Effect of Heat on Oxybutynin Release and Absorption From Oxybutynin Products

Study Overview
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Brief Summary
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This research study is intended to determine the effect of heat and occlusion on oxybutynin products.

Detailed Description
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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.

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

Conditions
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Heat Effect

Intervention / Treatment
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* Drug: oxybutynin
* Drug: oxybutynin


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 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. 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 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 90-165 mmHg Diastolic blood pressure 60-100 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 chronic obstructive pulmonary disease or cor pulmonale, or substantially decreased respiratory reserve, hypoxia, hypercapnia or pre-existing respiratory depression 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 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)] Donation or loss of greater than one pint of blood within 60 days of entry to the study Any prior allergies to oxybutynin, other ingredients in the patch, gel or oral tablet tested, to medical tape products or other skin patches Subject has problems with urinary retention, gastric retention or gastrointestinal obstruction Subject has ulcerative colitis Subject has gastric reflux disease or esophagitis Subject has uncontrolled narrow-angle glaucoma Subject has myasthenia gravis 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 volunteer 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 oxybutynin 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: baseline patch<br>patch | Drug: oxybutynin<br>* patch<br>|
| Other: baseline gel<br>gel | Drug: oxybutynin<br>* gel<br>|
| Other: patch with heat<br>patch | Drug: oxybutynin<br>* patch<br>|
| Other: gel with occlusion<br>gel | Drug: oxybutynin<br>* gel<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PK Parameter | Cmax (oxybutynin) during first heat period for patch (24-25.5 h) | 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 | 
| PK Parameter | Serum concentration (oxybutynin) at 30 h time point (patch removal) | 30 h post patch application | 
| PK Parameter | Cmax (oxybutynin) at second heat exposure (30-31.5 h); after patch removed | 30 h, 30 h 15 min, 30 h 30 min (patch removed at 30 h) | 
| PK Parameter | Cmax (oxybutynin) | 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 | 
| PK Parameter | Cmax (N-desethyl oxybutynin) | 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 |