E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
endometriosis associated pelvic pain |
|
MedDRA Classification |
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 |
safety, tolerability and efficacy of ZK 811752 compared to placebo given orally three times daily over 12 weeks in the treatment of endometriosis associated pelvic pain |
|
E.2.2 | Secondary objectives of the trial |
- Change of endometriosis associated pelvic pain every 4 weeks throughout the treatment period - Change of intake of rescue medication - Change of the Biberoglu and Behrman severity profile for symptoms and finding between baseline and end of treatment
|
|
E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1. Signed and dated informed consent. 2. Women between 18 and 45 years of age, inclusive 3. Pain associated with visually proven endometriosis as determined by diagnostic laparoscopy or laparotomy within 24 months prior to start of treatment (Baseline, Visit 2) but no later than 6 weeks prior to Screening (Visit 1) 4. Threshold for pelvic pain score: minimum 40 mm on VAS at Screening (Visit 1) and at Baseline (Visit 2) 5. Women with cyclic menstrual bleeding 6. Normal cervical smear within the last 6 months according to PAP classification 7. Good general health (except for findings related to endometriosis, with or without infertility) 8. Willingness to use a barrier contraceptive method (unless bilateral tubal ligation has been performed previously), but no hormonal contraception 9. Willingness to use only up to 3 Ibuprofen 400 tablets as pain killer for endometriosis-associated pelvic pain |
|
E.4 | Principal exclusion criteria |
1. Pregnancy, lactation (at least three cycles have to follow delivery, abortion or lactation before start of treatment) 2. Amenorrhea of more than 1 cycle within 3 months prior to study start 3. Bearing of an intra-uterine device (IUD, either hormonal or non-hormonal) 4. Signs and/or symptoms of therapy-resistent endometriosis despite various attempts of drug treatment or extensive surgical therapy 5. Need for primary surgical treatment of endometriosis according to the investigator 6. Previous / current use of hormonal agents including - GnRH agonists and depot contraceptives within 6 cycles prior to screening (Visit 1) - Progestins and danazol within 3 cycles prior to screening (Visit 1) - Hormonal contraception within 1 cycle prior to screening (Visit 1) - Phytoestrogen intake must be stopped at screening (Visit 1) 7. Significant, incompletely-healed preexisting illnesses for which it can be assumed that absorption, distribution, metabolism, elimination, and effects of the investigational product will not be normal (e.g. gastrointestinal, autoimmune, signs for immune deficiency) 8. No actual or history of cardiovascular disorders 9. Family history of long QT-syndrome 10. Clinically relevant ECG findings, in particular prolonged QT interval (QT interval after Bazett’s correction for heart rate >440 msec and signs of ventricular hypertrophy at screening (Visit 1) 11. Abnormal baseline laboratory values that are beyond inclusion range, as defined by the Sponsor or that are considered clinically significant by the investigator 12. Conditions or medications that are prone to electrolyte changes (e.g. hypokalemia, hypomagnesemia) 13. Treatment with drugs that are potent inductors or inhibitors of CYP3A4 or drugs that are predominantly metabolised via CYP3A4, 2C9 or 2C19 and the increased plasma levels or prolonged action of which may lead to potentially serious side effects (see attachment no. 3 to the protocol) 14. Treatment with drugs that prolong the QT interval or increase the risk for hypokalemia (see attachment no. 3 to the protocol) 15. Intake of grapefruit or grapefruit juice 16. Clinically relevant findings at gynecological examination 17. History or suspicion of cancer or precancerous lesions of any type 18. Positive HIV test, positive hepatitis serology 19. Metabolic disturbances (particularly severe disturbances of lipid metabolism, insulin-dependent diabetes mellitus, uncontrolled thyroid disorders) 20. Vital signs (after resting for at least 10 minutes, sitting position) - Systolic blood pressure > 140 mm Hg - Diastolic blood pressure > 90 mm Hg - Heart rate < 50 / min or heart rate > 100 / min 21. Known allergic reactions to constituents of the galenic formulation (Kollidon SR, lactose, fumaric acid, silicon dioxide, magnesium stearate, hydroxy propyl methyl cellulose, talcum, titanium dioxide and ferric oxide pigment), or to Ibuprofen 22. Wash out periods to be maintained before start of study medication: Less than 5 half life times following the treatment with drugs that may prolong the QT interval or increase the risk for hypokalemia or that are potent inductors or inhibitors of CYP3A4 or drugs that are predominantly metabolized via CYP3A4, 2C9, or 2C19 and the increased plasma levels or prolonged action of which may lead to potentially serìous side effects (see attachment) Less than two weeks following the use of chinidine and budipine and the first administration of the study drug Less than one day following the intake of colestyramin, colestipol, or of active charcoal (so as not to endanger absorption of ZK 811752). Less than two weeks have passed since last intake of grapefruit juice or grapefruit products and first intake of the investigational product 23. Current or history of clinically significant depression in the last year 24. History or suspicion of drug and/or alcohol abuse within the last 2 years 25. Scheduled surgery within the treatment period 26. Participation in another clinical trial within 1 month or intake of any investigational drug within the last 6 months prior to Screening or participation in any clinical trial during the whole duration of this study 27. Unwillingness to comply with study procedures or incapability of understanding them, or physical / psychological characteristics of the patient, which, in the opinion of the investigator, may interfere with the perception of pain (e.g., hysteria, neurosis) 28. Other criteria which, in the opinion of the investigators performing the pre-study examination, preclude participation for scientific reasons of compliance or for reasons of patient’s safety. 29. Patient is a dependent person, e.g. a relative, family member and/or is a member of the investigator’s staff
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
Individual absolute change of endometriosis associated pelvic pain between baseline and end of treatment evaluated by a composite parameter of both change of Visual Analog Scale and change of intake of rescue medication due to endometriosis-associated pelvic pain |
|
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 | No |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
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 | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
rescue medication allowed for pain (ibuprofen) |
|
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
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.8.5 | The trial involves multiple Member States | Yes |
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 | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |