Clinical trial NCT03915626: Effect of Heat on Rivastigmine TDS Products
Official title: Determination of Serum Rivastigmine Levels After Using Rivastigmine Transdermal Delivery Systems With and Without Standardized Heat Application in Healthy Human Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Bioavailability
Lead sponsor: University of Maryland, Baltimore
Sponsor class: OTHER
Collaborators: name: Food and Drug Administration (FDA)
First posted: 2019-04-16
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: The same healthy subjects are assigned to all four treatments.
Primary purpose: OTHER

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

1. Men or non-pregnant, non-lactating women who are of any ethnic background between the age of 18 to 45 years old
2. 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
3. Provide written informed consent before initiation of any of the study procedures
4. 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
5. Able to adhere to the study restrictions and protocol schedule
6. Able to participate in all study sessions
7. Subjects deemed to be healthy as judged by the Medically Accountable Investigator (MAI) and determined by medical history, physical examination and medication history
8. Negative urine drug screening test (cannabinoids, amphetamines, barbiturates, benzodiazepine, cocaine, methadone, opiates, PCP)
9. 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)
10. Have normal screening laboratories for urine protein and urine glucose
11. 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
12. Agree not to donate blood to a blood bank throughout participation in the study and for at least three months after last procedure day
13. 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)
14. 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:

1. 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
2. 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)
3. Participation in any ongoing investigational drug trial/study or clinical drug trial/study
4. History of lung, heart, respiratory or blood disease
5. Active positive Hepatitis B, C and/or HIV serologies
6. Positive urine drug screening test
7. 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)
8. Donation or loss of greater than one pint of blood within 60 days of entry to the study
9. Any prior allergies to rivastigmine, other carbamate derivatives, other ingredients in the patch, to medical tape products or other skin patches
10. Subject has problems with urinary retention, gastric retention or gastrointestinal obstruction
11. Subject has continuous spasms, muscle contractions, motor restlessness, rigidity, slowness of movement, tremors or irregular jerky movements
12. Subject has ulcers or gastrointestinal bleeding
13. Subject has asthma or blocked airflow making it hard to breathe (COPD)
14. 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
15. 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
16. Consumption (food or drink) of alcohol within 24 h prior to dose administration
17. 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)
18. History of diabetes
19. Hereditary skin disorders or any skin inflammatory conditions as reported by the subject or evident to the MAI
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 sites
21. 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
22. BMI ≥30 kg/m2

Primary outcomes:
measure: Total Area Under the Curve (AUC) 0-12 Hours
timeFrame: 0-12 hours for each subject for each of the four study sessions
Secondary outcomes:
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: General Clinical Research Center (GCRC) at the University of Maryland Medical Center
state: Maryland
Study officials:
affiliation: University of Maryland, Baltimore School of Pharmacy
name: Audra L Stinchcomb, PhD
role: PRINCIPAL_INVESTIGATOR
References: