Pharmacokinetics of Transdermal Metronidazole

NCT05929794 | Active Not Recruiting Phase 4 FDA Drug

• 1 other identifier: 202211064
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Healthy

Keywords

Microneedle; Micropatch; Transdermal; Metronidazole

Outcome Measures

Primary Outcomes (3)

• Measurement of maximum serum metronidazole concentration (Cmax)

  Cmax is the highest metronidazole concentration measured in the serum.

  0.5, 1, 1.5, 2, 4, 6, 8, 24, 48, 72, 96, 98, 100, 104, and 120 hours

• Time of maximum serum metronidazole concentration (Tmax)

  Tmax is the time point at which the maximum drug concentration in serum is measured.

  0.5, 1, 1.5, 2, 4, 6, 8, 24, 48, 72, 96, 98, 100, 104, and 120 hours

• Area under the serum-concentration curve from 0-120 hours

  Area under the serum-concentration-time curve is a mathematical measure of total systemic exposure to metronidazole in the body.

  0.5, 1, 1.5, 2, 4, 6, 8, 24, 48, 72, 96, 98, 100, 104, and 120 hours

Secondary Outcomes (3)

• Skin color

  Baseline (Day 1)

• Change in transepidermal water loss after micropatch application

  Baseline (Day 1) and post-micropatch application (Day 1)

• Change in electrical resistance after micropatch application

  Baseline (Day 1) and post-micropatch application (Day 1)

Study Arms (4)

Micropatch application + metronidazole 0.75% topical gel

ACTIVE COMPARATOR

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

Drug: Metronidazole 0.75% Topical Gel; Diagnostic Test: Transdermal water loss measurement; Diagnostic Test: Electrical Resistance; Diagnostic Test: Skin color measurement; Other: Micropatch application

Metronidazole 0.75% topical gel

ACTIVE COMPARATOR

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

Drug: Metronidazole 0.75% Topical Gel; Diagnostic Test: Transdermal water loss measurement; Diagnostic Test: Electrical Resistance; Diagnostic Test: Skin color measurement

Micropatch application + metronidazole 0.75% topical cream

ACTIVE COMPARATOR

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

Drug: Metronidazole 0.75% Topical Cream; Diagnostic Test: Transdermal water loss measurement; Diagnostic Test: Electrical Resistance; Diagnostic Test: Skin color measurement; Other: Micropatch application

Metronidazole 0.75% topical cream

ACTIVE COMPARATOR

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

Drug: Metronidazole 0.75% Topical Cream; Diagnostic Test: Transdermal water loss measurement; Diagnostic Test: Electrical Resistance; Diagnostic Test: Skin color measurement

Interventions

Metronidazole 0.75% Topical Gel 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.

Metronidazole 0.75% topical gel; Micropatch application + metronidazole 0.75% topical gel

Metronidazole 0.75% Topical Cream 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.

Metronidazole 0.75% topical cream; Micropatch application + metronidazole 0.75% topical cream

Transdermal water loss measurement 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).

Metronidazole 0.75% topical cream; Metronidazole 0.75% topical gel; Micropatch application + metronidazole 0.75% topical cream; Micropatch application + metronidazole 0.75% topical gel

Electrical Resistance 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.

Metronidazole 0.75% topical cream; Metronidazole 0.75% topical gel; Micropatch application + metronidazole 0.75% topical cream; Micropatch application + metronidazole 0.75% topical gel

Skin color measurement DIAGNOSTIC_TEST

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

Metronidazole 0.75% topical cream; Metronidazole 0.75% topical gel; Micropatch application + metronidazole 0.75% topical cream; Micropatch application + metronidazole 0.75% topical gel

Micropatch application 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.

Micropatch application + metronidazole 0.75% topical cream; Micropatch application + metronidazole 0.75% topical gel

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Iowa: lead

Study Sites (1)

University of Iowa

Iowa City, Iowa, 52242, United States

Location

MeSH Terms

Interventions

Metronidazole; Gels; Electric Impedance

Intervention Hierarchy (Ancestors)

Nitroimidazoles; Nitro Compounds; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Colloids; Complex Mixtures; Dosage Forms; Pharmaceutical Preparations; Electric Conductivity; Electricity; Electromagnetic Phenomena; Magnetic Phenomena; Physical Phenomena

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: 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.

Study Record Dates

• First Submitted: June 22, 2023
• First Posted: July 3, 2023
• Study Start: February 26, 2024
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: March 9, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)