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)
- Conditions
- Contraception
- Interventions
- Registration Number
- NCT00511355
- Lead Sponsor
- Organon and Co
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 121
- 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
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description LNG-EE Levonorgestrel and Ethinyl Estradiol Levonorgestrel and Ethinyl Estradiol Tablets (LNG-EE), 150 mcg LNG and 30 mcg EE NOMAC-E2 NOMAC-E2 Nomegestrol Acetate (NOMAC) and Estradiol (E2), 2.5 mg NOMAC and 1.5 mg E2 monophasic combined oral contraceptive
- Primary Outcome Measures
Name Time Method Serum Concentration of Clotting Factor VIII Baseline and Cycle 6 (between Days 15 and 21 of the cycle) Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.
Serum Concentration of Protein C Baseline and Cycle 6 (between Days 15 and 21 of the cycle) Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.
Serum Concentration of D-Dimer Baseline and Cycle 6 (between Days 15 and 21 of the cycle) Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.
Serum Concentration of HDL2-cholesterol Baseline and Cycle 6 (between Days 15 and 21 of the cycle) Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.
Serum Concentration of Protein S (Free) Baseline and Cycle 6 (between Days 15 and 21 of the cycle) Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.
Serum Concentration of Sex Hormone Binding Globulin (SHBG) Baseline and Cycle 6 (between Days 15 and 21 of the cycle) Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.
Serum Concentration of Apolipoprotein B Baseline and Cycle 6 (between Days 15 and 21 of the cycle) Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.
Serum Concentration of Prothrombin Fragments 1 + 2 Baseline and Cycle 6 (between Days 15 and 21 of the cycle) Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.
Activated Protein C (APC) Resistance Ratio (Endogenous Thrombin Potential [ETP]-Based) Baseline and Cycle 6 (between Days 15 and 21 of the cycle) 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.
Serum Concentration of Clotting Factor VIIa Baseline and Cycle 6 (between Days 15 and 21 of the cycle) Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.
Serum Concentration of Clotting Factor VIIc Baseline and Cycle 6 (between Days 15 and 21 of the cycle) Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.
Serum Concentration of Clotting Factor II Baseline and Cycle 6 (between Days 15 and 21 of the cycle) Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.
Serum Concentration of Antithrombin III Baseline and Cycle 6 (between Days 15 and 21 of the cycle) Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.
Serum Concentration of C-Reactive Protein (CRP) Baseline and Cycle 6 (between Days 15 and 21 of the cycle) Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.
Serum Concentration of High Density Lipoprotein (HDL)-Cholesterol Baseline and Cycle 6 (between Days 15 and 21 of the cycle) Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.
Serum Concentration of HDL3-cholesterol Baseline and Cycle 6 (between Days 15 and 21 of the cycle) Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.
Serum Concentration of Total Triglycerides Baseline and Cycle 6 (between Days 15 and 21 of the cycle) Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.
Serum Concentration of Protein S (Total) Baseline and Cycle 6 (between Days 15 and 21 of the cycle) Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.
APC Resistance Ratio (Activated Partial Thromboplastin Time [APTT]-Based) Baseline and Cycle 6 (between Days 15 and 21 of the cycle) 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.
Serum Concentration of Total Cholesterol Baseline and Cycle 6 (between Days 15 and 21 of the cycle) Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.
Serum Concentration of Low Density Lipoprotein (LDL)-Cholesterol Baseline and Cycle 6 (between Days 15 and 21 of the cycle) Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.
Serum Concentration of Apolipoprotein A-1 Baseline and Cycle 6 (between Days 15 and 21 of the cycle) Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.
Serum Concentration of Lipoprotein(a) Baseline and Cycle 6 (between Days 15 and 21 of the cycle) Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.
Serum Concentration of Corticosteroid Binding Globulin (CBG) Baseline to Cycle 6 (between Days 15 and 21 of the cycle) Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.
Incremental AUC3 for Glucose (OGTT) Baseline and Cycle 6 (between Days 15 and 21 of the cycle) 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.
Area Under the Curve Over 3 Hours (AUC3) for Glucose (Oral Glucose Tolerance Test [OGTT]) Baseline and Cycle 6 (between Days 15 and 21 of the cycle) 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.
AUC3 for Insulin (OGTT) Baseline and Cycle 6 (between Days 15 and 21 of the cycle) 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.
Serum Concentration of Total Cortisol Baseline and Cycle 6 (between Days 15 and 21 of the cycle) Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.
Serum Concentration of Thyroid Stimulating Hormone (TSH) Baseline and Cycle 6 (between Days 15 and 21 of the cycle) Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.
Serum Concentration of Free Thyroxine (T4) Baseline and Cycle 6 (between Days 15 and 21 of the cycle) Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.
Incremental AUC3 for Insulin (OGTT) Baseline and Cycle 6 (between Days 15 and 21 of the cycle) 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.
Serum Concentration of Hemoglobin Type A1c (HbA1c) Baseline and Cycle 6 (between Days 15 and 21 of the cycle) 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.
Serum Concentration of Thyroxin Binding Globulin (TBG) Baseline and Cycle 6 (between Days 15 and 21 of the cycle) Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.
- Secondary Outcome Measures
Name Time Method Serum Concentration of Total Testosterone Baseline and Cycle 6 (between Days 15 and 21 of the cycle) Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.
Serum Concentration of Dehydroepiandrosterone Sulphate (DHEAS) Baseline and Cycle 6 (between Days 15 and 21 of the cycle) Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.
Serum Concentration of Androstenedione Baseline and Cycle 6 (between Days 15 and 21 of the cycle) Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.
Number of In-treatment Pregnancies (With +2 Day Window) Per 100 Woman Years of Exposure (Pearl Index) 6 cycles In-treatment pregnancies were pregnancies with an estimated date of conception from the day of first intake of trial medication up to and including the day of last (active or placebo) intake of trial medication extended with a maximum of 2 days. Each 13 cycles (28 days per cycle) constitutes a woman year. The Pearl Index was obtained by dividing the number of in-treatment pregnancies that occurred by the time (in 100 women years) that the women were under risk of becoming pregnant.
Number of Participants With an Occurrence of Absence of Withdrawal Bleeding Every 28-day cycle for 6 cycles Cycle control was evaluated on the basis of vaginal bleeding pattern as recorded daily by participants using diary booklets. Participants documented whether vaginal bleeding was present, and if present, indicated whether it was considered to be spotting or bleeding. Absence of withdrawal bleeding was defined as no bleeding/spotting episode that began during or continued into the "expected bleeding period". Expected bleeding period: NOMAC-E2: 7-day period starting on Day 25 of the cycle and ending on Day 3 of the next cycle; LNG-EE: 7-day period starting on Day 22 of the cycle.
Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only) Every 28-day cycle for 6 cycles Cycle control was evaluated on the basis of vaginal bleeding pattern as recorded daily by participants using diary booklets. Participants documented whether vaginal bleeding was present, and if present, indicated whether it was considered to be spotting or bleeding. Breakthrough spotting was defined as any spotting episode that occurred during the "expected non-bleeding period" that was neither part of an early nor continued withdrawal bleeding. Expected non-bleeding period: NOMAC-E2: 21-day period starting on Day 4 of the cycle; LNG-EE: 21-day period starting on Day 1 of the cycle.
Number of Participants With an Occurrence of Continued Withdrawal Bleeding Every 28-day cycle for 5 cycles Cycle control was evaluated on the basis of vaginal bleeding pattern as recorded daily by participants using diary booklets. Participants documented whether vaginal bleeding was present, and if present, indicated whether it was considered to be spotting or bleeding. Continued withdrawal bleeding was defined as any withdrawal bleeding that continued into the "expected non-bleeding period" of the next cycle. Expected non-bleeding period: NOMAC-E2: 21-day period starting on Day 4 of the cycle; LNG-EE: 21-day period starting on Day 1 of the cycle.
Serum Concentration of Free Testosterone Baseline and Cycle 6 (between Days 15 and 21 of the cycle) Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.
Serum Concentration of Dihydrotestosterone (DHT) Baseline and Cycle 6 (between Days 15 and 21 of the cycle) Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.
Number of Participants With an Occurrence of Breakthrough Bleeding/Spotting Every 28-day cycle for 6 cycles Cycle control was evaluated on the basis of vaginal bleeding pattern as recorded daily by participants using diary booklets. Participants documented whether vaginal bleeding was present, and if present, indicated whether it was considered to be spotting or bleeding. Breakthrough bleeding/spotting was defined as any episode that occurred during the "expected non-bleeding period" that was neither an early nor a continued withdrawal bleeding. Expected non-bleeding period: NOMAC-E2: 21-day period starting on Day 4 of the cycle; LNG-EE: 21-day period starting on Day 1 of the cycle.
Number of Participants With an Occurrence of Breakthrough Bleeding Every 28-day cycle for 6 cycles Cycle control was evaluated on the basis of vaginal bleeding pattern as recorded daily by participants using diary booklets. Participants documented whether vaginal bleeding was present, and if present, indicated whether it was considered to be spotting or bleeding. Breakthrough bleeding was defined as any bleeding episode that occurred during the "expected non-bleeding period" that was neither part of an early nor continued withdrawal bleeding. Expected non-bleeding period: NOMAC-E2: 21-day period starting on Day 4 of the cycle; LNG-EE: 21-day period starting on Day 1 of the cycle.
Number of Participants With an Occurrence of Early Withdrawal Bleeding Every 28-day cycle for 6 cycles Cycle control was evaluated on the basis of vaginal bleeding pattern as recorded daily by participants using diary booklets. Participants documented whether vaginal bleeding was present, and if present, indicated whether it was considered to be spotting or bleeding. Early withdrawal bleeding was defined as any withdrawal bleeding that started before the current "expected bleeding period". Expected bleeding period: NOMAC-E2: 7-day period starting on Day 25 of the cycle and ending on Day 3 of the next cycle; LNG-EE: 7-day period starting on Day 22 of the cycle.
Average Number of Breakthrough Bleeding/Spotting Days Every 28-day cycle for 6 cycles Cycle control was evaluated on the basis of vaginal bleeding pattern as recorded daily by participants using diary booklets. Participants documented whether vaginal bleeding was present, and if present, indicated whether it was considered to be spotting or bleeding. Breakthrough bleeding/spotting was defined as any episode that occurred during the "expected non-bleeding period" that was neither an early nor a continued withdrawal bleeding. Expected non-bleeding period: NOMAC-E2: 21-day period starting on Day 4 of the cycle; LNG-EE: 21-day period starting on Day 1 of the cycle.
Average Number of Withdrawal Bleeding/Spotting Days Every 28-day cycle for 6 cycles Cycle control was evaluated on the basis of vaginal bleeding pattern as recorded daily by participants using diary booklets. Participants documented whether vaginal bleeding was present, and if present, indicated whether it was considered to be spotting or bleeding. Withdrawal bleeding/spotting was defined as any episode that occurred during the "expected bleeding period". Expected bleeding period: NOMAC-E2: 7-day period starting on Day 25 of the cycle and ending on Day 3 of the next cycle; LNG-EE: 7-day period starting on Day 22 of the cycle.