Clinical trial NCT03271983: Pharmacokinetics of Metronidazole Dermal Products
Official title: Evaluation of the Bioavailability of Metronidazole Dermal Products
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Bioequivalence
Lead sponsor: University of Maryland, Baltimore
Sponsor class: OTHER
Collaborators: name: Food and Drug Administration (FDA)
First posted: 2017-09-05
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: Generate human PK data by collecting data following the application of metronidazole formulations.

Detailed description: This research study is intended to develop models for in vitro/in vivo correlation (IVIVC) of drug absorption from dermal products. This study will use metronidazole products that have already been approved by the Food and Drug Administration (FDA) and are already sold to customers in the United States; will not include any placebos.

Eligibility criteria: Inclusion Criteria:

1. Men or non-pregnant, women who are of any ethnic background between the age of 18 to 45 years old
2. Subjects must be non-smokers/tobacco users (must have refrained from the use of nicotine-containing substances, including tobacco products (e.g., cigarettes, cigars, chewing tobacco, snuff, gum, patches or electronic cigarettes) over the previous 2 months and are not currently using tobacco products
3. Provide written informed consent before initiation of any of the study procedures
4. Agree not to participate in another clinical trial/study during the study period or to participate in an investigational drug study for at least 1 month after the last study session
5. Able to adhere to the study protocol and study restrictions
6. Able to participate in all study sessions
7. Subjects have upper arms large enough to allow for placement of 200 cm2 \[31 in2\] area for applications of gel or cream. The arm distance from the greater tubercle to the olecranon process should be a minimum of 30 cm. The circumference of the upper arms should be a minimum of 30 cm.
8. Subjects deemed to be healthy as judged by the Medically Accountable Investigator (MAI) and determined by medical history, physical examination and medication history
9. Negative urine drug screening test (cannabinoids, amphetamines, barbiturates, benzodiazepine, cocaine, methadone, opiates, PCP)
10. Have normal screening laboratories for white blood cells (WBC), hemoglobin (Hgb), platelets, sodium, potassium, chloride, bicarbonate, blood urea nitrogen (BUN), creatinine, alanine transaminase (ALT) and aspartate aminotransferase (AST)
11. Have normal screening laboratories for urine protein and urine glucose
12. Female subjects must be of non-childbearing potential (as defined as surgically sterile \[i.e. history of hysterectomy or tubal ligation\] or postmenopausal for more than 1 year), or if of childbearing potential must be non-pregnant at the time of enrollment and on the morning of each study session, and must agree to use reliable hormonal or barrier birth control such as implants, injectables, combined oral contraceptives, some intrauterine devices (IUDs), sexual abstinence, or a vasectomized partner
13. Agrees not to donate blood to a blood bank throughout participation in the study and for at least 3 months after last study session
14. Have a normal ECG; must not have the following to be acceptable: pathologic Q wave abnormalities, significant ST-T wave changes, left ventricular hypertrophy, right bundle branch block, left bundle branch block. (sinus rhythm is between 55-100 beats per minute)
15. Have normal vital signs:

    * Temperature 35-37.9°C (95-100.3°F)
    * Systolic blood pressure 90-165 mmHg
    * Diastolic blood pressure 60-100 mmHg
    * Heart rate 55-100 beats per minute
    * Respiration rate 12-20 breaths per minute

Exclusion criteria:

1. Women who are pregnant, lactating, breast feeding or have a positive serum pregnancy test at enrollment or positive urine pregnancy test on the morning of the first day of any study session
2. Smokers/tobacco users (current use or use over the previous 2 months of nicotine-containing substances (e.g., cigarettes, cigars, chewing tobacco, gum, snuff, patch or electronic cigarettes)
3. Current participation in any ongoing investigational drug trial/study or clinical drug trial/study
4. History as either reported by the subject or evident to the investigator of infectious disease or skin infection or of chronic skin disease (e.g., psoriasis, atopic dermatitis)
5. History of diabetes
6. History of significant skin cancers (e.g., melanoma, squamous cell carcinoma) except basal cell carcinomas that were superficial and did not involve the investigative sites
7. Body Mass Index (BMI) ≥30 kg/m2
8. History of chronic obstructive pulmonary disease or cor pulmonale, or substantially decreased respiratory reserve, hypoxia, hypercapnia or pre-existing respiratory depression
9. Active positive Hepatitis B, C and/or HIV test results
10. Positive urine drug screening test
11. Use of chronic prescription medications during the period 0 to 30 days; or over-the-counter medications (e.g. antihistamines, topical corticosteroids) and short term (\<30 days) prescription medications during the period 0-3 days before a study session (vitamins, herbal supplements and birth control medications not included)
12. Currently taking daily anticoagulants (warfarin, heparin, rivaroxaban, dabigatran, etc...) within the past month prior to entry into the study
13. History of blood dyscrasia (abnormal in structure, function and quality)
14. History of Crohn's disease
15. Donation or loss of greater than one pint of blood within 60 days of entry to the study
16. Any prior adverse reaction or hypersensitivity to metronidazole, parabens, other inactive ingredients in the topical gel or cream formulations
17. Received an experimental agent (vaccine, drug, biologic, device, blood product or medication) within 1 month before enrollment in this study or expects to receive an experimental agent during the study
18. Consumption (food or drink) of alcohol within 48 h prior to dose administration
19. Any condition that would, in the opinion of the Medically Accountable Investigator (MAI), place the subject at an unacceptable risk of injury or render the subject unable to meet the requirements of the protocol
20. Subject has an obvious difference in skin color between arms or the presence of a skin condition, excessive hair at the application site (upper arms), sunburn, raised moles or scars, open sores at application site (upper arms), scar tissue, tattoo, or coloration that would interfere with placement of metronidazole products, skin assessment, or reactions to metronidazole

Primary outcomes:
measure: PK Parameters
timeFrame: 3 study sessions/subject; each session was 25 h; blood samples obtained at the following time points: -60 min, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 23, 24, 25 h; at least one week washout period between each study session
Secondary outcomes:
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: General Clinical Research Center (GCRC) at the University of Maryland Medical Center
state: Maryland
Study officials:
affiliation: University of Maryland, Baltimore School of Pharmacy
name: Audra L Stinchcomb, PhD
role: PRINCIPAL_INVESTIGATOR
References: