A Randomized, Double-blind, 2-Way Crossover Bioequivalence and Adhesion Study of a Transdermal Contraceptive Patch Manufactured with Newly Sourced Adhesive Components at the End of Shelf Life and Currently Marketed EVRA® at the Beginning of Shelf Life in Healthy Adult Women

1. Subject must be a woman of childbearing potential 18 to 45 years of age,
inclusive, at screening
2. Subject has a body mass index (BMI) between 18 and 30 kg/m², inclusive, and
body weight not less than 50 kg and not more than 100 kg at screening.
3. Subject must be healthy on the basis of physical examination, medical
history, vital signs, and 12-lead electrocardiogram (ECG) performed at
screening. This determination will be recorded in the source documents and
signed by the investigator.
4. Subject must have a negative serum (Beta-human chorionic gonadotropin
[Beta-hCG]) pregnancy test at screening and a negative urine pregnancy test on
Day -1 of each treatment period.
5. Subject must be willing and able to adhere to the prohibitions and
restrictions specified in this protocol (see Section 4.4, Prohibitions and
Restrictions).
6. Subject must be surgically sterile with intact ovaries, sexually abstinent,
or, if sexually active with a non-sterilized male partner, be using a highly
effective method (ie, failure rate of <1% per year) of nonhormonal
contraception (eg, intrauterine device [IUD]) before admission until 1 month
after completion of the study.
7. Subject must agree not to donate eggs (ova, oocytes) for the purposes of
assisted reproduction during the study or within 1 month after completion of
the study.
8. Each subject must sign an ICF indicating that she understands the purpose
of, and procedures required for, the study, and is willing to participate in
the study.
9. Subject has a blood pressure (measured in supine position, after at least 5
minutes rest in supine position) between 90 and 140 mmHg systolic, inclusive,
and no higher than 90 mmHg diastolic at screening.
10. Subject has hematocrit of at least 36% at screening.
11. Subject must have a 12-lead ECG consistent with normal cardiac conduction
and function at screening, including:
Normal sinus rhythm with heart rate between 45 and 100 beats per minute (bpm),
extremes included. QT interval corrected for heart rate (QTc) according to
Fridericia's formula (QTcF)7 <=470 ms. QRS interval <=120 ms. PR interval <=220
ms. ECG morphology consistent with healthy cardiac conduction and function. Any
evidence of heart block and left or right bundle branch block is exclusionary.
12. Subject must be a non-smoker, or an ex-smoker for >6 months, must not use
nicotine-containing substances including tobacco products (eg, cigarettes,
e-cigarettes, cigars, chewing tobacco, gum, patch), and tests negative for
cotinine at screening and on Day -1 of each treatment period.

1. Subject has a history of or current clinically significant medical illness
including (but not limited to) cardiac arrhythmias or other cardiac disease,
hematologic disease, coagulation disorders (including any abnormal bleeding or
blood dyscrasias), lipid abnormalities, significant pulmonary disease,
including bronchospastic respiratory disease, diabetes mellitus, renal or
hepatic insufficiency, thyroid disease, neurologic or psychiatric disease,
infection, cholelithiasis (gall stone disease), chronic idiopathic jaundice,
family history of cholestatic jaundice, or any other illness that the
investigator considers should exclude the subject or that could interfere with
the interpretation of the study results.
2. Subject has clinically significant abnormal values for hematology,
biochemistry, or urinalysis at screening as deemed appropriate by the
investigator.
3. Subject has abnormal thyroid stimulating hormone level at screening.
4. Subject has clinically significant abnormal 12-lead ECG, vital signs, or
physical examination at screening as deemed appropriate by the investigator.
5. Subject has a history or presence of disorders commonly accepted as
contraindications to sex hormonal therapy including, but not limited to, the
following:
• Deep vein thrombophlebitis or thromboembolic disorders.
• Cerebral vascular or coronary artery disease, chronic untreated hypertension,
or migraines.
• Benign or malignant liver tumor that developed during the use of oral
contraceptives or other estrogen-containing products.
• Known or suspected estrogen-dependent neoplasia.
6. Subject has presence of disorders commonly accepted as contraindications to
combined oral contraceptives including, but not limited to, the following:
• Undiagnosed abnormal vaginal bleeding.
• Any neurovascular lesion of the eye or serious visual disturbance.
• Any impairment of liver function or liver disease, or renal disease.
7. Subject has evidence of cervical dysplasia as documented by a CytoRich test
or Papanicolaou (PAP) smear test within 10 months before screening. If a PAP
smear has been done within 10 months prior to screening and results are
available (documentation is available at the study site) a cervical smear does
not need to be performed.
8. Subject has used oral hormonal contraception, ie, contraceptive pills,
within 3 months before admission to the study site on Day -1 of Treatment
Period 1.
9. Subject currently has a contraceptive implant such as Implanon* or Norplant®
in place, or has had removal of contraceptive implant within the 3 months
before admission to the study site on Day -1 of Treatment Period 1.
10. Subject currently has a contraceptive vaginal ring such as NuvaRing® in
place, or has had removal of contraceptive vaginal ring within the 3 months
before admission to the study site on Day 1 of Treatment Period 1.
11. Subject received hormone injections such as Depo Provera® or deposubQ
Provera 104, within the 3 months before admission to the study site on Day 1 of
Treatment Period 1.
12. Subject used a steroid hormone-containing IUD such as Mirena® within the
screening period from Day 28 until admission to the study site on Day 1 of
Treatment Period 1.
13. Subject used any prescription or nonprescription medication (including
herbal supplements), that are known CYP enzyme inducers or inhibitors (eg, St.
John's Wort, cimetidine, or rifampin) within 30 days before the first patch
application (Day 1 of Treatment Period 1). See Attachment 1 of the protocol for
a list of medications that are known CYP enzyme inducers.
14. Subject used any prescription or nonprescription medication (including
vitamins and herbal supplements), except for paracetamol, within 14 days before
the first patch application is scheduled (Day 1 of Treatment Period 1).
15. Subject has a history of drug or alcohol abuse according to Diagnostic and
Statistical Manual of Mental Disorders (5th edition) (DSM-V) criteria within 5
years before screening or positive test result(s) for alcohol or drugs of abuse
(such as barbiturates, opiates, cocaine, amphetamines, methadone,
benzodiazepines, methamphetamine, tetrahydrocannabinol, phencyclidine, and
tricyclic antidepressants) at screening and on Day -1 of each treatment period.
Note: A positive urine drug test, urine cotinine test, and/or alcohol breath
test may be repeated once to exclude a technical error. Subjects with a
negative urine drug, urine cotinine test, and/or alcohol breath test at retest
may be included.
16. Subject has a known allergy to the study drug or any of the excipients of
the formulation.
17. Subject has a known allergy to heparin or history of heparin induced
thrombocytopenia.