To Compare SH T00658ID Over Ortho Tri-Cyclen Lo (US/Canada)

Study Overview
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Brief Summary
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The objective of the study is to compare the oral contraceptive (OC) SH T00658ID over Ortho Tri-Cyclen Lo administered for 13 cycles to healthy female volunteers between 18 and 50 years of age who request oral contraceptive protection. Subjects on a levonorgestrel (LNG), norgestimate (NGM), norethindrone or norethindrone acetate containing oral contraceptive in a 21-day regimen suffering from hormone withdrawal-associated symptoms such as pelvic pain or headache or both, and willing to continue OC use but to switch to SH T00658ID or Ortho Tri-Cyclen Lo.

Detailed Description
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Safety issues are addressed in the Adverse Events section.

Official Title
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A Multicenter, Randomized, Double-blind, Active-controlled, Parallel Group, 2-arm Study to Show Superiority of the Oral Contraceptive SH T00658ID Over Ortho Tri-Cyclen Lo on Hormone Withdrawal-associated Symptoms After 6 Cycles of Treatment.

Conditions
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Contraception

Intervention / Treatment
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* Drug: Estradiol valerate, Dienogest (Natazia, Qlaira, BAY86-5027)
* Drug: Ortho Tri Cyclen Lo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed and dated informed consent Age between 18 and 50 years (inclusive), smokers maximum age of 35 years (inclusive) at Visit 1 Otherwise healthy female subjects requesting contraception and currently using a LNG, NGM, or norethindrone/norethindrone acetate containing OC in a 21-day regimen and suffering from at least moderate pelvic pain, headache or both defined by an average of the highest 3 values of >/=35 mm on a VAS during cycle days 22-28 (35 mm VAS is the expected standard deviation of the population VAS reduction) Normal or clinically insignificant cervical smear not requiring further follow up (a cervical smear has to be taken at screening visit or a normal result has to be documented within the last 6 months before screening) Women with atypical squamous cell of undetermined significance (ASCUS) can be included if they have a negative human papilloma virus (HPV) test result. The laboratory will perform an HPV test if the Pap smear result is ASCUS. Able to tolerate ibuprofen and willing to use only ibuprofen supplied by the investigator Exclusion Criteria: Pregnancy or lactation (less than three cycles since delivery, abortion, or lactation before start of treatment) Body mass index (BMI) >32 kg/m2 Hypersensitivity to any of the study drug ingredients Individuals not willing to consume pork and beef products. Women may be included if they are willing to take the capsules Safety relevant laboratory values, provided by the central laboratory, outside inclusion range before start of treatment Any diseases or conditions that can compromise the function of the body systems and could result in altered absorption, excessive accumulation, impaired metabolism, or altered excretion of the study medication (such as but not limited to duodenal ulcers, gastritis, gastrectomy or gastric resection surgery, or renal compromise) Any diseases or conditions that might interfere with the conduct of the study or the interpretation of the results Any disease or condition that may worsen under hormonal treatment Undiagnosed abnormal genital bleeding Abuse of alcohol, drugs, or medicines (eg, laxatives) Other contraceptive methods Any medication that could result in excessive accumulation, impaired metabolism, or altered excretion of the study drug or interfere with the conduct of the study or the interpretation of the results Simultaneous participation in another clinical trial prior to study entry that might have an impact on the study objectives at the discretion of the investigator Major surgery scheduled for the study period Subject is a dependent person, eg: a family member or member of the Investigator's staff Inability to cooperate with the study procedures for any reason, including language comprehension, psychiatric illness, inability to get to the study site

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Estradiol valerate, Dienogest (Natazia, Qlaira, BAY86-5027)<br>Daily oral administration of one capsule BAY86-5027 [estradiol valerate (EV) / dienogest (DNG)] for 26 days, followed by one capsule placebo for 2 days (28 days total per cycle) for 13 treatment cycles (treatment encapsulated) | Drug: Estradiol valerate, Dienogest (Natazia, Qlaira, BAY86-5027)<br>* Estradiol valerate (EV) and dienogest (DNG). Sequential 4-phasic regimen. Daily oral administration of one encapsulated BAY86-5027 for 28 days per Cycle, for 13 treatment cycles: Days 1-2, 3.0 mg EV; Days 3-7, 2.0 mg EV+2.0 mg DNG; Days 8-24, 2.0 mg EV+3.0 mg DNG; Days 25-26, 1.0 mg EV; Days 27-28, placebo<br>|
| Active Comparator: Ortho Tri-Cyclen Lo<br>Daily oral administration of one capsule Ortho Tri-Cyclen Lo [Ethinylestradiol (EE)/ Norgestimate (NGM)] for 21 days, followed by one capsule placebo for 7 days (28 days total per cycle) for 13 treatment cycles (treatment encapsulated) | Drug: Ortho Tri Cyclen Lo<br>* Dose--Ethinylestradiol (EE) + Norgestimate (NGM) Triphasic 21-day regimen. Daily oral administration of one encapsulated Ortho Tri-Cyclen Lo for 28 days per Cycle, for 13 treatment cycles: Days 1-7, 0.025 mg EE+0.180 NGM; Days 8-14, 0.025 mg EE+0.215 NGM; Days 15-21, 0.025 mg EE+0.250 NGM; Days 27-28, placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Change in Average of the 3 Highest Visual Analog Scale (VAS) Values of the Hormone Withdrawal-associated Symptoms Pelvic Pain or Headache During Cycle Days 22 to 28 From Baseline to Cycle 6 | Subject self-assessed pelvic pain or headache per visual analog scale (VAS) values during the menstrual/withdrawal bleeding episode and Baseline. The VAS consists of a 100 mm long straight line, with verbal anchors at either end, representing a continuum of pain intensity. Accordingly, the scale ranges from 0 mm (absence of pain) to 100 mm (unbearable pain), and the change ranges from -100 mm (best) to 100 mm (worst). | Day 22-28 from Baseline to Day 22-28 from Cycle 6 (28 days per Cycle) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Change From Baseline to Cycle 6 in the Number of Ibuprofen Tablets Used as Rescue Medication | Rescue medication use was standardized intake of 200 mg Ibuprofen tablets. Baseline period: 7 days (Day 22) before the first menstrual bleeding until Day 28 (normalized to a standard 28-day cycle). Treatment period: 7 days (Day 22) before the withdrawal bleeding (WB) of the 6th treatment cycle until Day 28 of the same cycle (normalized to a standard 28-day cycle). Number of tablets taken by each subject, and then the Mean and standard deviation (SD) derived. | From Baseline to Cycle 6 (28 days per Cycle) | 
| The Change From Baseline to Cycle 13 in the Number of Ibuprofen Tablets Used as Rescue Medication | Rescue medication use was standardized intake of 200 mg Ibuprofen tablets. Baseline period: 7 days (Day 22) before the first menstrual bleeding until Day 28 (normalized to a standard 28-day cycle). Treatment period: 7 days (Day 22) before the withdrawal bleeding (WB) of the 13th treatment cycle until Day 28 before the same cycle (normalized to a standard 28-day cycle). Number of tablets taken by each subject, and then the Mean and standard deviation ((SD) derived. | From Baseline to Cycle 13 (28 days per Cycle) | 
| Change From Baseline to Cycle 6 in the Number of Days With at Least Moderate Pain/Intensity of Other Hormone-related Symptoms During Cycle Days 22-28 | Pain (pelvic, headache, bloating or swelling, breast tenderness, nausea or vomiting) during menstrual/withdrawal bleeding (WB) episode during cycle Days 22-28. Scores per day: 0 No pain; 1 Mild pain with no need for painkiller; 2 Moderate pain with need for painkiller; 3 Severe pain with need for painkiller. Baseline period: cycle Days 22-28 before 1st menstrual bleeding (normalized to a 7-day period). Treatment period: cycle Days 22-28 before WB of 6th treatment cycle until (normalized to a 7-day period). Score difference min -7 (best), max 7 (worst). | Day 22-28 from Baseline to Day 22-28 from Cycle 6 (28 days per Cycle) | 
| Change From Baseline to Cycle 13 in the Number of Days With at Least Moderate Pain/Intensity of Other Hormone-related Symptoms During Cycle Days 22-28 | Pain (pelvic, headache, bloating or swelling, breast tenderness, nausea or vomiting) during menstrual/withdrawal bleeding (WB) episode during cycle Days 22-28. Scores per day: 0 No pain; 1 Mild pain with no need for painkiller; 2 Moderate pain with need for painkiller; 3 Severe pain with need for painkiller. Baseline period: cycle Days 22-28 before 1st menstrual bleeding (normalized to a 7-day period). Treatment period: cycle Days 22-28 before WB of 13th treatment cycle (normalized to a 7-day period). Score difference min -7 (best), max 7 (worst). | Day 22-28 from Baseline to Day 22-28 from Cycle 13 (28 days per Cycle) | 
| Change From Baseline to Cycle 6 in the Number of Days With at Least Moderate Pain/Intensity of Individual Hormone-related Symptoms During Cycle Days 1-21 | Pain (pelvic, headache, bloating or swelling, breast tenderness, nausea or vomiting) during menstrual/withdrawal bleeding (WB) episode during cycle Days 1-21. Scores per day: 0 No pain; 1 Mild pain with no need for painkiller; 2 Moderate pain with need for painkiller; 3 Severe pain with need for painkiller. Baseline period: cycle Days 1-21 before 1st menstrual bleeding (normalized to a 21-day period). Treatment period: cycle Days 1-21 before WB of 6th treatment cycle (normalized to a 21-day period). Score difference min -21 (best), max 21 (worst). | Day 1-21 from Baseline to Day 1-21 from Cycle 6 (28 days per Cycle) | 
| Change From Baseline to Cycle 13 in the Number of Days With at Least Moderate Pain/Intensity of Individual Hormone-related Symptoms During Cycle Days 1-21 | Pain (pelvic, headache, bloating or swelling, breast tenderness, nausea or vomiting) during menstrual/withdrawal bleeding (WB) episode during cycle Days 1-21. Scores per day: 0 No pain; 1 Mild pain with no need for painkiller; 2 Moderate pain with need for painkiller; 3 Severe pain with need for painkiller. Baseline period: cycle Days 1-21 before 1st menstrual bleeding (normalized to a 21-day period). Treatment period: cycle Days 1-21 before WB of 13th treatment cycle (normalized to a 21-day period). Score difference min -21 (best), max 21 (worst). | Day 1-21 from Baseline to Day 1-21 from Cycle 13 (28 days per Cycle) | 
| Change From Baseline to Cycle 6 in the Number of Days With at Least Moderate Pain/Intensity of Individual Hormone-related Symptoms During the Hormone-free Interval Cycle Days 27 to 28 for EV/DNG and Cycle Days 22 to 28 for EE/NGM | Pain (pelvic, headache, bloating or swelling, breast tenderness, nausea or vomiting) during menstrual/withdrawal bleeding (WB) episode (cycle Days 22-28). Scores per day: 0 No pain; 1 Mild pain with no need for painkiller; 2 Moderate pain with need for painkiller; 3 Severe pain with need for painkiller. Score difference min -2 (best), max 2 (worst) for the estradiol valerate (EV)/dienogest (DNG) group and min -7 (best), max 7 (worst) for the ethinylestradiol (EE)/norgestimate (NGM) group. | From Baseline to Cycle 6 (cycle Days 27 to 28 for EV/DNG and cycle Days 22 to 28 for EE/NGM, 28 days per Cycle) | 
| Change From Baseline to Cycle 13 in the Number of Days With at Least Moderate Pain/Intensity of Individual Hormone-related Symptoms During the Hormone-free Interval Cycle Days 27 to 28 for EV/DNG and Cycle Days 22 to 28 for EE/NGM | Pain (pelvic, headache, bloating or swelling, breast tenderness, nausea or vomiting) during menstrual/withdrawal bleeding (WB) episode (cycle Days 22-28). Scores per day: 0 No pain; 1 Mild pain with no need for painkiller; 2 Moderate pain with need for painkiller; 3 Severe pain with need for painkiller. Score difference min -2 (best), max 2 (worst) for the EV/DNG group and min -7 (best), max 7 (worst) for the EE/NGM group. | From Baseline to Cycle 13 (cycle Days 27 to 28 for EV/DNG and cycle Days 22 to 28 for EE/NGM, 28 days per Cycle) | 
| Change From Baseline to Cycle 3 in the Average of the Three Highest VAS Values of the Hormone Withdrawal-associated Symptoms Pelvic Pain or Headache During Cycle Days 22 to 28 | Subject self-assessed pelvic pain or headache per visual analog scale (VAS) values during the menstrual/withdrawal bleeding episode and Baseline. The VAS consists of a 100 mm long straight line, with verbal anchors at either end, representing a continuum of pain intensity. Accordingly, the scale ranges from 0 mm (absence of pain) to 100 mm (unbearable pain), and the change ranges from -100 mm (best) to 100 mm (worst). | Days 22-28 from Baseline to Days 22-28 from Cycle 3 (28 days per Cycle) | 
| Change From Baseline to Cycle 13 in the Average of the Three Highest VAS Values of the Hormone Withdrawal-associated Symptoms Pelvic Pain or Headache During Cycle Days 22 to 28 | Subject self-assessed pelvic pain or headache per visual analog scale (VAS) values during the menstrual/withdrawal bleeding episode and Baseline. The VAS consists of a 100 mm long straight line, with verbal anchors at either end, representing a continuum of pain intensity. Accordingly, the scale ranges from 0 mm (absence of pain) to 100 mm (unbearable pain), and the change ranges from -100 mm (best) to 100 mm (worst). | Days 22-28 from Baseline to Days 22-28 from Cycle 13 (28 days per Cycle) | 
| Number of Days With Bleeding or Spotting in Reference Period 1 | Reference Period 1 is defined as Day 1 to Day 90 during study treatment and includes the initial bleeding episode that triggered the first intake of study medication, meaning that the first treatment cycle includes 2 bleeding episodes. | From Day 1 to Day 90 | 
| Number of Days With Bleeding or Spotting in Reference Period 2 | Reference Period 2 is defined as Day 91 to Day 180 during study treatment. | From Day 91 to Day 180 | 
| Number of Days With Bleeding or Spotting in Reference Period 3 | Reference Period 3 is defined as Day 181 to Day 270 during study treatment. | From Day 181 to Day 270 | 
| Number of Days With Bleeding or Spotting in Reference Period 4 | Reference Period 4 is defined as Day 271 to Day 360 during study treatment. | From Day 271 to Day 360 | 
| Number of Bleeding / Spotting Episodes in Reference Period 1 | Reference Period 1 is defined as Day 1 to Day 90 during study treatment and includes the initial bleeding episode that triggered the first intake of study medication, meaning that the first treatment cycle includes 2 bleeding episodes. (Episode is a set of days with bleeding/spotting) | From Day 1 to Day 90 | 
| Number of Bleeding / Spotting Episodes in Reference Period 2 | Reference Period 2 is defined as Day 91 to Day 180 during study treatment. (Episode is a set of days with bleeding/spotting) | From Day 91 to Day 180 | 
| Number of Bleeding / Spotting Episodes in Reference Period 3 | Reference Period 3 is defined as Day 181 to Day 270 during study treatment. (Episode is a set of days with bleeding/spotting) | From Day 181 to Day 270 | 
| Number of Bleeding / Spotting Episodes in Reference Period 4 | Reference Period 4 is defined as Day 271 to Day 360 during study treatment. (Episode is a set of days with bleeding/spotting) | From Day 271 to Day 360 | 
| Mean Length of Bleeding / Spotting Episodes in Reference Period 1 | Reference Period 1 is defined as Day 1 to Day 90 during study treatment and includes the initial bleeding episode that triggered the first intake of study medication, meaning that the first treatment cycle includes 2 bleeding episodes. | From Day 1 to Day 90 | 
| Mean Length of Bleeding / Spotting Episodes in Reference Period 2 | Reference Period 2 is defined as Day 91 to Day 180 during study treatment. | From Day 91 to Day 180 | 
| Mean Length of Bleeding / Spotting Episodes in Reference Period 3 | Reference Period 3 is defined as Day 181 to Day 270 during study treatment. | From Day 181 to Day 270 | 
| Mean Length of Bleeding / Spotting Episodes in Reference Period 4 | Reference Period 4 is defined as Day 271 to Day 360 during study treatment. | From Day 271 to Day 360 | 
| Maximum Length of Bleeding / Spotting Episodes in Reference Period 1 | Reference Period 1 is defined as Day 1 to Day 90 during study treatment and includes the initial bleeding episode that triggered the first intake of study medication, meaning that the first treatment cycle includes 2 bleeding episodes. | From Day 1 to Day 90 | 
| Maximum Length of Bleeding / Spotting Episodes in Reference Period 2 | Reference Period 2 is defined as Day 91 to Day 180 during study treatment. | From Day 91 to Day 180 | 
| Maximum Length of Bleeding / Spotting Episodes in Reference Period 3 | Reference Period 3 is defined as Day 181 to Day 270 during study treatment. | From Day 181 to Day 270 | 
| Maximum Length of Bleeding / Spotting Episodes in Reference Period 4 | Reference Period 4 is defined as Day 271 to Day 360 during study treatment. | From Day 271 to Day 360 | 
| Difference in Duration Between Longest and Shortest Bleeding / Spotting Episodes in Reference Period 1 | Reference Period 1 is defined as Day 1 to Day 90 during study treatment and includes the initial bleeding episode that triggered the first intake of study medication, meaning that the first treatment cycle includes 2 bleeding episodes. | From Day 1 to Day 90 | 
| Difference in Duration Between Longest and Shortest Bleeding / Spotting Episodes in Reference Period 2 | Reference Period 2 is defined as Day 91 to Day 180 during study treatment. | From Day 91 to Day 180 | 
| Difference in Duration Between Longest and Shortest Bleeding / Spotting Episodes in Reference Period 3 | Reference Period 3 is defined as Day 181 to Day 270 during study treatment. | From Day 181 to Day 270 | 
| Difference in Duration Between Longest and Shortest Bleeding / Spotting Episodes in Reference Period 4 | Reference Period 4 is defined as Day 271 to Day 360 during study treatment. | From Day 271 to Day 360 | 
| Number of Days With Spotting-only in Reference Period 1 | Reference Period 1 is defined as Day 1 to Day 90 during study treatment. | From Day 1 to Day 90 | 
| Number of Days With Spotting-only in Reference Period 2 | Reference Period 2 is defined as Day 91 to Day 180 during study treatment. | From Day 91 to Day 180 | 
| Number of Days With Spotting-only in Reference Period 3 | Reference Period 3 is defined as Day 181 to Day 270 during study treatment. | From Day 181 to Day 270 | 
| Number of Days With Spotting-only in Reference Period 4 | Reference Period 4 is defined as Day 271 to Day 360 during study treatment. | From Day 271 to Day 360 | 
| Number of Spotting-only Episodes in Reference Period 1 | Reference Period 1 is defined as Day 1 to Day 90 during study treatment. | From Day 1 to Day 90 | 
| Number of Spotting-only Episodes in Reference Period 2 | Reference Period 2 is defined as Day 91 to Day 180 during study treatment. | From Day 91 to Day 180 | 
| Number of Spotting-only Episodes in Reference Period 3 | Reference Period 3 is defined as Day 181 to Day 270 during study treatment. | From Day 181 to Day 270 | 
| Number of Spotting-only Episodes in Reference Period 4 | Reference Period 4 is defined as Day 271 to Day 360 during study treatment. | From Day 271 to Day 360 | 
| Mean Length of Spotting-only Episodes in Reference Period 1 | Reference Period 1 is defined as Day 1 to Day 90 during study treatment. | From Day 1 to Day 90 | 
| Mean Length of Spotting-only Episodes in Reference Period 2 | Reference Period 2 is defined as Day 91 to Day 180 during study treatment. | From Day 91 to Day 180 | 
| Mean Length of Spotting-only Episodes in Reference Period 3 | Reference Period 3 is defined as Day 181 to Day 270 during study treatment. | From Day 181 to Day 270 | 
| Mean Length of Spotting-only Episodes in Reference Period 4 | Reference Period 4 is defined as Day 271 to Day 360 during study treatment. | From Day 271 to Day 360 | 
| Maximum Length of Spotting-only Episodes in Reference Period 1 | Reference Period 1 is defined as Day 1 to Day 90 during study treatment. | From Day 1 to Day 90 | 
| Maximum Length of Spotting-only Episodes in Reference Period 2 | Reference Period 2 is defined as Day 91 to Day 180 during study treatment. | From Day 91 to Day 180 | 
| Maximum Length of Spotting-only Episodes in Reference Period 3 | Reference Period 3 is defined as Day 181 to Day 270 during study treatment. | From Day 181 to Day 270 | 
| Maximum Length of Spotting-only Episodes in Reference Period 4 | Reference Period 4 is defined as Day 271 to Day 360 during study treatment. | From Day 271 to Day 360 | 
| Difference in Duration Between Longest and Shortest Spotting-only Episodes in Reference Period 1 | Reference Period 1 is defined as Day 1 to Day 90 during study treatment and includes the initial bleeding episode that triggered the first intake of study medication, meaning that the first treatment cycle includes 2 bleeding episodes. | From Day 1 to Day 90 | 
| Difference in Duration Between Longest and Shortest Spotting-only Episodes in Reference Period 2 | Reference Period 2 is defined as Day 91 to Day 180 during study treatment. | From Day 91 to Day 180 | 
| Difference in Duration Between Longest and Shortest Spotting-only Episodes in Reference Period 3 | Reference Period 3 is defined as Day 181 to Day 270 during study treatment. | From Day 181 to Day 270 | 
| Difference in Duration Between Longest and Shortest Spotting-only Episodes in Reference Period 4 | Reference Period 4 is defined as Day 271 to Day 360 during study treatment. | From Day 271 to Day 360 | 
| Percentage of Participants With / Without Withdrawal Bleeding at Cycle 1 | Withdrawal bleeding is bleeding that occurs when using oral contraceptives (OCs) caused by falling levels and/or taking away external source of estrogen and progestogen toward cycle end. | At Cycle 1 (28 days per Cycle) | 
| Percentage of Participants With / Without Withdrawal Bleeding at Cycle 3 | Withdrawal bleeding is bleeding that occurs when using oral contraceptives (OCs) caused by falling levels and/or taking away external source of estrogen and progestogen toward cycle end. | At Cycle 3 (28 days per Cycle) | 
| Percentage of Participants With / Without Withdrawal Bleeding at Cycle 6 | Withdrawal bleeding is bleeding that occurs when using oral contraceptives (OCs) caused by falling levels and/or taking away external source of estrogen and progestogen toward cycle end. | At Cycle 6 (28 days per Cycle) | 
| Percentage of Participants With / Without Withdrawal Bleeding at Cycle 13 | Withdrawal bleeding is bleeding that occurs when using oral contraceptives (OCs) caused by falling levels and/or taking away external source of estrogen and progestogen toward cycle end. | At Cycle 13 (28 days per Cycle) | 
| Length of Withdrawal Bleeding Episodes at Cycle 1 | Withdrawal bleeding is bleeding that occurs when using oral contraceptives (OCs) caused by falling levels and/or taking away external source of estrogen and progestogen toward cycle end. | At Cycle 1 (28 days per Cycle) | 
| Length of Withdrawal Bleeding Episodes at Cycle 3 | Withdrawal bleeding is bleeding that occurs when using oral contraceptives (OCs) caused by falling levels and/or taking away external source of estrogen and progestogen toward cycle end. | At Cycle 3 (28 days per Cycle) | 
| Length of Withdrawal Bleeding Episodes at Cycle 6 | Withdrawal bleeding is bleeding that occurs when using oral contraceptives (OCs) caused by falling levels and/or taking away external source of estrogen and progestogen toward cycle end. | At Cycle 6 (28 days per Cycle) | 
| Length of Withdrawal Bleeding Episodes at Cycle 13 | Withdrawal bleeding is bleeding that occurs when using oral contraceptives (OCs) caused by falling levels and/or taking away external source of estrogen and progestogen toward cycle end. | At Cycle 13 (28 days per Cycle) | 
| Maximum Intensity of Withdrawal Bleeding Episodes at Cycle 1 | Intensity was scored as 1=none, 2=spotting, 3=light, 4=normal, or 5=heavy. | At Cycle 1 (28 days per Cycle) | 
| Maximum Intensity of Withdrawal Bleeding Episodes at Cycle 3 | Intensity was scored as 1=none, 2=spotting, 3=light, 4=normal, or 5=heavy. | At Cycle 3 (28 days per Cycle) | 
| Maximum Intensity of Withdrawal Bleeding Episodes at Cycle 6 | Intensity was scored as 1=none, 2=spotting, 3=light, 4=normal, or 5=heavy. | At Cycle 6 (28 days per Cycle) | 
| Maximum Intensity of Withdrawal Bleeding Episodes at Cycle 13 | Intensity was scored as 1=none, 2=spotting, 3=light, 4=normal, or 5=heavy. | At Cycle 13 (28 days per Cycle) | 
| Onset of Withdrawal Bleeding Episodes at Cycle 1 | Onset was defined as the number of days between progestogen withdrawal and the first day of the withdrawal bleeding episode (ie, starting on or after Day 25 for EV/DNG and on or after Day 22 for EE/NGM). | At Cycle 1 (28 days per Cycle) | 
| Onset of Withdrawal Bleeding Episodes at Cycle 3 | Onset was defined as the number of days between progestogen withdrawal and the first day of the withdrawal bleeding episode (ie, starting on or after Day 25 for EV/DNG and on or after Day 22 for EE/NGM). | At Cycle 3 (28 days per Cycle) | 
| Onset of Withdrawal Bleeding Episodes at Cycle 6 | Onset was defined as the number of days between progestogen withdrawal and the first day of the withdrawal bleeding episode (ie, starting on or after Day 25 for EV/DNG and on or after Day 22 for EE/NGM). | At Cycle 6 (28 days per Cycle) | 
| Onset of Withdrawal Bleeding Episodes at Cycle 13 | Onset was defined as the number of days between progestogen withdrawal and the first day of the withdrawal bleeding episode (ie, starting on or after Day 25 for EV/DNG and on or after Day 22 for EE/NGM). | At Cycle 13 (28 days per Cycle) | 
| Percentage of Participants With Presence or Absence of Intracyclic Bleeding at Cycle 1 | Intracyclic bleeding is any unexpected bleeding episode occurring in cyclical treatment regimens. | At Cycle 1 (28 days per Cycle) | 
| Percentage of Participants With Presence or Absence of Intracyclic Bleeding at Cycle 3 | Intracyclic bleeding is any unexpected bleeding episode occurring in cyclical treatment regimens. | At Cycle 3 (28 days per Cycle) | 
| Percentage of Participants With Presence or Absence of Intracyclic Bleeding at Cycle 6 | Intracyclic bleeding is any unexpected bleeding episode occurring in cyclical treatment regimens. | At Cycle 6 (28 days per Cycle) | 
| Percentage of Participants With Presence or Absence of Intracyclic Bleeding at Cycle 13 | Intracyclic bleeding is any unexpected bleeding episode occurring in cyclical treatment regimens. | At Cycle 13 (28 days per Cycle) | 
| Number of Intracyclic Bleeding Episodes at Cycle 1 | Intracyclic bleeding is any unexpected bleeding episode occurring in cyclical treatment regimens. (Episode is a set of days with intracyclic bleeding) | At Cycle 1 (28 days per Cycle) | 
| Number of Intracyclic Bleeding Episodes at Cycle 3 | Intracyclic bleeding is any unexpected bleeding episode occurring in cyclical treatment regimens. (Episode is a set of days with intracyclic bleeding) | At Cycle 3 (28 days per Cycle) | 
| Number of Intracyclic Bleeding Episodes at Cycle 6 | Intracyclic bleeding is any unexpected bleeding episode occurring in cyclical treatment regimens. (Episode is a set of days with intracyclic bleeding) | At Cycle 6 (28 days per Cycle) | 
| Number of Intracyclic Bleeding Episodes at Cycle 13 | Intracyclic bleeding is any unexpected bleeding episode occurring in cyclical treatment regimens. (Episode is a set of days with intracyclic bleeding) | At Cycle 13 (28 days per Cycle) | 
| Maximum Length of Intracyclic Bleeding Episodes at Cycle 1 | Intracyclic bleeding is any unexpected bleeding episode occurring in cyclical treatment regimens. | At Cycle 1 (28 days per Cycle) | 
| Maximum Length of Intracyclic Bleeding Episodes at Cycle 3 | Intracyclic bleeding is any unexpected bleeding episode occurring in cyclical treatment regimens. | At Cycle 3 (28 days per Cycle) | 
| Maximum Length of Intracyclic Bleeding Episodes at Cycle 6 | Intracyclic bleeding is any unexpected bleeding episode occurring in cyclical treatment regimens. | At Cycle 6 (28 days per Cycle) | 
| Maximum Length of Intracyclic Bleeding Episodes at Cycle 13 | Intracyclic bleeding is any unexpected bleeding episode occurring in cyclical treatment regimens. | At Cycle 13 (28 days per Cycle) | 
| Number of Intracyclic Bleeding Days at Cycle 1 | Intracyclic bleeding is any unexpected bleeding episode occurring in cyclical treatment regimens. | At Cycle 1 (28 days per Cycle) | 
| Number of Intracyclic Bleeding Days at Cycle 3 | Intracyclic bleeding is any unexpected bleeding episode occurring in cyclical treatment regimens. | At Cycle 3 (28 days per Cycle) | 
| Number of Intracyclic Bleeding Days at Cycle 6 | Intracyclic bleeding is any unexpected bleeding episode occurring in cyclical treatment regimens. | At Cycle 6 (28 days per Cycle) | 
| Number of Intracyclic Bleeding Days at Cycle 13 | Intracyclic bleeding is any unexpected bleeding episode occurring in cyclical treatment regimens. | At Cycle 13 (28 days per Cycle) | 
| Percentage of Participants by Maximum Intensity of Intracyclic Bleeding Episodes at Cycle 1 | Intracyclic bleeding is any unexpected bleeding episode occurring in cyclical treatment regimens. Intensity was scored as 1=none, 2=spotting, 3=light, 4=normal, or 5=heavy. | At Cycle 1 (28 days per Cycle) | 
| Percentage of Participants by Maximum Intensity of Intracyclic Bleeding Episodes at Cycle 3 | Intracyclic bleeding is any unexpected bleeding episode occurring in cyclical treatment regimens. Intensity was scored as 1=none, 2=spotting, 3=light, 4=normal, or 5=heavy. | At Cycle 3 (28 days per Cycle) | 
| Percentage of Participants by Maximum Intensity of Intracyclic Bleeding Episodes at Cycle 6 | Intracyclic bleeding is any unexpected bleeding episode occurring in cyclical treatment regimens. Intensity was scored as 1=none, 2=spotting, 3=light, 4=normal, or 5=heavy. | At Cycle 6 (28 days per Cycle) | 
| Percentage of Participants by Maximum Intensity of Intracyclic Bleeding Episodes at Cycle 13 | Intracyclic bleeding is any unexpected bleeding episode occurring in cyclical treatment regimens. Intensity was scored as 1=none, 2=spotting, 3=light, 4=normal, or 5=heavy. | At Cycle 13 (28 days per Cycle) | 
| Percentage of Participants With at Least 1 Intracyclic Bleeding Episode at Cycles 2 to 6 | Intracyclic bleeding is any unexpected bleeding episode occurring in cyclical treatment regimens. | Cycles 2 to 6 (28 days per Cycle) | 
| Percentage of Participants With at Least 1 Intracyclic Bleeding Episode at Cycles 2 to 13 | Intracyclic bleeding is any unexpected bleeding episode occurring in cyclical treatment regimens. | Cycles 2 to 13 (28 days per Cycle) | 
| Mean Change From Baseline to Cycle 6 in Psychological General Well-Being Index (PGWBI) | Change from Baseline to Cycle 6 in PGWBI Questionnaire's assessment of participant's overall sense of well-being or distress. The PGWBI includes 22 items that, apart from combining into a global overall score, are divided into 6 dimensions: anxiety, depressed mood, positive well-being, self-control, health, and vitality. The response format used a 6-grade Likert scale and the change in the normalized PGWBI global score as well as all the sub-domains score ranges from -100 (worst) to 100 (best). | Baseline up to Cycle 6 (28 days per Cycle) | 
| Mean Change From Baseline to Cycle 13 in Psychological General Well-Being Index (PGWBI) | Change from Baseline to Cycle 13 in PGWBI Questionnaire's assessment of participant's overall sense of well-being or distress. The PGWBI includes 22 items that, apart from combining into a global overall score, are divided into 6 dimensions: anxiety, depressed mood, positive well-being, self-control, health, and vitality. The response format used a 6-grade Likert scale and the change in the normalized PGWBI global score as well as all the sub-domains score ranges from -100 (worst) to 100 (best). | Baseline up to Cycle 13 (28 days per Cycle) | 
| Mean Change From Baseline to Cycle 6 in Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) - Physical Health | Change from Baseline to Cycle 6 in the overall enjoyment and satisfaction experienced during the past week as scored on the Q-LES-Q (physical health - 13 items). 1-5 scale (very poor, poor, fair, good, very good). The normalized score ranges from 0 (worst) to 100 (best). The change in the normalized score ranges from -100 (worst) to 100 (best). | Baseline up to Cycle 6 (28 days per Cycle) | 
| Mean Change From Baseline to Cycle 13 in Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) - Physical Health | Change from Baseline to Cycle 13 in the overall enjoyment and satisfaction experienced during the past week as scored on the Q-LES-Q (physical health - 13 items). 1-5 scale (very poor, poor, fair, good, very good). The normalized score ranges from 0 (worst) to 100 (best). The change in the normalized score ranges from -100 (worst) to 100 (best). | Baseline up to Cycle 13 (28 days per Cycle) | 
| Mean Change From Baseline to Cycle 6 in Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) - Participant Feeling | Change from Baseline to Cycle 6 in the overall enjoyment and satisfaction experienced during the past week as scored on the Q-LES-Q (participant feeling - 14 items). 1-5 scale (very poor, poor, fair, good, very good). The normalized score ranges from 0 (worst) to 100 (best). The change in the normalized score ranges from -100 (worst) to 100 (best). | Baseline up to Cycle 6 (28 days per Cycle) | 
| Mean Change From Baseline to Cycle 13 in Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) - Participant Feeling | Change from Baseline to Cycle 13 in the overall enjoyment and satisfaction experienced during the past week as scored on the Q-LES-Q (participant feeling - 14 items). 1-5 scale (very poor, poor, fair, good, very good). The normalized score ranges from 0 (worst) to 100 (best). The change in the normalized score ranges from -100 (worst) to 100 (best). | Baseline up to Cycle 13 (28 days per Cycle) | 
| Mean Change From Baseline to Cycle 6 in Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) - Work | Change from Baseline to Cycle 6 in the overall enjoyment and satisfaction experienced during the past week as scored on the Q-LES-Q (work - yes or no; if yes, then 4 choices, and 13 items with a scale of 1-5 [very poor, poor, fair, good, very good]). The normalized score ranges from 0 (worst) to 100 (best). The change in the normalized score ranges from -100 (worst) to 100 (best). | Baseline up to Cycle 6 (28 days per Cycle) | 
| Mean Change From Baseline to Cycle 13 in Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) - Work | Change from Baseline to Cycle 13 in the overall enjoyment and satisfaction experienced during the past week as scored on the Q-LES-Q (work - yes or no; if yes, then 4 choices, and 13 items with a scale of 1-5 [very poor, poor, fair, good, very good]). The normalized score ranges from 0 (worst) to 100 (best). The change in the normalized score ranges from -100 (worst) to 100 (best). | Baseline up to Cycle 13 (28 days per Cycle) | 
| Mean Change From Baseline to Cycle 6 in Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) - Household Duties | Change from Baseline to Cycle 6 in the overall enjoyment and satisfaction experienced during the past week as scored on the Q-LES-Q (household duties - yes or no; if yes, then 4 choices, and 10 items with a scale of 1-5 [very poor, poor, fair, good, very good]). The normalized score ranges from 0 (worst) to 100 (best). The change in the normalized score ranges from -100 (worst) to 100 (best). | Baseline up to Cycle 6 (28 days per Cycle) | 
| Mean Change From Baseline to Cycle 13 in Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) - Household Duties | Change from Baseline to Cycle 13 in the overall enjoyment and satisfaction experienced during the past week as scored on the Q-LES-Q (household duties - yes or no; if yes, then 4 choices, and 10 items with a scale of 1-5 [very poor, poor, fair, good, very good]). The normalized score ranges from 0 (worst) to 100 (best). The change in the normalized score ranges from -100 (worst) to 100 (best). | Baseline up to Cycle 13 (28 days per Cycle) | 
| Mean Change From Baseline to Cycle 6 in Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) - School/Course Work | Change from Baseline to Cycle 6 in the overall enjoyment and satisfaction experienced during the past week as scored on the Q-LES-Q (school / course work - yes or no; if yes, then 4 choices, and 10 items with a scale of 1-5 (very poor, poor, fair, good, very good). The normalized score ranges from 0 (worst) to 100 (best). The change in the normalized score ranges from -100 (worst) to 100 (best). | Baseline up to Cycle 6 (28 days per Cycle) | 
| Mean Change From Baseline to Cycle 13 in Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) - School/Course Work | Change from Baseline to Cycle 13 in the overall enjoyment and satisfaction experienced during the past week as scored on the Q-LES-Q (school / course work - yes or no; if yes, then 4 choices, and 10 items with a scale of 1-5 (very poor, poor, fair, good, very good). The normalized score ranges from 0 (worst) to 100 (best). The change in the normalized score ranges from -100 (worst) to 100 (best). | Baseline up to Cycle 13 (28 days per Cycle) | 
| Mean Change From Baseline to Cycle 6 in Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) - Leisure Time Activities | Change from Baseline to Cycle 6 in the overall enjoyment and satisfaction experienced during the past week as scored on the Q-LES-Q (leisure time activities - 6 items). 1-5 scale (very poor, poor, fair, good, very good). The normalized score ranges from 0 (worst) to 100 (best). The change in the normalized score ranges from -100 (worst) to 100 (best). | Baseline up to Cycle 6 (28 days per Cycle) | 
| Mean Change From Baseline to Cycle 13 in Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) - Leisure Time Activities | Change from Baseline to Cycle 13 in the overall enjoyment and satisfaction experienced during the past week as scored on the Q-LES-Q (leisure time activities - 6 items). 1-5 scale (very poor, poor, fair, good, very good). The normalized score ranges from 0 (worst) to 100 (best). The change in the normalized score ranges from -100 (worst) to 100 (best). | Baseline up to Cycle 13 (28 days per Cycle) | 
| Mean Change From Baseline to Cycle 6 in Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) - Social Relationship | Change from Baseline to Cycle 6 in the overall enjoyment and satisfaction experienced during the past week as scored on the Q-LES-Q (social relationship - 11 items). 1-5 scale (very poor, poor, fair, good, very good). The normalized score ranges from 0 (worst) to 100 (best). The change in the normalized score ranges from -100 (worst) to 100 (best). | Baseline up to Cycle 6 (28 days per Cycle) | 
| Mean Change From Baseline to Cycle 13 in Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) - Social Relationship | Change from Baseline to Cycle 13 in the overall enjoyment and satisfaction experienced during the past week as scored on the Q-LES-Q (social relationship - 11 items). 1-5 scale (very poor, poor, fair, good, very good). The normalized score ranges from 0 (worst) to 100 (best). The change in the normalized score ranges from -100 (worst) to 100 (best). | Baseline up to Cycle 13 (28 days per Cycle) | 
| Mean Change From Baseline to Cycle 6 in Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) - General Activities | Change from Baseline to Cycle 6 in the overall enjoyment and satisfaction experienced during the past week as scored on the Q-LES-Q (general activities - 16 items). 1-5 scale (very poor, poor, fair, good, very good). The normalized score ranges from 0 (worst) to 100 (best). The change in the normalized score ranges from -100 (worst) to 100 (best). | Baseline up to Cycle 6 (28 days per Cycle) | 
| Mean Change From Baseline to Cycle 13 in Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) - General Activities | Change from Baseline to Cycle 13 in the overall enjoyment and satisfaction experienced during the past week as scored on the Q-LES-Q (general activities - 16 items). 1-5 scale (very poor, poor, fair, good, very good). The normalized score ranges from 0 (worst) to 100 (best). The change in the normalized score ranges from -100 (worst) to 100 (best). | Baseline up to Cycle 13 (28 days per Cycle) | 
| Mean Change From Baseline to Cycle 6 in Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) - Item Satisfaction | Change from Baseline to Cycle 6 in the overall enjoyment and satisfaction experienced during the past week as scored on the Q-LES-Q (item satisfaction). 1-5 scale (very poor, poor, fair, good, very good). The normalized score ranges from 0 (worst) to 100 (best). The change in the normalized score ranges from -100 (worst) to 100 (best). | Baseline up to Cycle 6 (28 days per Cycle) | 
| Mean Change From Baseline to Cycle 13 in Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) - Item Satisfaction | Change from Baseline to Cycle 13 in the overall enjoyment and satisfaction experienced during the past week as scored on the Q-LES-Q (item satisfaction). 1-5 scale (very poor, poor, fair, good, very good). The normalized score ranges from 0 (worst) to 100 (best). The change in the normalized score ranges from -100 (worst) to 100 (best). | Baseline up to Cycle 13 (28 days per Cycle) | 
| Mean Change From Baseline to Cycle 6 in Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) - Overall Life Satisfaction and Contentment | Change from Baseline to Cycle 6 in the overall enjoyment and satisfaction experienced during the past week as scored on the Q-LES-Q (overall life satisfaction and contentment). 1-5 scale (very poor, poor, fair, good, very good). The normalized score ranges from 0 (worst) to 100 (best). The change in the normalized score ranges from -100 (worst) to 100 (best). | Baseline up to Cycle 6 (28 days per Cycle) | 
| Mean Change From Baseline to Cycle 13 in Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) - Overall Life Satisfaction and Contentment | Change from Baseline to Cycle 13 in the overall enjoyment and satisfaction experienced during the past week as scored on the Q-LES-Q (overall life satisfaction and contentment). 1-5 scale (very poor, poor, fair, good, very good). The normalized score ranges from 0 (worst) to 100 (best). The change in the normalized score ranges from -100 (worst) to 100 (best). | Baseline up to Cycle 13 (28 days per Cycle) | 
| Percentage of Participants With Improvement in the Investigator's Assessment in Clinical Global Impression (CGI) at Cycle 6 | CGI is used to collect information regarding the subject's total clinical experience. The assessment scale ranges from 0 to 7: (0=not assessed; 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; 7=very much worse). The scale of 1, 2, and 3 were categorized as improvement. | At Cycle 6 (28 days per Cycle) | 
| Percentage of Participants With Improvement in the Investigator's Assessment in Clinical Global Impression (CGI) at Cycle 13 | CGI is used to collect information regarding the subject's total clinical experience. The assessment scale ranges from 0 to 7: (0=not assessed; 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; 7=very much worse). The scale of 1, 2, and 3 were categorized as improvement. | At Cycle 13 (28 days per Cycle) | 
| Percentage of Participants With Improvement in the Participant's Assessment in Clinical Global Impression (CGI) at Cycle 6 | In 1 section of the CGI the subject rates their total improvement and rate of satisfaction with sexuality during treatment. The assessment scale ranges from 0 to 7: (0=not assessed; 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; 7=very much worse). The scale of 1, 2, and 3 were categorized as improvement. | At Cycle 6 (28 days per Cycle) | 
| Percentage of Participants With Improvement in the Participant's Assessment in Clinical Global Impression (CGI) at Cycle 13 | In 1 section of the CGI the subject rates their total improvement and rate of satisfaction with sexuality during treatment. The assessment scale ranges from 0 to 7: (0=not assessed; 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; 7=very much worse). The scale of 1, 2, and 3 were categorized as improvement. | At Cycle 13 (28 days per Cycle) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Oral contraceptive, Estradiol valerate and dienogest, EV/DNG, comparative tolerability