Intervention: Rivastigmine
Trial phase: Early Phase 1
ATC code: N06DA03
SMILES: CCN(C)C(=O)Oc1cccc([C@H](C)N(C)C)c1
Sex: All
Age groups: Adult
Healthy volunteers: Accepts Healthy Volunteers
Participants at risk: 6
Group description: generic rivastigmine patch (4.6 mg/24 hours); worn for 9 hours; 90 min heat application

Rivastigmine (generic) transdermal patch: generic patch
Eligibility criteria:
Inclusion Criteria:

Men or non-pregnant, non-lactating women who are of any ethnic background between the age of 18 to 45 years old
Subjects must be non-smokers/tobacco users (must have refrained from the use of nicotine-containing substances, including tobacco products (e.g., cigarettes, cigars, chewing tobacco, snuff, gum, patches or electronic cigarettes) over the previous 2 months and are not currently using tobacco products
Provide written informed consent before initiation of any of the study procedures
Agree not to participate in another clinical trial/study or to participate in an investigational drug study for at least one month after the last study session
Able to adhere to the study restrictions and protocol schedule
Able to participate in all study sessions
Subjects deemed to be healthy as judged by the Medically Accountable Investigator (MAI) and determined by medical history, physical examination and medication history
Negative urine drug screening test (cannabinoids, amphetamines, barbiturates, benzodiazepine, cocaine, methadone, opiates, PCP)
Have normal screening laboratories for white blood cells (WBC), hemoglobin (Hgb), platelets, sodium, potassium, chloride, bicarbonate, blood urea nitrogen (BUN), creatinine, alanine transaminase (ALT) and aspartate aminotransferase (AST)
Have normal screening laboratories for urine protein and urine glucose
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 reliable hormonal or barrier birth control such as implants, injectables, combined oral contraceptives, some intrauterine devices (IUDs), sexual abstinence or a vasectomized partner
Agree not to donate blood to a blood bank throughout participation in the study and for at least three months after last procedure day
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)

Have normal vital signs:

Temperature 35-37.9°C (95-100.3°F)
Systolic blood pressure 90-140 mmHg
Diastolic blood pressure 60-90 mmHg
Heart rate 55-100 beats per minute
Respiration rate 12-20 breaths per minute

Exclusion Criteria:

Women who are pregnant, lactating, breast feeding or have a positive serum pregnancy test at enrollment or positive urine pregnancy test on the morning of any study session
Smokers/tobacco users (current use or use over the previous 2 months of nicotine-containing substances, including tobacco products (e.g., cigarettes, cigars, chewing tobacco, snuff, gum, patch or electronic cigarettes)
Participation in any ongoing investigational drug trial/study or clinical drug trial/study
History of lung, heart, respiratory or blood disease
Active positive Hepatitis B, C and/or HIV serologies
Positive urine drug screening test
Use of chronic prescription medications during the period 0 to 30 days; or over-the-counter medications (e.g. cholinomimetic drugs [used to treat diseases like acid reflux in children, glaucoma, dry mouth associated with Sjögren's Syndrome], anticholinergics [used to treat diseases like asthma, incontinence, gastrointestinal cramps, and muscular spasms], antihistamines, topical corticosteroids) and short term (<30 days) prescription medications during the period 0-3 days before a study session vitamin, herbal supplements and birth control medications not included)
Donation or loss of greater than one pint of blood within 60 days of entry to the study
Any prior allergies to rivastigmine, other carbamate derivatives, other ingredients in the patch, to medical tape products or other skin patches
Subject has problems with urinary retention, gastric retention or gastrointestinal obstruction
Subject has continuous spasms, muscle contractions, motor restlessness, rigidity, slowness of movement, tremors or irregular jerky movements
Subject has ulcers or gastrointestinal bleeding
Subject has asthma or blocked airflow making it hard to breathe (COPD)
Received an experimental agent (vaccine, drug, biologic, device, blood product or medication) within one month before enrollment in this study or expects to receive an experimental agent during the study
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
Consumption (food or drink) of alcohol within 24 h prior to dose administration
History as either reported by the subject or evident to the investigator of infectious disease or skin infection or of chronic skin disease (e.g., psoriasis, atopic dermatitis)
History of diabetes
Hereditary skin disorders or any skin inflammatory conditions as reported by the subject or evident to the MAI
History of significant dermatologic cancers (e.g., melanoma, squamous cell carcinoma) except basal cell carcinomas that were superficial and did not involve the investigative sites
Subject has an obvious difference in skin color between arms or the presence of a skin condition, excessive hair at the application site (upper arms), sunburn, raised moles and scars, open sores at application site (upper arms), scar tissue, tattoo, or coloration that would interfere with placement of products, skin assessment, or reactions to rivastigmine
BMI ≥30 kg/m2