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CompletedNCT00511355Updated Feb 9, 2022Results posted

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)

A Phase 3 interventional study of NOMAC-E2 and Levonorgestrel and Ethinyl Estradiol in Contraception, sponsored by Organon and Co. Completed. Open to female participants aged 18 Years to 50 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2022-02-09.

Sponsored by Organon and Co · Phase 3, Interventional, and Prevention

Phase
Phase 3
Study type
Interventional
Enrollment
121
Allocation
Randomized
Ages
18 Years to 50 Years
Sex
Female
01

Study 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.

02

Conditions studied

  • Contraception
03

In context

Lead sponsor

Organon and Co is the lead sponsor of 478 studies on the registry; none are open to participants now.

Of its 21 completed or terminated interventional studies of FDA-regulated products, 17 (81%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 50 Years
Sexes eligible
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

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.
05

Study design

Phase
Phase 3
Primary purpose
Prevention
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
121 participants (actual)

Study arms

  • 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

  • Active comparator
    LNG-EE

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

    Drug: Levonorgestrel and Ethinyl Estradiol

Interventions

  • DrugNOMAC-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.

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

  • DrugLevonorgestrel 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.

06

What researchers measure

Primary outcomes

  1. Serum Concentration of Prothrombin Fragments 1 + 2

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

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

  2. Serum Concentration of D-Dimer

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

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

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

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

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

  4. Serum Concentration of Clotting Factor VIIa

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

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

  5. Serum Concentration of Clotting Factor VIIc

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

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

  6. Serum Concentration of Clotting Factor VIII

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

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

  7. Serum Concentration of Clotting Factor II

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

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

  8. Serum Concentration of Antithrombin III

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

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

  9. Serum Concentration of Protein S (Free)

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

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

  10. Serum Concentration of Protein S (Total)

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

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

  11. Serum Concentration of Protein C

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

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

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

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

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

  13. Serum Concentration of Sex Hormone Binding Globulin (SHBG)

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

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

  14. Serum Concentration of C-Reactive Protein (CRP)

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

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

  15. Serum Concentration of Total Cholesterol

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

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

  16. Serum Concentration of High Density Lipoprotein (HDL)-Cholesterol

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

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

  17. Serum Concentration of HDL2-cholesterol

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

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

  18. Serum Concentration of HDL3-cholesterol

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

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

  19. Serum Concentration of Low Density Lipoprotein (LDL)-Cholesterol

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

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

  20. Serum Concentration of Apolipoprotein A-1

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

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

  21. Serum Concentration of Apolipoprotein B

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

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

  22. Serum Concentration of Lipoprotein(a)

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

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

  23. Serum Concentration of Total Triglycerides

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

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

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

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

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

  25. Incremental AUC3 for Glucose (OGTT)

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

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

  26. AUC3 for Insulin (OGTT)

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

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

  27. Incremental AUC3 for Insulin (OGTT)

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

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

  28. Serum Concentration of Hemoglobin Type A1c (HbA1c)

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

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

  29. Serum Concentration of Total Cortisol

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

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

  30. Serum Concentration of Corticosteroid Binding Globulin (CBG)

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

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

  31. Serum Concentration of Thyroid Stimulating Hormone (TSH)

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

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

  32. Serum Concentration of Free Thyroxine (T4)

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

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

  33. Serum Concentration of Thyroxin Binding Globulin (TBG)

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

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

Secondary outcomes

  1. Serum Concentration of Total Testosterone

    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)

  2. Serum Concentration of Free Testosterone

    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)

  3. Serum Concentration of Dehydroepiandrosterone Sulphate (DHEAS)

    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)

  4. Serum Concentration of Androstenedione

    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)

  5. Serum Concentration of Dihydrotestosterone (DHT)

    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)

  6. Number of In-treatment Pregnancies (With +2 Day Window) Per 100 Woman Years of Exposure (Pearl Index)

    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

  7. Number of Participants With an Occurrence of Breakthrough Bleeding/Spotting

    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

  8. Number of Participants With an Occurrence of Absence of Withdrawal Bleeding

    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

  9. Number of Participants With an Occurrence of Breakthrough Bleeding

    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

  10. Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only)

    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

  11. Number of Participants With an Occurrence of Early Withdrawal Bleeding

    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

  12. Number of Participants With an Occurrence of Continued Withdrawal Bleeding

    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

  13. Average Number of Breakthrough Bleeding/Spotting Days

    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

  14. Average Number of Withdrawal Bleeding/Spotting Days

    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

07

Results

Posted Aug 30, 2011

Participant flow

Participant flow — Overall Study
MilestoneNOMAC-E2LNG-EE
Started6061
Completed5352
Not completed79
Withdrew: Adverse event44
Withdrew: Pregnancy wish10
Withdrew: Lost to follow-up21
Withdrew: Other reason01
Withdrew: Pre-treatment (serious) adverse event01
Withdrew: Withdrawal of informed consent01
Withdrew: Other reason pre-treatment01

Outcome measures

PrimarySerum Concentration of Prothrombin Fragments 1 + 2

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

Time frame:
Baseline and Cycle 6 (between Days 15 and 21 of the cycle)
Reported as:
Mean · nmol/L
Serum Concentration of Prothrombin Fragments 1 + 2
nmol/LNOMAC-E2LNG-EE
Baseline (n=60 NOMAC-E2; n=58 LNG-EE)0.18 ± 0.200.19 ± 0.08
Cycle 6 (n=53 NOMAC-E2; n=52 LNG-EE)0.31 ± 1.060.42 ± 1.17
Statistical analysis
  • NOMAC-E2 vs LNG-EE · Cochran-Mantel-Haenszel · p = 0.0849 (No correction for multiple testing was made.)Cochran-Mantel-Haenszel test adjusted for age class applied on the changes from baseline.
PrimarySerum Concentration of D-Dimer

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

Time frame:
Baseline and Cycle 6 (between Days 15 and 21 of the cycle)
Reported as:
Mean · mg/L Fibrinogen Equivalent Units (FEU)
Serum Concentration of D-Dimer
mg/L Fibrinogen Equivalent Units (FEU)NOMAC-E2LNG-EE
Baseline (n=60; NOMAC-E2; n=58)0.21 ± 0.160.19 ± 0.14
Cycle 6 (n=53 NOMAC-E2; n=52 LNG-EE)0.18 ± 0.140.26 ± 0.21
PrimaryActivated Protein C (APC) Resistance Ratio (Endogenous Thrombin Potential [ETP]-Based)

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

Time frame:
Baseline and Cycle 6 (between Days 15 and 21 of the cycle)
Reported as:
Mean · Ratio
Activated Protein C (APC) Resistance Ratio (Endogenous Thrombin Potential [ETP]-Based)
RatioNOMAC-E2LNG-EE
Baseline (n=59 NOMAC-E2; n=58 LNG-EE)0.80 ± 0.330.83 ± 0.40
Cycle 6 (n=53 NOMAC-E2; n=52 LNG-EE)1.14 ± 0.451.99 ± 0.76
Statistical analysis
  • NOMAC-E2 vs LNG-EE · Cochran-Mantel-Haenszel · p = <.0001 (No correction for multiple testing was made.)Cochran-Mantel-Haenszel test adjusted for age class applied on the changes from baseline.
PrimarySerum Concentration of Clotting Factor VIIa

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

Time frame:
Baseline and Cycle 6 (between Days 15 and 21 of the cycle)
Reported as:
Mean · U/L
Serum Concentration of Clotting Factor VIIa
U/LNOMAC-E2LNG-EE
Baseline (n=60 NOMAC-E2; n=58 LNG-EE)84 ± 3285 ± 37
Cycle 6 (n=53 NOMAC-E2; n=52 LNG-EE)118 ± 18098 ± 66
Statistical analysis
  • NOMAC-E2 vs LNG-EE · Cochran-Mantel-Haenszel · p = 0.4191 (No correction for multiple testing was made.)Cochran-Mantel-Haenszel test adjusted for age class applied on the changes from baseline.
PrimarySerum Concentration of Clotting Factor VIIc

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

Time frame:
Baseline and Cycle 6 (between Days 15 and 21 of the cycle)
Reported as:
Mean · Percent of normal
Serum Concentration of Clotting Factor VIIc
Percent of normalNOMAC-E2LNG-EE
Baseline (n=60 NOMAC-E2; n=58 LNG-EE)105 ± 24105 ± 22
Cycle 6 (n=53 NOMAC-E2; n=52 LNG-EE)109 ± 3196 ± 25
Statistical analysis
  • NOMAC-E2 vs LNG-EE · Cochran-Mantel-Haenszel · p = 0.0010 (No correction for multiple testing was made.)Cochran-Mantel-Haenszel test adjusted for age class applied on the changes from baseline.
SecondarySerum Concentration of Total Testosterone

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)
Reported as:
Mean · nmol/L
Serum Concentration of Total Testosterone
nmol/LNOMAC-E2LNG-EE
Baseline (n=60, NOMAC-E2; n=58 LNG-EE)1.68 ± 0.751.90 ± 0.94
Cycle 6 (n=53, NOMAC-E2; n=52 LNG-EE)1.23 ± 0.860.91 ± 0.57
SecondarySerum Concentration of Free Testosterone

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)
Reported as:
Mean · pmol/L
Serum Concentration of Free Testosterone
pmol/LNOMAC-E2LNG-EE
Baseline (n=60, NOMAC-E2; n=58 LNG-EE)24.5 ± 14.926.3 ± 16.6
Cycle 6 (n=53, NOMAC-E2; n=52 LNG-EE)12.8 ± 8.89.9 ± 6.7
SecondarySerum Concentration of Dehydroepiandrosterone Sulphate (DHEAS)

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)
Reported as:
Mean · umol/L
Serum Concentration of Dehydroepiandrosterone Sulphate (DHEAS)
umol/LNOMAC-E2LNG-EE
Baseline (n=60, NOMAC-E2; n=58 LNG-EE)4.94 ± 2.245.19 ± 2.26
Cycle 6 (n=53, NOMAC-E2; n=52 LNG-EE)4.32 ± 1.824.00 ± 1.91
PrimarySerum Concentration of Clotting Factor VIII

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

Time frame:
Baseline and Cycle 6 (between Days 15 and 21 of the cycle)
Reported as:
Mean · Percent of normal
Serum Concentration of Clotting Factor VIII
Percent of normalNOMAC-E2LNG-EE
Baseline (n=60 NOMAC-E2; n=58 LNG-EE)93 ± 3295 ± 32
Cycle 6 (n=53 NOMAC-E2; n=52 LNG-EE)89 ± 3498 ± 30
Statistical analysis
  • NOMAC-E2 vs LNG-EE · Cochran-Mantel-Haenszel · p = 0.3779 (No correction for multiple testing was made.)Cochran-Mantel-Haenszel test adjusted for age class applied on the changes from baseline.
PrimarySerum Concentration of Clotting Factor II

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

Time frame:
Baseline and Cycle 6 (between Days 15 and 21 of the cycle)
Reported as:
Mean · Percent of normal
Serum Concentration of Clotting Factor II
Percent of normalNOMAC-E2LNG-EE
Baseline (n=60 NOMAC-E2; n=58 LNG-EE)94 ± 1194 ± 12
Cycle 6 (n=53 NOMAC-E2; n=52 LNG-EE)95 ± 1397 ± 11
Statistical analysis
  • NOMAC-E2 vs LNG-EE · Cochran-Mantel-Haenszel · p = 0.5027 (No correction for multiple testing was made.)Cochran-Mantel-Haenszel test adjusted for age class applied on the changes from baseline.
PrimarySerum Concentration of Antithrombin III

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

Time frame:
Baseline and Cycle 6 (between Days 15 and 21 of the cycle)
Reported as:
Mean · Percent of normal
Serum Concentration of Antithrombin III
Percent of normalNOMAC-E2LNG-EE
Baseline (n=60 NOMAC-E2; n=58 LNG-EE)100 ± 1099 ± 11
Cycle 6 (n=53 NOMAC-E2; n=52 LNG-EE)102 ± 996 ± 12
Statistical analysis
  • NOMAC-E2 vs LNG-EE · Cochran-Mantel-Haenszel · p = 0.0041 (No correction for multiple testing was made.)Cochran-Mantel-Haenszel test adjusted for age class applied on the changes from baseline.
PrimarySerum Concentration of Protein S (Free)

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

Time frame:
Baseline and Cycle 6 (between Days 15 and 21 of the cycle)
Reported as:
Mean · Percent of normal
Serum Concentration of Protein S (Free)
Percent of normalNOMAC-E2LNG-EE
Baseline (n=60 NOMAC-E2; n=58 LNG-EE)85 ± 1686 ± 14
Cycle 6 (n=53 NOMAC-E2; n=52 LNG-EE)99 ± 2099 ± 17
Statistical analysis
  • NOMAC-E2 vs LNG-EE · Cochran-Mantel-Haenszel · p = 0.9662 (No correction for multiple testing was made.)Cochran-Mantel-Haenszel test adjusted for age class applied on the changes from baseline.
PrimarySerum Concentration of Protein S (Total)

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

Time frame:
Baseline and Cycle 6 (between Days 15 and 21 of the cycle)
Reported as:
Mean · Percent of normal
Serum Concentration of Protein S (Total)
Percent of normalNOMAC-E2LNG-EE
Baseline (n=60 NOMAC-E2; n=58 LNG-EE)78 ± 1279 ± 10
Cycle 6 (n=53 NOMAC-E2; n=52 LNG-EE)83 ± 1276 ± 9
Statistical analysis
  • NOMAC-E2 vs LNG-EE · Cochran-Mantel-Haenszel · p = 0.0004 (No correction for multiple testing was made.)Cochran-Mantel-Haenszel test adjusted for age class applied on the changes from baseline.
PrimarySerum Concentration of Protein C

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

Time frame:
Baseline and Cycle 6 (between Days 15 and 21 of the cycle)
Reported as:
Mean · Percent of normal
Serum Concentration of Protein C
Percent of normalNOMAC-E2LNG-EE
Baseline (n=60 NOMAC-E2; n=58 LNG-EE)107 ± 18103 ± 19
Cycle 6 (n=53 NOMAC-E2; n=52 LNG-EE)108 ± 21113 ± 20
Statistical analysis
  • NOMAC-E2 vs LNG-EE · Cochran-Mantel-Haenszel · p = 0.0019 (No correction for multiple testing was made.)Cochran-Mantel-Haenszel test adjusted for age class applied on the changes from baseline.
PrimaryAPC Resistance Ratio (Activated Partial Thromboplastin Time [APTT]-Based)

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

Time frame:
Baseline and Cycle 6 (between Days 15 and 21 of the cycle)
Reported as:
Mean · Ratio
APC Resistance Ratio (Activated Partial Thromboplastin Time [APTT]-Based)
RatioNOMAC-E2LNG-EE
Baseline (n=60 NOMAC-E2; n=58 LNG-EE)1.01 ± 0.131.00 ± 0.13
Cycle 6 (n=53 NOMAC-E2; n=52 LNG-EE)1.05 ± 0.131.03 ± 0.12
Statistical analysis
  • NOMAC-E2 vs LNG-EE · Cochran-Mantel-Haenszel · p = 0.9662 (No correction for multiple testing was made.)Cochran-Mantel-Haenszel test adjusted for age class applied on the changes from baseline.
PrimarySerum Concentration of Sex Hormone Binding Globulin (SHBG)

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

Time frame:
Baseline and Cycle 6 (between Days 15 and 21 of the cycle)
Reported as:
Mean · nmol/L
Serum Concentration of Sex Hormone Binding Globulin (SHBG)
nmol/LNOMAC-E2LNG-EE
Baseline (n=60 NOMAC-E2; n=58 LNG-EE)74 ± 3477 ± 26
Cycle 6 (n=53 NOMAC-E2; n=52 LNG-EE)108 ± 44100 ± 31
Statistical analysis
  • NOMAC-E2 vs LNG-EE · Cochran-Mantel-Haenszel · p = 0.0187 (No correction for multiple testing was made.)Cochran-Mantel-Haenszel test adjusted for age class applied on the changes from baseline.
PrimarySerum Concentration of C-Reactive Protein (CRP)

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

Time frame:
Baseline and Cycle 6 (between Days 15 and 21 of the cycle)
Reported as:
Mean · mg/L
Serum Concentration of C-Reactive Protein (CRP)
mg/LNOMAC-E2LNG-EE
Baseline (n=60 NOMAC-E2; n=58 LNG-EE)0.82 ± 1.160.98 ± 1.35
Cycle 6 (n=53 NOMAC-E2; n=52 LNG-EE)1.32 ± 2.364.43 ± 8.43
Statistical analysis
  • NOMAC-E2 vs LNG-EE · Cochran-Mantel-Haenszel · p = <.0001 (No correction for multiple testing was made.)Cochran-Mantel-Haenszel test adjusted for age class applied on the changes from baseline.
PrimarySerum Concentration of Total Cholesterol

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

Time frame:
Baseline and Cycle 6 (between Days 15 and 21 of the cycle)
Reported as:
Mean · mmol/L
Serum Concentration of Total Cholesterol
mmol/LNOMAC-E2LNG-EE
Baseline (n=60 NOMAC-E2; n=58 LNG-EE)4.48 ± 0.874.53 ± 0.82
Cycle 6 (n=53 NOMAC-E2; n=51 LNG-EE)4.51 ± 0.834.48 ± 0.75
Statistical analysis
  • NOMAC-E2 vs LNG-EE · Cochran-Mantel-Haenszel · p = 0.6886 (No correction for multiple testing was made.)Cochran-Mantel-Haenszel test adjusted for age class applied on the changes from baseline.
PrimarySerum Concentration of High Density Lipoprotein (HDL)-Cholesterol

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

Time frame:
Baseline and Cycle 6 (between Days 15 and 21 of the cycle)
Reported as:
Mean · mmol/L
Serum Concentration of High Density Lipoprotein (HDL)-Cholesterol
mmol/LNOMAC-E2LNG-EE
Baseline (n=60 NOMAC-E2; n=58 LNG-EE)1.63 ± 0.361.68 ± 0.33
Cycle 6 (n=53 NOMAC-E2; n=51 LNG-EE)1.65 ± 0.341.41 ± 0.26
Statistical analysis
  • NOMAC-E2 vs LNG-EE · Cochran-Mantel-Haenszel · p = <.0001 (No correction for multiple testing was made.)Cochran-Mantel-Haenszel test adjusted for age class applied on the changes from baseline.
PrimarySerum Concentration of HDL2-cholesterol

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

Time frame:
Baseline and Cycle 6 (between Days 15 and 21 of the cycle)
Reported as:
Mean · mmol/L
Serum Concentration of HDL2-cholesterol
mmol/LNOMAC-E2LNG-EE
Baseline (n=58 NOMAC-E2; n=50 LNG-EE)0.63 ± 0.260.69 ± 0.29
Cycle 6 (n=52 NOMAC-E2; n=51 LNG-EE)0.55 ± 0.250.40 ± 0.18
Statistical analysis
  • NOMAC-E2 vs LNG-EE · Cochran-Mantel-Haenszel · p = <.0001 (No correction for multiple testing was made.)Cochran-Mantel-Haenszel test adjusted for age class applied on the changes from baseline.
PrimarySerum Concentration of HDL3-cholesterol

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

Time frame:
Baseline and Cycle 6 (between Days 15 and 21 of the cycle)
Reported as:
Mean · mmol/L
Serum Concentration of HDL3-cholesterol
mmol/LNOMAC-E2LNG-EE
Baseline (n=58 NOMAC-E2; n=50 LNG-EE)1.10 ± 0.161.14 ± 0.19
Cycle 6 (n=52 NOMAC-E2; n=51 LNG-EE)1.16 ± 0.161.10 ± 0.14
Statistical analysis
  • NOMAC-E2 vs LNG-EE · Cochran-Mantel-Haenszel · p = 0.0083 (No correction for multiple testing was made.)Cochran-Mantel-Haenszel test adjusted for age class applied on the changes from baseline.
PrimarySerum Concentration of Low Density Lipoprotein (LDL)-Cholesterol

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

Time frame:
Baseline and Cycle 6 (between Days 15 and 21 of the cycle)
Reported as:
Mean · mmol/L
Serum Concentration of Low Density Lipoprotein (LDL)-Cholesterol
mmol/LNOMAC-E2LNG-EE
Baseline (n=60 NOMAC-E2; n=58 LNG-EE)2.41 ± 0.732.47 ± 0.66
Cycle 6 (n=53 NOMAC-E2; n=51 LNG-EE)2.40 ± 0.712.61 ± 0.74
Statistical analysis
  • NOMAC-E2 vs LNG-EE · Cochran-Mantel-Haenszel · p = 0.0455 (No correction for multiple testing was made.)Cochran-Mantel-Haenszel test adjusted for age class applied on the changes from baseline.
PrimarySerum Concentration of Apolipoprotein A-1

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

Time frame:
Baseline and Cycle 6 (between Days 15 and 21 of the cycle)
Reported as:
Mean · g/L
Serum Concentration of Apolipoprotein A-1
g/LNOMAC-E2LNG-EE
Baseline (n=60 NOMAC-E2; n=58 LNG-EE)1.58 ± 0.271.60 ± 0.25
Cycle 6 (n=53 NOMAC-E2; n=51 LNG-EE)1.78 ± 0.271.67 ± 0.20
Statistical analysis
  • NOMAC-E2 vs LNG-EE · Cochran-Mantel-Haenszel · p = 0.0063 (No correction for multiple testing was made.)Cochran-Mantel-Haenszel test adjusted for age class applied on the changes from baseline.
PrimarySerum Concentration of Apolipoprotein B

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

Time frame:
Baseline and Cycle 6 (between Days 15 and 21 of the cycle)
Reported as:
Mean · g/L
Serum Concentration of Apolipoprotein B
g/LNOMAC-E2LNG-EE
Baseline (n=60 NOMAC-E2; n=58 LNG-EE)0.64 ± 0.170.64 ± 0.15
Cycle 6 (n=53 NOMAC-E2; n=51 LNG-EE)0.68 ± 0.170.80 ± 0.21
Statistical analysis
  • NOMAC-E2 vs LNG-EE · Cochran-Mantel-Haenszel · p = <.0001 (No correction for multiple testing was made.)Cochran-Mantel-Haenszel test adjusted for age class applied on the changes from baseline.
PrimarySerum Concentration of Lipoprotein(a)

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

Time frame:
Baseline and Cycle 6 (between Days 15 and 21 of the cycle)
Reported as:
Mean · g/L
Serum Concentration of Lipoprotein(a)
g/LNOMAC-E2LNG-EE
Baseline (n=60 NOMAC-E2; n=57 LNG-EE)0.15 ± 0.180.15 ± 0.14
Cycle 6 (n=53 NOMAC-E2; n=51 LNG-EE)0.17 ± 0.220.12 ± 0.11
Statistical analysis
  • NOMAC-E2 vs LNG-EE · Cochran-Mantel-Haenszel · p = <.0001 (No correction for multiple testing was made.)Cochran-Mantel-Haenszel test adjusted for age class applied on the changes from baseline.
PrimarySerum Concentration of Total Triglycerides

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

Time frame:
Baseline and Cycle 6 (between Days 15 and 21 of the cycle)
Reported as:
Mean · mmol/L
Serum Concentration of Total Triglycerides
mmol/LNOMAC-E2LNG-EE
Baseline (n=60 NOMAC-E2; n=58 LNG-EE)0.94 ± 0.300.82 ± 0.23
Cycle 6 (n=53 NOMAC-E2; n=51 LNG-EE)1.00 ± 0.371.02 ± 0.32
Statistical analysis
  • NOMAC-E2 vs LNG-EE · Cochran-Mantel-Haenszel · p = 0.0078 (No correction for multiple testing was made.)Cochran-Mantel-Haenszel test adjusted for age class applied on the changes from baseline.
PrimaryArea Under the Curve Over 3 Hours (AUC3) for Glucose (Oral Glucose Tolerance Test [OGTT])

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

Time frame:
Baseline and Cycle 6 (between Days 15 and 21 of the cycle)
Reported as:
Mean · hrs*mmol/L
Area Under the Curve Over 3 Hours (AUC3) for Glucose (Oral Glucose Tolerance Test [OGTT])
hrs*mmol/LNOMAC-E2LNG-EE
Baseline (n=59 NOMAC-E2; n=55 LNG-EE)15.82 ± 3.2714.44 ± 2.47
Cycle 6 (n=52 NOMAC-E2; n=50 LNG-EE)16.09 ± 3.0516.69 ± 3.15
Statistical analysis
  • NOMAC-E2 vs LNG-EE · Cochran-Mantel-Haenszel · p = 0.0016 (No correction for multiple testing was made.)Cochran-Mantel-Haenszel test adjusted for age class applied on the changes from baseline.
PrimaryIncremental AUC3 for Glucose (OGTT)

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

Time frame:
Baseline and Cycle 6 (between Days 15 and 21 of the cycle)
Reported as:
Mean · hrs*mmol/L
Incremental AUC3 for Glucose (OGTT)
hrs*mmol/LNOMAC-E2LNG-EE
Baseline (n=59 NOMAC-E2; n=55 LNG-EE)1.58 ± 3.051.06 ± 2.55
Cycle 6 (n=52 NOMAC-E2; n=50 LNG-EE)1.76 ± 2.723.19 ± 3.03
Statistical analysis
  • NOMAC-E2 vs LNG-EE · Cochran-Mantel-Haenszel · p = 0.0003 (No correction for multiple testing was made.)Cochran-Mantel-Haenszel test adjusted for age class applied on the changes from baseline.
PrimaryAUC3 for Insulin (OGTT)

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

Time frame:
Baseline and Cycle 6 (between Days 15 and 21 of the cycle)
Reported as:
Mean · hrs*pmol/L
AUC3 for Insulin (OGTT)
hrs*pmol/LNOMAC-E2LNG-EE
Baseline (n=51 NOMAC-E2; n=50 LNG-EE)650 ± 298558 ± 182
Cycle 6 (n=46 NOMAC-E2; n=47 LNG-EE)658 ± 281721 ± 264
Statistical analysis
  • NOMAC-E2 vs LNG-EE · Cochran-Mantel-Haenszel · p = 0.0009 (No correction for multiple testing was made.)Cochran-Mantel-Haenszel test adjusted for age class applied on the changes from baseline.
PrimaryIncremental AUC3 for Insulin (OGTT)

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

Time frame:
Baseline and Cycle 6 (between Days 15 and 21 of the cycle)
Reported as:
Mean · hrs*pmol/L
Incremental AUC3 for Insulin (OGTT)
hrs*pmol/LNOMAC-E2LNG-EE
Baseline (n=51 NOMAC-E2; n=50 LNG-EE)517 ± 268451 ± 160
Cycle 6 (n=46 NOMAC-E2; n=47 LNG-EE)534 ± 239603 ± 237
Statistical analysis
  • NOMAC-E2 vs LNG-EE · Cochran-Mantel-Haenszel · p = 0.0024 (No correction for multiple testing was made.)Cochran-Mantel-Haenszel test adjusted for age class applied on the changes from baseline.
PrimarySerum Concentration of Hemoglobin Type A1c (HbA1c)

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

Time frame:
Baseline and Cycle 6 (between Days 15 and 21 of the cycle)
Reported as:
Mean · Percent of glycosylated hemoglobin
Serum Concentration of Hemoglobin Type A1c (HbA1c)
Percent of glycosylated hemoglobinNOMAC-E2LNG-EE
Baseline (n=60 NOMAC-E2; n=58 LNG-EE)5.3 ± 0.35.3 ± 0.2
Cycle 6 (n=53 NOMAC-E2; n=51 LNG-EE)5.3 ± 0.25.4 ± 0.2
Statistical analysis
  • NOMAC-E2 vs LNG-EE · Cochran-Mantel-Haenszel · p = 0.3653 (No correction for multiple testing was made.)Cochran-Mantel-Haenszel test adjusted for age class applied on the changes from baseline.
PrimarySerum Concentration of Total Cortisol

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

Time frame:
Baseline and Cycle 6 (between Days 15 and 21 of the cycle)
Reported as:
Mean · nmol/L
Serum Concentration of Total Cortisol
nmol/LNOMAC-E2LNG-EE
Baseline (n=60 NOMAC-E2; n=58 LNG-EE)482 ± 128502 ± 153
Cycle 6 (n=53 NOMAC-E2; n=52 LNG-EE)608 ± 167944 ± 183
Statistical analysis
  • NOMAC-E2 vs LNG-EE · Cochran-Mantel-Haenszel · p = <.0001 (No correction for multiple testing was made.)Cochran-Mantel-Haenszel test adjusted for age class applied on the changes from baseline.
PrimarySerum Concentration of Corticosteroid Binding Globulin (CBG)

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

Time frame:
Baseline to Cycle 6 (between Days 15 and 21 of the cycle)
Reported as:
Mean · nmol/L
Serum Concentration of Corticosteroid Binding Globulin (CBG)
nmol/LNOMAC-E2LNG-EE
Baseline (n=60 NOMAC-E2; n=58 LNG-EE)910 ± 201932 ± 163
Cycle 6 (n=53 NOMAC-E2; n=52 LNG-EE)1116 ± 2521980 ± 389
Statistical analysis
  • NOMAC-E2 vs LNG-EE · Cochran-Mantel-Haenszel · p = <.0001 (No correction for multiple testing was made.)Cochran-Mantel-Haenszel test adjusted for age class applied on the changes from baseline.
PrimarySerum Concentration of Thyroid Stimulating Hormone (TSH)

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

Time frame:
Baseline and Cycle 6 (between Days 15 and 21 of the cycle)
Reported as:
Mean · mU/L
Serum Concentration of Thyroid Stimulating Hormone (TSH)
mU/LNOMAC-E2LNG-EE
Baseline (n=60 NOMAC-E2; n=58 LNG-EE)2.69 ± 1.282.20 ± 1.08
Cycle 6 (n=53 NOMAC-E2; n=52 LNG-EE)2.96 ± 2.052.75 ± 3.36
Statistical analysis
  • NOMAC-E2 vs LNG-EE · Cochran-Mantel-Haenszel · p = 0.5668 (No correction for multiple testing was made.)Cochran-Mantel-Haenszel test adjusted for age class applied on the changes from baseline.
PrimarySerum Concentration of Free Thyroxine (T4)

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

Time frame:
Baseline and Cycle 6 (between Days 15 and 21 of the cycle)
Reported as:
Mean · pmol/L
Serum Concentration of Free Thyroxine (T4)
pmol/LNOMAC-E2LNG-EE
Baseline (n=60 NOMAC-E2; n=58 LNG-EE)14.0 ± 1.514.1 ± 1.5
Cycle 6 (n=53 NOMAC-E2; n=52 LNG-EE)15.9 ± 2.015.7 ± 2.1
Statistical analysis
  • NOMAC-E2 vs LNG-EE · Cochran-Mantel-Haenszel · p = 0.1770 (No correction for multiple testing was made.)Cochran-Mantel-Haenszel test adjusted for age class applied on the changes from baseline.
PrimarySerum Concentration of Thyroxin Binding Globulin (TBG)

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

Time frame:
Baseline and Cycle 6 (between Days 15 and 21 of the cycle)
Reported as:
Mean · mg/L
Serum Concentration of Thyroxin Binding Globulin (TBG)
mg/LNOMAC-E2LNG-EE
Baseline (n=60 NOMAC-E2; n=58 LNG-EE)20.3 ± 2.920.3 ± 3.3
Cycle 6 (n=53 NOMAC-E2; n=52 LNG-EE)24.2 ± 3.628.4 ± 5.3
Statistical analysis
  • NOMAC-E2 vs LNG-EE · Cochran-Mantel-Haenszel · p = <.0001 (No correction for multiple testing was made.)Cochran-Mantel-Haenszel test adjusted for age class applied on the changes from baseline.
SecondarySerum Concentration of Androstenedione

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)
Reported as:
Mean · nmol/L
Serum Concentration of Androstenedione
nmol/LNOMAC-E2LNG-EE
Baseline (n=60, NOMAC-E2; n=58 LNG-EE)9.60 ± 3.4510.27 ± 3.91
Cycle 6 (n=53, NOMAC-E2; n=52 LNG-EE)8.23 ± 3.016.96 ± 3.37
SecondarySerum Concentration of Dihydrotestosterone (DHT)

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)
Reported as:
Mean · nmol/L
Serum Concentration of Dihydrotestosterone (DHT)
nmol/LNOMAC-E2LNG-EE
Baseline (n=60, NOMAC-E2; n=58 LNG-EE)0.59 ± 0.210.62 ± 0.26
Cycle 6 (n=53, NOMAC-E2; n=52 LNG-EE)0.53 ± 0.280.36 ± 0.19
SecondaryNumber of In-treatment Pregnancies (With +2 Day Window) Per 100 Woman Years of Exposure (Pearl Index)

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
Reported as:
Number · Pregnancies per 100 woman years
Number of In-treatment Pregnancies (With +2 Day Window) Per 100 Woman Years of Exposure (Pearl Index)
Pregnancies per 100 woman yearsNOMAC-E2LNG-EE
Number of In-treatment Pregnancies (With +2 Day Window) Per 100 Woman Years of Exposure (Pearl Index)0 (0 to 16.1)0 (0 to 17.1)
SecondaryNumber of Participants With an Occurrence of Breakthrough Bleeding/Spotting

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
Reported as:
Number · Participants
Number of Participants With an Occurrence of Breakthrough Bleeding/Spotting
ParticipantsNOMAC-E2LNG-EE
Cycle 1 (n=56 NOMAC-E2; n=53 LNG-EE)1816
Cycle 2 (n=55 NOMAC-E2; n=51 LNG-EE)119
Cycle 3 (n=54 NOMAC-E2; n=52 LNG-EE)55
Cycle 4 (n=54 NOMAC-E2; n=52 LNG-EE)82
Cycle 5 (n=52 NOMAC-E2; n=51 LNG-EE)64
Cycle 6 (n=52 NOMAC-E2; n=50 LNG-EE)63
SecondaryNumber of Participants With an Occurrence of Absence of Withdrawal Bleeding

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
Reported as:
Number · Participants
Number of Participants With an Occurrence of Absence of Withdrawal Bleeding
ParticipantsNOMAC-E2LNG-EE
Cycle 1 (n=56 NOMAC-E2; n=53 LNG-EE)60
Cycle 2 (n=55 NOMAC-E2; n=51 LNG-EE)81
Cycle 3 (n=54 NOMAC-E2; n=52 LNG-EE)50
Cycle 4 (n=54 NOMAC-E2; n=52 LNG-EE)80
Cycle 5 (n=52 NOMAC-E2; n=51 LNG-EE)50
Cycle 6 (n=52 NOMAC-E2; n=50 LNG-EE)101
SecondaryNumber of Participants With an Occurrence of Breakthrough Bleeding

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
Reported as:
Number · Participants
Number of Participants With an Occurrence of Breakthrough Bleeding
ParticipantsNOMAC-E2LNG-EE
Cycle 1 (n=56 NOMAC-E2; n=53 LNG-EE)31
Cycle 2 (n=55 NOMAC-E2; n=51 LNG-EE)10
Cycle 3 (n=54 NOMAC-E2; n=52 LNG-EE)10
Cycle 4 (n=54 NOMAC-E2; n=52 LNG-EE)10
Cycle 5 (n=52 NOMAC-E2; n=51 LNG-EE)20
Cycle 6 (n=52 NOMAC-E2; n=50 LNG-EE)30
SecondaryNumber of Participants With an Occurrence of Breakthrough Spotting (Spotting Only)

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
Reported as:
Number · Participants
Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only)
ParticipantsNOMAC-E2LNG-EE
Cycle 1 (n=56 NOMAC-E2; n=53 LNG-EE)1716
Cycle 2 (n=55 NOMAC-E2; n=51 LNG-EE)109
Cycle 3 (n=54 NOMAC-E2; n=52 LNG-EE)45
Cycle 4 (n=54 NOMAC-E2; n=52 LNG-EE)72
Cycle 5 (n=52 NOMAC-E2; n=51 LNG-EE)44
Cycle 6 (n=52 NOMAC-E2; n=50 LNG-EE)43
SecondaryNumber of Participants With an Occurrence of Early Withdrawal Bleeding

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
Reported as:
Number · Participants
Number of Participants With an Occurrence of Early Withdrawal Bleeding
ParticipantsNOMAC-E2LNG-EE
Cycle 1 (n=56 NOMAC-E2; n=53 LNG-EE)54
Cycle 2 (n=55 NOMAC-E2; n=51 LNG-EE)41
Cycle 3 (n=54 NOMAC-E2; n=52 LNG-EE)31
Cycle 4 (n=54 NOMAC-E2; n=52 LNG-EE)20
Cycle 5 (n=52 NOMAC-E2; n=51 LNG-EE)10
Cycle 6 (n=52 NOMAC-E2; n=50 LNG-EE)22
SecondaryNumber of Participants With an Occurrence of Continued Withdrawal Bleeding

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
Reported as:
Number · Participants
Number of Participants With an Occurrence of Continued Withdrawal Bleeding
ParticipantsNOMAC-E2LNG-EE
Cycle 1 (n=56 NOMAC-E2; n=53 LNG-EE)1525
Cycle 2 (n=54 NOMAC-E2; n=50 LNG-EE)1128
Cycle 3 (n=54 NOMAC-E2; n=52 LNG-EE)1326
Cycle 4 (n=53 NOMAC-E2; n=52 LNG-EE)1127
Cycle 5 (n=52 NOMAC-E2; n=51 LNG-EE)1329
SecondaryAverage Number of Breakthrough Bleeding/Spotting Days

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
Reported as:
Mean · Days
Average Number of Breakthrough Bleeding/Spotting Days
DaysNOMAC-E2LNG-EE
Cycle 1 (n=18 NOMAC-E2; n=16 LNG-EE)3.5 ± 2.74.6 ± 3.6
Cycle 2 (n=11 NOMAC-E2; n=9 LNG-EE)4.3 ± 1.43.3 ± 2.2
Cycle 3 (n=5 NOMAC-E2; n=5 LNG-EE)4.6 ± 2.53.2 ± 2.2
Cycle 4 (n=8 NOMAC-E2; n=2 LNG-EE)3.8 ± 2.34.0 ± 0.0
Cycle 5 (n=6 NOMAC-E2; n=4 LNG-EE)3.3 ± 2.52.0 ± 2.0
Cycle 6 (n=6 NOMAC-E2; n=3 LNG-EE)4.7 ± 3.73.0 ± 2.0
SecondaryAverage Number of Withdrawal Bleeding/Spotting Days

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
Reported as:
Mean · Days
Average Number of Withdrawal Bleeding/Spotting Days
DaysNOMAC-E2LNG-EE
Cycle 1 (n=50 NOMAC-E2; n=53 LNG-EE)4.8 ± 2.35.8 ± 3.6
Cycle 2 (n=47 NOMAC-E2; n=50 LNG-EE)4.7 ± 3.64.9 ± 1.2
Cycle 3 (n=49 NOMAC-E2); n=52 LNG-EE)3.9 ± 2.04.9 ± 1.4
Cycle 4 (n=46 NOMAC-E2; n=52 LNG-EE)4.0 ± 2.55.0 ± 1.5
Cycle 5 (n=47 NOMAC-E2; n=51 LNG-EE)3.8 ± 1.74.9 ± 1.5
Cycle 6 (n=42 NOMAC-E2; n=49 LNG-EE)3.5 ± 1.24.2 ± 1.7

Adverse events

Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
NOMAC-E2—1/60 (1.7%)9/60 (15%)
LNG-EE—0/58 (0%)18/58 (31%)
Most frequent serious events
Most frequent serious events
EventNOMAC-E2LNG-EE
Congenital mitral valve incompetenceCongenital, familial and genetic disorders1/600/58
Most frequent other events
Most frequent other events
EventNOMAC-E2LNG-EE
HeadacheNervous system disorders3/607/58
Upper respiratory tract infectionInfections and infestations6/605/58
InfluenzaInfections and infestations1/604/58
AcneSkin and subcutaneous tissue disorders2/604/58

Baseline characteristics

Age, Continuous
Age, Continuous(years)NOMAC-E2LNG-EETotal
Mean28.2 ± 8.229.1 ± 7.828.7 ± 8.0
Sex: Female, Male
Sex: Female, Male(Participants)NOMAC-E2LNG-EETotal
Female6058118
Male000
08

Study locations

No study locations are listed for this record.

09

References and documents

Publications

  • Agren UM, Anttila M, Maenpaa-Liukko K, Rantala ML, Rautiainen H, Sommer WF, Mommers E. Effects of a monophasic combined oral contraceptive containing nomegestrol acetate and 17beta-oestradiol compared with one containing levonorgestrel and ethinylestradiol on haemostasis, lipids and carbohydrate metabolism. Eur J Contracept Reprod Health Care. 2011 Dec;16(6):444-57. doi: 10.3109/13625187.2011.604450. PubMed 22066891 ↗
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Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Feb 9, 2022, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
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Registry details

Key details

Study ID
NCT00511355
Lead sponsor
Organon and Co
Responsible party
Sponsor
First posted
Aug 3, 2007
Start date
Oct 2006
Primary completion
Jan 2008
Completion
Jan 2008
Results posted
Aug 30, 2011
Last update
Feb 9, 2022

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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