Evaluation of Dermal Pharmacokinetics of Metronidazole Cream in Healthy Subjects Using Open Flow Microperfusion
- Trial ID
- 2024-515780-62-00
- Protocol
- FDA03A1
- Sponsor
- Medical University Of Graz
Trial statistics
Objectives
The primary objective of this clinical trial is to assess the impact of different removal times on **dermal pharmacokinetics (PK)**. This study is significant as it aims to understand how the timing of topical product removal affects the absorption and distribution of the active substance, **metronidazole**, in the skin. Such insights are crucial for optimizing the therapeutic efficacy and safety of topical formulations. No secondary objectives are specified for this trial.
Participants
The clinical trial involves a study population comprising **healthy subjects** aged 18 to 65 years, inclusive, with a **Body Mass Index (BMI)** ranging from 18 to 30 kg/m². Both male and female participants are included, provided that females are non-pregnant, non-breastfeeding, and adhere to adequate contraceptive methods or abstain from sexual activity. Participants are required to be non-smokers and free from existing medical conditions or medications, except as specified in the exclusion criteria. The trial does not focus on any specific medical condition, and the sponsor has not provided the total number of participants. The selection criteria emphasize the inclusion of individuals capable of providing informed consent and complying with the study's requirements and restrictions. The trial does not involve a vulnerable population, and no specific lifestyle considerations such as diet or physical activity are highlighted.
Plans and Procedures
The clinical trial is designed as a **single-center, open-label pilot study** aimed at evaluating the impact of different removal times on dermal pharmacokinetics (PK) using **metronidazole** cream. The study will involve healthy subjects, aged 18 to 65, who meet specific inclusion criteria, such as a body mass index (BMI) within the range of 18-30 kg/m² and the ability to provide informed consent. The trial will not investigate any specific medical condition, as it primarily focuses on bioanalytical matrix validation and the exploration of dermal kinetics following topical product removal.
The trial will commence with a screening visit to assess eligibility based on the inclusion criteria. Participants will be required to attend multiple study visits, including follow-up visits, where dermal open flow microperfusion will be utilized to collect body fluids for analysis. The primary endpoints include the dermal PK profile and parameters such as area under the curve (AUC), maximum concentration (Cmax), and time to reach maximum concentration (tmax) for defined removal times, as well as the serum PK profile. The study is expected to conclude with an end-of-study visit, where final assessments will be conducted.
The overall duration of the trial is estimated to extend until June 30, 2025, with recruitment anticipated to start on December 23, 2024. Participant involvement is expected to last for a maximum treatment period of one day, with a maximum daily dose of 2.4 grams of metronidazole cream applied topically. Conditions that may lead to early termination from the study include non-compliance with the protocol or withdrawal of consent by the participant. The trial is categorized as an exploratory pilot study and is not considered a low-intervention trial.
Treatment
The clinical trial involves the use of **METRONIDAZOLE**, a topical cream formulation, as the experimental medication. **Metronidazole** is classified therapeutically as an antiprotozoal and anti-bacterial agent. The active substance is of chemical origin. The cream is applied topically, with a maximum daily dose of 2.4 grams. The treatment period is limited to a maximum of one day. The study aims to assess the impact of different removal times on dermal pharmacokinetics (PK). Participant compliance with the dosing schedule is monitored to ensure adherence to the protocol.
No non-experimental treatments, such as standard-of-care therapy, placebo, or comparator treatments, are utilized in this study. The focus is solely on the effects of the **METRONIDAZOLE** cream and its removal on dermal kinetics. The study is conducted in a single-center, open-label format, allowing for the collection of body fluids for bioanalytical matrix validation. The trial does not involve any pediatric formulations or orphan drug designations.
Efficacy
Efficacy in this clinical trial will be assessed by evaluating the **dermal pharmacokinetic (PK) profile** and parameters of the investigational product, Metronidazole cream, when applied topically. The primary endpoints include the measurement of drug concentration over time in the dermal layer and serum, as well as specific PK parameters such as area under the curve (AUC), maximum concentration (Cmax), and time to reach maximum concentration (tmax) for defined removal times. These assessments will be conducted to determine the impact of different removal times on dermal PK. The study will utilize dermal open flow microperfusion to collect body fluids for bioanalytical matrix validation. The trial is designed as a single-center, open-label pilot study involving healthy subjects. The data collection will be scheduled at various timepoints to capture the necessary PK profiles and parameters, ensuring a comprehensive analysis of the efficacy of the topical application of Metronidazole.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Subject must be 18 to 65 years of age inclusive, at the time of signing the informed consent.
- “Healthy Subjects” according to definition in the FDA draft guidance on BE studies with PK endpoints (Aug. 2021)), i.e. subjects who are non-smoking adults 18 years of age or older without existing medical conditions or required medications other then allowed as per Exclusion Criterium (EC) no. 5. The criteria for “healthy subjects” in the FDA guidance are closely followed due to the fact that study Part A aims to obtain matrices characteristic of the matrices of future BE study populations.
- BMI within the range 18-30 kg/m2 (inclusive)
- Males or non-pregnant, non-breast-feeding females using adequate contraceptive methods or abstinence
- Capable of giving signed informed consent as described in Appendix 1 which includes compliance with the requirements and restrictions listed in this protocol
Exclusion Criteria
- Known or suspected hypersensitivity to the study interventions or related products, including but not limited to nitroimidazoles or benzyl alcohol.
- Positive urine drug screen.
- Clinically significant abnormal laboratory evaluation results, as deemed by the investigator.
- Positive results to the test for hepatitis B antigen or hepatitis C antibodies.
- Positive human immunodeficiency virus (HIV) test.
- Any abnormalities found during physical examination or vital signs, unless deemed not clinically significant by the investigator.
- Current Smokers.
- History of drug and/or alcohol abuse within one year of start of study as judged by the investigator.
- Any reason, which in the opinion of the investigator, would prevent the subject from safely participating in the study.
- Tattoos or broken and/or damaged skin and/or scarring at the application sites.
- History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrinological, hematological, neurological or inherited blood disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study interventions; or interfering with the interpretation of data.
- Presence of any clinically relevant acute or chronic disease, which in the investigator´s opinion might jeopardize subject’s safety, evaluation of results or compliance with the protocol.
- Recent and/or recurrent history of autonomic dysfunction (e.g., recurrent episodes of fainting, palpitations, etc.), as judged by the investigator.
- Use of any medications other than hormonal contraceptive, hormone replacement therapy within 7 days (or 5 half-life periods, whichever is longer) before dosing of study interventions.
- Current enrollment or past participation in another investigational study in which an investigational intervention (e.g., drug, vaccine, invasive device) was administered within 30 days before signing of consent in this clinical study.
- Blood donation within 30 days or significant loss of blood or plasma (more than 550 mL) within 90 days before screening.
- Clinically significant abnormal 12-lead ECG at screening, as deemed by the investigator.
- Positive alcohol breath test.
- Subjects prone to keloid or hypertrophic scar formation or any known wound healing disorder.
- History of severe allergies to drugs or foods, as well as plaster allergy, or a history of severe anaphylactic reaction.
- Not willing to avoid excessive sun exposure, steam baths, sauna, swimming, and other strenuous activities for 14 days after Visit 2 to ensure good tissue regeneration
- Pronounced hairiness on the planned application sites that may negatively affect BE testing.
- Not willing to refrain from shaving the planned application sites or using skin care products on the planned application sites for at least 5 days before Visit 2.
- Presence of needle phobia.
- Increased risk of thrombosis e.g., personal or first-degree relative(s) history of deep vein thrombosis.
- Intervention Visit Exclusion Criteria: Presence of any medical condition that may confound the results of the study or pose an unacceptable risk to the subject, as judged by the investigator.
- Intervention Visit Exclusion Criteria: Consumption of alcohol within 24 hours before the study, or positive result of alcohol breath test.
- Intervention Visit Exclusion Criteria: Positive result of urine drug test.
- Intervention Visit Exclusion Criteria: Any use of metronidazole products within 7 days before the study.
- Intervention Visit Exclusion Criteria: Shaving and any use of cosmetic products within 5 days before the study on the thighs.
- Intervention Visit Exclusion Criteria: Positive pregnancy test.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Austria | Not Recruiting | 23 Dec 2024 | 10 |
Sites & Investigators
Research sites
Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
METRONIDAZOLE | Test | — | TOPICAL | 2.4 | 1 | SUB08922MIG |