Pharmacokinetics of Transdermal Metronidazole

NCT ID: NCT05929794

Last Updated: 2025-02-14

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE4

Total Enrollment

24 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-02-26

Study Completion Date

2025-12-31

Brief Summary

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This is a crossover pharmacokinetic clinical study in healthy volunteers to compare metronidazole delivery through skin when a gel or cream metronidazole product is applied to skin treated with a micropatch.

Detailed Description

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The goal of this crossover pharmacokinetic clinical study in healthy volunteers is to compare metronidazole delivery through skin when a gel or cream metronidazole product is applied to skin treated with a micropatch. The main questions this study aims to answer are:

* Is micropatch transdermal delivery dependent on the metronidazole product formulation?
* Is transdermal delivery dependent on micropore lifetime of the skin after micropatch application?

Participants will be divided into groups based on metronidazole product (gel or cream).

* The metronidazole product will be applied to micropatch-treated skin in study period one. Measurements of the skin barrier will be made before and after micropatch treatment.
* Daily blood samples will be collected for up to 5 days after the micropatch and metronidazole are first applied.
* Following a one-week washout period, the same study process will be repeated except that metronidazole product will be applied to skin without micropatch pretreatment.

Conditions

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Healthy

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

CROSSOVER

This is an open-label, 2-way crossover, non-placebo controlled pharmacokinetic assessment study in n=24 health adult subjects. In this crossover study, all subjects will receive treatment with either metronidazole gel or cream, depending on assigned study group. During different periods of the study, the metronidazole product will be applied to skin treated with a micropatch (period 1) and to skin not treated with a micropatch (period 2) on the upper arm.
Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

NONE

Study Groups

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Micropatch application + metronidazole 0.75% topical gel

Participants will have pre-treatment micropatch application followed by metronidazole 0.75% topical gel

Group Type ACTIVE_COMPARATOR

Metronidazole 0.75% Topical Gel

Intervention Type DRUG

Half of enrolled subjects will undergo this intervention. Baseline measurements of transepidermal water loss, electrical resistance, and color will be made at 3 sites on the upper arm. Color will only be measured at baseline. Micropatch application will occur at 2 sites, followed by application of metronidazole gel and then covered with an occlusive covering. One site will be covered with an occlusive covering only (no micropatch or gel). At 48 hours occlusive coverings and gel are removed and electrical resistance measurements are repeated. Fresh gel and occlusive patches are reapplied. At 96 hours the patches are removed and electrical resistance measurements repeated. Blood samples are taken daily for 5 days. Measurements from the 3rd site allow each subject to serve as their own control in data analysis. After a minimum 7 days washout period, all of these procedures will be repeated again except that there will be no micropatch application at any of the 3 sites.

Transdermal water loss measurement

Intervention Type DIAGNOSTIC_TEST

Baseline measurements of transepidermal water loss will be made at 3 sites on the upper arm. In the study periods that have micropatch application, the measurements will be repeated after micropatch application and removal (before any metronidazole product is applied).

Electrical Resistance

Intervention Type DIAGNOSTIC_TEST

Baseline measurements of electrical resistance will be made at 3 sites on the upper arm. In the study periods that have micropatch application, the measurements will be repeated after micropatch application and removal (before any metronidazole product is applied). In all study periods the measurements will also be repeated at 48 hours and 96 hours, when metronidazole product and occlusive coverings are removed from the skin.

Skin color measurement

Intervention Type DIAGNOSTIC_TEST

Baseline measurements of skin color will be made at 3 sites on the upper arm.

Micropatch application

Intervention Type OTHER

All subjects will undergo this intervention. Baseline measurements of transepidermal water loss, electrical resistance, and color will be made at 3 sites on the upper arm (color only measured at baseline). Two sites will have micropatch application + metronidazole product with occlusive covering. One site will have micropatch application + occlusive covering, no metronidazole product. Micropatch application will only occur on day 1 (a micropatch is a patch of 50 microneedles). Transepidermal water loss and electrical resistance are repeated after micropatch application and removal. At 48 hours occlusive coverings and metronidazole are removed; electrical resistance measurements are repeated. Metronidazole product and fresh occlusive patches are reapplied. At 96 hours patches are removed and electrical resistance measurements repeated. Blood samples are taken daily for 5 days. Measurements from the 3rd site allow each subject to serve as their own control in data analysis.

Metronidazole 0.75% topical gel

Participants will have metronidazole 0.75% topical gel applied without the pre-treatment micropatch application

Group Type ACTIVE_COMPARATOR

Metronidazole 0.75% Topical Gel

Intervention Type DRUG

Half of enrolled subjects will undergo this intervention. Baseline measurements of transepidermal water loss, electrical resistance, and color will be made at 3 sites on the upper arm. Color will only be measured at baseline. Micropatch application will occur at 2 sites, followed by application of metronidazole gel and then covered with an occlusive covering. One site will be covered with an occlusive covering only (no micropatch or gel). At 48 hours occlusive coverings and gel are removed and electrical resistance measurements are repeated. Fresh gel and occlusive patches are reapplied. At 96 hours the patches are removed and electrical resistance measurements repeated. Blood samples are taken daily for 5 days. Measurements from the 3rd site allow each subject to serve as their own control in data analysis. After a minimum 7 days washout period, all of these procedures will be repeated again except that there will be no micropatch application at any of the 3 sites.

Transdermal water loss measurement

Intervention Type DIAGNOSTIC_TEST

Baseline measurements of transepidermal water loss will be made at 3 sites on the upper arm. In the study periods that have micropatch application, the measurements will be repeated after micropatch application and removal (before any metronidazole product is applied).

Electrical Resistance

Intervention Type DIAGNOSTIC_TEST

Baseline measurements of electrical resistance will be made at 3 sites on the upper arm. In the study periods that have micropatch application, the measurements will be repeated after micropatch application and removal (before any metronidazole product is applied). In all study periods the measurements will also be repeated at 48 hours and 96 hours, when metronidazole product and occlusive coverings are removed from the skin.

Skin color measurement

Intervention Type DIAGNOSTIC_TEST

Baseline measurements of skin color will be made at 3 sites on the upper arm.

Micropatch application + metronidazole 0.75% topical cream

Participants will have pre-treatment micropatch application followed by metronidazole 0.75% topical cream

Group Type ACTIVE_COMPARATOR

Metronidazole 0.75% Topical Cream

Intervention Type DRUG

Half of enrolled subjects will undergo this intervention. Baseline measurements of transepidermal water loss, electrical resistance, and color will be made at 3 sites on the upper arm. Color will only be measured at baseline. Micropatch application will occur at 2 sites, followed by application of metronidazole cream and then covered with an occlusive covering. One site will be covered with an occlusive covering only (no micropatch or cream). At 48 hours occlusive coverings and cream are removed and electrical resistance measurements are repeated. Fresh cream and occlusive patches are reapplied. At 96 hours the patches are removed and electrical resistance measurements repeated. Blood samples are taken daily for 5 days. Measurements from the 3rd site allow each subject to serve as their own control in data analysis. After a minimum 7 days washout period, all of these procedures will be repeated again except that there will be no micropatch application at any of the 3 sites.

Transdermal water loss measurement

Intervention Type DIAGNOSTIC_TEST

Baseline measurements of transepidermal water loss will be made at 3 sites on the upper arm. In the study periods that have micropatch application, the measurements will be repeated after micropatch application and removal (before any metronidazole product is applied).

Electrical Resistance

Intervention Type DIAGNOSTIC_TEST

Baseline measurements of electrical resistance will be made at 3 sites on the upper arm. In the study periods that have micropatch application, the measurements will be repeated after micropatch application and removal (before any metronidazole product is applied). In all study periods the measurements will also be repeated at 48 hours and 96 hours, when metronidazole product and occlusive coverings are removed from the skin.

Skin color measurement

Intervention Type DIAGNOSTIC_TEST

Baseline measurements of skin color will be made at 3 sites on the upper arm.

Micropatch application

Intervention Type OTHER

All subjects will undergo this intervention. Baseline measurements of transepidermal water loss, electrical resistance, and color will be made at 3 sites on the upper arm (color only measured at baseline). Two sites will have micropatch application + metronidazole product with occlusive covering. One site will have micropatch application + occlusive covering, no metronidazole product. Micropatch application will only occur on day 1 (a micropatch is a patch of 50 microneedles). Transepidermal water loss and electrical resistance are repeated after micropatch application and removal. At 48 hours occlusive coverings and metronidazole are removed; electrical resistance measurements are repeated. Metronidazole product and fresh occlusive patches are reapplied. At 96 hours patches are removed and electrical resistance measurements repeated. Blood samples are taken daily for 5 days. Measurements from the 3rd site allow each subject to serve as their own control in data analysis.

Metronidazole 0.75% topical cream

Participants will have metronidazole 0.75% topical cream applied without the pre-treatment micropatch application

Group Type ACTIVE_COMPARATOR

Metronidazole 0.75% Topical Cream

Intervention Type DRUG

Half of enrolled subjects will undergo this intervention. Baseline measurements of transepidermal water loss, electrical resistance, and color will be made at 3 sites on the upper arm. Color will only be measured at baseline. Micropatch application will occur at 2 sites, followed by application of metronidazole cream and then covered with an occlusive covering. One site will be covered with an occlusive covering only (no micropatch or cream). At 48 hours occlusive coverings and cream are removed and electrical resistance measurements are repeated. Fresh cream and occlusive patches are reapplied. At 96 hours the patches are removed and electrical resistance measurements repeated. Blood samples are taken daily for 5 days. Measurements from the 3rd site allow each subject to serve as their own control in data analysis. After a minimum 7 days washout period, all of these procedures will be repeated again except that there will be no micropatch application at any of the 3 sites.

Transdermal water loss measurement

Intervention Type DIAGNOSTIC_TEST

Baseline measurements of transepidermal water loss will be made at 3 sites on the upper arm. In the study periods that have micropatch application, the measurements will be repeated after micropatch application and removal (before any metronidazole product is applied).

Electrical Resistance

Intervention Type DIAGNOSTIC_TEST

Baseline measurements of electrical resistance will be made at 3 sites on the upper arm. In the study periods that have micropatch application, the measurements will be repeated after micropatch application and removal (before any metronidazole product is applied). In all study periods the measurements will also be repeated at 48 hours and 96 hours, when metronidazole product and occlusive coverings are removed from the skin.

Skin color measurement

Intervention Type DIAGNOSTIC_TEST

Baseline measurements of skin color will be made at 3 sites on the upper arm.

Interventions

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Metronidazole 0.75% Topical Gel

Half of enrolled subjects will undergo this intervention. Baseline measurements of transepidermal water loss, electrical resistance, and color will be made at 3 sites on the upper arm. Color will only be measured at baseline. Micropatch application will occur at 2 sites, followed by application of metronidazole gel and then covered with an occlusive covering. One site will be covered with an occlusive covering only (no micropatch or gel). At 48 hours occlusive coverings and gel are removed and electrical resistance measurements are repeated. Fresh gel and occlusive patches are reapplied. At 96 hours the patches are removed and electrical resistance measurements repeated. Blood samples are taken daily for 5 days. Measurements from the 3rd site allow each subject to serve as their own control in data analysis. After a minimum 7 days washout period, all of these procedures will be repeated again except that there will be no micropatch application at any of the 3 sites.

Intervention Type DRUG

Metronidazole 0.75% Topical Cream

Half of enrolled subjects will undergo this intervention. Baseline measurements of transepidermal water loss, electrical resistance, and color will be made at 3 sites on the upper arm. Color will only be measured at baseline. Micropatch application will occur at 2 sites, followed by application of metronidazole cream and then covered with an occlusive covering. One site will be covered with an occlusive covering only (no micropatch or cream). At 48 hours occlusive coverings and cream are removed and electrical resistance measurements are repeated. Fresh cream and occlusive patches are reapplied. At 96 hours the patches are removed and electrical resistance measurements repeated. Blood samples are taken daily for 5 days. Measurements from the 3rd site allow each subject to serve as their own control in data analysis. After a minimum 7 days washout period, all of these procedures will be repeated again except that there will be no micropatch application at any of the 3 sites.

Intervention Type DRUG

Transdermal water loss measurement

Baseline measurements of transepidermal water loss will be made at 3 sites on the upper arm. In the study periods that have micropatch application, the measurements will be repeated after micropatch application and removal (before any metronidazole product is applied).

Intervention Type DIAGNOSTIC_TEST

Electrical Resistance

Baseline measurements of electrical resistance will be made at 3 sites on the upper arm. In the study periods that have micropatch application, the measurements will be repeated after micropatch application and removal (before any metronidazole product is applied). In all study periods the measurements will also be repeated at 48 hours and 96 hours, when metronidazole product and occlusive coverings are removed from the skin.

Intervention Type DIAGNOSTIC_TEST

Skin color measurement

Baseline measurements of skin color will be made at 3 sites on the upper arm.

Intervention Type DIAGNOSTIC_TEST

Micropatch application

All subjects will undergo this intervention. Baseline measurements of transepidermal water loss, electrical resistance, and color will be made at 3 sites on the upper arm (color only measured at baseline). Two sites will have micropatch application + metronidazole product with occlusive covering. One site will have micropatch application + occlusive covering, no metronidazole product. Micropatch application will only occur on day 1 (a micropatch is a patch of 50 microneedles). Transepidermal water loss and electrical resistance are repeated after micropatch application and removal. At 48 hours occlusive coverings and metronidazole are removed; electrical resistance measurements are repeated. Metronidazole product and fresh occlusive patches are reapplied. At 96 hours patches are removed and electrical resistance measurements repeated. Blood samples are taken daily for 5 days. Measurements from the 3rd site allow each subject to serve as their own control in data analysis.

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* Men or non-pregnant women ≥18 years old, of any ethnic background
* Provide written informed consent before initiation of any study procedures
* Available for follow-up for the planned duration of the study
* Able to communicate well with the investigators
* Able to adhere to the study protocol schedule, study restrictions and examination schedule
* Subjects deemed to be healthy, as determined by the study physician, based on medical history, current medical conditions, and medication history
* Agrees not to participate in another clinical study during the study period unless the study is in the follow up phase and it has been 1 month since the subject received any experimental agents or treatments. The subject also agrees not to participate in an investigational drug study for at least 1 month after last procedure day
* Agrees not to donate blood to a blood bank throughout participation in the study and for at least 2 months after last procedure day.

Exclusion Criteria

* Unable to give consent
* Inability to communicate or cooperate with the investigators
* Known previous adverse reaction to microneedle insertion
* Known allergy or adverse reaction to medical tape/adhesive, or aloe vera
* Women who are pregnant or lactating
* Abnormal vital signs or lab values deemed to be medically significant by the study physician or Principal Investigator
* Positive urine drug screening test
* Known prior serious adverse reaction or hypersensitivity to metronidazole or any metronidazole products
* History of anaphylaxis to an antibiotic, antimicrobial, antifungal, antipartisitic, or antiviral drug
* Current smoker or regular use of nicotine or tobacco products
* Participation in any ongoing investigational drug trial or clinical drug trial unless the study is in the follow up phase and it has been ≥1 month since the subject received any experimental agents or treatments
* Current use of medications in the following therapeutic classes: HMGCoA reductase inhibitors ("statins"), beta-blockers, oral or topical steroids, oral antibiotics, topical antibiotics at the local treatment site, topical antihistamines at the local treatment site, and oral or topical NSAIDs/analgesics. A subject who has recently used oral or topical steroids, antibiotics, antihistamines, or NSAIDs/analgesics may be enrolled if more than 5 elimination half-lives of the drug have passed since the last dose. The estimated elimination half-life for any specific drug will be obtained from standard pharmacy references such as Micromedex or other comparable references.
* Current or recent use of any prescription medication that, in the opinion of the study physician or Principal Investigator, would present a safety risk when used concomitantly with metronidazole
* Any current medical conditions (acute or chronic) that may pose a risk for study participation, as determined by the study physician or Principal Investigator
* Any condition that would, in the opinion of the study physician or Principal Investigator, place the subject at an unacceptable risk of injury or render the subject unable to meet the requirements of the protocol
* Uncontrolled mental illness that would, in the opinion of the study physician or Principal Investigator, affect the subject's ability to understand or reliably participate in the study
* Subject has presence of a skin condition, excessive hair at the application site, sunburn, raised moles and scars, open sores at application site, scar tissue, tattoo, coloration, or any other local condition that would interfere with placement of patches, microneedles, study drug, skin assessment, or reactions to drug
* Medical history of significant dermatologic diseases or conditions, such as atopy, psoriasis, vitiligo or conditions known to alter skin appearance or physiologic response (e.g. diabetes, porphyria).
* Any current malignancy or history of malignancy at the treatment site
* Prior history of keloids or excessive scarring
* Prior history of skin pigmentation changes or significant dermal reaction to a topically applied drug product
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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University of Iowa

OTHER

Sponsor Role lead

Responsible Party

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Nicole K Brogden

Associate Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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University of Iowa

Iowa City, Iowa, United States

Site Status

Countries

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United States

Other Identifiers

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202211064

Identifier Type: -

Identifier Source: org_study_id

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