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

NCT ID: NCT06067256

Last Updated: 2023-10-04

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 228 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-07-20
• Study Completion Date: 2024-06-30

Brief Summary

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.

Conditions

Contraception

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: PREVENTION
• Blinding Strategy: SINGLE

Interventions

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.

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 35 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

Italfarmaco

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Angelo Cagnacci, MD

Role: PRINCIPAL_INVESTIGATOR

IRCCS Ospedale Policlinico San Martino, Clinica Ostetrica e Ginecologica

Locations

IRCCS Ospedale Policlinico

San Martino, Genova, Italy

Site Status: RECRUITING

Countries

Italy

Central Contacts

Roberto Piazza, MD

Role: CONTACT

r.piazza@italfarmaco.com

+39 0264432516

Facility Contacts

Angelo Cagnacci, MD

Role: primary

References

Mosher WD, Martinez GM, Chandra A, Abma JC, Willson SJ. Use of contraception and use of family planning services in the United States: 1982-2002. Adv Data. 2004 Dec 10;(350):1-36.

Reference Type: BACKGROUND

PMID: 15633582 (View on PubMed)

Trussell J. Contraceptive failure in the United States. Contraception. 2011 May;83(5):397-404. doi: 10.1016/j.contraception.2011.01.021. Epub 2011 Mar 12.

Reference Type: BACKGROUND

PMID: 21477680 (View on PubMed)

Brynhildsen J. Combined hormonal contraceptives: prescribing patterns, compliance, and benefits versus risks. Ther Adv Drug Saf. 2014 Oct;5(5):201-13. doi: 10.1177/2042098614548857.

Reference Type: BACKGROUND

PMID: 25360241 (View on PubMed)

Sitruk-Ware R, Nath A. Characteristics and metabolic effects of estrogen and progestins contained in oral contraceptive pills. Best Pract Res Clin Endocrinol Metab. 2013 Feb;27(1):13-24. doi: 10.1016/j.beem.2012.09.004. Epub 2012 Oct 10.

Reference Type: BACKGROUND

PMID: 23384742 (View on PubMed)

European Medicines Agency Benefits of combined hormonal contraceptives (CHCs) continue to outweigh risks - CHMP endorses PRAC recommendation EMA/709120/2013 Available at: http://www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/news/2013/11/news_d etail_001969.jsp&mid=WC0b01ac058004d5c1

Reference Type: BACKGROUND

Phillips A, Hahn DW, McGuire JL. Preclinical evaluation of norgestimate, a progestin with minimal androgenic activity. Am J Obstet Gynecol. 1992 Oct;167(4 Pt 2):1191-6. doi: 10.1016/s0002-9378(12)90410-x.

Reference Type: BACKGROUND

PMID: 1415445 (View on PubMed)

Bottiger LE, Boman G, Eklund G, Westerholm B. Oral contraceptives and thromboembolic disease: effects of lowering oestrogen content. Lancet. 1980 May 24;1(8178):1097-101. doi: 10.1016/s0140-6736(80)91550-0.

Reference Type: BACKGROUND

PMID: 6103437 (View on PubMed)

Goldzieher JW. Selected aspects of the pharmacokinetics and metabolism of ethinyl estrogens and their clinical implications. Am J Obstet Gynecol. 1990 Jul;163(1 Pt 2):318-22. doi: 10.1016/0002-9378(90)90575-r.

Reference Type: BACKGROUND

PMID: 2196804 (View on PubMed)

Gallo MF, Nanda K, Grimes DA, Lopez LM, Schulz KF. 20 microg versus >20 microg estrogen combined oral contraceptives for contraception. Cochrane Database Syst Rev. 2013 Aug 1;2013(8):CD003989. doi: 10.1002/14651858.CD003989.pub5.

Reference Type: BACKGROUND

PMID: 23904209 (View on PubMed)

Van Vliet HA, Raps M, Lopez LM, Helmerhorst FM. Quadriphasic versus monophasic oral contraceptives for contraception. Cochrane Database Syst Rev. 2011 Nov 9;(11):CD009038. doi: 10.1002/14651858.CD009038.pub2.

Reference Type: BACKGROUND

PMID: 22071862 (View on PubMed)

Runnebaum B, Grunwald K, Rabe T. The efficacy and tolerability of norgestimate/ethinyl estradiol (250 micrograms of norgestimate/35 micrograms of ethinyl estradiol): results of an open, multicenter study of 59,701 women. Am J Obstet Gynecol. 1992 Jun;166(6 Pt 2):1963-8. doi: 10.1016/0002-9378(92)91396-r.

Reference Type: BACKGROUND

PMID: 1605286 (View on PubMed)

National Research Council (US) Committee on Population. Contraception and Reproduction: Health Consequences for Women and Children in the Developing World. Washington (DC): National Academies Press (US); 1989. Available from http://www.ncbi.nlm.nih.gov/books/NBK235072/

Reference Type: BACKGROUND

PMID: 25144060 (View on PubMed)

Dayal M, Barnhart KT. Noncontraceptive benefits and therapeutic uses of the oral contraceptive pill. Semin Reprod Med. 2001 Dec;19(4):295-303. doi: 10.1055/s-2001-18637.

Reference Type: BACKGROUND

PMID: 11727171 (View on PubMed)

PASS 2021 Power Analysis and Sample Size Software (2021). NCSS, LLC. Kaysville, Utah, USA, ncss.com/software/pass

Reference Type: BACKGROUND

Doshi A, Zaheer A, Stiller MJ. A comparison of current acne grading systems and proposal of a novel system. Int J Dermatol. 1997 Jun;36(6):416-8. doi: 10.1046/j.1365-4362.1997.00099.x. No abstract available.

Reference Type: BACKGROUND

PMID: 9248884 (View on PubMed)

Alsulaimani H, Kokandi A, Khawandanh S, Hamad R. Severity of Acne Vulgaris: Comparison of Two Assessment Methods. Clin Cosmet Investig Dermatol. 2020 Sep 28;13:711-716. doi: 10.2147/CCID.S266320. eCollection 2020.

Reference Type: BACKGROUND

PMID: 33061511 (View on PubMed)

McNair, D. M., Lorr, M., & Droppleman, L. F. (1971). Manual for the Profile of Mood States. San Diego, CA: Educational and Industrial Testing Services.

Reference Type: BACKGROUND

McNair, D. M., Lorr, M., & Droppleman, L. (1971/1981). Manual for the Profile of Mood States. San Diego, CA: Educational and Industrial Testing Service.

Reference Type: BACKGROUND

McNair DM et al. Manual for the profile of Mood States. Toronto, ON, Multi-Health Systems Inc.1992.

Reference Type: BACKGROUND

Evans SM, Haney M, Levin FR, Foltin RW, Fischman MW. Mood and performance changes in women with premenstrual dysphoric disorder: acute effects of alprazolam. Neuropsychopharmacology. 1998 Dec;19(6):499-516. doi: 10.1016/S0893-133X(98)00064-5.

Reference Type: BACKGROUND

PMID: 9803426 (View on PubMed)

Rapkin Andrea, L. H. Chang & A. E. Reading (1987) Premenstrual syndrome: a double blind placebo controlled study of treatment with progesterone vaginal suppositories, Journal of Obstetrics and Gynaecology, 7:3, 217-220, DOI: 10.3109/01443618709068522

Reference Type: BACKGROUND

Wyatt K, Dimmock P, Jones P, Obhrai M, O'Brien S. Efficacy of progesterone and progestogens in management of premenstrual syndrome: systematic review. BMJ. 2001 Oct 6;323(7316):776-80. doi: 10.1136/bmj.323.7316.776.

Reference Type: BACKGROUND

PMID: 11588078 (View on PubMed)

Mannarini, S., Polimeni, S., Shams, M., & Giacobbo, M. (2012). Assessing negative and positive mood states: The identification of a short form of the POMS scale in Italian oncology outpatients. TPM - Testing, Psychometrics, Methodology in Applied Psychology, 19(2), 135- 145. https://doi.org/10.4473/TPM19.2.5

Reference Type: BACKGROUND

Farnè, M., Sebellico, A., Gnugnoli, D., & Corallo, A. (1991). POMS: Profile Of Mood States. Adattamento italiano [POMS: Profile Of Mood States. Italian Adaptation]. Firenze, Italy: Organizzazioni Speciali.

Reference Type: BACKGROUND

Rosen R, Brown C, Heiman J, Leiblum S, Meston C, Shabsigh R, Ferguson D, D'Agostino R Jr. The Female Sexual Function Index (FSFI): a multidimensional self-report instrument for the assessment of female sexual function. J Sex Marital Ther. 2000 Apr-Jun;26(2):191-208. doi: 10.1080/009262300278597.

Reference Type: BACKGROUND

PMID: 10782451 (View on PubMed)

Wiegel M, Meston C, Rosen R. The female sexual function index (FSFI): cross-validation and development of clinical cutoff scores. J Sex Marital Ther. 2005 Jan-Feb;31(1):1-20. doi: 10.1080/00926230590475206.

Reference Type: BACKGROUND

PMID: 15841702 (View on PubMed)

Filocamo MT, Serati M, Li Marzi V, Costantini E, Milanesi M, Pietropaolo A, Polledro P, Gentile B, Maruccia S, Fornia S, Lauri I, Alei R, Arcangeli P, Sighinolfi MC, Manassero F, Andretta E, Palazzetti A, Bertelli E, Del Popolo G, Villari D. The Female Sexual Function Index (FSFI): linguistic validation of the Italian version. J Sex Med. 2014 Feb;11(2):447-53. doi: 10.1111/jsm.12389. Epub 2013 Nov 13.

Reference Type: BACKGROUND

PMID: 24224761 (View on PubMed)

Rosner W, Auchus RJ, Azziz R, Sluss PM, Raff H. Position statement: Utility, limitations, and pitfalls in measuring testosterone: an Endocrine Society position statement. J Clin Endocrinol Metab. 2007 Feb;92(2):405-13. doi: 10.1210/jc.2006-1864. Epub 2006 Nov 7.

Reference Type: BACKGROUND

PMID: 17090633 (View on PubMed)

Bhatt A. Protocol deviation and violation. Perspect Clin Res. 2012 Jul;3(3):117. doi: 10.4103/2229-3485.100663. No abstract available.

Reference Type: BACKGROUND

PMID: 23125964 (View on PubMed)

Ghooi RB, Bhosale N, Wadhwani R, Divate P, Divate U. Assessment and classification of protocol deviations. Perspect Clin Res. 2016 Jul-Sep;7(3):132-6. doi: 10.4103/2229-3485.184817.

Reference Type: BACKGROUND

PMID: 27453830 (View on PubMed)

Fraser IS, Critchley HO, Munro MG, Broder M; Writing Group for this Menstrual Agreement Process. A process designed to lead to international agreement on terminologies and definitions used to describe abnormalities of menstrual bleeding. Fertil Steril. 2007 Mar;87(3):466-76. doi: 10.1016/j.fertnstert.2007.01.023.

Reference Type: BACKGROUND

PMID: 17362717 (View on PubMed)

Fraser IS, Critchley HO, Munro MG, Broder M. Can we achieve international agreement on terminologies and definitions used to describe abnormalities of menstrual bleeding? Hum Reprod. 2007 Mar;22(3):635-43. doi: 10.1093/humrep/del478. Epub 2007 Jan 4.

Reference Type: BACKGROUND

PMID: 17204526 (View on PubMed)

Fraser IS, Critchley HO, Broder M, Munro MG. The FIGO recommendations on terminologies and definitions for normal and abnormal uterine bleeding. Semin Reprod Med. 2011 Sep;29(5):383-90. doi: 10.1055/s-0031-1287662. Epub 2011 Nov 7.

Reference Type: BACKGROUND

PMID: 22065325 (View on PubMed)

Cagnacci A, Grandi G, Capobianco G, Fulghesu AM, Morgante G, Biondelli V, Piccolo E, Casolati E, Mangrella M. Effects of a Monophasic Hormonal Contraceptive With Norgestimate+Ethinyl Estradiol on Menstrual Bleeding: Protocol and Design of a Multicenter, Prospective, Open-Label, Noncomparative Study in Italy. JMIR Res Protoc. 2025 Mar 31;14:e63683. doi: 10.2196/63683.

Reference Type: DERIVED

PMID: 40164172 (View on PubMed)

Other Identifiers

EFFI2021/01

Identifier Type: -

Identifier Source: org_study_id