Bioequivalence Study of Patches With Different Equilibration Profiles
Information source: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Female Contraception
Intervention: norelgestromin/ethinyl estradiol (NGMN/EE) transdermal contraceptive system. (Drug)
Phase: Phase 1
Status: Completed
Sponsored by: Johnson & Johnson Pharmaceutical Research & Development, L.L.C. Official(s) and/or principal investigator(s): Johnson & Johnson Pharmaceutical Research and Development, L.L.C. Clinical Trial, Study Director, Affiliation: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
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.
Clinical Details
Official title: A Definitive Bioequivalence Study of ORTHO EVRA Exhibiting Faster Equilibration Profile and Currently Marketed ORTHO EVRA in Healthy Female Volunteers
Study design: Allocation: Randomized, Endpoint Classification: Bio-equivalence Study, Intervention Model: Crossover Assignment, Masking: Double-Blind, Primary Purpose: Health Services Research
Primary outcome: The faster equilibrating patches were bioequivalent to the currently marketed patch
Secondary outcome: Safe and well tolerated
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.
Eligibility
Minimum age: 18 Years.
Maximum age: 45 Years.
Gender(s): Female.
Criteria:
Inclusion Criteria:
- Healthy as determined by physical and gynecologic examinations, clinical laboratory
assessments, vital sign measurements, and a 12-lead electrocardiogram (ECG)
Exclusion Criteria:
- Pregnant
- Lactating
- Currently using hormonal contraceptive
Locations and Contacts
Additional Information
Bioequivalence study of patches with different equilibration profiles
Starting date: May 2004
Last updated: June 6, 2011
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