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)
Overview
- Phase
- Phase 4
- Intervention
- Levonorgestrel (LNG)/Ethinylestradiol (EE) oral contraceptive tablets
- Conditions
- Contraception
- Sponsor
- Organon and Co
- Enrollment
- 24
- Primary Endpoint
- Maximum Concentration (Cmax) (Pharmacokinentic Parameter (PK)) for All Subjects in the Pharmacokinetically Evaluable (ASPE) Group
- Status
- Completed
- Last Updated
- 4 years ago
Overview
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).
Investigators
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.
Arms & Interventions
Levonorgestrel/ethinylestradiol oral contraceptive pill
Microgynon(R), 1 tablet every day for 21 days; each tablet contains 0.150 mg levonorgestrel (LNG) and 0.030 mg ethinylestradiol (EE).
Intervention: Levonorgestrel (LNG)/Ethinylestradiol (EE) oral contraceptive tablets
Norelgestrominum and ethinylestradiol contraceptive patch
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.
Intervention: norelgestrominum and ethinylestradiol patch oral contraceptive patch
Etonogestrel and ethinylestradiol contraceptive vaginal ring
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.
Intervention: Nuvaring ™ (etonorgestrel/ethinylestradiol)
Outcomes
Primary Outcomes
Maximum Concentration (Cmax) (Pharmacokinentic Parameter (PK)) for All Subjects in the Pharmacokinetically Evaluable (ASPE) Group
Time Frame: 21 days of active treatment and washout period thereafter
Cmax was measured using ethinylstradiol serum concentration at several time points during the 21 days of active treatment and the washout thereafter.
Area Under the Curve (AUC) 0-21 Days (PK Parameter) Measured for the ASPE Group
Time Frame: 21 days
AUC 0-21 days was measured using ethinylestradiol serum concentration using a radio-immune assay at several time points during the 21 days of active treatment
AUC 0-tlast (PK Parameter) for the ASPE Group.
Time Frame: 21 days of active treatment and washout period thereafter
AUC 0-tlast was measured using ethinylestradiol serum concentrations using a radio-immune assay at several time points during the 21 days of active treatment and the washout period thereafter.
AUC 0-infinity (PK Parameter) for the ASPE Group.
Time Frame: 21 days of active treatment and the washout period thereafter
AUC 0-infinity was measured using ethinylestradiol serum concentration using a radio-immune assay at several time points during the 21 days of active treatment and the washout period thereafter. AUC 0-infinity was calculated as AUC 0-tlast extrapolated to infinity using the regression line from which t 1/2 was calculated.