgroups (2) | without pregnancy history | -1.8 scores on a scale | Standard Deviation 1.61 |
| DRSP 3 mg/EE 20 μg | Change From Baseline in Total Dysmenorrheal Score at Final Evaluation in Subgroups (2) | with pregnancy history | -2.2 scores on a scale | Standard Deviation 1.72 |
| DRSP 3 mg/EE 20 μg | Change From Baseline in Total Dysmenorrheal Score at Final Evaluation in Subgroups (2) | with previous medication | -1.9 scores on a scale | Standard Deviation 1.63 |
| DRSP 3 mg/EE 20 μg | Change From Baseline in Total Dysmenorrheal Score at Final Evaluation in Subgroups (2) | without birth history | -1.9 scores on a scale | Standard Deviation 1.55 |
| Placebo | Change From Baseline in Total Dysmenorrheal Score at Final Evaluation in Subgroups (2) | without birth history | -1.0 scores on a scale | Standard Deviation 1.35 |
| Placebo | Change From Baseline in Total Dysmenorrheal Score at Final Evaluation in Subgroups (2) | with birth history | -1.1 scores on a scale | Standard Deviation 2 |
| Placebo | Change From Baseline in Total Dysmenorrheal Score at Final Evaluation in Subgroups (2) | total dysmenorrheal score at baseline: 3 or 4 | -1.0 scores on a scale | Standard Deviation 1.49 |
| Placebo | Change From Baseline in Total Dysmenorrheal Score at Final Evaluation in Subgroups (2) | with previous medication | -1.0 scores on a scale | Standard Deviation 1.53 |
| Placebo | Change From Baseline in Total Dysmenorrheal Score at Final Evaluation in Subgroups (2) | without pregnancy history | -1.0 scores on a scale | Standard Deviation 1.22 |
| Placebo | Change From Baseline in Total Dysmenorrheal Score at Final Evaluation in Subgroups (2) | with pregnancy history | -1.0 scores on a scale | Standard Deviation 2.03 |
| Placebo | Change From Baseline in Total Dysmenorrheal Score at Final Evaluation in Subgroups (2) | total dysmenorrheal score at baseline: 5 or 6 | -1.1 scores on a scale | Standard Deviation 1.65 |