Clinical trial NCT01044056: 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)
Official title: An Open-label, Randomized, Parallel Group 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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Contraception
Lead sponsor: Organon and Co
Sponsor class: INDUSTRY
First posted: 2010-01-07
Enrollment: 24
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief 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.

Primary outcomes:
measure: Maximum Concentration (Cmax) (Pharmacokinentic Parameter (PK)) for All Subjects in the Pharmacokinetically Evaluable (ASPE) Group
timeFrame: 21 days of active treatment and washout period thereafter
measure: Area Under the Curve (AUC) 0-21 Days (PK Parameter) Measured for the ASPE Group
timeFrame: 21 days
measure: AUC 0-tlast (PK Parameter) for the ASPE Group.
timeFrame: 21 days of active treatment and washout period thereafter
measure: AUC 0-infinity (PK Parameter) for the ASPE Group.
timeFrame: 21 days of active treatment and the washout period thereafter
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
References:
citation: van den Heuvel MW, van Bragt AJ, Alnabawy AK, Kaptein MC. Comparison of ethinylestradiol pharmacokinetics in three hormonal contraceptive formulations: the vaginal ring, the transdermal patch and an oral contraceptive. Contraception. 2005 Sep;72(3):168-74. doi: 10.1016/j.contraception.2005.03.005.