Bioavailability
Conditions
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.
Interventions
DRUGRivastigmine (RLD) transdermal patch
brand name patch
DRUGRivastigmine (generic) transdermal patch
generic patch
Sponsors
Food and Drug Administration (FDA)
University of Maryland, Baltimore
Study design
Allocation
NON_RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Intervention model description
The same healthy subjects are assigned to all four treatments.
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total Area Under the Curve (AUC) 0-12 Hours | 0-12 hours for each subject for each of the four study sessions | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Rivastigmine RLD and Generic Patches Session 1: RLD patch worn for 9 hours, then at least one week wash out period, Session 2: Generic patch worn for 9 hours, then at least one week wash out period, Session 3: RLD patch worn for 9 hours includes 90 minute heat application (5 h-6 h 30 min), then at least one week wash out period Session 4: Generic patch worn for 9 hours includes 90 minute heat application (5 h-6 h 30 min) | 7 |
| Total | 7 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | study was halted due to COVID-19; once started again volunteer could no longer participate | 1 |
Baseline characteristics
| Characteristic | Rivastigmine RLD and Generic Patches |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants |
| Age, Continuous | 28.57 years STANDARD_DEVIATION 4.43 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 5 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 1 Participants |
| Region of Enrollment United States | 7 participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 7 | 0 / 7 | 0 / 6 | 0 / 6 |
| other Total, other adverse events | 7 / 7 | 7 / 7 | 4 / 6 | 6 / 6 |
| serious Total, serious adverse events | 0 / 7 | 0 / 7 | 0 / 6 | 0 / 6 |
Outcome results
Primary
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.
Time frame: 0-12 hours for each subject for each of the four study sessions
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| RLD Patch | Total Area Under the Curve (AUC) 0-12 Hours | 19.99 ng*h/mL | Standard Deviation 14.35 |
| Generic Patch | Total Area Under the Curve (AUC) 0-12 Hours | 19.22 ng*h/mL | Standard Deviation 11.41 |
| RLD Patch With Heat | Total Area Under the Curve (AUC) 0-12 Hours | 19.22 ng*h/mL | Standard Deviation 11.41 |
| Generic Patch With Heat | Total Area Under the Curve (AUC) 0-12 Hours | 16.57 ng*h/mL | Standard Deviation 9.66 |