Official Title: “A Randomized, Open-Label, Comparative, Multi -Center Trial to Evaluate the Effects on Hemostasis, Lipids, Carbohydrate Metabolism, and on Adrenal and Thyroid Function of a Monophasic COC Containing 2.5 mg NOMAC and 1.5 mg E2 Compared to a Monophasic COC Containing 150 ug LNG and 30 ug EE”

The primary purpose of this study is to evaluate the effects of the combined oral contraceptive NOMAC-E2 on hemostasis, lipids, carbohydrate metabolism, adrenal function, and thyroid function.

Study Type: Interventional

Study Design: Prevention, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: January 2008

Intervention(s) in this Clinical Trial

• Drug: NOMAC-E2
  • Estradiol and Nomegestrol Acetate Tablets, 24 active plus 4 placebo tablets per cycle, 2.5 mg NOMAC and 1.5 mg E2
• Drug: Levonorgestrel and Ethinyl Estradiol
  • Levonorgestrel and Ethinyl Estradiol Tablets, 150 µg LNG and 30 µg EE, up to 6 cycles of 28 days

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: 1
  • Estradiol and Nomegestrol Acetate
• Active Comparator: 2
  • Levonorgestrel and Ethinyl Estradiol Tablets

Primary Measures

• Effects on hemostasis as determined by prothrombin fragment 1+2, D-dimer, APC resistance ratio (ETP-based), factors VIIa / VIIc / VIII / II, antithrombin, protein S (free and total), protein C, APC resistance ratio (APTT -based), SHBG and CRP
  • Time Frame: 6 months
    Safety Issue?: No
• Effects on lipid metabolism as determined by total cholesterol, HDL-, HDL2, HDL3 and LDL cholesterol, apolipoproteins A-1 and B, lipoprotein (a) and total triglycerides.
  • Time Frame: 6 months
    Safety Issue?: No
• Effects on carbohydrate metabolism as determined by oral glucose tolerance test (including fasting glucose and insulin) and HbA1C.
  • Time Frame: 6 months
    Safety Issue?: No
• Effects on adrenal function as determined by total cortisol and corticosteroid binding globulin (CBG).
  • Time Frame: 6 months
    Safety Issue?: No
• Effects on thyroid function as determined by thyroid stimulating hormone (TSH), free T4, thyroxin binding globulin (TBG).
  • Time Frame: 6 months
    Safety Issue?: No

Secondary Measures

• Effects on androgen levels as determined by total and free testosterone, dehydroepiandrosterone sulphate (DHEAS), androstenedione, dihydrotestosterone (DHT).
  • Time Frame: 6 months
    Safety Issue?: No
• Contraceptive efficacy as determined by serum HCG pregnancy test (or home pregnancy test).
  • Time Frame: 6 months
    Safety Issue?: No
• Drug safety as determined by [S]AE monitoring, cervical cytology, physical & gynecological exams, vital signs, and routine laboratory parameters.
  • Time Frame: 6 months
    Safety Issue?: Yes
• Cycle control as determined by patient diary records.
  • Time Frame: 6 months
    Safety Issue?: No

Inclusion Criteria:

• Sexually active women, at risk for pregnancy and not planning to use during trial medication use;
• Women in need for contraception and willing to use an oral contraceptive (OC) for 6 months (6 cycles);
• At least 18 but not older than 50 years of age at the time of screening;
• Body mass index = 17 and = 29 kg/m^2;
• Good physical and mental health;
• Willing to give informed consent in writing

Exclusion Criteria:

• Present use or use within 2 months prior to screening of any other hormonal treatment including sex hormones (other than contraceptives), insulin, thyroid and corticosteroid hormones (with the exception for local dermatological use);
• Contraindications for contraceptive steroids
• Presence or history (within 1 year before screening) of alcohol or drug abuse as judged by the (sub)investigator.
• An abnormal cervical smear (i.e.: dysplasia, cervical intraepithelial neoplasia [CIN], 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 (sub) investigator;
• Use of an injectable hormonal method of contraception prior to screening; within 6 months of an injection with a 3 -month duration, within 4 months to screening of an injection with a 2-month duration, within 2 months of an injection with a 1-month duration;
• Before spontaneous menstruation has occurred following a delivery or abortion;
• Breastfeeding or within 2 months after stopping breastfeeding prior to the start of trial medication;
• Present use or use within 2 months prior to the start of the trial medication of the following drugs: phenytoin, barbiturates, primidone, carbamazepine, oxcarbazepine, topiramate, felbamate, rifampicin, nelfinavir, ritonavir, griseofulvin, ketoconazole, lipid-lowering drugs, anticoagulants and herbal remedies containing Hypericum perforatum (St John's Wort);
• Use of pharmacological agents which affect the hemostatic system during the pretreatment blood sampling: vitamin K (only prohibited within two weeks prior to sampling), nonsteroidal anti-inflammatory drugs (NSAIDS) and aspirin (both only prohibited during the week prior to sampling);
• Administration of 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.

Gender Eligibility for this Clinical Trial: Female

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 50 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: Accepts Healthy Volunteers

Lead Sponsor: Organon

Information obtained from ClinicalTrials.gov on October 10, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00511355

Study ID Number: Protocol No. 292004

ClinicalTrials.gov Identifier: NCT00511355

Health Authority: Finland: National Agency for Medicines