Heat Effect
Conditions
Brief summary
This research study is intended to determine the effect of heat and occlusion on oxybutynin products.
Detailed description
This research study is intended to determine the effect of heat and occlusion on oxybutynin products. This study will use an oxybutynin patch and gel that have been approved by the Food and Drug Administration (FDA) and are already sold to customers in the United States; will not include any placebos.
Interventions
DRUGoxybutynin
patch
Sponsors
Food and Drug Administration (FDA)
University of Maryland, Baltimore
Study design
Allocation
NON_RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
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 have upper arms large enough to allow for placement of 200 cm2 \[31 in2\] area for applications of gel. The arm distance from the greater tubercle to the olecranon process should be a minimum of 30 cm. The circumference of the upper arms should be a minimum of 30 cm. 8. Subjects deemed to be healthy as judged by the Medically Accountable Investigator (MAI) and determined by medical history, physical examination and medication history 9. Negative urine drug screening test (cannabinoids, amphetamines, barbiturates, benzodiazepine, cocaine, methadone, opiates, PCP) 10. 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) 11. Have normal screening laboratories for urine protein and urine glucose 12. 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 hormonal or barrier birth control such as implants, injectables, combined oral contraceptives, some intrauterine devices (IUDs), sexual abstinence or a vasectomized partner 13. Agree not to donate blood to a blood bank throughout participation in the study and for at least three months after last procedure day 14. 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) 15. Have normal vital signs: * Temperature 35-37.9°C (95-100.3°F) * Systolic blood pressure 90-165 mmHg * Diastolic blood pressure 60-100 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 chronic obstructive pulmonary disease or cor pulmonale, or substantially decreased respiratory reserve, hypoxia, hypercapnia or pre-existing respiratory depression 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 medication (e.g. bisphosphonates \[to treat osteoporosis\], 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 oxybutynin, other ingredients in the patch, gel or oral tablet tested, to medical tape products or other skin patches 10. Subject has problems with urinary retention, gastric retention or gastrointestinal obstruction 11. Subject has ulcerative colitis 12. Subject has gastric reflux disease or esophagitis 13. Subject has uncontrolled narrow-angle glaucoma 14. Subject has myasthenia gravis 15. 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 16. 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 17. Consumption (food or drink) of alcohol within 24 h prior to dose administration 18. 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) 19. History of diabetes 20. Hereditary skin disorders or any skin inflammatory conditions as reported by the volunteer or evident to the MAI 21. 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 22. 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 oxybutynin 23. BMI ≥30 kg/m2
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PK Parameter | 24 h, 24 h 15 min, 24 h 30 min, 24 h 45 min, 25 h, 25 h 15 min, 25 h 30 min post patch application | Cmax (oxybutynin) during first heat period for patch (24-25.5 h) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Oxybutynin Patch and Gel First study session received one oxybutynin patch (Oxytrol for Women), then at least one week washout period Second study session received oxybutynin gel (Gelnique), then at least one week washout period Third study session received one oxybutynin patch (Oxytrol for Women) with early and late heat (90 minutes) exposure, then at least one week washout period Fourth study session received oxybutynin gel (Gelnique) with occlusion (3 hours) | 13 |
| Total | 13 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Oxybutynin Patch and Gel |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 13 Participants |
| Age, Continuous | 34.08 years STANDARD_DEVIATION 8.07 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 13 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 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 | 10 Participants |
| Region of Enrollment United States | 13 participants |
| Sex: Female, Male Female | 8 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 / 13 | 0 / 13 | 0 / 12 | 0 / 12 |
| other Total, other adverse events | 13 / 13 | 7 / 13 | 10 / 12 | 10 / 12 |
| serious Total, serious adverse events | 0 / 13 | 0 / 13 | 0 / 12 | 0 / 12 |
Outcome results
Primary
PK Parameter
Cmax (oxybutynin) during first heat period for patch (24-25.5 h)
Time frame: 24 h, 24 h 15 min, 24 h 30 min, 24 h 45 min, 25 h, 25 h 15 min, 25 h 30 min post patch application
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oxytrol for Women Patch (Baseline) | PK Parameter | 3.38 ng/mL | Standard Error 0.63 |
| Oxytrol for Women Patch (Heat Exposure) | PK Parameter | 30.75 ng/mL | Standard Error 20.31 |
Primary
PK Parameter
Serum concentration (oxybutynin) at 30 h time point (patch removal)
Time frame: 30 h post patch application
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oxytrol for Women Patch (Baseline) | PK Parameter | 4.06 ng/mL | Standard Error 1.24 |
| Oxytrol for Women Patch (Heat Exposure) | PK Parameter | 12.99 ng/mL | Standard Error 10.02 |
Primary
PK Parameter
Cmax (oxybutynin) at second heat exposure (30-31.5 h); after patch removed
Time frame: 30 h, 30 h 15 min, 30 h 30 min (patch removed at 30 h)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oxytrol for Women Patch (Baseline) | PK Parameter | 4.96 ng/mL | Standard Error 1.19 |
| Oxytrol for Women Patch (Heat Exposure) | PK Parameter | 22.43 ng/mL | Standard Error 15.14 |
Primary
PK Parameter
Cmax (oxybutynin)
Time frame: 0 h, 1 h, 2 h, 3 h, 4 h, 5 h, 6 h, 7 h, 7 h 15 min, 7 h 30 min, 7 h 45 min, 8 h, 8 h 15 min, 8 h 30 min, 8 h 45 min, 9 h, 9 h 15 min, 9 h 30 min, 9 h 45 min, 10 h, 10 h 30 min, 11 h, 11 h 30 min, 12 h post gel application
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oxytrol for Women Patch (Baseline) | PK Parameter | 5.00 ng/mL | Standard Error 2.09 |
| Oxytrol for Women Patch (Heat Exposure) | PK Parameter | 71.93 ng/mL | Standard Error 32.21 |
Primary
PK Parameter
Cmax (N-desethyl oxybutynin)
Time frame: 0 h, 1 h, 2 h, 3 h, 4 h, 5 h, 6 h, 7 h, 7 h 15 min, 7 h 30 min, 7 h 45 min, 8 h, 8 h 15 min, 8 h 30 min, 8 h 45 min, 9 h, 9 h 15 min, 9 h 30 min, 9 h 45 min, 10 h, 10 h 30 min, 11 h, 11 h 30 min, 12 h post gel application
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oxytrol for Women Patch (Baseline) | PK Parameter | 0.36 ng/mL | Standard Error 0.09 |
| Oxytrol for Women Patch (Heat Exposure) | PK Parameter | 2.38 ng/mL | Standard Error 0.62 |