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)

Contraception Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01044056
• Other study ID #: P06650
• Status: Completed
• Phase: Phase 4
• Start date: March 2004
• Est. completion date: June 2004

Study information

• Verified date: February 2022
• Source: Organon and Co
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: June 2004
• Est. primary completion date: June 2004
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 40 Years

Eligibility

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.

Related Conditions & MeSH terms

• Contraception

Intervention

Drug:
• Levonorgestrel (LNG)/Ethinylestradiol (EE) oral contraceptive tablets
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.
• norelgestrominum and ethinylestradiol patch oral contraceptive patch
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 ™ (etonorgestrel/ethinylestradiol)
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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Organon and Co

References & Publications (1)

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Concentration (Cmax) (Pharmacokinentic Parameter (PK)) for All Subjects in the Pharmacokinetically Evaluable (ASPE) Group	Cmax was measured using ethinylstradiol serum concentration at several time points during the 21 days of active treatment and the washout thereafter.	21 days of active treatment and washout period thereafter
Primary	Area Under the Curve (AUC) 0-21 Days (PK Parameter) Measured for the ASPE Group	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	21 days
Primary	AUC 0-tlast (PK Parameter) for the ASPE Group.	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.	21 days of active treatment and washout period thereafter
Primary	AUC 0-infinity (PK Parameter) for the ASPE Group.	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.	21 days of active treatment and the washout period thereafter