E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Hormonal oral contraception in healthy women |
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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 |
To assess ovarian function with the NOMAC-E2 combined oral contraceptive |
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E.2.2 | Secondary objectives of the trial |
• To assess the timing of return of ovulation after discontinuing use of the NOMAC-E2 combined oral contraceptive • To assess the effects of the NOMAC-E2 combined oral contraceptive on: - cervical mucus and endometrial thickness - androgen levels and SHBG - folic acid levels • To collect additional data on contraceptive efficacy, cycle control and safety of the NOMAC-E2 combined oral contraceptive • To explore the aforementioned effects in comparison to the DRSP-EE combined oral contraceptive
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Women willing to use a combined oral contraceptive for 6 cycles; • At least 18 but not older than 35 years of age at the time of screening; • Body mass index ≥17 and ≤35; • Good physical and mental health; • Willing to use condoms as the sole contraceptive method during the screening cycle and during one post-treatment cycle. • Willing to give informed consent in writing.
Additional inclusion criterion for entering the treatment phase • Confirmed ovulation in the screening cycle on or before Cycle Day 27;
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E.4 | Principal exclusion criteria |
• Contraindications for contraceptive steroids: - Presence or a history of venous or arterial thrombotic/thromboembolic events (e.g. deep venous thrombosis, pulmonary embolism, myocardial infarction) or of a cerebrovascular accident; - Presence or history of prodromi of a thrombosis (e.g. transient ischaemic attack, angina pectoris); - History of migraine with focal neurological symptoms; - Diabetes mellitus with vascular involvement; - The presence of a severe or multiple risk factor(s) for venous or arterial thrombosis (to be judged by the (sub)-investigator). e.g. increasing age; smoking (with heavier smoking and increasing age the risk further increases, especially in women over 35 years of age); a positive family history (i.e. venous or arterial thromboembolism ever in a sibling or parent at a relatively early age); obesity (body mass index over 30 kg/m2); dyslipoproteinaemia; hypertension, migraine, valvular heart disease, atrial fibrillation; prolonged immobilization, major surgery, any surgery to the legs, or major trauma (in these situations it is advisable to discontinue the COC use and not to resume until two weeks after full remobilization); systemic lupus erythematosus; haemolytic uraemic syndrome; chronic inflammatory bowel disease (Crohn’s disease or ulcerative colitis); sickle cell disease. - Severe dyslipoproteinemia - Severe hypertension - Hereditary or acquired predisposition for venous or arterial thrombosis, such as APC resistance, antithrombin-III-deficiency, protein C deficiency, protein S deficiency, hyperhomocysteinemia and antiphospholipid-antibodies (anticardiolipin-antibodies, lupus anticoagulant). - Pancreatitis or a history thereof if associated with severe hypertriglyceridaemia; - Presence or history of severe hepatic disease as long as liver function values have not returned to normal; - Presence or history of liver tumors (benign or malignant); - Known or suspected sex steroid-influenced malignancies (e.g. of the genital organs or the breasts); - Undiagnosed vaginal bleeding; - Known or suspected pregnancy; - Hypersensitivity to the active substances or to any of the excipients of the investigational product. • In accordance with the SmPC/Package Insert of DRSP-EE, additional contraindications related to the antimineralocorticoid activity of drospirenone (conditions that predipose to hyperkalemia): - Renal insufficiency; - Hepatic dysfunction; - Adrenal insufficiency. • Breastfeeding; • Present use or use within 2 months prior to the start of the trial medication of the following drugs: phenytoin, barbiturates, primidone, carbamazapine, oxcarbazepine, topiramate, felbamate, rifampicin, nelfinavir, ritonavir, griseofulvin, ketoconazole, sex steroids (other than pre- and post treatment contraceptive method) and herbal remedies containing Hypericum perforatum (St John’s Wort); • Administration of any other investigational drugs and/or participation in another clinical trial within 2 months prior to the start of the trial medication or during the trial period. • An abnormal cervical smear (i.e.: dysplasia, cervical intraepithelial neoplasia (CIN), Squamous Intraepithelial Lesion (SIL), carcinoma in situ, invasive carcinoma) at screening, or documentation of an abnormal smear performed within 6 months before screening; • Clinically relevant abnormal laboratory result at screening as judged by the investigator.
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E.5 End points |
E.5.1 | Primary end point(s) |
Ovarian function: incidence of ovulation, follicular development, hormone determinations for ovarian function evaluation |
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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 | Yes |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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.8.3 |
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 | Information not present in EudraCT |
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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The date of the last assessment of the last subject undergoing the trial. Pregnancy follow-up may continue after the end of the trial. |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 3 |