Effect of Heat on Rivastigmine TDS Products

Study Overview
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Brief Summary
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This research study is designed to measure the amount of medicine in blood over time after the patch is placed on the skin with and without external heat application.

Official Title
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Determination of Serum Rivastigmine Levels After Using Rivastigmine Transdermal Delivery Systems With and Without Standardized Heat Application in Healthy Human Volunteers

Conditions
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Bioavailability

Intervention / Treatment
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* Drug: Rivastigmine (RLD) transdermal patch
* Drug: Rivastigmine (generic) transdermal patch


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: The same healthy subjects are assigned to all four treatments.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RLD patch<br>RLD rivastigmine patch (4.6 mg/24 hours); worn for 9 hours | Drug: Rivastigmine (RLD) transdermal patch<br>* brand name patch<br>* Other names: brand name patch;|
| Experimental: generic patch<br>generic rivastigmine patch (4.6 mg/24 hours); worn for 9 hours | Drug: Rivastigmine (generic) transdermal patch<br>* generic patch<br>* Other names: generic patch;|
| Experimental: RLD patch with heat<br>RLD rivastigmine patch (4.6 mg/24 hours); worn for 9 hours; 90 min heat application | Drug: Rivastigmine (RLD) transdermal patch<br>* brand name patch<br>* Other names: brand name patch;|
| Experimental: generic patch with heat<br>generic rivastigmine patch (4.6 mg/24 hours); worn for 9 hours; 90 min heat application | Drug: Rivastigmine (generic) transdermal patch<br>* generic patch<br>* Other names: generic patch;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Area Under the Curve (AUC) 0-12 Hours | Blood samples were obtained at the following time points: -60 min (before patch application) and then 2 h, 3 h, 4 h, 5 h, 5 h 15 min, 5 h 30 min, 5 h 45 min, 6 h, 6 h 15 min, 6 h 30 min, 6 h 45 min, 7 h, 7 h 30 min, 8 h, 8 h 30 min, 9 h, 9 h 15 min, 9 h 30 min, 10 h, 11 h, 12 h post patch administration. | 0-12 hours for each subject for each of the four study sessions |