Effect of Heat on Oxybutynin Release and Absorption From Oxybutynin Products

• Sponsor: University of Maryland, Baltimore (Other)
• Overall Status: Completed
• CT.gov ID: NCT03205605
• Collaborator: Food and Drug Administration (FDA) (U.S. Fed)
• Enrollment: 13
• Location: 1
• Arms: 4
• Actual Duration (Months): 22.3
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Heat Effect	Drug: oxybutynin; Drug: oxybutynin	Early Phase 1

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 13 participants
• Allocation: Non-Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: Determination of Serum Oxybutynin Levels After Using Oxybutynin Transdermal Delivery System and Transdermal Gel With and Without Standardized Heat Application in Healthy Human Volunteers
• Actual Study Start Date: Jan 2, 2018
• Actual Primary Completion Date: Nov 13, 2019
• Actual Study Completion Date: Nov 13, 2019

Arms and Interventions

Arm	Intervention/Treatment
Other: baseline patch patch	Drug: oxybutynin; patch
Other: baseline gel gel	Drug: oxybutynin; gel
Other: patch with heat patch	Drug: oxybutynin; patch
Other: gel with occlusion gel	Drug: oxybutynin; gel

Outcome Measures

Primary Outcome Measures

1. 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)

2. PK Parameter [30 h post patch application]

   Serum concentration (oxybutynin) at 30 h time point (patch removal)

3. PK Parameter [30 h, 30 h 15 min, 30 h 30 min (patch removed at 30 h)]

   Cmax (oxybutynin) at second heat exposure (30-31.5 h); after patch removed

4. PK Parameter [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]

   Cmax (oxybutynin)

5. PK Parameter [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]

   Cmax (N-desethyl oxybutynin)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 45 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	General Clinical Research Center (GCRC) at the University of Maryland Medical Center	Baltimore	Maryland	United States	21201

Sponsors and Collaborators

• University of Maryland, Baltimore
• Food and Drug Administration (FDA)

Investigators

• Principal Investigator: Audra L Stinchcomb, PhD, University of Maryland Baltimore School of Pharmacy
• Principal Investigator: Hazem E Hassan, PhD, University of Maryland Baltimore School of Pharmacy

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Mar 17, 2020

More Information

Publications

None provided.

• Responsible Party: Audra Stinchcomb, Professor, University of Maryland, Baltimore
• ClinicalTrials.gov Identifier: NCT03205605
• Other Study ID Numbers: HP-00070850
• First Posted: Jul 2, 2017
• Last Update Posted: Apr 11, 2022
• Last Verified: Mar 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Additional relevant MeSH terms: Mandelic Acids; Oxybutynin

Study Results

Participant Flow

Arm/Group Title	Oxybutynin Patch and Gel
Arm/Group Description	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)
Period Title: Overall Study
STARTED	13
COMPLETED	12
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Oxybutynin Patch and Gel
Arm/Group Description	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)
Overall Participants	13
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	13 100%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	34.08 (8.07)
Sex: Female, Male (Count of Participants)
Female	8 61.5%
Male	5 38.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	13 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	1 7.7%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	1 7.7%
White	10 76.9%
More than one race	1 7.7%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	13 100%

Outcome Measures

1. Primary Outcome

Title	PK Parameter
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Oxytrol for Women Patch (Baseline)	Oxytrol for Women Patch (Heat Exposure)
Arm/Group Description	baseline (no heat exposure)	external heat exposure at 24-25.5 h and 30-31.5 h
Measure Participants	13	12
Mean (Standard Error) [ng/mL]	3.38 (0.63)	30.75 (20.31)

2. Primary Outcome

Title	PK Parameter
Description	Serum concentration (oxybutynin) at 30 h time point (patch removal)
Time Frame	30 h post patch application

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Oxytrol for Women Patch (Baseline)	Oxytrol for Women Patch (Heat Exposure)
Arm/Group Description	baseline (no heat exposure)	external heat exposure at 24-25.5 h and 30-31.5 h
Measure Participants	13	12
Mean (Standard Error) [ng/mL]	4.06 (1.24)	12.99 (10.02)

3. Primary Outcome

Title	PK Parameter
Description	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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Oxytrol for Women Patch (Baseline)	Oxytrol for Women Patch (Heat Exposure)
Arm/Group Description	baseline (no heat exposure)	external heat exposure at 24-25.5 h and 30-31.5 h
Measure Participants	13	12
Mean (Standard Error) [ng/mL]	4.96 (1.19)	22.43 (15.14)

4. Primary Outcome

Title	PK Parameter
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Gelnique Gel (Baseline)	Gelnique Gel (Occlusion)
Arm/Group Description	Gelnique gel applied for 12 h duration; no occlusion	Gelnique gel applied for 12 h duration; occluded from 7-10 h
Measure Participants	12	12
Mean (Standard Error) [ng/mL]	5.00 (2.09)	71.93 (32.21)

5. Primary Outcome

Title	PK Parameter
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Gelnique Gel (Baseline)	Gelnique Gel (Occlusion)
Arm/Group Description	Gelnique gel applied for 12 h duration; no occlusion	Gelnique gel applied for 12 h duration; occluded from 7-10 h
Measure Participants	12	12
Mean (Standard Error) [ng/mL]	0.36 (0.09)	2.38 (0.62)

Adverse Events

Time Frame	For Study Session 1 & 3, 34 h 30 min post initial patch application followed by up to 72 h phone follow up. For Study Session 2 & 4, 12 h during gel application followed by up to 72 h phone follow up. If there was an adverse event, volunteers were followed up until adverse event resolved.
Arm/Group Title	Baseline Patch		Baseline Gel		Patch With Heat		Gel With Occlusion
Arm/Group Description	patch oxybutynin: patch		gel oxybutynin: gel		patch oxybutynin: patch		gel oxybutynin: gel
All Cause Mortality
	Baseline Patch		Baseline Gel		Patch With Heat		Gel With Occlusion
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/13 (0%)		0/13 (0%)		0/12 (0%)		0/12 (0%)
Serious Adverse Events
	Baseline Patch		Baseline Gel		Patch With Heat		Gel With Occlusion
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/13 (0%)		0/13 (0%)		0/12 (0%)		0/12 (0%)
Other (Not Including Serious) Adverse Events
	Baseline Patch		Baseline Gel		Patch With Heat		Gel With Occlusion
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	13/13 (100%)		7/13 (53.8%)		10/12 (83.3%)		10/12 (83.3%)
Blood and lymphatic system disorders
Hematoma	0/13 (0%)	0	1/13 (7.7%)	1	0/12 (0%)	0	0/12 (0%)	0
Cardiac disorders
Decreased heart rate	1/13 (7.7%)	1	0/13 (0%)	0	0/12 (0%)	0	2/12 (16.7%)	2
Decreased blood pressure	1/13 (7.7%)	1	2/13 (15.4%)	2	1/12 (8.3%)	1	3/12 (25%)	3
Gastrointestinal disorders
Constipation	2/13 (15.4%)	2	0/13 (0%)	0	0/12 (0%)	0	0/12 (0%)	0
General disorders
Headache	1/13 (7.7%)	1	0/13 (0%)	0	0/12 (0%)	0	0/12 (0%)	0
Skin and subcutaneous tissue disorders
vesicle (blister)	0/13 (0%)	0	0/13 (0%)	0	1/12 (8.3%)	1	1/12 (8.3%)	2
ERYTHEMA (skin reddening)	11/13 (84.6%)	11	7/13 (53.8%)	7	10/12 (83.3%)	10	10/12 (83.3%)	15
Surgical and medical procedures
Pain at IV site	0/13 (0%)	0	2/13 (15.4%)	2	0/12 (0%)	0	0/12 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.