Scopolamine Patch Pharmacokinetics in Healthy Adults

Transdermal drug delivery systems (TDDS) available in the form of patches are convenient,
attractive, and easy to use systems. Scopolamine patches are very popular TDDS available on
the United States market today. Accurate determination of the rate and extent of drug release
and absorption is crucial to ensure the safety of individuals using these and other types of
patches. Delivery rate can be determined early in the development process by using in vitro
skin flux permeation studies, and later in humans by accurately quantifying residual drug
from patches post-wear and in pharmacokinetic studies. In this proposal, the investigators
will employ two types of evaluation to determine the rate and extent of drug release and
absorption from RLD (reference listed drug) Transderm Scop® TDDS (transdermal drug delivery
system), namely residual drug analysis post-wear and pharmacokinetic analysis in healthy
adult volunteers. In addition, the investigators will compare the plasma drug concentrations
following patch and intravenous administration of Scopolamine, in order to determine the
absolute bioavailability of these patches. The investigators will conduct residual drug
analysis of TDDS following in vivo wear using highly sensitive validated quantification
methods. Positive outcomes of this project will identify appropriate methods to determine the
rate and extent of drug release and absorption from TDDS, and will help regulatory agencies
in the development of Guidances for Industry regarding the characterization of drug release
and absorption kinetics to ensure the safety of individuals utilizing these types of products

Inclusion Criteria:

1. Men or non-pregnant women of any ethnic background between the age of 18 and 65 years
old.

2. Subjects must be non-smokers (must have refrained from the use of nicotine-containing
substances, including tobacco products (e.g., cigarettes, cigars, chewing tobacco,
gum, patch or electronic cigarettes) over the previous 12 months and are not currently
using tobacco products.

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 protocol schedule, study restrictions and examination
schedule.

7. Subjects who are within their ideal body weight (BMI between 18-29.9 kg/m2).

8. Demonstrate comprehension of the protocol procedures and knowledge of study, as
demonstrated a study member filling out a consent checklist form to verify that the
subject understands all aspects of the study including the purpose, procedures, risks
and benefits.

9. Subjects deemed to be healthy as judged by the Medically Accountable Investigator
(MAI) and determined by medical history, physical examination, and medication history.

10. Negative urine drug screening test.

11. Have a normal blood pressure (systolic: 90-140 mmHg; diastolic: 50-90 mmHg) and heart
rate (55-100 bpm).

12. Have normal screening laboratories for WBC, Hgb, Hct, platelets, sodium, potassium,
chloride, bicarbonate, BUN, creatinine, ALT, AST, and total bilirubin.

13. Have normal screening laboratories for urine protein and urine glucose.

14. Female subjects must be of non-childbearing potential (defined as surgically sterile
[i.e. history of hysterectomy or tubal ligation] or postmenopausal for more than 1
year [no bleeding for 12 consecutive months]), or if of childbearing potential must be
non-pregnant at the time of enrollment and on the morning of the first day of each
study treatment session, 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.

15. Agrees not to participate in another clinical study during the study period unless the
study is in the follow up phase and it has been 1 month since the subject received any
experimental agents or treatments. The subject also agrees not to participate in an
investigational drug study for at least 1 month after last procedure day.

16. Agrees not to donate blood to a blood bank throughout participation in the study and
for at least 2 months after last procedure day.

17. Have a normal ECG; must not have the following to be acceptable: pathologic Q wave
abnormalities, significant ST-T wave changes, left ventricular hypertrophy, right
bundle branch block, left bundle branch block (sinus rhythm is between 55-100 beats
per minute).

Exclusion Criteria:

1. Women who are pregnant or lactating or have a positive serum pregnancy test at
enrollment or positive urine pregnancy test on the morning of the first day of any
procedure session.

2. Smokers (current use or use over the previous 12 months of nicotine-containing
substances, including tobacco products (e.g., cigarettes, cigars, chewing tobacco,
gum, patch or electronic cigarettes)).

3. Participation in any ongoing investigational drug trial or clinical drug trial period
unless the study is in the follow up phase and it has been ≥ 1 month since the subject
received any experimental agents or treatments..

4. Abnormal vital signs, defined as:

- Hypertension (systolic blood pressure >140 mmHg or diastolic blood pressure >90
mmHg) at rest on 2 separate days.

- Heart rate <55 at rest on 2 separate days

- Respiratory rate ≤ 11 to ≥ 18 breaths per minute

5. Temperature >38.0ºC (100.4ºF) or symptoms of an acute self-limited illness such as an
upper respiratory infection or gastroenteritis within 7 days of application of the
scopolamine TDDS.

6. History of chronic obstructive pulmonary disease.

7. Positive urine drug screening test.

8. Use of any prescription medication during the period 0 to 30 days or over-the counter
medication during the period 0 to 3 days before entry to the study (vitamins, herbal
supplements and birth control medications not included).

9. Use of medications or treatments that would significantly influence or exaggerate
responses to the test product or that would alter inflammatory or immune response to
the product (e.g. antihistamines [within 72 hours prior to dosing], systemic or
topical corticosteroids [within 3 weeks prior to dosing], cyclosporine, tacrolimus,
cytotoxic drugs, immune globulin, Bacillus Calmette-Guerin [BCG], monoclonal
antibodies, radiation therapy).

10. Donation or loss of greater than one pint of blood within 60 days of entry to the
study.

11. Any prior serious adverse reaction or hypersensitivity to scopolamine, or any of the
inactive ingredients in the TDDS (light mineral oil, polyisobutylene, polypropylene
and aluminized polyester film).

12. Have a diagnosis of schizophrenia or other major psychiatric diagnosis.

13. 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.

14. Medical history of a serious chronic condition, including (but not limited to):
allergic conditions such as anaphylaxis, asthma or generalized drug reactions; any
seizure disorder; glaucoma (open or closed angle); history of pyloric or urinary
bladder neck obstruction; intestinal obstruction; difficulty swallowing; stomach or
bowel problems (e.g, blockage, muscle weakness, ulcerative colitis, Crohn's disease);
bleeding disorders; acid reflux disease; myasthenia gravis; allergy to belladonna
alkaloids; impaired hepatic or renal function.

15. Any condition that would, in the opinion of the MAI, place the subject at an
unacceptable risk of injury or render the subject unable to meet the requirements of
the protocol.

16. Inability to communicate or co-operate with the investigators.

17. 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).

18. 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.

19. History of consumption of alcohol within 24 hours prior to dose administration.

20. Subject has an obvious difference in skin color between arms or the presence of a skin
condition, excessive hair at the application site, sunburn, raised moles and scars,
open sores at application site, scar tissue, tattoo, or coloration that would
interfere with placement of test articles, skin assessment, or reactions to drug.

21. Use of monoamine oxidase inhibitors 21 days prior to study.

22. Within 4 weeks prior to dosing, use of medications or treatments that would
significantly influence or exaggerate responses to the test product or that would
alter inflammatory or immune response to the product or agents deemed to be
immunosuppressive as determined by physician investigator.

23. Planned MRI scan of the head during TDDS wear.