Bioequivalence Study of Patches With Different Release Profiles
Information source: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Female Contraception
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 study was to determine the bioequivalence of a norelgestronim/ethinyl
estradiol (NGMN/EE) transdermal contraceptive system.
Clinical Details
Official title: A Bioequivalence Study Of A Low Cumulative Release Lot Of Norgelgestromin (NGMN)/Ethinyl Estradiol (EE) Transdermal Contraceptive Systems Compared With Currently Marketed Ortho-Evra In Healthy Female Volunteers
Study design: Prospective
Detailed description:
The primary objective was to determine the bioequivalence of a norelgestromin/ethinyl
estradiol (NGMN/EE) transdermal contraceptive system lot with a cumulative release profile
below the lower limit of the specifications (low spec lot) compared with a currently marketed
lot of EVRANORELGESTROMIN/ETHINYL ESTRADIOL with a cumulative release profile well within the
specifications limits (reference lot), 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 28 day washout period. Safety was
assessed throughout the study. The study population was comprised of healthy women aged 18 to
45 years, inclusive, 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 patient were randomly assigned to
1 of 2 treatment sequence groups. A 20 cm2 NGMN/EE transdermal contraceptive patch (low spec
lot [test] or EVRANORELGESTROMIN/ETHINYL ESTRADIOL [reference]) was applied to each patient
on the buttock and worn for 7 days. Twenty-eight days after removal of the first patch (Day
36 of Period 2), 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 on Day 46, or in
instances where the patient withdrew early from the study, post treatment 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 low spec lot and EVRANORELGESTROMIN/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 post dose (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 (low spec lot to
EVRANORELGESTROMIN/ETHINYL ESTRADIOL ) pharmacokinetic parameters, AUC240 and Css for NGMN
and EE. The 2 formulations will be considered bioequivalent if the 90% confidence intervals
fall 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 single low spec lot or EVRANORELGESTROMIN/ETHINYL ESTRADIOL patch (20 cm2 transdermal
contraceptive system) contains NGMN 6. 0 mg and EE 0. 75 mg. Each subject wore a patch (low
spec lot or EVRANORELGESTROMIN/ETHINYL ESTRADIOL ) on the buttock for 7 days, according to a
computer-generated randomization schedule. There was a 28-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
- Llactating
- Currently using hormonal contraceptive
Locations and Contacts
Additional Information
Bioequivalence study of patches with different release profiles
Starting date: March 2003
Ending date: July 2003
Last updated: June 11, 2008
|
