Clinical trial NCT05929794: Pharmacokinetics of Transdermal Metronidazole
Official title: Impact of Formulation on the Pharmacokinetics of Micropatch-assisted Delivery of Metronidazole
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE4
Conditions: Healthy
Keywords: Microneedle
Micropatch
Transdermal
Metronidazole
Lead sponsor: University of Iowa
Sponsor class: OTHER
First posted: 2023-07-03
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: 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 purpose: BASIC_SCIENCE

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.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Measurement of maximum serum metronidazole concentration (Cmax)
timeFrame: 0.5, 1, 1.5, 2, 4, 6, 8, 24, 48, 72, 96, 98, 100, 104, and 120 hours
measure: Time of maximum serum metronidazole concentration (Tmax)
timeFrame: 0.5, 1, 1.5, 2, 4, 6, 8, 24, 48, 72, 96, 98, 100, 104, and 120 hours
measure: Area under the serum-concentration curve from 0-120 hours
timeFrame: 0.5, 1, 1.5, 2, 4, 6, 8, 24, 48, 72, 96, 98, 100, 104, and 120 hours
Secondary outcomes:
measure: Skin color
timeFrame: Baseline (Day 1)
measure: Change in transepidermal water loss after micropatch application
timeFrame: Baseline (Day 1) and post-micropatch application (Day 1)
measure: Change in electrical resistance after micropatch application
timeFrame: Baseline (Day 1) and post-micropatch application (Day 1)
Other outcomes:
Locations:
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
Study officials:
References: