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

Keywords

• Oral contraceptive
• Estradiol valerate and dienogest
• EV/DNG
• comparative tolerability

Lead sponsor

Bayer is the lead sponsor of 1,643 studies on the registry; 57 are open to participants now.

Of its 209 completed or terminated interventional studies of FDA-regulated products, 129 (62%) have results posted.

Study arms

• Experimental
  Estradiol valerate, Dienogest (Natazia, Qlaira, BAY86-5027)

  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)

• Active comparator
  Ortho Tri-Cyclen Lo

  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

Interventions

• DrugEstradiol valerate, Dienogest (Natazia, Qlaira, BAY86-5027)

  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

• DrugOrtho Tri Cyclen Lo

  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

Primary outcomes

1. 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).

   Time frame: Day 22-28 from Baseline to Day 22-28 from Cycle 6 (28 days per Cycle)

Secondary outcomes

1. 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.

   Time frame: From Baseline to Cycle 6 (28 days per Cycle)

2. 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.

   Time frame: From Baseline to Cycle 13 (28 days per Cycle)

3. 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).

   Time frame: Day 22-28 from Baseline to Day 22-28 from Cycle 6 (28 days per Cycle)

4. 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).

   Time frame: Day 22-28 from Baseline to Day 22-28 from Cycle 13 (28 days per Cycle)

5. 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).

   Time frame: Day 1-21 from Baseline to Day 1-21 from Cycle 6 (28 days per Cycle)

6. 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).

   Time frame: Day 1-21 from Baseline to Day 1-21 from Cycle 13 (28 days per Cycle)

7. 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.

   Time frame: 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)

8. 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.

   Time frame: 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)

9. 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).

   Time frame: Days 22-28 from Baseline to Days 22-28 from Cycle 3 (28 days per Cycle)

10. 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).

    Time frame: Days 22-28 from Baseline to Days 22-28 from Cycle 13 (28 days per Cycle)

11. 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.

    Time frame: From Day 1 to Day 90

12. 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.

    Time frame: From Day 91 to Day 180

13. 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.

    Time frame: From Day 181 to Day 270

14. 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.

    Time frame: From Day 271 to Day 360

15. 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)

    Time frame: From Day 1 to Day 90

16. 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)

    Time frame: From Day 91 to Day 180

17. 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)

    Time frame: From Day 181 to Day 270

18. 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)

    Time frame: From Day 271 to Day 360

19. 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.

    Time frame: From Day 1 to Day 90

20. Mean Length of Bleeding / Spotting Episodes in Reference Period 2

    Reference Period 2 is defined as Day 91 to Day 180 during study treatment.

    Time frame: From Day 91 to Day 180

21. Mean Length of Bleeding / Spotting Episodes in Reference Period 3

    Reference Period 3 is defined as Day 181 to Day 270 during study treatment.

    Time frame: From Day 181 to Day 270

22. Mean Length of Bleeding / Spotting Episodes in Reference Period 4

    Reference Period 4 is defined as Day 271 to Day 360 during study treatment.

    Time frame: From Day 271 to Day 360

23. 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.

    Time frame: From Day 1 to Day 90

24. Maximum Length of Bleeding / Spotting Episodes in Reference Period 2

    Reference Period 2 is defined as Day 91 to Day 180 during study treatment.

    Time frame: From Day 91 to Day 180

25. Maximum Length of Bleeding / Spotting Episodes in Reference Period 3

    Reference Period 3 is defined as Day 181 to Day 270 during study treatment.

    Time frame: From Day 181 to Day 270

26. Maximum Length of Bleeding / Spotting Episodes in Reference Period 4

    Reference Period 4 is defined as Day 271 to Day 360 during study treatment.

    Time frame: From Day 271 to Day 360

27. 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.

    Time frame: From Day 1 to Day 90

28. 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.

    Time frame: From Day 91 to Day 180

29. 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.

    Time frame: From Day 181 to Day 270

30. 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.

    Time frame: From Day 271 to Day 360

31. Number of Days With Spotting-only in Reference Period 1

    Reference Period 1 is defined as Day 1 to Day 90 during study treatment.

    Time frame: From Day 1 to Day 90

32. Number of Days With Spotting-only in Reference Period 2

    Reference Period 2 is defined as Day 91 to Day 180 during study treatment.

    Time frame: From Day 91 to Day 180

33. Number of Days With Spotting-only in Reference Period 3

    Reference Period 3 is defined as Day 181 to Day 270 during study treatment.

    Time frame: From Day 181 to Day 270

34. Number of Days With Spotting-only in Reference Period 4

    Reference Period 4 is defined as Day 271 to Day 360 during study treatment.

    Time frame: From Day 271 to Day 360

35. Number of Spotting-only Episodes in Reference Period 1

    Reference Period 1 is defined as Day 1 to Day 90 during study treatment.

    Time frame: From Day 1 to Day 90

36. Number of Spotting-only Episodes in Reference Period 2

    Reference Period 2 is defined as Day 91 to Day 180 during study treatment.

    Time frame: From Day 91 to Day 180

37. Number of Spotting-only Episodes in Reference Period 3

    Reference Period 3 is defined as Day 181 to Day 270 during study treatment.

    Time frame: From Day 181 to Day 270

38. Number of Spotting-only Episodes in Reference Period 4

    Reference Period 4 is defined as Day 271 to Day 360 during study treatment.

    Time frame: From Day 271 to Day 360

39. Mean Length of Spotting-only Episodes in Reference Period 1

    Reference Period 1 is defined as Day 1 to Day 90 during study treatment.

    Time frame: From Day 1 to Day 90

40. Mean Length of Spotting-only Episodes in Reference Period 2

    Reference Period 2 is defined as Day 91 to Day 180 during study treatment.

    Time frame: From Day 91 to Day 180

41. Mean Length of Spotting-only Episodes in Reference Period 3

    Reference Period 3 is defined as Day 181 to Day 270 during study treatment.

    Time frame: From Day 181 to Day 270

42. Mean Length of Spotting-only Episodes in Reference Period 4

    Reference Period 4 is defined as Day 271 to Day 360 during study treatment.

    Time frame: From Day 271 to Day 360

43. Maximum Length of Spotting-only Episodes in Reference Period 1

    Reference Period 1 is defined as Day 1 to Day 90 during study treatment.

    Time frame: From Day 1 to Day 90

44. Maximum Length of Spotting-only Episodes in Reference Period 2

    Reference Period 2 is defined as Day 91 to Day 180 during study treatment.

    Time frame: From Day 91 to Day 180

45. Maximum Length of Spotting-only Episodes in Reference Period 3

    Reference Period 3 is defined as Day 181 to Day 270 during study treatment.

    Time frame: From Day 181 to Day 270

46. Maximum Length of Spotting-only Episodes in Reference Period 4

    Reference Period 4 is defined as Day 271 to Day 360 during study treatment.

    Time frame: From Day 271 to Day 360

47. 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.

    Time frame: From Day 1 to Day 90

48. 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.

    Time frame: From Day 91 to Day 180

49. 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.

    Time frame: From Day 181 to Day 270

50. 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.

    Time frame: From Day 271 to Day 360

51. 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.

    Time frame: At Cycle 1 (28 days per Cycle)

52. 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.

    Time frame: At Cycle 3 (28 days per Cycle)

53. 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.

    Time frame: At Cycle 6 (28 days per Cycle)

54. 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.

    Time frame: At Cycle 13 (28 days per Cycle)

55. 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.

    Time frame: At Cycle 1 (28 days per Cycle)

56. 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.

    Time frame: At Cycle 3 (28 days per Cycle)

57. 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.

    Time frame: At Cycle 6 (28 days per Cycle)

58. 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.

    Time frame: At Cycle 13 (28 days per Cycle)

59. Maximum Intensity of Withdrawal Bleeding Episodes at Cycle 1

    Intensity was scored as 1=none, 2=spotting, 3=light, 4=normal, or 5=heavy.

    Time frame: At Cycle 1 (28 days per Cycle)

60. Maximum Intensity of Withdrawal Bleeding Episodes at Cycle 3

    Intensity was scored as 1=none, 2=spotting, 3=light, 4=normal, or 5=heavy.

    Time frame: At Cycle 3 (28 days per Cycle)

61. Maximum Intensity of Withdrawal Bleeding Episodes at Cycle 6

    Intensity was scored as 1=none, 2=spotting, 3=light, 4=normal, or 5=heavy.

    Time frame: At Cycle 6 (28 days per Cycle)

62. Maximum Intensity of Withdrawal Bleeding Episodes at Cycle 13

    Intensity was scored as 1=none, 2=spotting, 3=light, 4=normal, or 5=heavy.

    Time frame: At Cycle 13 (28 days per Cycle)

63. 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).

    Time frame: At Cycle 1 (28 days per Cycle)

64. 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).

    Time frame: At Cycle 3 (28 days per Cycle)

65. 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).

    Time frame: At Cycle 6 (28 days per Cycle)

66. 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).

    Time frame: At Cycle 13 (28 days per Cycle)

67. 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.

    Time frame: At Cycle 1 (28 days per Cycle)

68. 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.

    Time frame: At Cycle 3 (28 days per Cycle)

69. 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.

    Time frame: At Cycle 6 (28 days per Cycle)

70. 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.

    Time frame: At Cycle 13 (28 days per Cycle)

71. 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)

    Time frame: At Cycle 1 (28 days per Cycle)

72. 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)

    Time frame: At Cycle 3 (28 days per Cycle)

73. 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)

    Time frame: At Cycle 6 (28 days per Cycle)

74. 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)

    Time frame: At Cycle 13 (28 days per Cycle)

75. Maximum Length of Intracyclic Bleeding Episodes at Cycle 1

    Intracyclic bleeding is any unexpected bleeding episode occurring in cyclical treatment regimens.

    Time frame: At Cycle 1 (28 days per Cycle)

76. Maximum Length of Intracyclic Bleeding Episodes at Cycle 3

    Intracyclic bleeding is any unexpected bleeding episode occurring in cyclical treatment regimens.

    Time frame: At Cycle 3 (28 days per Cycle)

77. Maximum Length of Intracyclic Bleeding Episodes at Cycle 6

    Intracyclic bleeding is any unexpected bleeding episode occurring in cyclical treatment regimens.

    Time frame: At Cycle 6 (28 days per Cycle)

78. Maximum Length of Intracyclic Bleeding Episodes at Cycle 13

    Intracyclic bleeding is any unexpected bleeding episode occurring in cyclical treatment regimens.

    Time frame: At Cycle 13 (28 days per Cycle)

79. Number of Intracyclic Bleeding Days at Cycle 1

    Intracyclic bleeding is any unexpected bleeding episode occurring in cyclical treatment regimens.

    Time frame: At Cycle 1 (28 days per Cycle)

80. Number of Intracyclic Bleeding Days at Cycle 3

    Intracyclic bleeding is any unexpected bleeding episode occurring in cyclical treatment regimens.

    Time frame: At Cycle 3 (28 days per Cycle)

81. Number of Intracyclic Bleeding Days at Cycle 6

    Intracyclic bleeding is any unexpected bleeding episode occurring in cyclical treatment regimens.

    Time frame: At Cycle 6 (28 days per Cycle)

82. Number of Intracyclic Bleeding Days at Cycle 13

    Intracyclic bleeding is any unexpected bleeding episode occurring in cyclical treatment regimens.

    Time frame: At Cycle 13 (28 days per Cycle)

83. 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.

    Time frame: At Cycle 1 (28 days per Cycle)

84. 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.

    Time frame: At Cycle 3 (28 days per Cycle)

85. 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.

    Time frame: At Cycle 6 (28 days per Cycle)

86. 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.

    Time frame: At Cycle 13 (28 days per Cycle)

87. 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.

    Time frame: Cycles 2 to 6 (28 days per Cycle)

88. 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.

    Time frame: Cycles 2 to 13 (28 days per Cycle)

89. 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).

    Time frame: Baseline up to Cycle 6 (28 days per Cycle)

90. 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).

    Time frame: Baseline up to Cycle 13 (28 days per Cycle)

91. 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).

    Time frame: Baseline up to Cycle 6 (28 days per Cycle)

92. 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).

    Time frame: Baseline up to Cycle 13 (28 days per Cycle)

93. 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).

    Time frame: Baseline up to Cycle 6 (28 days per Cycle)

94. 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).

    Time frame: Baseline up to Cycle 13 (28 days per Cycle)

95. 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).

    Time frame: Baseline up to Cycle 6 (28 days per Cycle)

96. 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).

    Time frame: Baseline up to Cycle 13 (28 days per Cycle)

97. 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).

    Time frame: Baseline up to Cycle 6 (28 days per Cycle)

98. 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).

    Time frame: Baseline up to Cycle 13 (28 days per Cycle)

99. 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).

    Time frame: Baseline up to Cycle 6 (28 days per Cycle)

100. 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).

     Time frame: Baseline up to Cycle 13 (28 days per Cycle)

101. 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).

     Time frame: Baseline up to Cycle 6 (28 days per Cycle)

102. 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).

     Time frame: Baseline up to Cycle 13 (28 days per Cycle)

103. 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).

     Time frame: Baseline up to Cycle 6 (28 days per Cycle)

104. 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).

     Time frame: Baseline up to Cycle 13 (28 days per Cycle)

105. 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).

     Time frame: Baseline up to Cycle 6 (28 days per Cycle)

106. 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).

     Time frame: Baseline up to Cycle 13 (28 days per Cycle)

107. 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).

     Time frame: Baseline up to Cycle 6 (28 days per Cycle)

108. 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).

     Time frame: Baseline up to Cycle 13 (28 days per Cycle)

109. 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).

     Time frame: Baseline up to Cycle 6 (28 days per Cycle)

110. 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).

     Time frame: Baseline up to Cycle 13 (28 days per Cycle)

111. 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.

     Time frame: At Cycle 6 (28 days per Cycle)

112. 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.

     Time frame: At Cycle 13 (28 days per Cycle)

113. 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.

     Time frame: At Cycle 6 (28 days per Cycle)

114. 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.

     Time frame: At Cycle 13 (28 days per Cycle)

Other outcomes

1. Percentage of Participants With no Increase in Rescue Medication and VAS Decrease During Cycle Days 22 to 28 From Baseline to Cycle 6

   Rescue medication was standardized intake of 200 mg Ibuprofen tablets. Baseline: 7 days (Day 22) before first menstrual bleeding to Day 28. Treatment: 7 days (Day 22) before withdrawal bleeding of 6th cycle to Day 28 before the same cycle. The visual analog scale (VAS) is a subject-assessed measure of pelvic pain or headache consisting 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).

   Time frame: Day 22-28 from Baseline to Day 22-28 from Cycle 6 (28 days per Cycle)

2. The Change of Pelvic Pain or Headache as Determined by the Highest Visual Analog Scale (VAS) Values 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).

   Time frame: Days 22-28 from Baseline to Days 22-28 from Cycle 6 (28 days per Cycle)

Baseline characteristics

Publications

• Jensen JT, Parke S, Mellinger U, Serrani M, Mabey RG Jr. Hormone withdrawal-associated symptoms: comparison of oestradiol valerate/dienogest versus ethinylestradiol/norgestimate. Eur J Contracept Reprod Health Care. 2013 Aug;18(4):274-83. doi: 10.3109/13625187.2013.785516. Epub 2013 May 2. PubMed 23638631 ↗