Transdermal Metronidazole Absorption in Healthy Volunteers

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Iowa

Must not be taking: Statins, Beta-blockers, Steroids, others

Disqualifiers: Pregnancy, Smoking, Diabetes, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine how metronidazole, a medication for skin conditions, absorbs through the skin when applied as a cream or gel. Researchers use a special micropatch to assess whether it enhances medication delivery. The trial compares four methods: cream with micropatch, cream without, gel with micropatch, and gel without. Healthy individuals without a history of adverse reactions to skin treatments may qualify for this study. As a Phase 4 trial, this research seeks to understand how the already FDA-approved and effective treatment benefits more patients.

Will I have to stop taking my current medications?

Yes, you may need to stop taking certain medications. The trial excludes participants who are currently using medications like statins, beta-blockers, steroids, antibiotics, antihistamines, and NSAIDs. If you've recently used these, you can join if enough time has passed since your last dose.

What is the safety track record for these treatments?

Research has shown that metronidazole, in both cream and gel forms, is generally safe for topical use. Studies have found that these forms do not absorb into the body through the skin, reducing the risk of systemic side effects. Common side effects include mild skin irritation, such as redness or dryness, and occasionally a metallic taste in the mouth. These effects are typically short-lived.

For the cream and gel used with a micropatch, similar minor side effects have been observed. Some cases of allergic reactions and skin rashes have occurred with topical use, but these are uncommon.

Overall, both the cream and gel forms of metronidazole are considered safe for most people when used as directed. These findings can reassure prospective trial participants about the safety of the treatments being tested. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Unlike the typical treatments for skin conditions like rosacea, which usually involve oral antibiotics or standard topical applications, these investigational treatments use a unique transdermal delivery method with a micropatch. This method could potentially enhance the absorption of metronidazole, a common antibiotic, making it more effective. Researchers are excited because this could lead to faster, more efficient treatment with potentially fewer side effects, as the medication is delivered directly to the affected area, minimizing systemic exposure.

What evidence suggests that this trial's treatments could be effective for transdermal metronidazole absorption?

Research has shown that metronidazole 0.75% cream and gel effectively treat skin conditions like rosacea. One study found that 77% of patients using metronidazole gel remained symptom-free for six months, compared to 58% using a placebo. Both the cream and gel versions penetrate the skin better than other forms, enhancing the delivery of the active ingredient. In this trial, some participants will receive metronidazole 0.75% cream or gel with a micropatch application, which may further improve absorption, while others will receive the cream or gel without the micropatch. Overall, metronidazole 0.75% in both forms has proven effective for skin issues. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

Healthy adults over 18, of any ethnic background, who are not pregnant or lactating and do not smoke or use nicotine products. Participants must have no significant skin conditions, allergies to antibiotics, or history of adverse reactions to metronidazole. They should not be on certain medications like steroids or beta-blockers and must agree to avoid other clinical studies during the trial.

Inclusion Criteria

Provide written informed consent before initiation of any study procedures

Available for follow-up for the planned duration of the study

Subjects deemed to be healthy, as determined by the study physician, based on medical history, current medical conditions, and medication history

Exclusion Criteria

History of anaphylaxis to an antibiotic, antimicrobial, antifungal, antipartisitic, or antiviral drug

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

I have or had cancer at the site where I am seeking treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment Period 1

Participants receive metronidazole product applied to micropatch-treated skin, with daily blood samples collected for up to 5 days

5 days

Daily visits for blood sampling

Washout

One-week washout period between treatment periods

1 week

Treatment Period 2

Participants receive metronidazole product applied to skin without micropatch pretreatment, with daily blood samples collected for up to 5 days

5 days

Daily visits for blood sampling

Follow-up

Participants are monitored for safety and effectiveness after treatment

1-2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Metronidazole 0.75% Topical Cream
• Metronidazole 0.75% Topical Gel
• Micropatch application

Trial Overview

The study is testing how well a gel and cream form of Metronidazole (an antibiotic) pass through the skin after micropatch treatment. It's a crossover study where participants will try both forms in different periods to compare their effectiveness.

How Is the Trial Designed?

Group I: Micropatch application + metronidazole 0.75% topical cream Active Control 5 Interventions

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

Group II: Metronidazole 0.75% topical gel Active Control 4 Interventions

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

Group III: Micropatch application + metronidazole 0.75% topical gel Active Control 5 Interventions

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

Group IV: Metronidazole 0.75% topical cream Active Control 4 Interventions

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

Who Is Running the Clinical Trial?

University of Iowa

Lead Sponsor

Trials

486

Recruited

934,000+

Published Research Related to This Trial

The new 1.0% metronidazole gel formulation for treating rosacea is effective in reducing inflammatory lesions and erythema, and it is designed to be more user-friendly and cosmetically appealing than the previous 0.75% gel.

Safety evaluations showed that the 1% gel has low irritation potential, minimal risk of sensitization, and no evidence of phototoxic or photoallergic reactions, making it a safe option for patients with rosacea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A look at the safety of metronidazole 1% gel: cumulative irritation, contact sensitization, phototoxicity, and photoallergy potential. Beutner, KR., Lemke, S., Calvarese, B.[2013]

Citations

1.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/11702300/

Topical metronidazole. A review of its use in rosacea

Metronidazole 0.75% gel seems to be effective in maintaining remission of rosacea symptoms in patients successfully treated with both oral tetracycline and ...

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withpower.com

withpower.com/trial/phase-4-healthy-subjects-hs-9-2023-27089

Transdermal Metronidazole Absorption in Healthy Volunteers

Research shows that Metronidazole 0.75% cream and gel penetrate the skin more effectively than other formulations, suggesting that the way the drug is ...

3.

complexgenerics.org

complexgenerics.org/wp-content/uploads/crcg/post-Senemar20190812-GRC.pdf

Evaluating the Bioequivalence of Topical Dermatological ...

➢ Creams (Reference: MetroCream® topical cream, 0.75% from Galderma Laboratories. “brand cream” and Test: metronidazole topical cream, 0.75% from Fougera.

4.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11156253/

Impact of formulation and microneedle length on ...

This study aimed to determine the impact of formulation (gel vs cream) and microneedle characteristics (length, number) on permeation of metronidazole through ...

5.

hmpgloballearningnetwork.com

hmpgloballearningnetwork.com/site/thederm/article/4857

A Closer Look at Topical Metronidazole 1% Gel

Metronidazole 1% gel (HSA-3) does not increase transepidermal water loss in patients with rosacea, indicating no impairment of epidermal barrier function, and ...

6.

medline.com

medline.com/media/catalog/Docs/MSDS/MSD_SDSD11784.pdf

MATERIAL SAFETY DATA SHEET

SKIN ABSORPTION: The components of this product are not known to be absorbed through the skin. Page 4. METRONIDAZOLE TOPICAL GEL 0.75% MSDS.

7.

medcentral.com

medcentral.com/drugs/monograph/75148-389011/metronidazole-topical

Metronidazole (topical): uses, dosing, warnings, adverse ...

To minimize the risk of local irritation, some clinicians suggest that application of the drug be delayed for about 15-20 minutes after cleansing the skin.

8.

accessdata.fda.gov

accessdata.fda.gov/drugsatfda_docs/label/2010/021789s003lbl.pdf

METROGEL (metronidazole) Gel, 1% - accessdata.fda.gov

The following additional adverse experiences have been reported with the topical use of metronidazole: skin irritation, transient redness, metallic taste ...

9.

pdf.hres.ca

pdf.hres.ca/dpd_pm/00023369.PDF

METROGEL 0.75% and 1%, METROCREAM, METROLOTION

The results of the safety analyses indicate topical application of metronidazole is well tolerated.

10.

healio.com

healio.com/clinical-guidance/drugs/metrocream

Metrocream: Uses, Side Effects & Dosage

Find clinical guidance on Metrocream, including indications, dosing, safety, side effects and evidence-based insights for healthcare professionals.