A Study to Evaluate the Exposure of Norelgestromin and Ethinyl Estradiol From Commercial Lots of EVRA (a Transdermal Contraceptive Patch Manufactured by LOHMANN Therapie-Systeme) and CILEST (an Oral Contraceptive)
Condition: Contraception; Female Contraception
Study type: Interventional
Phase: Phase 1

Summary: 
      The objective of this study is to estimate exposure to the hormones norelgestromin,
      norgestrel, and ethinyl estradiol in healthy female volunteers across multiple commercial
      lots of EVRAÂ® (a transdermal contraceptive patch manufactured by LOHMANN Therapie-Systeme),
      to compare these data to exposure data from one clinical lot, and to compare these data to
      exposure data from a commercially available oral contraceptive.
    

Detailed description: 
      This single-center, open-label, randomized, partially-balanced, incomplete block design study
      will consist of a pre-treatment phase (a screening period lasting up to 21 days), an
      open-label treatment phase (three 7-day treatment periods separated by 21-day washouts), and
      a post-treatment phase (a follow-up or early withdrawal visit). Total participation in the
      study is approximately 67 days. Approximately 54 subjects will be enrolled. The study
      population comprises healthy women, ages 18 to 45 years inclusive, who weigh at least 110
      pounds, have a body mass index (BMI) between 16 and 29.9 kg per meter squared.

      Subjects will wear an EVRA® patch or take CILEST® during each of the three 7-day treatment
      periods; treatment periods will be separated by a 21-day washout period. When a subject is to
      wear EVRA®, a patch from 1 of the 6 selected commercial lots will be applied on the buttock
      and worn for 7 days. Patches will be applied by the investigator or designated study unit
      personnel. All patches will be worn on the upper outer quadrant of the same buttock, but not
      necessarily in the exact same position. The investigator or designated study unit personnel
      will remove the patches and will evaluate the adhesion of the patches before removal. When a
      subject is to receive CILEST®, tablets from 1 of the 3 selected commercial lots will be
      administered daily for 7 consecutive days. A minimum of 21 days after removal of the patch or
      the seventh dose of CILEST®, the subject will begin another treatment period, until she
      completes 3 open-label treatment periods.

      Subjects will be confined to the study unit for blood sample collections for determination of
      NGMN, NG, and EE plasma concentrations. Blood samples will be collected (via venipuncture)
      immediately before each dose and at specified time points after each dose is administered.
      Pharmacokinetic parameters of NGMN, NG, and EE, including Cmax, tmax, and AUC, after each
      treatment will be estimated by standard methods. Safety will be assessed throughout the
      study, and will be based on adverse events and changes in physical and gynecologic
      examinations (including breast examinations), vital signs, electrocardiograms (ECGs), and
      clinical laboratory test results. Three 7-day treatment periods; treatments separated by
      21-day washout. Based on the randomization schedule, some subjects will wear an EVRA® patch
      in all 3 periods (on the upper outer quadrant of the buttock for 7 days), some will wear a
      patch in 2 periods and take CILEST® oral tablets once daily in 1 period, and some will wear a
      patch in 1 period and take CILEST® oral tablets once daily in 2 periods.
    

Intervention name(s): EVRA® transdermal contraceptive patch containing 6 mg of norelgestromin and 0.60 mg of ethinyl estradiol (versus CILEST® tablets).
Intervention type(s): Drug
Intervention MeSH terms: Ethinyl Estradiol; Norelgestromin; Contraceptive Agents; Estradiol
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Transdermal contraception; contraceptive; hormonal, steroid contraception; ethinyl estradiol; progesterone; EVRA; CILEST; ORTHO EVRA