Effects on Hemostasis, Lipids, Carbohydrate Metabolism, Adrenal & Thyroid Function of the Combined Oral Contraceptive NOMAC-E2 Compared to a COC Containing LNG-EE (292004)(COMPLETED)(P05764)

NCT00511355 | Completed Phase 3 Results

• 2 other identifiers: P05764Organon Protocol No. 292004
• Study Type: interventional
• Target: 121
• Locations: 0 countries
• Sites: N/A

Brief Summary

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

Conditions

Contraception

Outcome Measures

Primary Outcomes (33)

• Serum Concentration of Prothrombin Fragments 1 + 2

  Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.

  Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

• Serum Concentration of D-Dimer

  Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.

  Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

• Activated Protein C (APC) Resistance Ratio (Endogenous Thrombin Potential [ETP]-Based)

  Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). APC resistance ratio (ETP-based) measures the anticoagulation response of plasma to APC after activation of the extrinsic coagulation pathway. An increase in the ratio indicates a reduced responsiveness to APC. Each cycle consists of 28 days.

  Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

• Serum Concentration of Clotting Factor VIIa

  Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.

  Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

• Serum Concentration of Clotting Factor VIIc

  Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.

  Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

• Serum Concentration of Clotting Factor VIII

  Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.

  Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

• Serum Concentration of Clotting Factor II

  Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.

  Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

• Serum Concentration of Antithrombin III

  Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.

  Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

• Serum Concentration of Protein S (Free)

  Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.

  Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

• Serum Concentration of Protein S (Total)

  Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.

  Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

• Serum Concentration of Protein C

  Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.

  Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

• APC Resistance Ratio (Activated Partial Thromboplastin Time [APTT]-Based)

  Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). APC resistance ratio (APTT-based) measures the anticoagulation response of plasma to APC after activation of the intrinsic coagulation pathway. An increase in the ratio indicates a increased responsiveness to APC. Each cycle consists of 28 days.

  Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

• Serum Concentration of Sex Hormone Binding Globulin (SHBG)

  Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.

  Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

• Serum Concentration of C-Reactive Protein (CRP)

  Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.

  Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

• Serum Concentration of Total Cholesterol

  Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.

  Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

• Serum Concentration of High Density Lipoprotein (HDL)-Cholesterol

  Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.

  Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

• Serum Concentration of HDL2-cholesterol

  Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.

  Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

• Serum Concentration of HDL3-cholesterol

  Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.

  Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

• Serum Concentration of Low Density Lipoprotein (LDL)-Cholesterol

  Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.

  Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

• Serum Concentration of Apolipoprotein A-1

  Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.

  Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

• Serum Concentration of Apolipoprotein B

  Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.

  Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

• Serum Concentration of Lipoprotein(a)

  Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.

  Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

• Serum Concentration of Total Triglycerides

  Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.

  Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

• Area Under the Curve Over 3 Hours (AUC3) for Glucose (Oral Glucose Tolerance Test [OGTT])

  Blood glucose levels were determined as fasting values just before oral glucose intake and each half hour thereafter for 2 hours and again after 3 hours. Oral glucose tolerance was analysed using the (unadjusted) area under the curve over the 3 hours (AUC3). Each cycle consists of 28 days.

  Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

• Incremental AUC3 for Glucose (OGTT)

  Blood glucose levels were determined as fasting values just before oral glucose intake and each half hour thereafter for 2 hours and again after 3 hours. Oral glucose tolerance was analysed using the (unadjusted) area under the curve over the 3 hours (AUC3). Incremental area under the curve was defined as incremental AUC3 = AUC3 - 3\*fasting concentration. Each cycle consists of 28 days.

  Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

• AUC3 for Insulin (OGTT)

  Blood insulin levels were determined as fasting values just before oral glucose intake and each half hour thereafter for 2 hours and again after 3 hours. Oral glucose tolerance was analysed using the (unadjusted) area under the curve over the 3 hours (AUC3). Each cycle consists of 28 days.

  Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

• Incremental AUC3 for Insulin (OGTT)

  Blood insulin levels were determined as fasting values just before oral glucose intake and each half hour thereafter for 2 hours and again after 3 hours. Oral glucose tolerance was analysed using the (unadjusted) area under the curve over the 3 hours (AUC3). Incremental area under the curve was defined as incremental AUC3 = AUC3 - 3\*fasting concentration. Each cycle consists of 28 days.

  Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

• Serum Concentration of Hemoglobin Type A1c (HbA1c)

  Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). HbA1c was determined before glucose loading. Each cycle consists of 28 days.

  Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

• Serum Concentration of Total Cortisol

  Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.

  Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

• Serum Concentration of Corticosteroid Binding Globulin (CBG)

  Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.

  Baseline to Cycle 6 (between Days 15 and 21 of the cycle)

• Serum Concentration of Thyroid Stimulating Hormone (TSH)

  Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.

  Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

• Serum Concentration of Free Thyroxine (T4)

  Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.

  Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

• Serum Concentration of Thyroxin Binding Globulin (TBG)

  Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.

  Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

Secondary Outcomes (14)

• Serum Concentration of Total Testosterone

  Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

• Serum Concentration of Free Testosterone

  Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

• Serum Concentration of Dehydroepiandrosterone Sulphate (DHEAS)

  Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

• Serum Concentration of Androstenedione

  Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

• Serum Concentration of Dihydrotestosterone (DHT)

  Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

Study Arms (2)

NOMAC-E2

EXPERIMENTAL

Nomegestrol Acetate (NOMAC) and Estradiol (E2), 2.5 mg NOMAC and 1.5 mg E2 monophasic combined oral contraceptive

Drug: NOMAC-E2

LNG-EE

ACTIVE COMPARATOR

Levonorgestrel and Ethinyl Estradiol Tablets (LNG-EE), 150 mcg LNG and 30 mcg EE

Drug: Levonorgestrel and Ethinyl Estradiol

Interventions

NOMAC-E2 DRUG

Nomegestrol Acetate and Estradiol (NOMAC-E2) Tablets, 2.5 mg NOMAC and 1.5 mg E2 taken once daily from Day 1 of menstrual period up to and including Day 28 for 6 consecutive 28-day cycles.

Also known as: SCH 900121, Org 10486-0 (NOMAC), Org 2317 (E2)

NOMAC-E2

Levonorgestrel and Ethinyl Estradiol DRUG

Levonorgestrel and Ethinyl Estradiol (LNG-EE) Tablets, 150 mcg LNG and 30 mcg EE taken once daily from Day 1 of menstrual period up to and including Day 28 for 6 consecutive 28-day cycles.

LNG-EE

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Organon and Co: lead

Related Publications (1)

• Agren UM, Anttila M, Maenpaa-Liukko K, Rantala ML, Rautiainen H, Sommer WF, Mommers E. Effects of a monophasic combined oral contraceptive containing nomegestrol acetate and 17beta-oestradiol compared with one containing levonorgestrel and ethinylestradiol on haemostasis, lipids and carbohydrate metabolism. Eur J Contracept Reprod Health Care. 2011 Dec;16(6):444-57. doi: 10.3109/13625187.2011.604450.

  PMID: 22066891 RESULT

MeSH Terms

Interventions

ethinyl estradiol, levonorgestrel drug combination

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 2, 2007
• First Posted: August 3, 2007
• Study Start: October 1, 2006
• Primary Completion: January 1, 2008
• Study Completion: January 1, 2008
• Last Updated: February 9, 2022
• Results First Posted: August 30, 2011

Record last verified: 2022-02