Clinical trial NCT00511355: 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)
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Contraception
Lead sponsor: Organon and Co
Sponsor class: INDUSTRY
First posted: 2007-08-03
Enrollment: 121
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Serum Concentration of Prothrombin Fragments 1 + 2
timeFrame: Baseline and Cycle 6 (between Days 15 and 21 of the cycle)
measure: Serum Concentration of D-Dimer
timeFrame: Baseline and Cycle 6 (between Days 15 and 21 of the cycle)
measure: Activated Protein C (APC) Resistance Ratio (Endogenous Thrombin Potential [ETP]-Based)
timeFrame: Baseline and Cycle 6 (between Days 15 and 21 of the cycle)
measure: Serum Concentration of Clotting Factor VIIa
timeFrame: Baseline and Cycle 6 (between Days 15 and 21 of the cycle)
measure: Serum Concentration of Clotting Factor VIIc
timeFrame: Baseline and Cycle 6 (between Days 15 and 21 of the cycle)
measure: Serum Concentration of Clotting Factor VIII
timeFrame: Baseline and Cycle 6 (between Days 15 and 21 of the cycle)
measure: Serum Concentration of Clotting Factor II
timeFrame: Baseline and Cycle 6 (between Days 15 and 21 of the cycle)
measure: Serum Concentration of Antithrombin III
timeFrame: Baseline and Cycle 6 (between Days 15 and 21 of the cycle)
measure: Serum Concentration of Protein S (Free)
timeFrame: Baseline and Cycle 6 (between Days 15 and 21 of the cycle)
measure: Serum Concentration of Protein S (Total)
timeFrame: Baseline and Cycle 6 (between Days 15 and 21 of the cycle)
measure: Serum Concentration of Protein C
timeFrame: Baseline and Cycle 6 (between Days 15 and 21 of the cycle)
measure: APC Resistance Ratio (Activated Partial Thromboplastin Time [APTT]-Based)
timeFrame: Baseline and Cycle 6 (between Days 15 and 21 of the cycle)
measure: Serum Concentration of Sex Hormone Binding Globulin (SHBG)
timeFrame: Baseline and Cycle 6 (between Days 15 and 21 of the cycle)
measure: Serum Concentration of C-Reactive Protein (CRP)
timeFrame: Baseline and Cycle 6 (between Days 15 and 21 of the cycle)
measure: Serum Concentration of Total Cholesterol
timeFrame: Baseline and Cycle 6 (between Days 15 and 21 of the cycle)
measure: Serum Concentration of High Density Lipoprotein (HDL)-Cholesterol
timeFrame: Baseline and Cycle 6 (between Days 15 and 21 of the cycle)
measure: Serum Concentration of HDL2-cholesterol
timeFrame: Baseline and Cycle 6 (between Days 15 and 21 of the cycle)
measure: Serum Concentration of HDL3-cholesterol
timeFrame: Baseline and Cycle 6 (between Days 15 and 21 of the cycle)
measure: Serum Concentration of Low Density Lipoprotein (LDL)-Cholesterol
timeFrame: Baseline and Cycle 6 (between Days 15 and 21 of the cycle)
measure: Serum Concentration of Apolipoprotein A-1
timeFrame: Baseline and Cycle 6 (between Days 15 and 21 of the cycle)
measure: Serum Concentration of Apolipoprotein B
timeFrame: Baseline and Cycle 6 (between Days 15 and 21 of the cycle)
measure: Serum Concentration of Lipoprotein(a)
timeFrame: Baseline and Cycle 6 (between Days 15 and 21 of the cycle)
measure: Serum Concentration of Total Triglycerides
timeFrame: Baseline and Cycle 6 (between Days 15 and 21 of the cycle)
measure: Area Under the Curve Over 3 Hours (AUC3) for Glucose (Oral Glucose Tolerance Test [OGTT])
timeFrame: Baseline and Cycle 6 (between Days 15 and 21 of the cycle)
measure: Incremental AUC3 for Glucose (OGTT)
timeFrame: Baseline and Cycle 6 (between Days 15 and 21 of the cycle)
measure: AUC3 for Insulin (OGTT)
timeFrame: Baseline and Cycle 6 (between Days 15 and 21 of the cycle)
measure: Incremental AUC3 for Insulin (OGTT)
timeFrame: Baseline and Cycle 6 (between Days 15 and 21 of the cycle)
measure: Serum Concentration of Hemoglobin Type A1c (HbA1c)
timeFrame: Baseline and Cycle 6 (between Days 15 and 21 of the cycle)
measure: Serum Concentration of Total Cortisol
timeFrame: Baseline and Cycle 6 (between Days 15 and 21 of the cycle)
measure: Serum Concentration of Corticosteroid Binding Globulin (CBG)
timeFrame: Baseline to Cycle 6 (between Days 15 and 21 of the cycle)
measure: Serum Concentration of Thyroid Stimulating Hormone (TSH)
timeFrame: Baseline and Cycle 6 (between Days 15 and 21 of the cycle)
measure: Serum Concentration of Free Thyroxine (T4)
timeFrame: Baseline and Cycle 6 (between Days 15 and 21 of the cycle)
measure: Serum Concentration of Thyroxin Binding Globulin (TBG)
timeFrame: Baseline and Cycle 6 (between Days 15 and 21 of the cycle)
Secondary outcomes:
measure: Serum Concentration of Total Testosterone
timeFrame: Baseline and Cycle 6 (between Days 15 and 21 of the cycle)
measure: Serum Concentration of Free Testosterone
timeFrame: Baseline and Cycle 6 (between Days 15 and 21 of the cycle)
measure: Serum Concentration of Dehydroepiandrosterone Sulphate (DHEAS)
timeFrame: Baseline and Cycle 6 (between Days 15 and 21 of the cycle)
measure: Serum Concentration of Androstenedione
timeFrame: Baseline and Cycle 6 (between Days 15 and 21 of the cycle)
measure: Serum Concentration of Dihydrotestosterone (DHT)
timeFrame: Baseline and Cycle 6 (between Days 15 and 21 of the cycle)
measure: Number of In-treatment Pregnancies (With +2 Day Window) Per 100 Woman Years of Exposure (Pearl Index)
timeFrame: 6 cycles
measure: Number of Participants With an Occurrence of Breakthrough Bleeding/Spotting
timeFrame: Every 28-day cycle for 6 cycles
measure: Number of Participants With an Occurrence of Absence of Withdrawal Bleeding
timeFrame: Every 28-day cycle for 6 cycles
measure: Number of Participants With an Occurrence of Breakthrough Bleeding
timeFrame: Every 28-day cycle for 6 cycles
measure: Number of Participants With an Occurrence of Breakthrough Spotting (Spotting Only)
timeFrame: Every 28-day cycle for 6 cycles
measure: Number of Participants With an Occurrence of Early Withdrawal Bleeding
timeFrame: Every 28-day cycle for 6 cycles
measure: Number of Participants With an Occurrence of Continued Withdrawal Bleeding
timeFrame: Every 28-day cycle for 5 cycles
measure: Average Number of Breakthrough Bleeding/Spotting Days
timeFrame: Every 28-day cycle for 6 cycles
measure: Average Number of Withdrawal Bleeding/Spotting Days
timeFrame: Every 28-day cycle for 6 cycles
Other outcomes:
Locations:
Study officials:
References:
citation: 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.