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)

NCT01044056 | Completed Phase 4 Results

• 1 other identifier: P06650
• Study Type: interventional
• Target: 24
• Locations: 0 countries
• Sites: N/A

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).

Conditions

Contraception

Outcome Measures

Primary Outcomes (4)

• 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

• 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

• 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

• 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

Study Arms (3)

Levonorgestrel/ethinylestradiol oral contraceptive pill

ACTIVE COMPARATOR

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

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

Norelgestrominum and ethinylestradiol contraceptive patch

ACTIVE COMPARATOR

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.

Drug: norelgestrominum and ethinylestradiol patch oral contraceptive patch

Etonogestrel and ethinylestradiol contraceptive vaginal ring

ACTIVE COMPARATOR

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.

Drug: Nuvaring ™ (etonorgestrel/ethinylestradiol)

Interventions

Levonorgestrel (LNG)/Ethinylestradiol (EE) oral contraceptive tablets DRUG

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.

Also known as: Microgynon, Batch Number: 374A 01K05

Levonorgestrel/ethinylestradiol oral contraceptive pill

norelgestrominum and ethinylestradiol patch oral contraceptive patch DRUG

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.

Also known as: EVRA ™, Batch number : 0311264

Norelgestrominum and ethinylestradiol contraceptive patch

Nuvaring ™ (etonorgestrel/ethinylestradiol) DRUG

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.

Etonogestrel and ethinylestradiol contraceptive vaginal ring

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Organon and Co: lead

Related 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. doi: 10.1016/j.contraception.2005.03.005.

  PMID: 16102549 RESULT

MeSH Terms

Interventions

Levonorgestrel; Contraceptives, Oral; ethinyl estradiol, levonorgestrel drug combination; Ortho Evra; NuvaRing; Ethinyl Estradiol

Intervention Hierarchy (Ancestors)

Norgestrel; Norpregnenes; Norpregnanes; Norsteroids; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Contraceptive Agents, Female; Contraceptive Agents; Reproductive Control Agents; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Therapeutic Uses; Norpregnatrienes; Estrogenic Steroids, Alkylated; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 5, 2010
• First Posted: January 7, 2010
• Study Start: March 1, 2004
• Primary Completion: June 1, 2004
• Study Completion: June 1, 2004
• Last Updated: February 4, 2022
• Results First Posted: March 31, 2010

Record last verified: 2022-02