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)

Sponsor
Organon and Co (Industry)
Overall Status
Completed
CT.gov ID
NCT00511355
Collaborator
(none)
121
2
15

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
121 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Prevention
Official Title:
A Randomized, Open-Label, Comparative, Multi -Center Trial to Evaluate the Effects on Hemostasis, Lipids and 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
Study Start Date :
Oct 1, 2006
Actual Primary Completion Date :
Jan 1, 2008
Actual Study Completion Date :
Jan 1, 2008

Arms and Interventions

Arm Intervention/Treatment
Experimental: NOMAC-E2

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

Drug: NOMAC-E2
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.
Other Names:
  • SCH 900121
  • Org 10486-0 (NOMAC)
  • Org 2317 (E2)
  • Active Comparator: LNG-EE

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

    Drug: Levonorgestrel and Ethinyl Estradiol
    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.

    Outcome Measures

    Primary Outcome Measures

    1. 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.

    2. 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.

    3. 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.

    4. 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.

    5. 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.

    6. 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.

    7. 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.

    8. 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.

    9. 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.

    10. 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.

    11. 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.

    12. 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.

    13. 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.

    14. 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.

    15. 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.

    16. 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.

    17. 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.

    18. 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.

    19. 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.

    20. 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.

    21. 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.

    22. 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.

    23. 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.

    24. 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.

    25. 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.

    26. 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.

    27. 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.

    28. 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.

    29. 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.

    30. 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.

    31. 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.

    32. 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.

    33. 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

    1. 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.

    2. 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.

    3. 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.

    4. 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.

    5. 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.

    6. 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.

    7. 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.

    8. 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.

    9. 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.

    10. 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.

    11. 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.

    12. 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.

    13. 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.

    14. 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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 50 Years
    Sexes Eligible for Study:
    Female
    Accepts Healthy Volunteers:
    Yes
    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.

    Contacts and Locations

    Locations

    No locations specified.

    Sponsors and Collaborators

    • Organon and Co

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Organon and Co
    ClinicalTrials.gov Identifier:
    NCT00511355
    Other Study ID Numbers:
    • P05764
    • Organon Protocol No. 292004
    First Posted:
    Aug 3, 2007
    Last Update Posted:
    Feb 9, 2022
    Last Verified:
    Feb 1, 2022

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title NOMAC-E2 LNG-EE
    Arm/Group Description Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles. Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.
    Period Title: Overall Study
    STARTED 60 61
    COMPLETED 53 52
    NOT COMPLETED 7 9

    Baseline Characteristics

    Arm/Group Title NOMAC-E2 LNG-EE Total
    Arm/Group Description All-participants-treated group. Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles All-participants-treated group. Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28, placebo tablets) for 6 consecutive 28-day cycles Total of all reporting groups
    Overall Participants 60 58 118
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    28.2
    (8.2)
    29.1
    (7.8)
    28.7
    (8.0)
    Sex: Female, Male (Count of Participants)
    Female
    60
    100%
    58
    100%
    118
    100%
    Male
    0
    0%
    0
    0%
    0
    0%

    Outcome Measures

    1. Primary Outcome
    Title Serum Concentration of Prothrombin Fragments 1 + 2
    Description Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.
    Time Frame Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

    Outcome Measure Data

    Analysis Population Description
    All-participants-treated group; n = number of participants with non-missing baseline value and non-missing change from baseline to Cycle 6
    Arm/Group Title NOMAC-E2 LNG-EE
    Arm/Group Description Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles. Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.
    Measure Participants 60 58
    Baseline (n=60 NOMAC-E2; n=58 LNG-EE)
    0.18
    (0.20)
    0.19
    (0.08)
    Cycle 6 (n=53 NOMAC-E2; n=52 LNG-EE)
    0.31
    (1.06)
    0.42
    (1.17)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection NOMAC-E2, LNG-EE
    Comments P-value compares the change from baseline to Cycle 6 between treatment groups.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0849
    Comments No correction for multiple testing was made.
    Method Cochran-Mantel-Haenszel
    Comments Cochran-Mantel-Haenszel test adjusted for age class applied on the changes from baseline.
    2. Primary Outcome
    Title Serum Concentration of D-Dimer
    Description Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.
    Time Frame Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

    Outcome Measure Data

    Analysis Population Description
    All-participants-treated group; n = number of participants with non-missing baseline value and non-missing change from baseline to Cycle 6
    Arm/Group Title NOMAC-E2 LNG-EE
    Arm/Group Description Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles. Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.
    Measure Participants 60 58
    Baseline (n=60; NOMAC-E2; n=58)
    0.21
    (0.16)
    0.19
    (0.14)
    Cycle 6 (n=53 NOMAC-E2; n=52 LNG-EE)
    0.18
    (0.14)
    0.26
    (0.21)
    3. Primary Outcome
    Title Activated Protein C (APC) Resistance Ratio (Endogenous Thrombin Potential [ETP]-Based)
    Description 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.
    Time Frame Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

    Outcome Measure Data

    Analysis Population Description
    All-participants-treated group; n = number of participants with non-missing baseline value and non-missing change from baseline to Cycle 6
    Arm/Group Title NOMAC-E2 LNG-EE
    Arm/Group Description Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles. Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.
    Measure Participants 60 58
    Baseline (n=59 NOMAC-E2; n=58 LNG-EE)
    0.80
    (0.33)
    0.83
    (0.40)
    Cycle 6 (n=53 NOMAC-E2; n=52 LNG-EE)
    1.14
    (0.45)
    1.99
    (0.76)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection NOMAC-E2, LNG-EE
    Comments P-value compares the change from baseline to Cycle 6 between treatment groups.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <.0001
    Comments No correction for multiple testing was made.
    Method Cochran-Mantel-Haenszel
    Comments Cochran-Mantel-Haenszel test adjusted for age class applied on the changes from baseline.
    4. Primary Outcome
    Title Serum Concentration of Clotting Factor VIIa
    Description Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.
    Time Frame Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

    Outcome Measure Data

    Analysis Population Description
    All-participants-treated group; n = number of participants with non-missing baseline value and non-missing change from baseline to Cycle 6
    Arm/Group Title NOMAC-E2 LNG-EE
    Arm/Group Description Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles. Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.
    Measure Participants 60 58
    Baseline (n=60 NOMAC-E2; n=58 LNG-EE)
    84
    (32)
    85
    (37)
    Cycle 6 (n=53 NOMAC-E2; n=52 LNG-EE)
    118
    (180)
    98
    (66)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection NOMAC-E2, LNG-EE
    Comments P-value compares the change from baseline to Cycle 6 between treatment groups.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.4191
    Comments No correction for multiple testing was made.
    Method Cochran-Mantel-Haenszel
    Comments Cochran-Mantel-Haenszel test adjusted for age class applied on the changes from baseline.
    5. Primary Outcome
    Title Serum Concentration of Clotting Factor VIIc
    Description Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.
    Time Frame Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

    Outcome Measure Data

    Analysis Population Description
    All-participants-treated group; n = number of participants with non-missing baseline value and non-missing change from baseline to Cycle 6
    Arm/Group Title NOMAC-E2 LNG-EE
    Arm/Group Description Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles. Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.
    Measure Participants 60 58
    Baseline (n=60 NOMAC-E2; n=58 LNG-EE)
    105
    (24)
    105
    (22)
    Cycle 6 (n=53 NOMAC-E2; n=52 LNG-EE)
    109
    (31)
    96
    (25)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection NOMAC-E2, LNG-EE
    Comments P-value compares the change from baseline to Cycle 6 between treatment groups.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0010
    Comments No correction for multiple testing was made.
    Method Cochran-Mantel-Haenszel
    Comments Cochran-Mantel-Haenszel test adjusted for age class applied on the changes from baseline.
    6. Secondary Outcome
    Title Serum Concentration of Total Testosterone
    Description Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.
    Time Frame Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

    Outcome Measure Data

    Analysis Population Description
    All-participants-treated group; n = number of participants with non-missing baseline value and non-missing change from baseline to Cycle 6
    Arm/Group Title NOMAC-E2 LNG-EE
    Arm/Group Description Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles. Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.
    Measure Participants 60 58
    Baseline (n=60, NOMAC-E2; n=58 LNG-EE)
    1.68
    (0.75)
    1.90
    (0.94)
    Cycle 6 (n=53, NOMAC-E2; n=52 LNG-EE)
    1.23
    (0.86)
    0.91
    (0.57)
    7. Secondary Outcome
    Title Serum Concentration of Free Testosterone
    Description Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.
    Time Frame Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

    Outcome Measure Data

    Analysis Population Description
    All-participants-treated group; n = number of participants with non-missing baseline value and non-missing change from baseline to Cycle 6
    Arm/Group Title NOMAC-E2 LNG-EE
    Arm/Group Description Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles. Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.
    Measure Participants 60 58
    Baseline (n=60, NOMAC-E2; n=58 LNG-EE)
    24.5
    (14.9)
    26.3
    (16.6)
    Cycle 6 (n=53, NOMAC-E2; n=52 LNG-EE)
    12.8
    (8.8)
    9.9
    (6.7)
    8. Secondary Outcome
    Title Serum Concentration of Dehydroepiandrosterone Sulphate (DHEAS)
    Description Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.
    Time Frame Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

    Outcome Measure Data

    Analysis Population Description
    All-participants-treated group; n = number of participants with non-missing baseline value and non-missing change from baseline to Cycle 6
    Arm/Group Title NOMAC-E2 LNG-EE
    Arm/Group Description Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles. Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.
    Measure Participants 60 58
    Baseline (n=60, NOMAC-E2; n=58 LNG-EE)
    4.94
    (2.24)
    5.19
    (2.26)
    Cycle 6 (n=53, NOMAC-E2; n=52 LNG-EE)
    4.32
    (1.82)
    4.00
    (1.91)
    9. Primary Outcome
    Title Serum Concentration of Clotting Factor VIII
    Description Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.
    Time Frame Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

    Outcome Measure Data

    Analysis Population Description
    All-participants-treated group; n = number of participants with non-missing baseline value and non-missing change from baseline to Cycle 6
    Arm/Group Title NOMAC-E2 LNG-EE
    Arm/Group Description Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles. Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.
    Measure Participants 60 58
    Baseline (n=60 NOMAC-E2; n=58 LNG-EE)
    93
    (32)
    95
    (32)
    Cycle 6 (n=53 NOMAC-E2; n=52 LNG-EE)
    89
    (34)
    98
    (30)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection NOMAC-E2, LNG-EE
    Comments P-value compares the change from baseline to Cycle 6 between treatment groups.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.3779
    Comments No correction for multiple testing was made.
    Method Cochran-Mantel-Haenszel
    Comments Cochran-Mantel-Haenszel test adjusted for age class applied on the changes from baseline.
    10. Primary Outcome
    Title Serum Concentration of Clotting Factor II
    Description Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.
    Time Frame Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

    Outcome Measure Data

    Analysis Population Description
    All-participants-treated group; n = number of participants with non-missing baseline value and non-missing change from baseline to Cycle 6
    Arm/Group Title NOMAC-E2 LNG-EE
    Arm/Group Description Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles. Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.
    Measure Participants 60 58
    Baseline (n=60 NOMAC-E2; n=58 LNG-EE)
    94
    (11)
    94
    (12)
    Cycle 6 (n=53 NOMAC-E2; n=52 LNG-EE)
    95
    (13)
    97
    (11)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection NOMAC-E2, LNG-EE
    Comments P-value compares the change from baseline to Cycle 6 between treatment groups.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.5027
    Comments No correction for multiple testing was made.
    Method Cochran-Mantel-Haenszel
    Comments Cochran-Mantel-Haenszel test adjusted for age class applied on the changes from baseline.
    11. Primary Outcome
    Title Serum Concentration of Antithrombin III
    Description Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.
    Time Frame Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

    Outcome Measure Data

    Analysis Population Description
    All-participants-treated group; n = number of participants with non-missing baseline value and non-missing change from baseline to Cycle 6
    Arm/Group Title NOMAC-E2 LNG-EE
    Arm/Group Description Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles. Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.
    Measure Participants 60 58
    Baseline (n=60 NOMAC-E2; n=58 LNG-EE)
    100
    (10)
    99
    (11)
    Cycle 6 (n=53 NOMAC-E2; n=52 LNG-EE)
    102
    (9)
    96
    (12)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection NOMAC-E2, LNG-EE
    Comments P-value compares the change from baseline to Cycle 6 between treatment groups.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0041
    Comments No correction for multiple testing was made.
    Method Cochran-Mantel-Haenszel
    Comments Cochran-Mantel-Haenszel test adjusted for age class applied on the changes from baseline.
    12. Primary Outcome
    Title Serum Concentration of Protein S (Free)
    Description Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.
    Time Frame Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

    Outcome Measure Data

    Analysis Population Description
    All-participants-treated group; n = number of participants with non-missing baseline value and non-missing change from baseline to Cycle 6
    Arm/Group Title NOMAC-E2 LNG-EE
    Arm/Group Description Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles. Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.
    Measure Participants 60 58
    Baseline (n=60 NOMAC-E2; n=58 LNG-EE)
    85
    (16)
    86
    (14)
    Cycle 6 (n=53 NOMAC-E2; n=52 LNG-EE)
    99
    (20)
    99
    (17)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection NOMAC-E2, LNG-EE
    Comments P-value compares the change from baseline to Cycle 6 between treatment groups.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.9662
    Comments No correction for multiple testing was made.
    Method Cochran-Mantel-Haenszel
    Comments Cochran-Mantel-Haenszel test adjusted for age class applied on the changes from baseline.
    13. Primary Outcome
    Title Serum Concentration of Protein S (Total)
    Description Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.
    Time Frame Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

    Outcome Measure Data

    Analysis Population Description
    All-participants-treated group; n = number of participants with non-missing baseline value and non-missing change from baseline to Cycle 6
    Arm/Group Title NOMAC-E2 LNG-EE
    Arm/Group Description Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles. Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.
    Measure Participants 60 58
    Baseline (n=60 NOMAC-E2; n=58 LNG-EE)
    78
    (12)
    79
    (10)
    Cycle 6 (n=53 NOMAC-E2; n=52 LNG-EE)
    83
    (12)
    76
    (9)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection NOMAC-E2, LNG-EE
    Comments P-value compares the change from baseline to Cycle 6 between treatment groups.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0004
    Comments No correction for multiple testing was made.
    Method Cochran-Mantel-Haenszel
    Comments Cochran-Mantel-Haenszel test adjusted for age class applied on the changes from baseline.
    14. Primary Outcome
    Title Serum Concentration of Protein C
    Description Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.
    Time Frame Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

    Outcome Measure Data

    Analysis Population Description
    All-participants-treated group; n = number of participants with non-missing baseline value and non-missing change from baseline to Cycle 6
    Arm/Group Title NOMAC-E2 LNG-EE
    Arm/Group Description Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles. Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.
    Measure Participants 60 58
    Baseline (n=60 NOMAC-E2; n=58 LNG-EE)
    107
    (18)
    103
    (19)
    Cycle 6 (n=53 NOMAC-E2; n=52 LNG-EE)
    108
    (21)
    113
    (20)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection NOMAC-E2, LNG-EE
    Comments P-value compares the change from baseline to Cycle 6 between treatment groups.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0019
    Comments No correction for multiple testing was made.
    Method Cochran-Mantel-Haenszel
    Comments Cochran-Mantel-Haenszel test adjusted for age class applied on the changes from baseline.
    15. Primary Outcome
    Title APC Resistance Ratio (Activated Partial Thromboplastin Time [APTT]-Based)
    Description 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.
    Time Frame Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

    Outcome Measure Data

    Analysis Population Description
    All-participants-treated group; n = number of participants with non-missing baseline value and non-missing change from baseline to Cycle 6
    Arm/Group Title NOMAC-E2 LNG-EE
    Arm/Group Description Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles. Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.
    Measure Participants 60 58
    Baseline (n=60 NOMAC-E2; n=58 LNG-EE)
    1.01
    (0.13)
    1.00
    (0.13)
    Cycle 6 (n=53 NOMAC-E2; n=52 LNG-EE)
    1.05
    (0.13)
    1.03
    (0.12)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection NOMAC-E2, LNG-EE
    Comments P-value compares the change from baseline to Cycle 6 between treatment groups.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.9662
    Comments No correction for multiple testing was made.
    Method Cochran-Mantel-Haenszel
    Comments Cochran-Mantel-Haenszel test adjusted for age class applied on the changes from baseline.
    16. Primary Outcome
    Title Serum Concentration of Sex Hormone Binding Globulin (SHBG)
    Description Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.
    Time Frame Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

    Outcome Measure Data

    Analysis Population Description
    All-participants-treated group; n = number of participants with non-missing baseline value and non-missing change from baseline to Cycle 6
    Arm/Group Title NOMAC-E2 LNG-EE
    Arm/Group Description Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles. Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.
    Measure Participants 60 58
    Baseline (n=60 NOMAC-E2; n=58 LNG-EE)
    74
    (34)
    77
    (26)
    Cycle 6 (n=53 NOMAC-E2; n=52 LNG-EE)
    108
    (44)
    100
    (31)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection NOMAC-E2, LNG-EE
    Comments P-value compares the change from baseline to Cycle 6 between treatment groups.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0187
    Comments No correction for multiple testing was made.
    Method Cochran-Mantel-Haenszel
    Comments Cochran-Mantel-Haenszel test adjusted for age class applied on the changes from baseline.
    17. Primary Outcome
    Title Serum Concentration of C-Reactive Protein (CRP)
    Description Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.
    Time Frame Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

    Outcome Measure Data

    Analysis Population Description
    All-participants-treated group; n = number of participants with non-missing baseline value and non-missing change from baseline to Cycle 6
    Arm/Group Title NOMAC-E2 LNG-EE
    Arm/Group Description Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles. Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.
    Measure Participants 60 58
    Baseline (n=60 NOMAC-E2; n=58 LNG-EE)
    0.82
    (1.16)
    0.98
    (1.35)
    Cycle 6 (n=53 NOMAC-E2; n=52 LNG-EE)
    1.32
    (2.36)
    4.43
    (8.43)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection NOMAC-E2, LNG-EE
    Comments P-value compares the change from baseline to Cycle 6 between treatment groups.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <.0001
    Comments No correction for multiple testing was made.
    Method Cochran-Mantel-Haenszel
    Comments Cochran-Mantel-Haenszel test adjusted for age class applied on the changes from baseline.
    18. Primary Outcome
    Title Serum Concentration of Total Cholesterol
    Description Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.
    Time Frame Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

    Outcome Measure Data

    Analysis Population Description
    All-participants-treated group; n = number of participants with non-missing baseline value and non-missing change from baseline to Cycle 6
    Arm/Group Title NOMAC-E2 LNG-EE
    Arm/Group Description Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles. Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.
    Measure Participants 60 58
    Baseline (n=60 NOMAC-E2; n=58 LNG-EE)
    4.48
    (0.87)
    4.53
    (0.82)
    Cycle 6 (n=53 NOMAC-E2; n=51 LNG-EE)
    4.51
    (0.83)
    4.48
    (0.75)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection NOMAC-E2, LNG-EE
    Comments P-value compares the change from baseline to Cycle 6 between treatment groups.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.6886
    Comments No correction for multiple testing was made.
    Method Cochran-Mantel-Haenszel
    Comments Cochran-Mantel-Haenszel test adjusted for age class applied on the changes from baseline.
    19. Primary Outcome
    Title Serum Concentration of High Density Lipoprotein (HDL)-Cholesterol
    Description Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.
    Time Frame Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

    Outcome Measure Data

    Analysis Population Description
    All-participants-treated group; n = number of participants with non-missing baseline value and non-missing change from baseline to Cycle 6
    Arm/Group Title NOMAC-E2 LNG-EE
    Arm/Group Description Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles. Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.
    Measure Participants 60 58
    Baseline (n=60 NOMAC-E2; n=58 LNG-EE)
    1.63
    (0.36)
    1.68
    (0.33)
    Cycle 6 (n=53 NOMAC-E2; n=51 LNG-EE)
    1.65
    (0.34)
    1.41
    (0.26)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection NOMAC-E2, LNG-EE
    Comments P-value compares the change from baseline to Cycle 6 between treatment groups.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <.0001
    Comments No correction for multiple testing was made.
    Method Cochran-Mantel-Haenszel
    Comments Cochran-Mantel-Haenszel test adjusted for age class applied on the changes from baseline.
    20. Primary Outcome
    Title Serum Concentration of HDL2-cholesterol
    Description Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.
    Time Frame Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

    Outcome Measure Data

    Analysis Population Description
    All-participants-treated group; n = number of participants with non-missing baseline value and non-missing change from baseline to Cycle 6
    Arm/Group Title NOMAC-E2 LNG-EE
    Arm/Group Description Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles. Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.
    Measure Participants 60 58
    Baseline (n=58 NOMAC-E2; n=50 LNG-EE)
    0.63
    (0.26)
    0.69
    (0.29)
    Cycle 6 (n=52 NOMAC-E2; n=51 LNG-EE)
    0.55
    (0.25)
    0.40
    (0.18)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection NOMAC-E2, LNG-EE
    Comments P-value compares the change from baseline to Cycle 6 between treatment groups.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <.0001
    Comments No correction for multiple testing was made.
    Method Cochran-Mantel-Haenszel
    Comments Cochran-Mantel-Haenszel test adjusted for age class applied on the changes from baseline.
    21. Primary Outcome
    Title Serum Concentration of HDL3-cholesterol
    Description Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.
    Time Frame Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

    Outcome Measure Data

    Analysis Population Description
    All-participants-treated group; n = number of participants with non-missing baseline value and non-missing change from baseline to Cycle 6
    Arm/Group Title NOMAC-E2 LNG-EE
    Arm/Group Description Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles. Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.
    Measure Participants 60 58
    Baseline (n=58 NOMAC-E2; n=50 LNG-EE)
    1.10
    (0.16)
    1.14
    (0.19)
    Cycle 6 (n=52 NOMAC-E2; n=51 LNG-EE)
    1.16
    (0.16)
    1.10
    (0.14)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection NOMAC-E2, LNG-EE
    Comments P-value compares the change from baseline to Cycle 6 between treatment groups.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0083
    Comments No correction for multiple testing was made.
    Method Cochran-Mantel-Haenszel
    Comments Cochran-Mantel-Haenszel test adjusted for age class applied on the changes from baseline.
    22. Primary Outcome
    Title Serum Concentration of Low Density Lipoprotein (LDL)-Cholesterol
    Description Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.
    Time Frame Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

    Outcome Measure Data

    Analysis Population Description
    All-participants-treated group; n = number of participants with non-missing baseline value and non-missing change from baseline to Cycle 6
    Arm/Group Title NOMAC-E2 LNG-EE
    Arm/Group Description Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles. Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.
    Measure Participants 60 58
    Baseline (n=60 NOMAC-E2; n=58 LNG-EE)
    2.41
    (0.73)
    2.47
    (0.66)
    Cycle 6 (n=53 NOMAC-E2; n=51 LNG-EE)
    2.40
    (0.71)
    2.61
    (0.74)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection NOMAC-E2, LNG-EE
    Comments P-value compares the change from baseline to Cycle 6 between treatment groups.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0455
    Comments No correction for multiple testing was made.
    Method Cochran-Mantel-Haenszel
    Comments Cochran-Mantel-Haenszel test adjusted for age class applied on the changes from baseline.
    23. Primary Outcome
    Title Serum Concentration of Apolipoprotein A-1
    Description Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.
    Time Frame Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

    Outcome Measure Data

    Analysis Population Description
    All-participants-treated group; n = number of participants with non-missing baseline value and non-missing change from baseline to Cycle 6
    Arm/Group Title NOMAC-E2 LNG-EE
    Arm/Group Description Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles. Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.
    Measure Participants 60 58
    Baseline (n=60 NOMAC-E2; n=58 LNG-EE)
    1.58
    (0.27)
    1.60
    (0.25)
    Cycle 6 (n=53 NOMAC-E2; n=51 LNG-EE)
    1.78
    (0.27)
    1.67
    (0.20)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection NOMAC-E2, LNG-EE
    Comments P-value compares the change from baseline to Cycle 6 between treatment groups.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0063
    Comments No correction for multiple testing was made.
    Method Cochran-Mantel-Haenszel
    Comments Cochran-Mantel-Haenszel test adjusted for age class applied on the changes from baseline.
    24. Primary Outcome
    Title Serum Concentration of Apolipoprotein B
    Description Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.
    Time Frame Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

    Outcome Measure Data

    Analysis Population Description
    All-participants-treated group; n = number of participants with non-missing baseline value and non-missing change from baseline to Cycle 6
    Arm/Group Title NOMAC-E2 LNG-EE
    Arm/Group Description Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles. Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.
    Measure Participants 60 58
    Baseline (n=60 NOMAC-E2; n=58 LNG-EE)
    0.64
    (0.17)
    0.64
    (0.15)
    Cycle 6 (n=53 NOMAC-E2; n=51 LNG-EE)
    0.68
    (0.17)
    0.80
    (0.21)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection NOMAC-E2, LNG-EE
    Comments P-value compares the change from baseline to Cycle 6 between treatment groups.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <.0001
    Comments No correction for multiple testing was made.
    Method Cochran-Mantel-Haenszel
    Comments Cochran-Mantel-Haenszel test adjusted for age class applied on the changes from baseline.
    25. Primary Outcome
    Title Serum Concentration of Lipoprotein(a)
    Description Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.
    Time Frame Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

    Outcome Measure Data

    Analysis Population Description
    All-participants-treated group; n = number of participants with non-missing baseline value and non-missing change from baseline to Cycle 6
    Arm/Group Title NOMAC-E2 LNG-EE
    Arm/Group Description Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles. Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.
    Measure Participants 60 58
    Baseline (n=60 NOMAC-E2; n=57 LNG-EE)
    0.15
    (0.18)
    0.15
    (0.14)
    Cycle 6 (n=53 NOMAC-E2; n=51 LNG-EE)
    0.17
    (0.22)
    0.12
    (0.11)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection NOMAC-E2, LNG-EE
    Comments P-value compares the change from baseline to Cycle 6 between treatment groups.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <.0001
    Comments No correction for multiple testing was made.
    Method Cochran-Mantel-Haenszel
    Comments Cochran-Mantel-Haenszel test adjusted for age class applied on the changes from baseline.
    26. Primary Outcome
    Title Serum Concentration of Total Triglycerides
    Description Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.
    Time Frame Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

    Outcome Measure Data

    Analysis Population Description
    All-participants-treated group; n = number of participants with non-missing baseline value and non-missing change from baseline to Cycle 6
    Arm/Group Title NOMAC-E2 LNG-EE
    Arm/Group Description Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles. Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.
    Measure Participants 60 58
    Baseline (n=60 NOMAC-E2; n=58 LNG-EE)
    0.94
    (0.30)
    0.82
    (0.23)
    Cycle 6 (n=53 NOMAC-E2; n=51 LNG-EE)
    1.00
    (0.37)
    1.02
    (0.32)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection NOMAC-E2, LNG-EE
    Comments P-value compares the change from baseline to Cycle 6 between treatment groups.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0078
    Comments No correction for multiple testing was made.
    Method Cochran-Mantel-Haenszel
    Comments Cochran-Mantel-Haenszel test adjusted for age class applied on the changes from baseline.
    27. Primary Outcome
    Title Area Under the Curve Over 3 Hours (AUC3) for Glucose (Oral Glucose Tolerance Test [OGTT])
    Description 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.
    Time Frame Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

    Outcome Measure Data

    Analysis Population Description
    All-participants-treated group; n = number of participants with non-missing baseline value and non-missing change from baseline to Cycle 6
    Arm/Group Title NOMAC-E2 LNG-EE
    Arm/Group Description Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles. Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.
    Measure Participants 60 58
    Baseline (n=59 NOMAC-E2; n=55 LNG-EE)
    15.82
    (3.27)
    14.44
    (2.47)
    Cycle 6 (n=52 NOMAC-E2; n=50 LNG-EE)
    16.09
    (3.05)
    16.69
    (3.15)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection NOMAC-E2, LNG-EE
    Comments P-value compares the change from baseline to Cycle 6 between treatment groups.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0016
    Comments No correction for multiple testing was made.
    Method Cochran-Mantel-Haenszel
    Comments Cochran-Mantel-Haenszel test adjusted for age class applied on the changes from baseline.
    28. Primary Outcome
    Title Incremental AUC3 for Glucose (OGTT)
    Description 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.
    Time Frame Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

    Outcome Measure Data

    Analysis Population Description
    All-participants-treated group; n = number of participants with non-missing baseline value and non-missing change from baseline to Cycle 6
    Arm/Group Title NOMAC-E2 LNG-EE
    Arm/Group Description Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles. Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.
    Measure Participants 60 58
    Baseline (n=59 NOMAC-E2; n=55 LNG-EE)
    1.58
    (3.05)
    1.06
    (2.55)
    Cycle 6 (n=52 NOMAC-E2; n=50 LNG-EE)
    1.76
    (2.72)
    3.19
    (3.03)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection NOMAC-E2, LNG-EE
    Comments P-value compares the change from baseline to Cycle 6 between treatment groups.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0003
    Comments No correction for multiple testing was made.
    Method Cochran-Mantel-Haenszel
    Comments Cochran-Mantel-Haenszel test adjusted for age class applied on the changes from baseline.
    29. Primary Outcome
    Title AUC3 for Insulin (OGTT)
    Description 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.
    Time Frame Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

    Outcome Measure Data

    Analysis Population Description
    All-participants-treated group; n = number of participants with non-missing baseline value and non-missing change from baseline to Cycle 6
    Arm/Group Title NOMAC-E2 LNG-EE
    Arm/Group Description Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles. Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.
    Measure Participants 60 58
    Baseline (n=51 NOMAC-E2; n=50 LNG-EE)
    650
    (298)
    558
    (182)
    Cycle 6 (n=46 NOMAC-E2; n=47 LNG-EE)
    658
    (281)
    721
    (264)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection NOMAC-E2, LNG-EE
    Comments P-value compares the change from baseline to Cycle 6 between treatment groups.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0009
    Comments No correction for multiple testing was made.
    Method Cochran-Mantel-Haenszel
    Comments Cochran-Mantel-Haenszel test adjusted for age class applied on the changes from baseline.
    30. Primary Outcome
    Title Incremental AUC3 for Insulin (OGTT)
    Description 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.
    Time Frame Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

    Outcome Measure Data

    Analysis Population Description
    All-participants-treated group; n = number of participants with non-missing baseline value and non-missing change from baseline to Cycle 6
    Arm/Group Title NOMAC-E2 LNG-EE
    Arm/Group Description Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles. Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.
    Measure Participants 60 58
    Baseline (n=51 NOMAC-E2; n=50 LNG-EE)
    517
    (268)
    451
    (160)
    Cycle 6 (n=46 NOMAC-E2; n=47 LNG-EE)
    534
    (239)
    603
    (237)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection NOMAC-E2, LNG-EE
    Comments P-value compares the change from baseline to Cycle 6 between treatment groups.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.0024
    Comments No correction for multiple testing was made.
    Method Cochran-Mantel-Haenszel
    Comments Cochran-Mantel-Haenszel test adjusted for age class applied on the changes from baseline.
    31. Primary Outcome
    Title Serum Concentration of Hemoglobin Type A1c (HbA1c)
    Description 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.
    Time Frame Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

    Outcome Measure Data

    Analysis Population Description
    All-participants-treated group; n = number of participants with non-missing baseline value and non-missing change from baseline to Cycle 6
    Arm/Group Title NOMAC-E2 LNG-EE
    Arm/Group Description Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles. Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.
    Measure Participants 60 58
    Baseline (n=60 NOMAC-E2; n=58 LNG-EE)
    5.3
    (0.3)
    5.3
    (0.2)
    Cycle 6 (n=53 NOMAC-E2; n=51 LNG-EE)
    5.3
    (0.2)
    5.4
    (0.2)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection NOMAC-E2, LNG-EE
    Comments P-value compares the change from baseline to Cycle 6 between treatment groups.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.3653
    Comments No correction for multiple testing was made.
    Method Cochran-Mantel-Haenszel
    Comments Cochran-Mantel-Haenszel test adjusted for age class applied on the changes from baseline.
    32. Primary Outcome
    Title Serum Concentration of Total Cortisol
    Description Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.
    Time Frame Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

    Outcome Measure Data

    Analysis Population Description
    All-participants-treated group; n = number of participants with non-missing baseline value and non-missing change from baseline to Cycle 6
    Arm/Group Title NOMAC-E2 LNG-EE
    Arm/Group Description Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles. Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.
    Measure Participants 60 58
    Baseline (n=60 NOMAC-E2; n=58 LNG-EE)
    482
    (128)
    502
    (153)
    Cycle 6 (n=53 NOMAC-E2; n=52 LNG-EE)
    608
    (167)
    944
    (183)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection NOMAC-E2, LNG-EE
    Comments P-value compares the change from baseline to Cycle 6 between treatment groups.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <.0001
    Comments No correction for multiple testing was made.
    Method Cochran-Mantel-Haenszel
    Comments Cochran-Mantel-Haenszel test adjusted for age class applied on the changes from baseline.
    33. Primary Outcome
    Title Serum Concentration of Corticosteroid Binding Globulin (CBG)
    Description Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.
    Time Frame Baseline to Cycle 6 (between Days 15 and 21 of the cycle)

    Outcome Measure Data

    Analysis Population Description
    All-participants-treated group; n = number of participants with non-missing baseline value and non-missing change from baseline to Cycle 6
    Arm/Group Title NOMAC-E2 LNG-EE
    Arm/Group Description Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles. Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.
    Measure Participants 60 58
    Baseline (n=60 NOMAC-E2; n=58 LNG-EE)
    910
    (201)
    932
    (163)
    Cycle 6 (n=53 NOMAC-E2; n=52 LNG-EE)
    1116
    (252)
    1980
    (389)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection NOMAC-E2, LNG-EE
    Comments P-value compares the change from baseline to Cycle 6 between treatment groups.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <.0001
    Comments No correction for multiple testing was made.
    Method Cochran-Mantel-Haenszel
    Comments Cochran-Mantel-Haenszel test adjusted for age class applied on the changes from baseline.
    34. Primary Outcome
    Title Serum Concentration of Thyroid Stimulating Hormone (TSH)
    Description Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.
    Time Frame Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

    Outcome Measure Data

    Analysis Population Description
    All-participants-treated group; n = number of participants with non-missing baseline value and non-missing change from baseline to Cycle 6
    Arm/Group Title NOMAC-E2 LNG-EE
    Arm/Group Description Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles. Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.
    Measure Participants 60 58
    Baseline (n=60 NOMAC-E2; n=58 LNG-EE)
    2.69
    (1.28)
    2.20
    (1.08)
    Cycle 6 (n=53 NOMAC-E2; n=52 LNG-EE)
    2.96
    (2.05)
    2.75
    (3.36)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection NOMAC-E2, LNG-EE
    Comments P-value compares the change from baseline to Cycle 6 between treatment groups.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.5668
    Comments No correction for multiple testing was made.
    Method Cochran-Mantel-Haenszel
    Comments Cochran-Mantel-Haenszel test adjusted for age class applied on the changes from baseline.
    35. Primary Outcome
    Title Serum Concentration of Free Thyroxine (T4)
    Description Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.
    Time Frame Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

    Outcome Measure Data

    Analysis Population Description
    All-participants-treated group; n = number of participants with non-missing baseline value and non-missing change from baseline to Cycle 6
    Arm/Group Title NOMAC-E2 LNG-EE
    Arm/Group Description Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles. Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.
    Measure Participants 60 58
    Baseline (n=60 NOMAC-E2; n=58 LNG-EE)
    14.0
    (1.5)
    14.1
    (1.5)
    Cycle 6 (n=53 NOMAC-E2; n=52 LNG-EE)
    15.9
    (2.0)
    15.7
    (2.1)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection NOMAC-E2, LNG-EE
    Comments P-value compares the change from baseline to Cycle 6 between treatment groups.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value 0.1770
    Comments No correction for multiple testing was made.
    Method Cochran-Mantel-Haenszel
    Comments Cochran-Mantel-Haenszel test adjusted for age class applied on the changes from baseline.
    36. Primary Outcome
    Title Serum Concentration of Thyroxin Binding Globulin (TBG)
    Description Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.
    Time Frame Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

    Outcome Measure Data

    Analysis Population Description
    All-participants-treated group; n = number of participants with non-missing baseline value and non-missing change from baseline to Cycle 6
    Arm/Group Title NOMAC-E2 LNG-EE
    Arm/Group Description Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles. Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.
    Measure Participants 60 58
    Baseline (n=60 NOMAC-E2; n=58 LNG-EE)
    20.3
    (2.9)
    20.3
    (3.3)
    Cycle 6 (n=53 NOMAC-E2; n=52 LNG-EE)
    24.2
    (3.6)
    28.4
    (5.3)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection NOMAC-E2, LNG-EE
    Comments P-value compares the change from baseline to Cycle 6 between treatment groups.
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value <.0001
    Comments No correction for multiple testing was made.
    Method Cochran-Mantel-Haenszel
    Comments Cochran-Mantel-Haenszel test adjusted for age class applied on the changes from baseline.
    37. Secondary Outcome
    Title Serum Concentration of Androstenedione
    Description Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.
    Time Frame Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

    Outcome Measure Data

    Analysis Population Description
    All-participants-treated group; n = number of participants with non-missing baseline value and non-missing change from baseline to Cycle 6
    Arm/Group Title NOMAC-E2 LNG-EE
    Arm/Group Description Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles. Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.
    Measure Participants 60 58
    Baseline (n=60, NOMAC-E2; n=58 LNG-EE)
    9.60
    (3.45)
    10.27
    (3.91)
    Cycle 6 (n=53, NOMAC-E2; n=52 LNG-EE)
    8.23
    (3.01)
    6.96
    (3.37)
    38. Secondary Outcome
    Title Serum Concentration of Dihydrotestosterone (DHT)
    Description Serum samples were obtained under fasting conditions (no food or alcoholic beverages within 12 hours of serum sampling). Each cycle consists of 28 days.
    Time Frame Baseline and Cycle 6 (between Days 15 and 21 of the cycle)

    Outcome Measure Data

    Analysis Population Description
    All-participants-treated group; n = number of participants with non-missing baseline value and non-missing change from baseline to Cycle 6
    Arm/Group Title NOMAC-E2 LNG-EE
    Arm/Group Description Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles. Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.
    Measure Participants 60 58
    Baseline (n=60, NOMAC-E2; n=58 LNG-EE)
    0.59
    (0.21)
    0.62
    (0.26)
    Cycle 6 (n=53, NOMAC-E2; n=52 LNG-EE)
    0.53
    (0.28)
    0.36
    (0.19)
    39. Secondary Outcome
    Title Number of In-treatment Pregnancies (With +2 Day Window) Per 100 Woman Years of Exposure (Pearl Index)
    Description 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.
    Time Frame 6 cycles

    Outcome Measure Data

    Analysis Population Description
    The "restricted ITT" set included all participants treated and excluded nonpregnant participants who didn't have >=1 cycle expected to be at risk for pregnancy (with recorded use of condoms or w/o sexual intercourse per diary card data).
    Arm/Group Title NOMAC-E2 LNG-EE
    Arm/Group Description Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles. Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.
    Measure Participants 57 56
    Measure Woman years (rounded to nearest integer) 23 22
    Number (95% Confidence Interval) [Pregnancies per 100 woman years]
    0
    0
    40. Secondary Outcome
    Title Number of Participants With an Occurrence of Breakthrough Bleeding/Spotting
    Description 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.
    Time Frame Every 28-day cycle for 6 cycles

    Outcome Measure Data

    Analysis Population Description
    The ITT group consisted of all participants who were treated; ITT analyses of vaginal bleeding patterns were based on all participants in the ITT group who had at least one evaluable cycle. Cycles were considered to be non-evaluable in case of insufficient bleeding data or improper cycle length. n=number of participants with evaluable cycles.
    Arm/Group Title NOMAC-E2 LNG-EE
    Arm/Group Description Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles. Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.
    Measure Participants 56 53
    Cycle 1 (n=56 NOMAC-E2; n=53 LNG-EE)
    18
    30%
    16
    27.6%
    Cycle 2 (n=55 NOMAC-E2; n=51 LNG-EE)
    11
    18.3%
    9
    15.5%
    Cycle 3 (n=54 NOMAC-E2; n=52 LNG-EE)
    5
    8.3%
    5
    8.6%
    Cycle 4 (n=54 NOMAC-E2; n=52 LNG-EE)
    8
    13.3%
    2
    3.4%
    Cycle 5 (n=52 NOMAC-E2; n=51 LNG-EE)
    6
    10%
    4
    6.9%
    Cycle 6 (n=52 NOMAC-E2; n=50 LNG-EE)
    6
    10%
    3
    5.2%
    41. Secondary Outcome
    Title Number of Participants With an Occurrence of Absence of Withdrawal Bleeding
    Description 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.
    Time Frame Every 28-day cycle for 6 cycles

    Outcome Measure Data

    Analysis Population Description
    The ITT group consisted of all participants who were treated; ITT analyses of vaginal bleeding patterns were based on all participants in the ITT group who had at least one evaluable cycle. Cycles were considered to be non-evaluable in case of insufficient bleeding data or improper cycle length. n=number of participants with evaluable cycles.
    Arm/Group Title NOMAC-E2 LNG-EE
    Arm/Group Description Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles. Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.
    Measure Participants 56 53
    Cycle 1 (n=56 NOMAC-E2; n=53 LNG-EE)
    6
    10%
    0
    0%
    Cycle 2 (n=55 NOMAC-E2; n=51 LNG-EE)
    8
    13.3%
    1
    1.7%
    Cycle 3 (n=54 NOMAC-E2; n=52 LNG-EE)
    5
    8.3%
    0
    0%
    Cycle 4 (n=54 NOMAC-E2; n=52 LNG-EE)
    8
    13.3%
    0
    0%
    Cycle 5 (n=52 NOMAC-E2; n=51 LNG-EE)
    5
    8.3%
    0
    0%
    Cycle 6 (n=52 NOMAC-E2; n=50 LNG-EE)
    10
    16.7%
    1
    1.7%
    42. Secondary Outcome
    Title Number of Participants With an Occurrence of Breakthrough Bleeding
    Description 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.
    Time Frame Every 28-day cycle for 6 cycles

    Outcome Measure Data

    Analysis Population Description
    The ITT group consisted of all participants who were treated; ITT analyses of vaginal bleeding patterns were based on all participants in the ITT group who had at least one evaluable cycle. Cycles were considered to be non-evaluable in case of insufficient bleeding data or improper cycle length. n=number of participants with evaluable cycles.
    Arm/Group Title NOMAC-E2 LNG-EE
    Arm/Group Description Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles. Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.
    Measure Participants 56 53
    Cycle 1 (n=56 NOMAC-E2; n=53 LNG-EE)
    3
    5%
    1
    1.7%
    Cycle 2 (n=55 NOMAC-E2; n=51 LNG-EE)
    1
    1.7%
    0
    0%
    Cycle 3 (n=54 NOMAC-E2; n=52 LNG-EE)
    1
    1.7%
    0
    0%
    Cycle 4 (n=54 NOMAC-E2; n=52 LNG-EE)
    1
    1.7%
    0
    0%
    Cycle 5 (n=52 NOMAC-E2; n=51 LNG-EE)
    2
    3.3%
    0
    0%
    Cycle 6 (n=52 NOMAC-E2; n=50 LNG-EE)
    3
    5%
    0
    0%
    43. Secondary Outcome
    Title Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only)
    Description 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.
    Time Frame Every 28-day cycle for 6 cycles

    Outcome Measure Data

    Analysis Population Description
    The ITT group consisted of all participants who were treated; ITT analyses of vaginal bleeding patterns were based on all participants in the ITT group who had at least one evaluable cycle. Cycles were considered to be non-evaluable in case of insufficient bleeding data or improper cycle length. n=number of participants with evaluable cycles.
    Arm/Group Title NOMAC-E2 LNG-EE
    Arm/Group Description Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles. Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.
    Measure Participants 56 53
    Cycle 1 (n=56 NOMAC-E2; n=53 LNG-EE)
    17
    28.3%
    16
    27.6%
    Cycle 2 (n=55 NOMAC-E2; n=51 LNG-EE)
    10
    16.7%
    9
    15.5%
    Cycle 3 (n=54 NOMAC-E2; n=52 LNG-EE)
    4
    6.7%
    5
    8.6%
    Cycle 4 (n=54 NOMAC-E2; n=52 LNG-EE)
    7
    11.7%
    2
    3.4%
    Cycle 5 (n=52 NOMAC-E2; n=51 LNG-EE)
    4
    6.7%
    4
    6.9%
    Cycle 6 (n=52 NOMAC-E2; n=50 LNG-EE)
    4
    6.7%
    3
    5.2%
    44. Secondary Outcome
    Title Number of Participants With an Occurrence of Early Withdrawal Bleeding
    Description 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.
    Time Frame Every 28-day cycle for 6 cycles

    Outcome Measure Data

    Analysis Population Description
    The ITT group consisted of all participants who were treated; ITT analyses of vaginal bleeding patterns were based on all participants in the ITT group who had at least one evaluable cycle. Cycles were considered to be non-evaluable in case of insufficient bleeding data or improper cycle length. n=number of participants with evaluable cycles.
    Arm/Group Title NOMAC-E2 LNG-EE
    Arm/Group Description Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles. Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.
    Measure Participants 56 53
    Cycle 1 (n=56 NOMAC-E2; n=53 LNG-EE)
    5
    8.3%
    4
    6.9%
    Cycle 2 (n=55 NOMAC-E2; n=51 LNG-EE)
    4
    6.7%
    1
    1.7%
    Cycle 3 (n=54 NOMAC-E2; n=52 LNG-EE)
    3
    5%
    1
    1.7%
    Cycle 4 (n=54 NOMAC-E2; n=52 LNG-EE)
    2
    3.3%
    0
    0%
    Cycle 5 (n=52 NOMAC-E2; n=51 LNG-EE)
    1
    1.7%
    0
    0%
    Cycle 6 (n=52 NOMAC-E2; n=50 LNG-EE)
    2
    3.3%
    2
    3.4%
    45. Secondary Outcome
    Title Number of Participants With an Occurrence of Continued Withdrawal Bleeding
    Description 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.
    Time Frame Every 28-day cycle for 5 cycles

    Outcome Measure Data

    Analysis Population Description
    The ITT group consisted of all participants who were treated; ITT analyses of vaginal bleeding patterns were based on all participants in the ITT group who had at least one evaluable cycle. Cycles were considered to be non-evaluable in case of insufficient bleeding data or improper cycle length.
    Arm/Group Title NOMAC-E2 LNG-EE
    Arm/Group Description Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles. n= number of participants with evaluable cycles (except for the very last cycle of a participant for which this parameter was not defined). Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles. n= number of participants with evaluable cycles (except for the very last cycle of a participant for which this parameter was not defined).
    Measure Participants 56 53
    Cycle 1 (n=56 NOMAC-E2; n=53 LNG-EE)
    15
    25%
    25
    43.1%
    Cycle 2 (n=54 NOMAC-E2; n=50 LNG-EE)
    11
    18.3%
    28
    48.3%
    Cycle 3 (n=54 NOMAC-E2; n=52 LNG-EE)
    13
    21.7%
    26
    44.8%
    Cycle 4 (n=53 NOMAC-E2; n=52 LNG-EE)
    11
    18.3%
    27
    46.6%
    Cycle 5 (n=52 NOMAC-E2; n=51 LNG-EE)
    13
    21.7%
    29
    50%
    46. Secondary Outcome
    Title Average Number of Breakthrough Bleeding/Spotting Days
    Description 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.
    Time Frame Every 28-day cycle for 6 cycles

    Outcome Measure Data

    Analysis Population Description
    ITT analyses of vaginal bleeding patterns were based on all participants in the ITT group who had at least one evaluable cycle. Cycles were considered to be non-evaluable in case of insufficient bleeding data or improper cycle length. n=number of participants who had breakthrough bleeding/spotting for the respective cycle.
    Arm/Group Title NOMAC-E2 LNG-EE
    Arm/Group Description Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles. Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.
    Measure Participants 56 53
    Cycle 1 (n=18 NOMAC-E2; n=16 LNG-EE)
    3.5
    (2.7)
    4.6
    (3.6)
    Cycle 2 (n=11 NOMAC-E2; n=9 LNG-EE)
    4.3
    (1.4)
    3.3
    (2.2)
    Cycle 3 (n=5 NOMAC-E2; n=5 LNG-EE)
    4.6
    (2.5)
    3.2
    (2.2)
    Cycle 4 (n=8 NOMAC-E2; n=2 LNG-EE)
    3.8
    (2.3)
    4.0
    (0.0)
    Cycle 5 (n=6 NOMAC-E2; n=4 LNG-EE)
    3.3
    (2.5)
    2.0
    (2.0)
    Cycle 6 (n=6 NOMAC-E2; n=3 LNG-EE)
    4.7
    (3.7)
    3.0
    (2.0)
    47. Secondary Outcome
    Title Average Number of Withdrawal Bleeding/Spotting Days
    Description 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.
    Time Frame Every 28-day cycle for 6 cycles

    Outcome Measure Data

    Analysis Population Description
    ITT analyses of vaginal bleeding patterns were based on all participants in the ITT group who had at least one evaluable cycle. Cycles were considered to be non-evaluable in case of insufficient bleeding data or improper cycle length. n=number of participants who had withdrawal bleeding/spotting for the respective cycle.
    Arm/Group Title NOMAC-E2 LNG-EE
    Arm/Group Description Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles. Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.
    Measure Participants 56 53
    Cycle 1 (n=50 NOMAC-E2; n=53 LNG-EE)
    4.8
    (2.3)
    5.8
    (3.6)
    Cycle 2 (n=47 NOMAC-E2; n=50 LNG-EE)
    4.7
    (3.6)
    4.9
    (1.2)
    Cycle 3 (n=49 NOMAC-E2); n=52 LNG-EE)
    3.9
    (2.0)
    4.9
    (1.4)
    Cycle 4 (n=46 NOMAC-E2; n=52 LNG-EE)
    4.0
    (2.5)
    5.0
    (1.5)
    Cycle 5 (n=47 NOMAC-E2; n=51 LNG-EE)
    3.8
    (1.7)
    4.9
    (1.5)
    Cycle 6 (n=42 NOMAC-E2; n=49 LNG-EE)
    3.5
    (1.2)
    4.2
    (1.7)

    Adverse Events

    Time Frame
    Adverse Event Reporting Description
    Arm/Group Title NOMAC-E2 LNG-EE
    Arm/Group Description Monophasic combined oral contraceptive (COC) tablets containing 2.5 mg Nomegestrol Acetate (NOMAC) and 1.5 mg Estradiol (E2) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-24, active tablets; Days 25-28, placebo tablets) for 6 consecutive 28-day cycles. Monophasic combined oral contraceptive (COC) tablets containing 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE) taken once daily from Day 1 of menstrual period up to and including Day 28 (Days 1-21, active tablets; Days 22-28 placebo tablets) for 6 consecutive 28-day cycles.
    All Cause Mortality
    NOMAC-E2 LNG-EE
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN)
    Serious Adverse Events
    NOMAC-E2 LNG-EE
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 1/60 (1.7%) 0/58 (0%)
    Congenital, familial and genetic disorders
    Congenital mitral valve incompetence 1/60 (1.7%) 1 0/58 (0%) 0
    Other (Not Including Serious) Adverse Events
    NOMAC-E2 LNG-EE
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 9/60 (15%) 18/58 (31%)
    Infections and infestations
    Influenza 1/60 (1.7%) 1 4/58 (6.9%) 4
    Upper respiratory tract infection 6/60 (10%) 14 5/58 (8.6%) 6
    Nervous system disorders
    Headache 3/60 (5%) 5 7/58 (12.1%) 14
    Skin and subcutaneous tissue disorders
    Acne 2/60 (3.3%) 2 4/58 (6.9%) 4

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    The SPONSOR recognizes the right of the investigator(s) to publish, but all publications must be based on data validated and released by the SPONSOR. Any such scientific paper, presentation, or other communication concerning the clinical trial will first be submitted to the SPONSOR, at least six weeks ahead of estimated publication or presentation, for consent, which shall not be withheld unreasonably.

    Results Point of Contact

    Name/Title Senior Vice President, Global Clinical Development
    Organization Merck Sharp & Dohme Corp.
    Phone
    Email ClinicalTrialsDisclosure@merck.com
    Responsible Party:
    Organon and Co
    ClinicalTrials.gov Identifier:
    NCT00511355
    Other Study ID Numbers:
    • P05764
    • Organon Protocol No. 292004
    First Posted:
    Aug 3, 2007
    Last Update Posted:
    Feb 9, 2022
    Last Verified:
    Feb 1, 2022