E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Endometriosis is a disease where the tissue that normally occurs within the womb grows in other parts of the body, usually in the pelvic cavity. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Female diseases of the urinary and reproductive systems and pregancy complications [C13] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 15.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10014778 |
E.1.2 | Term | Endometriosis |
E.1.2 | System Organ Class | 10038604 - Reproductive system and breast disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To demonstrate safety of dienogest (DNG) in the treatment of endometriosis in adolescents |
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E.2.2 | Secondary objectives of the trial |
To demonstrate efficacy of dienogest (DNG) in the treatment of endometriosis in adolescents |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 |
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E.4 | Principal 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 |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in BMD (spine scan) as measured by DEXA after 52 weeks of starting treatment. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
From baseline to week 52. |
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E.5.2 | Secondary end point(s) |
1. 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
2. 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)
3. 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)
4. Global assessment of efficacy based on the CGI scale
5. Haematology (Erythrocytes, Hemoglobin, Hematocrit, Leukocytes, Platelets), Coagulation (PT, aPTT), Blood hemetry, Liver enzymes, Total cholesterol, Triglyceride, HDL, LDL, HbA1c
6. Number of vaginal bleeding events
7. Blood pressure, Pulse
8. Gynecological examinations (pregnancy tests)
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Start of treatment and after 52 weeks. Follow-up 26 weeks after end of treatment in patients with decrease of BMD at end of treatment.
2. At week 24
3. Once in a month over 12 months
4. Four times in 12 months
5. Four times in 12 months
6. Daily assessment during 12 months
7. Five times in 12 months
8. Five times in 12 months (monthly)
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 30 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Last visit of the last subject. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 7 |
E.8.9.2 | In all countries concerned by the trial days | 0 |