Bioequivalence Study of Patches With Different Equilibration Profiles
Condition: Female Contraception
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of this single center, randomized, double-blind, 2 way crossover study was to
      determine the bioequivalence of a norelgestromin/ethinyl estradiol (NGMN/EE) transdermal
      contraceptive system.
    

Detailed description: 
      The primary objective was to determine the bioequivalence of a norelgestromin/ethinyl
      estradiol (NGMN/EE) transdermal contraceptive system lot with a faster equilibration profile
      compared to currently marketed lot of NORELGESTROMIN/ETHINYL ESTRADIOL, after application to
      the buttock. This was a single center, randomized, double-blind, 2 way crossover study. The
      double-blind treatment phase included two 7-day treatment periods separated by a 21-day
      washout period. Safety was assessed throughout the study. The study population was comprised
      of healthy women who weighed at least 110 pounds with a body mass index (BMI) between 16 and
      29.9 kg/m2, and a hematocrit of at least 36%. Eligible patients were randomly assigned to 1
      of 2 treatment sequence groups. A 20 cm2 NGMN/EE transdermal contraceptive patch (test or
      NORELGESTROMIN/ETHINYL ESTRADIOL (reference) was applied to each patient on the buttock and
      worn for 7 days. Twenty-one days after removal of the first patch the patient crossed over to
      the other treatment. After each patch was removed, the skin was checked for redness and
      swelling. Blood samples were collected for measurement of drug concentrations during the
      7-day wear periods and for 3 days after each patch was removed. Patients were telephoned
      weekly during the washout period to remind them to use back-up contraception. After the last
      blood sample collection in Period 2, or in instances where the patient withdrew early from
      the study, posttreatment procedures including physical and gynecologic examinations, vital
      signs, laboratory evaluations, and a serum pregnancy test were performed. The following
      pharmacokinetic parameters were to be estimated for NGMN, NG, and EE after test and
      NORELGESTROMIN/ETHINYL ESTRADIOL patch application: Cmax - maximum observed serum
      concentration after patch application; tmax - time of maximum serum concentration after patch
      application; Css - mean steady-state concentration for NGMN and EE after patch application
      calculated as the mean concentration between 48 and 168 hours; Cavg - average concentration
      for NG calculated as AUC168/168; AUC - the area under the serum concentration-time curve for
      NGMN, NG, and EE using linear trapezoidal summation from the data obtained after patch
      application from time 0 (dosing) to 168 hours postdose (AUC168), from time 0 to 240 hours
      postdose (AUC240), from time 0 to infinity (AUCinf), and from time 0 to the last measurable
      concentration for EE (AUClast); and t½ - apparent terminal half-life, computed as (ln2/ke)
      where ke is the slope of the terminal log-linear phase of the serum concentration-time curve.
      Patch adhesion was assessed and scores summarized. Assessment of bioequivalence will be based
      on the use of 90% confidence intervals (for 2 one-sided test procedures) for the ratios of
      mean (test to reference) pharmacokinetic parameters, AUC240 and Css for NGMN and EE. The 2
      patches were considered bioequivalent if the 90% confidence intervals fell within 80% to 125%
      limits for both AUC240 and Css for NGMN and EE. Safety evaluations were based on adverse
      events, including erythema and application site reaction and changes in physical and
      gynecologic examinations (including breast exams), vital signs, 12-lead ECGs, and clinical
      laboratory test results from pre- to poststudy. Serum pregnancy testing and urine drug
      screening was performed. Changes from screening were summarized using descriptive statistics.

      A fast equilibratin patch or NORELGESTROMIN/ETHINYL ESTRADIOL patch (20 cm2 transdermal
      contraceptive system) contains NGMN 6.0 mg and EE 0.75 mg. Each patient wore a patch (test or
      NORELGESTROMIN/ETHINYL ESTRADIOL) on the buttock for 7 days, according to a
      computer-generated randomization schedule. There was a 21-day washout period. Patients then
      crossed over to the other treatment for 7 days.
    

Intervention name(s): norelgestromin/ethinyl estradiol (NGMN/EE) transdermal contraceptive system.
Intervention type(s): Drug
Intervention MeSH terms: Ethinyl Estradiol; Norelgestromin; Contraceptive Agents; Estradiol
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double
Primary purpose: Health Services Research
Keywords: ORTHO EVRA; contraception; NGMN; contraceptive patch; bioequivalence; EE; norelgestromin; ethinyl estradiol