This is a single-dose, Open-label, Non-Randomized, 2-way Crossover Bioequivalence Study to
compare nicotine release after heating of a brand name (Nicoderm CQ) and generic (Aveva skin
patch) nicotine skin patches in adult smokers.
This research study is intended to determine the effect of heat on FDA-approved nicotine
transdermal patches and whether the heat applied will result in more nicotine being absorbed
through the skin than without applying heat. This is important given that little is known
about how the release of nicotine is affected by heat, particularly for generic products
that are also available over the counter. This study will use nicotine patches (brand name
and generic patches) that have been approved by the Food and Drug Administration (FDA) and
are already sold over the counter to customers in the United States, and will not include
- 1. Men or non-pregnant women of any ethnic background between the age of 18 and 45
- 2. Subjects should be cigarette smokers who smoke at least 5 cigarettes per day for
one year or more.
- 3. Provide written informed consent before initiation of any study procedures.
- 4. Available for follow-up for the planned duration of the study
- 5. Able to communicate well with the investigators
- 6. Able to adhere to the study restrictions and examination schedule.
- 7. Subjects who are within their ideal body weight (BMI >17 and <= 25)
- 8. Demonstrate comprehension of the protocol procedures and knowledge of study by
passing (>70% correct responses) a written examination containing 20 multiple choice
and true false questions covering all aspects of the study including the purpose,
procedures, risks and benefits.
- 9. Subjects deemed to be eligible as judged by the Medically Accountable Investigator
(MAI) and determined by medical history, physical examination, and medication
- 10. Have a normal blood pressure (systolic: 90-140 mmHg; diastolic: 50-90 mmHg) and
heart rate (55-100 bpm),
- 11. Have normal screening laboratories for WBC, Hgb, platelets, sodium, potassium,
chloride, bicarbonate, BUN, creatinine, ALT and AST
- 12. Have normal screening laboratories for urine protein and urine glucose.
- 13. Female subjects must be of non-childbearing potential (as defined as surgically
sterile [i.e. history of hysterectomy or tubal ligation] or postmenopausal for more
than 1 year), or if of childbearing potential, must be non-pregnant at the time of
enrollment and on the morning of each procedure day, and must agree to use hormonal
or barrier birth control such as implants, injectables, combined oral contraceptives,
some intrauterine devices (IUDs), sexual abstinence, or a vasectomized partner.
- 14. Agrees not to participate in another clinical study during the study period.
- 15. Agrees not to donate blood to a blood bank throughout participation in the study
and for at least 3 months after last procedure day.
- 16. Have a normal ECG
- 17. Be a smoker willing to refrain from smoking 10 hours prior to, and during, each
procedure day of the study.
- 1. Subjects who are nonsmokers or smoke less than 5 cigarettes per day
- 2. Women who are pregnant or lactating or have a positive serum pregnancy test at
enrollment or on the morning of any procedure day.
- 3. Participation in any ongoing investigational drug trial or clinical drug trial
- 4. Abnormal Vital signs, defined as:
- Hypertension (systolic blood pressure >140 mm Hg or diastolic blood pressure >90
mm Hg) at rest on 2 separate days)
- Heart rate <55 at rest on 2 separate days
- Respiratory rate >20
- 5. Temperature > 38.0 ºC (100.4 ºF) or symptoms of an acute self-limited illness such
as an upper respiratory infection or gastroenteritis within 7 days of administration
of the transdermal patch.
- 6. Active positive Hepatitis B, C, and HIV serologies
- 7. Positive urine drug screening test
- 8. Use of any prescription medication during the period 0 to 30 days or over-the
counter medication (vitamin, herbal supplements and birth control medications not
included) during the period 0 to 5 days before entry to the study
- 9. Donation or loss of greater than one pint of blood within 60 days of entry to the
- 10. Any prior serious adverse reaction or hypersensitivity to nicotine or any of the
inactive ingredients in the patch (acrylate adhesive, polyester, silicone, ethylene
vinyl acetate-copolymer polyisobutylene and polyethylene)
- 11. Have a diagnosis of schizophrenia or other major psychiatric diagnosis.
- 12. Received an experimental agent (vaccine, drug, biologic, device, blood product or
medication) within 1 month before enrollment in this study or expects to receive an
experimental agent during the study.
- 13. Any condition that would, in the opinion of the Medically Accountable
Investigator (MAI), place the subject at an unacceptable risk of injury or render the
subject unable to meet the requirements of the protocol.
- 14. Inability to communicate or co-operate with the investigators
- 15. History of consumption of alcohol within 24 hours prior to dose administration
- 16. Scarring on upper arms, including tattoos at planned site of patch placement
making skin reactions not evaluable
- 17. Subject who currently has any of the following conditions:
1. Thrombophlebitis, thromboembolic disorders
2. A past history of deep vein thrombophlebitis or thromboembolic disorders
3. Cerebrovascular or coronary artery disease (current or past history)
4. Valvular heart disease with complications
5. Severe hypertension
6. Diabetes with vascular involvement
7. Headaches with focal neurological symptoms
8. Major surgery with prolonged immobilization
- 18. Medical history of a serious chronic condition (e.g. allergic conditions such as
anaphylaxis, asthma or generalized drug reaction).
- 19. Medical history of significant dermatologic diseases or conditions, such as
atopy, psoriasis, vitiligo or conditions known to alter skin appearance or
physiologic response (e.g. diabetes, porphyria).
- 20. History of significant dermatologic cancers (e.g. melanoma, squamous cell
carcinoma), except basal cell carcinomas that were superficial and did not involve
the investigative site.
- 21. Within 10 hours prior to dosing, use of other nicotine products (e.g. nicotine
gum or other nicotine-containing products) that would significantly influence or
exaggerate responses to the nicotine patches used in this study.
- 22. Within 72 hours prior to dosing, use of antihistamines or use of topical drugs at
- 23. Subject has an obvious difference in skin color between arms or the presence of a
skin condition, open sores, scar tissue, tattoo, or coloration that would interfere
with placement of test articles, skin assessment, or reactions to drug.