Investigation of ovulation inhibition for indication of contraception
Conditions
Interventions
Product Name: EVE116 0/3
Pharmaceutical Form: Vaginal delivery system
INN or Proposed INN: TRIMEGESTONE
CAS Number: 74513-62-5
Other descriptive name: TMG
Concentration unit: mg milligram(s)
Concentra
Sponsors
Evestra GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. written informed consent, after having been informed about benefits and potential risks of the clinical trial, as well as details of the insurance taken out to cover the subjects participating in the clinical trial 2. sex: female 3. age: 18 years to 38 years inclusive 4. body-mass index (BMI): >= 18 kg/m² and = 30.0 kg/m² 5. good state of health 6. non-smoker or ex-smoker for at least 3 months aged >30 years or moderate smoker (10 cigarettes or 2 cigars or 2 pipes per day) aged = 30 years only; questioned at screening examination 7. both ovaries visible upon transvaginal ultrasonography; observed at screening examination Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 100 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. existing cardiac and/or haematological diseases or pathological findings, which might interfere with the safety or tolerability of the active ingredient 2.existing hepatic and/or renal diseases (e.g. severe renal insufficiency or acute renal failure) or pathological findings, which might interfere with the safety or tolerability, and/or pharmacokinetics of the active ingredient 3. existing diseases or pathological findings of genital organs, which might interfere with the safety, tolerability, absorption and/or pharmacokinetics of the active ingredient 4. history of relevant CNS and/or psychiatric disorders and/or currently treated CNS and/or psychiatric disorders 5. known allergic reactions to the active ingredients used or to constituents of the pharmaceutical preparations 6. subjects with severe allergies or multiple drug allergies unless it is judged as not relevant for the clinical trial by the investigator 7. systolic blood pressure = 140 mmHg 8. diastolic blood pressure = 90 mmHg 9. pulse rate 90 bpm 10. laboratory values out of normal range unless the deviation from normal is judged as not relevant for the clinical trial by the investigator 11. ASAT > 20 % ULN, ALAT > 10 % ULN, bilirubin > 20% ULN (except in case of existing Morbus Gilbert-Meulengracht deduced from anamnesis/medical history) 12. positive anti-HIV-test (if positive to be verified by western blot), HBs-AG-test (if positive to be verified by test for HBc-IgM) or anti-HCV-test 13. presence or history of venous or arterial thrombosis (e.g. deep venous thrombosis, pulmonary embolism, myocardial infarction or prodromal conditions (e.g. angina pectoris, transient ischaemic attack)), cerebrovascular accident, inborn or acquired predisposition for venous or arterial thrombosis 14. anamnestic hints for increased risk of thrombosis events in family history 15. known hereditary or acquired predisposition for venous thromboembolism, such as APC resistance, antithrombin-III-deficiency, protein-C or -S-deficiency 16. known hereditary or acquired predisposition for arterial thromboembolism, such as hyperhomocysteinaemia and antiphospholipid-antibodies (anticardiolipin-antibodies, lupus anticoagulant). 17. Known medical factors coming along with an increased risk of venous and/or arterial thromboembolism as e.g. systemic lupus erythematosus, haemolytic uraemic syndrome, chronic inflammatory bowel disease (Crohn’s disease or ulcerative colitis), sickle cell disease, and dyslipoproteinaemia 18. Presence or history of liver tumours (benign or malignant) or known or suspected malignancies of the genital organs or breasts (mammae), regardless of the hormone status 19. Presence or history of leiomyoma, endometriosis, or endometrial hyperplasia 20. Known severe lipopathy 21. Fibrocystic mastopathy 22. Diabetes mellitus 23. Hereditary angioedema 24. Unclarified vaginal bleeding 25. Existing cervicitis, vaginitis or bleeding cervical erosions at day of randomisation 26. Diagnosis of latest PAP smear: findings classified in a group higher than PAP I 27. Prolapse of uterine cervix, cystocele and/or rectocele 28. History of severe or chronic constipation 29. Presence or history of migraine as defined by criteria of International Headache Society 30. Acute or chronic diseases, which may interfere with the aims of the clinical trial 31. history of or current drug or alcohol dependence 32. regular intake of alcoholic food or beverages of > 20 units alcohol
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • to determine the lowest dose at which no ovulation occurs (lowest effective dose), as well as, • to determine the next lower dose at which at least one ovulation occurs (dose below the lowest effective dose), if among the tested range, and • to determine the next higher dose above the one preventing ovulation (dose above the lowest effective dose), if among the tested range. ;Secondary Objective: • descriptive characterisation of the influence of test products on ovarian activity determined by means of Hoogland and Skouby score • descriptive characterisation of the influence of test products on ovarian activity determined by means of maximum follicular diameter • descriptive characterisation of the effect of test products on endometrial thickness as well as on the pituitary and ovarian hormones the latter determined via follicle stimulating hormone (FSH), luteinising hormone (LH), estradiol (E2) and progesterone (P) • descriptive evaluation of corpus luteum function after suspected ovulation (TVUS) by progesterone level • descriptive characterisation of the effect of test products on bleeding pattern • investigation of the influence of systemic trimegestone concentrations on SHBG levels • descriptive characterisation of overall safety and tolerability (including local tolerability) in the trial population;Primary end point(s): Primary efficacy parameter • ovulation inhibition rate • ovarian activity by means of Hoogland and Skouby score ;Timepoint(s) of evaluation of this end point: after data base lock | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary efficacy parameters • maximum follicular diameter • endometrial thickness • pituitary and ovarian hormones (FSH, LH, E2, P) • evaluation of Landgren criteria (if applicable) ;Timepoint(s) of evaluation of this end point: after data base lock | — |
Countries
Germany
Contacts
Public ContactDr. Maika Friedrich
Evestra GmbH
Outcome results
None listed