Visanne Study to Assess Safety in Adolescents (VISADO)

• BMD on whole body. BMD values and height will also be calculated relative to the age normalized percentiles (Z-scores for BMD) to allow for comparison with historical control groups [ Time Frame: Start of treatment and after 52 weeks ] [ Designated as safety issue: Yes ]
• Percentage of responders at week 24, where a response is defined as a reduction in pain intensity from baseline of at least 30% in the Visual Analogue Scale (VAS) [ Time Frame: At week 24 ] [ Designated as safety issue: No ]
• Monthly physician led assessments of the symptoms dysmenorrhea, non menstrual pelvic pain and dyspareunia with the signs pelvic tenderness and induration (full B&B pain grading scale, if specifically agreed by the subject) [ Time Frame: Once in a month over 12 months ] [ Designated as safety issue: No ]
• Global assessment of efficacy based on the CGI scale [ Time Frame: Four times in 12 months ] [ Designated as safety issue: No ]
• Haematology (Erythrocytes, Hemoglobin, Hematocrit, Leukocytes, Platelets), Coagulation (PT, aPTT), Blood chemistry, Liver enzymes, Total cholesterol, Triglyceride, HDL, LDL, HbA1c [ Time Frame: Four times in 12 months ] [ Designated as safety issue: Yes ]
• Number of vaginal bleeding events [ Time Frame: Daily assessment during 12 months ] [ Designated as safety issue: Yes ]
• Blood pressure, Pulse [ Time Frame: Five times in 12 months ] [ Designated as safety issue: Yes ]
• Gynecological examinations (pregnancy tests) [ Time Frame: Five times in 12 months ] [ Designated as safety issue: Yes ]

• BMD on whole body. BMD values and height will also be calculated relative to the age normalized percentiles (Z-scores for BMD) to allow for comparison with historical control groups [ Time Frame: Start of treatment and after 52 weeks ] [ Designated as safety issue: Yes ]
• Percentage of responders at week 24, where a response is defined as a reduction in pain intensity from baseline of at least 30% in the Visual Analogue Scale (VAS) [ Time Frame: At week 24 ] [ Designated as safety issue: No ]
• Monthly physician led assessments of the symptoms dysmenorrhea, non menstrual pelvic pain and dyspareunia with the signs pelvic tenderness and induration (full B&B pain grading scale, if specifically agreed by the subject) [ Time Frame: Once in a month over 12 months ] [ Designated as safety issue: No ]
• Global assessment of efficacy based on the CGI scale [ Time Frame: Four times in 12 months ] [ Designated as safety issue: No ]
• Haematology (Erythrocytes, Hemoglobin, Hematocrit, Leukocytes, Platelets), Coagulation (PT, aPTT), Blood hemetry, Liver enzymes, Total cholesterol, Triglyceride, HDL, LDL, HbA1c [ Time Frame: Four times in 12 months ] [ Designated as safety issue: Yes ]
• Number of vaginal bleeding events [ Time Frame: Daily assessment during 12 months ] [ Designated as safety issue: Yes ]
• Blood pressure, Pulse [ Time Frame: Five times in 12 months ] [ Designated as safety issue: Yes ]
• Gynecological examinations (pregnancy tests) [ Time Frame: Five times in 12 months ] [ Designated as safety issue: Yes ]

A clinical trial which was designed to demonstrate the safety and efficacy of Visanne (approved in endometriosis for adults) in the adolescent population.

Inclusion Criteria:

• Female adolescents after menarche (12 - less than 18 years of age) at screening. For Finland: Adolescents aged 12 - 14 years old who present with clinical features of endometriosis will only be enrolled into the study if their diagnosis of endometriosis has been confirmed by laparoscopy.

• Dysmenorrhea of at least moderate intensity, with or without chronic pelvic pain, for at least 2 cycles in the previous 4 months and one of the following conditions:

  • Clinically suspected endometriosis based on the presence of pelvic pain incompletely relieved by non steroidal anti-inflammatory drugs and/or oral contraceptives
  • Any abdominal pain associated with ultrasound findings suggestive of endometriosis (abdominal, vaginal or rectal; only after additional specific consent and assent)
  • Failure of surgical treatment for endometriosis (with cyclic or chronic pelvic pain of at least 4 months duration postsurgery)
  • Threshold for endometriosis-associated pelvic pain (EAPP) score: at least 30 on a 100 units visual analog scale retrospectively evaluated at screening for the last 4 weeks

Exclusion Criteria:

• Absence of endometriosis at laparoscopy
• Previous application of hormonal agents including oral contraceptives within 2 months, progestins, danazol within 3 months, and Gonadotropin Releasing Hormone (GnRH) agonists within 6 months prior to start of treatment
• Chronic pelvic pain that might be related to genitourinary disease or to chronic or recurrent gastrointestinal disease, including irritable bowel syndrome (defined as a disease characterized by pain relieved by defecation and irregular defecation patterns lasting at least 3 months)
• Clinically established need for primary surgical treatment of endometriosis