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)

Organon

Status and phase: Completed; Phase 4

Conditions: Contraception

Treatments: Drug: norelgestrominum and ethinylestradiol patch oral contraceptive patch; Drug: Levonorgestrel (LNG)/Ethinylestradiol (EE) oral contraceptive tablets; Drug: Nuvaring ™ (etonorgestrel/ethinylestradiol)

Study type: Interventional

Funder types: Industry

Identifiers

NCT01044056

P06650

Details and patient eligibility

About

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).

Enrollment: 24 patients

Sex: Female

Ages: 18 to 40 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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24 participants in 3 patient groups

Levonorgestrel/ethinylestradiol oral contraceptive pill

Active Comparator group

Description:

Microgynon(R), 1 tablet every day for 21 days; each tablet contains 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE).

Treatment:

Drug: Levonorgestrel (LNG)/Ethinylestradiol (EE) oral contraceptive tablets

Norelgestrominum and ethinylestradiol contraceptive patch

Active Comparator group

Description:

Evra(TM), One patch applied on lower abdomen for 7 days for 3 consecutive weeks, 3 patches in total. Each patch contains 6 mg norelgestromin and 0.750 mg EE releasing 0.150 mg norelgestromin and 0.020 mg EE per day.

Treatment:

Drug: norelgestrominum and ethinylestradiol patch oral contraceptive patch

Etonogestrel and ethinylestradiol contraceptive vaginal ring

Active Comparator group

Description:

Nuvaring(R), Place the ring in the vagina for 21 days, remove for one week. Repeat with new Ring. Dose: per ring 11.7 mg ENG and 2.7 mg EE releasing a daily average amount of 0.120 mg ENG and 0.015 mg EE.

Treatment:

Drug: Nuvaring ™ (etonorgestrel/ethinylestradiol)