E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Investigation of ovulation inhibition for indication of contraception. |
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E.1.1.1 | Medical condition in easily understood language |
Investigation of ovulation inhibition for indication of contraception. |
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E.1.1.2 | Therapeutic area | Body processes [G] - Reproductive physiologi cal processes [G08] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10073728 |
E.1.2 | Term | Hormonal contraception |
E.1.2 | System Organ Class | 100000004865 |
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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 |
The primary aim of this clinical trial is: •To show the non-inferior efficacy of the Test Product (EVE112) compared to the Reference Product (NuvaRing®) in terms of ovulation inhibition rate based on Hoogland score
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E.2.2 | Secondary objectives of the trial |
The secondary aims of this clinical trial are: •Descriptive characterisation of the influence of Test or Reference on ovarian activity determined by means of Hoogland score •Descriptive characterisation of the influence of Test or Reference on ovarian activity determined by means maximum follicular diameter •Descriptive characterisation of the effect of Test or Reference 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 characterisation of overall safety and tolerability in the study population
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Sex: female 2.Age: ≥ 18 years and ≤ 35 years 3.Body-mass index (BMI): ≥ 18.5 kg/m² and ≤ 30.0 kg/m² 4.Good state of health 5.Non-smoker, ex-smoker for at least 3 months or moderate smoker (10 cigarettes or 2 cigars or 2 pipes per day) aged ≤30 years only; questioned at screening examination 6.Both ovaries visible upon transvaginal ultrasonography; observed at screening examination 7.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
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E.4 | Principal exclusion criteria |
1.Existing cardiac and/or haematological diseases or pathological findings which might interfere with the efficacy, safety and/or tolerability of the active ingredients 2.Existing hepatic and/or renal diseases or pathological findings which might interfere with the efficacy, the safety and/or tolerability of the active ingredients 3.Existing diseases or pathological findings of genital organs which might interfere with efficacy, safety and/or tolerability of the IMPs 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 < 50 bpm or > 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.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 12.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 13.Anamnestic hints for increased risk of thrombosis events in family history 14.Known hereditary or acquired predisposition for venous thromboembolism, such as APC resistance, antithrombin-III-deficiency, protein-C or –S-deficiency 15.Known hereditary or acquired predisposition for arterial thromboembolism, such as hyperhomocysteinaemia and antiphospholipid-antibodies (anticardiolipin-antibodies, lupus anticoagulant)). 16.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 17.Presence or history of liver tumours (benign or malignant) or known or suspected sex-hormone influenced malignancies of the genital organs or breasts 18.Severe lipopathy 19.Diabetes mellitus 20.Unclarified vaginal bleeding 21.Existing cervicitis, vaginitis or bleeding cervical erosions 22.Diagnosis of a cervical smear: Bethesda classification AGC, LISL or HSIL (corresponds to Papanicolaou class III or higher) 23.Prolapse of uterine cervix, cystocele and/or rectocele 24.Severe or chronic constipation 25.History of migraine with focal neurological symptoms 26.Acute or chronic diseases which may interfere with the aims of the clinical trial 27.History of or current drug or alcohol dependence 28.Regular intake of alcoholic food or beverages of ≥ 20 g pure alcohol per day 29.Blood donation or other blood loss of more than 400 mL within the last 2 months prior to individual start of pre-treatment cycle of the subject 30.Participation in a clinical trial during the last 2 months prior to individual start of pre-treatment cycle of the subject 31.Regular treatment with any systemically available medication during the last 2 weeks prior to start of pre-treatment cycle which might interfere with pharmacodynamics or safety of the IMPs 32.Use of any sexual hormone containing preparations within 1 cycle (oral, transdermal, vaginal, intrauterine), 2 months (intramuscularly administered depot preparations used once per month) or 6 months (intramuscularly administered depot preparations used once per 3 months) prior to individual start of pre-treatment cycle of the subject 33.No ovulation observed by TVUS on or before day 27 (±1) of the pre-treatment cycle 34.Progesterone blood concentration < 16 nmol/L within 5 days after ovulation has been observed during pre-treatment cycle 35.Use of intrauterine device/coil (copper) 36.Subjects, who report frequent infections of the urogenital tract (e.g. vaginitis, cervicitis) 37.Menstrual bleeding prior to randomisation in the pre-treatment cycle 38.Positive pregnancy test at screening examination 39.Pregnant or lactating women 40.Female subjects who do not agree to apply a barrier method for contraception (e.g. male condom) 41.Subjects suspected or known not to follow instructions 42.Subjects who are unable to understand the written and verbal instructions, in particular regarding the risks and inconveniences they will be exposed to during their participation in the clinical trial 43.Subject is a dependent person, e.g. a relative, family member, or member of the investigator’s or sponsor’s staff 44.Subject in custody or submitted to an institution due to a judicial order
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E.5 End points |
E.5.1 | Primary end point(s) |
primary efficacy Parameters: •Ovarian activity (Hoogland score) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Secondary efficacy parameters •Maximum follicular diameter •Endometrial thickness •Pituitary and ovarian hormones |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
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 | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
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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End of the clinical trial is defined as the day of shipment of the last Case Report Form (CRF) to the company responsible for clinical biometrics. |
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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 | |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |