A Trial in Healthy Female Subjects to Compare the Pharmacokinetics of Ethinyl Estradiol of NuvaRing®, a Contraceptive Patch (EVRA(TM)) and an Oral Contraceptive (Microgynon® 30) (Study 34237 (P06650)) (COMPLETED)
Condition: Contraception
Intervention: Levonorgestrel (LNG)/Ethinylestradiol (EE) oral contraceptive tablets; norelgestrominum and ethinylestradiol patch oral contraceptive patch; Nuvaring ™ (etonorgestrel/ethinylestradiol)
Intervention description: LNG/EE oral contraceptive tablets (Microgynon® 30), 21 in total, containing 0.150 mg LNG and 0.030 mg EE per tablet administered once daily orally for 21 consecutive days.; A contraceptive patch (EVRA ™), one patch for 7 days for three consecutive weeks, 3 patches in total, applied on the lower abdomen. Dose: per patch 6 mg norelgestromin and 0.750 mg EE releasing 0.150 mg norelgestromin and 0.020 mg EE per day.; NuvaRing ™ , one ring for a period of 21 days, inserted vaginally. Dose: per ring 11.7 mg etonogestrel and 2.7 mg EE releasing a daily average amount of 0.120 mg etonogestrel and 0.015 mg EE.
Intervention MeSH terms: Contraceptive Agents; Levonorgestrel; Ethinyl Estradiol; Ethinyl estradiol, levonorgestrel drug combination; NuvaRing; Contraceptives, Oral
Phase: Phase 4
Study type: Interventional
Primary purpose: Basic Science
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 24.0
Sex: Female
Minimum age: 18 Years
Maximum age: 40 Years
Healthy volunteers: No

Summary:

      An open-label, randomized, parallel group trial in healthy female subjects to compare the
      pharmacokinetics of ethinyl estradiol (EE) of NuvaRing®, a contraceptive patch (EVRA(TM)) and
      an oral contraceptive (Microgynon® 30).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Subject is at least 18 but not older than 40 years of age on Day 1 of treatment.

          -  Subject has uterus and ovaria in situ

          -  Subject who does not use hormonal contraception and is willing to use adequate
             nonhormonal contraceptive measures during the timeframe between screening and start
             treatment.

          -  Subject is able and willing to refrain from caffeine and/or xanthine containing food
             and/or beverages (e.g. coffee, tea, cola or chocolate) from 24 hours before the first
             administration of the trial medication until the last PK blood sample.

          -  Subject is willing not to consume grapefruit containing products 14 days prior to the
             start of the first administration of the trial medication until the last PK blood
             sample.

          -  Subject is willing to refrain from smoking from 7 days prior to first administration
             of the trial medication until the last pharmacokinetic blood sample.

          -  Subject is willing to refrain from alcohol containing products from 24 hours prior to
             first administration of the trial medication until the last pharmacokinetic blood
             sample.

        Exclusion Criteria:

          -  Contraindications for use of NuvaRing, contraceptive patch and oral contraceptive:

          -  Presence or history of venous thrombosis, with or without the involvement of pulmonary
             embolism.

          -  Presence or history of arterial thrombosis (e.g. cerebrovascular accident, myocardial
             infarction) or prodromi of a thrombosis (e.g. angina pectoris or transient ischaemic
             attack).

          -  Known predisposition for venous or arterial thrombosis, with or without hereditary
             involvement such as Activated Protein C (APC) resistance, antithrombin-III deficiency,
             protein C deficiency, protein S deficiency, hyperhomocysteinaemia, antiphospholipid
             antibodies (anticardiolipin antibodies, lupus anticoagulant) and Factor V Leiden
             mutation.

          -  Diabetes mellitus with vascular involvement

          -  The presence of a severe or multiple risk factor(s) for venous or arterial thrombosis
             (to be judged by the (sub-) investigator

          -  Presence or history of severe hepatic disease as long as liver function values had not
             returned to normal or were judged to be clinically significant by the investigator.

          -  Presence or history of liver tumours (benign or malignant).

          -  Known or suspected malignant conditions of the genital organs or the breasts, if
             sex-steroid-influenced.

          -  Undiagnosed vaginal bleeding.

          -  Hypersensitivity to the active substances or to any of the excipients of NuvaRing,
             contraceptive patch and oral contraceptive.

          -  Migraine with focal aura

          -  Known or suspected pregnancy

          -  Breastfeeding, or within 2 months after stopping breastfeeding on the day preceding
             the first administration of trial medication (Day -1).

          -  Clinically significant abnormal laboratory, ECG (electrocardiogram) vital signs,
             physical and gynecological findings at screening.

          -  A significant (history of) allergic or other serious disease, particularly
             gastrointestinal tract disease.

          -  Smoking more than 5 cigarettes or 1 pipe or 1 cigar per day for a period of at least 3
             months prior to screening.

          -  Using any systemic medication (including over the counter (OTC) medication) during the
             14 days prior to the day preceding the first administration of trial medication (Day
             -1), except for oral contraceptive used for synchronization and occasional Ibuprofen.

          -  Used any drug or substance that is known to induce drug-metabolizing enzymes within
             two months prior to the start of synchronization.

          -  Received a contraceptive by injection, an implant or hormonal intra-uterine device
             within 6 months of the day preceding the first administration of trial medication (Day
             -1), or a hormonal implant or hormonal intra-uterine device removed within 6 months of
             the day preceding the first administration of trial medication (Day -1).

          -  Participated in a drug trial and was administered an investigational drug during the
             90 days prior to start of synchronization.

          -  Donated blood during the 90 days prior to the day preceding the first administration
             of trial medication (Day -1).

          -  History (within the last 2 years) of excessive alcohol use, use of solvents or of drug
             abuse.

          -  Positive drug test at screening and/or admission (Day -1), or a positive alcohol test
             at admission (Day -1).

          -  Clinically significant abnormal cervical smear result (papaninecolaou (PAP) III or
             higher) at screening.

          -  Acute or chronic hepatitis B/C or human immune deficiency virus (HIV) 1&2 infection.