Bioequivalence Study of Patches With Different Release Profiles

This study has been completed.
Sponsor:
Information provided by:
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
ClinicalTrials.gov Identifier:
NCT00697307
First received: June 5, 2008
Last updated: June 6, 2011
Last verified: March 2010
  Purpose

The purpose of this study was to determine the bioequivalence of a norelgestromin/ethinyl estradiol (NGMN/EE) transdermal contraceptive system.


Condition
Female Contraception

Study Type: Observational
Study Design: Time Perspective: Prospective
Official Title: A Bioequivalence Study Of A Low Cumulative Release Lot Of Norelgestromin (NGMN)/Ethinyl Estradiol (EE) Transdermal Contraceptive Systems Compared With Currently Marketed Ortho-Evra In Healthy Female Volunteers

Resource links provided by NLM:


Further study details as provided by Johnson & Johnson Pharmaceutical Research & Development, L.L.C.:

Enrollment: 43
Study Start Date: March 2003
Study Completion Date: July 2003
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

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00697307

Sponsors and Collaborators
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Investigators
Study Director: Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00697307     History of Changes
Other Study ID Numbers: CR002626
Study First Received: June 5, 2008
Last Updated: June 6, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Johnson & Johnson Pharmaceutical Research & Development, L.L.C.:
bioequivalence
contraception
contraceptive patch
ORTHO EVRA
norelgestromin
NGMN
ethinyl estradiol
EE

Additional relevant MeSH terms:
Contraceptive Agents
Norelgestromin
Ortho Evra
Ethinyl Estradiol
Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
Estrogens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Contraceptives, Oral, Combined
Contraceptives, Oral
Contraceptive Agents, Female

ClinicalTrials.gov processed this record on August 01, 2014