A Multicentre, Prospective, Open-label, Non-comparative Study

Study Overview
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Brief Summary
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As there are no recent studies conducted in Italy on the profile of this COC, the purpose of this study is to evaluate its efficacy and tolerability in a given subset of women residing in Italy that are in need of contraception. Evaluate the cycle control: breakthrough bleeding (bleeding and/or spotting between cyclically regular onset of menses) of monophasic oral contraceptive pill Effimia® (NGM250 + EE35) in a population of women residing in Italy.

Official Title
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A Multicentre, Prospective, Open-label, Non-comparative Study to Evaluate Menstrual Bleeding Typology, Tolerability, and Compliance During a Monophasic Hormonal Contraceptive Treatment With Norgestimate + Ethinylestradiol in Italy.

Conditions
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Contraception

Intervention / Treatment
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* Drug: Female Contraceptive


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All the following criteria must be met. Healthy women aged between 18 and 35 years (inclusive) in need of contraception. Subjects residing in Italy and having a good knowledge of the Italian language, such as to correctly understand the Informed Consent Form, the instructions for use, and to ensure potential adhesion to the study. Subjects providing written Informed Consent Form. Subjects willing to comply with the study protocol. Exclusion Criteria: Subjects who meet even one of the following criteria will be excluded from the study. Subjects presenting any contraindications to the use of Combined Oral Contraceptives (COC) according to the current Summary of Product Characteristics (SmPC) of Effimia®, i.e. subjects presenting (or have ever presented) myocardial infarction, transient ischemic attack (TIA), stroke, angina pectoris, deep vein thrombosis (DVT), pulmonary embolism (PE) (or presence of blood clot in other organs than legs and lungs), any blood clotting disorder (such as protein C deficiency, protein S deficiency, antithrombin-III deficiency), or subjects that need to undergo surgery or that have to lie down for a long period of time (including the risk of previous deep vein thrombosis (DVT), arterial thromboembolism (ATE), hypertension in course of treatment and diabetes). If any of the listed conditions should appear during the use of the tested COC, the product must be stopped immediately, and the subject withdrawn from the study. Subjects presenting severe diabetes with blood vessel damages, heart valve disease with complications, severe hypertension, severe hypercholesterolemia, or hypertriglyceridemia, hyperhomocysteinaemia, migraine with aura, hepatitis C (and taking medications for this condition), endometrial hyperplasia, unexplained vaginal bleeding, that are breastfeeding or pregnant or that are suspecting a pregnancy. Subjects presenting (or have ever presented) any liver disease not yet recovered (liver function not yet normalized), any benign or malignant tumour of the liver, any breast or genital organs cancer (even suspected), jaundice during pregnancy or while using hormonal contraceptives. Subjects presenting galactose intolerance, total lactase deficiency or glucosegalactose malabsorption syndrome. Subjects presenting hypersensitivity to the active substances or to any excipients of the tested COC (e.g., norgestimate, ethinylstradiol or lactose). Subjects using the following not allowed treatments during the whole study period (according to the SmPC of the Investigational Medicinal Product - IMP): treatments for tuberculosis (e.g. rifampicin), for epilepsy (e.g. primidone, phenytoin, barbiturates, carbamazepine, oxcarbazepine), for HIV and hepatitis C virus infection (protease inhibitor drugs and non-nucleoside reverse transcriptase inhibitors such as ritonavir, nevirapine, efavirenz and also ombitasvir, paritaprevir, ritonavir and dasabuvir), for fungal infections (e.g. griseofulvin), for arthritis, for osteoarthritis (etoricoxib ), for pulmonary arterial hypertension (bosentan) and St. John's wort used as an antidepressant. Medicines containing cyclosporine, the antiepileptic lamotrigine, tranexamic acid, theophylline (used to treat respiratory problems) and tizanidine (used to treat muscle pain and / or cramps) should not be taken as well. Subjects who have used hormonal contraceptives in the previous month. Subjects presenting a Body Mass Index - BMI ≥ 30 kg/m2 (class I obesity). Subjects smoking > 15 cigarettes per day. Subjects using COC off-label (e.g., for polycystic ovarian syndrome - PCOS, endometriosis, or recurrent menometrorrhagia). Subjects currently taking part or who took part in clinical studies with experimental products in the previous month. Subjects showing incapacity / inability to comply with the study protocol (unreliability in the intake of the product or in the completion of the diary) according to the Investigator's opinion.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Single


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Female Contraceptive|Effimia® exerts its action by means of a gonadotropin suppression mechanism through the estrogenic and progestin action exerted by EE and NGM. The contraceptive effect of Effimia® is based on the interaction of various factors, the most important of which consist of ovulation inhibition and endometrial modifications.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cycle control evaluation parameter | breakthrough bleeding (bleeding and/or spotting between cyclically regular onset of menses) by calculating the intermenstrual spotting occurrence rate at sixth cycle only (value to be intended as not cumulative with values from the other 5 cycles taking place during the whole study period). A comparison within group will be performed at V3 with respect to Baseline (V1) | 180 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cycle control evaluation parameters | frequency, duration, regularity, flow volume (subject determined), unscheduled bleeding. A comparison within group will be performed at V2 and V3 with respect to Baseline (V1). | 180 days | 
| Global Acne Grading System (GAGS). | A comparison within group will be performed at V2 and V3 with respect to Baseline (V1). | 180 days | 
| Profile of Mood State (POMS). | A comparison within group will be performed at V2 and V3 with respect to Baseline (V1). | 180 days | 
| Female Sexual Function Index (FSFI). | A comparison within group will be performed at V2 and V3 with respect to Baseline (V1). | 180 days | 
| Dysmenorrhea - VAS scale. | A comparison within group will be performed at V2 and V3 with respect to Baseline (V1) | 180 days | 
| Compliance | Adherence to treatment | 180 days | 
| Contraception failure rate during the 6-month treatment | the contraception failure rate is defined as the proportion of women who will become pregnant during the study period. The reasons for any contraception failure occurrence will be identified and listed (e.g., discontinuation or poor compliance). | 180 days | 
| Metabolic and hormonal parameters | blood lipid and glucose parameters (total cholesterol, High Density Lipoprotein - Cholesterol HDL-C, Low Density Lipoprotein - Cholesterol LDL-C, triglycerides, total testosterone, dehydroepiandrosterone - DHEAS, androstenedione, glucose, insulin, Sex Hormone Binding Globulin - SHBG) and hyperandrogenism (Free Androgenicity Index - FAI) - only in a subgroup of 28 subjects recruited only in the centre of Genova. They will be evaluated in comparison with Baseline (V1). | 180 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Female contraception