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.”

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Italfarmaco S.p.A.

Participant type

Patients

Age range

18-64 years

Gender

Female

Therapeutic area

Not possible to specify

Decision date (initial)

2025-02-03

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-519403-10-00

EudraCT number

2021-003027-15

ClinicalTrials.gov

NCT06067256

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Others, Efficacy

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.

Secondary objectives 6

1. Evaluate the cycle control in terms of frequency, duration, regularity, flow volume (subject determined) and unscheduled bleeding and/or spotting.
2. Evaluate presence of possible correlations between cycle irregularities and age and / or condition of starter or switcher of contraception.
3. Evaluate impact on sexual life.
4. Evaluate impact in subjects affected by pre-treatment acne problems.
5. Evaluate impact in subjects with premenstrual syndrome (PMS).
6. Evaluate effects on lipid and glucose metabolism, on hormonal parameters related to hyperandrogenism (by means of calculus of Free Androgenicity Index - FAI) and plasma coagulation parameters – only in a subgroup of 28 subjects recruited only in the centre of Genova.

Conditions and MedDRA coding

Female contraception.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Healthy women aged between 18 and 35 years (inclusive) in need of contraception.
2. 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.
3. Subjects providing written Informed Consent Form.
4. Subjects willing to comply with the study protocol

Exclusion criteria 12

1. 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.
2. Subjects presenting severe diabetes with blood vessel damages, heart valve disease with complications, severe hypertension, hyperhomocysteinaemia, migraine with aura, hepatitis C (and taking medications for this severe hypercholesterolemia, or hypertriglyceridemia,condition), endometrial hyperplasia, unexplained vaginal bleeding, that are breastfeeding,pregnant or that are suspecting a pregnancy.
3. 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 orgenital organs cancer (even suspected), jaundice during pregnancy or while using hormonal contraceptives.
4. Subjects presenting galactose intolerance, total lactase deficiency or glucose-galactose malabsorption syndrome.
5. Subjects presenting hypersensitivity to the active substances or to any excipients of the tested COC (e.g., norgestimate, ethinylstradiol or lactose).
6. 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.
7. Subjects who have used hormonal contraceptives in the previous month.
8. Subjects presenting a Body Mass Index - BMI ≥ 30 kg/m 2 (class I obesity).
9. Subjects smoking > 15 cigarettes per day.
10. Subjects using COC off-label (e.g., for polycystic ovarian syndrome – PCOS, endometriosis, or recurrent menometrorrhagia).
11. Subjects currently taking part or who took part in clinical studies with experimental products in the previous month.
12. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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).

Secondary endpoints 8

1. 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).
2. Global Acne Grading System (GAGS). A comparison within group will be performed at V2 and V3 with respect to Baseline (V1).
3. Profile of Mood State (POMS). A comparison within group will be performed at V2 and V3 with respect to Baseline (V1).
4. Female Sexual Function Index (FSFI). A comparison within group will be performed at V2 and V3 with respect to Baseline (V1).
5. Dysmenorrhea - VAS scale. A comparison within group will be performed at V2 and V3 with respect to Baseline (V1).
6. Compliance (adherence to treatment).
7. 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).
8. Metabolic and hormonal parameters

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Italfarmaco S.p.A.

Sponsor organisation

Italfarmaco S.p.A.

Address

Via Dei Lavoratori 54

City

Cinisello Balsamo

Postcode

20092

Country

Italy

Scientific contact point

Organisation

Italfarmaco S.p.A.

Contact name

Roberto Piazza

Public contact point

Organisation

Italfarmaco S.p.A.

Contact name

Roberto Piazza

Third parties 1

Locations

1 EU/EEA country · 6 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 12 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications