Pharmaco-Scintigraphic Study to Evaluate the Release Profile of Metronidazole Benzoate Capsules

Study Overview
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Brief Summary
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This is a Phase I, open label, single-site trial to evaluate the in vivo release characteristics in the gastrointestinal tract of metronidazole benzoate capsules designed to disintegrate in the large intestine. This will be examined by means of metronidazole plasma levels and scintigraphic images in healthy subjects. Overall, nine subjects will be evaluated for each formulation prototype. Two formulation prototypes will be investigated. Each subject will receive one radio-labelled capsule only.

Official Title
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An Open Label, Single-site Pharmaco-Scintigraphic Phase I - Study in Healthy Subjects to Evaluate the Gastrointestinal Transit and Release Profile of Radio-labelled Metronidazole Benzoate Capsules

Conditions
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Healthy

Intervention / Treatment
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* Drug: Metronidazole Benzoate gastro-resistant capsule with radio-labelled mucoadhesive formulation
* Drug: Metronidazole Benzoate gastro-resistant capsule with radio-labelled non-mucoadhesive formulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy subjects, male or non-pregnant, non-lactating females, between 18 and 55 years old. Females of child bearing potential must have a negative urine pregnancy test prior to the intake of study drug, and must use a hormonal (oral, implantable or injectable) or a double barrier method of birth control throughout the study. Females unable to bear children must have documentation of such in the source records (i.e., tubal ligation, hysterectomy, or post-menopausal with as a minimum of one year since the last menstrual period). Ability of subject to participate fully in all aspects of this clinical trial. Voluntary signed informed consent must be obtained and documented. Accept not to use any kind of tobacco, including cigarettes nor E-Cigarettes or pipe smoking, nicotine replacements nor oral tobacco and not to consume any alcohol or drugs during screening, treatment and following two days. Exclusion Criteria: Participating in a clinical study involving investigational drugs or dosage forms within the previous 30 days. Radiation exposure from clinical trials, including that from the present study and from diagnostic X-ray but excluding background radiation, exceeds 5 mSv in the last five years. No subject whose occupational exposure is monitored will participate in the study. Any nuclear medicine procedure prior to study day 1 that might interfere with the scintigraphic images that are acquired. Clinically significant deviation of biochemistry or haematology parameters from the normal range History of gastrointestinal surgery, with the exception of appendectomy unless it was performed within the previous 12 months. Clinically relevant cardiovascular, renal, hepatic, metabolic, autoimmune, pulmonary and particularly gastrointestinal diseases, especially peptic ulceration, gastrointestinal bleeding, ulcerative colitis, Crohn's disease or Irritable Bowel Syndrome (within the previous 12 months). Acute diarrhoea or constipation in the 14 days before the predicted first study day. If screening occurs >14 days before first study day, this criterion is to be determined on the first study day. Diarrhoea will be defined as the passage of liquid faeces and/or a stool frequency of greater than three times per day. Constipation will be defined as a failure to defecate more frequently than every three days. History of adverse reaction or allergy to metronidazole or any study drug or formulation components/ingredients. Hypersensitivity to imidazole derivatives History of any malignancy removed or adequately treated. History of alcohol or drug abuse. Donation of blood (or plasma) within the previous three months and donation of Plasma the last 14 days. Over-the-counter (OTC) and prescription medication (including laxatives, vitamins and natural herbal remedies including St. John's Wort) between screening visit (visit 1) and completion of the study. Occasional paracetamol or acetyl-salicylic acid is permitted. Ingestion of grapefruit juice, coffee, caffeine containing beverages on treatment day. Failure to satisfy the Investigator to participate for any other reason. Known allergy to crustaceans (due to Chitosan)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mucoadhesive formulation<br>A single dose of 100 mg Metronidazole Benzoate gastro-resistant capsule with radio-labelled mucoadhesive formulation is administered to subject in fasted state | Drug: Metronidazole Benzoate gastro-resistant capsule with radio-labelled mucoadhesive formulation<br> <br> |
| Active Comparator: Non-mucoadhesive formulation<br>A single dose of 100 mg Metronidazole Benzoate gastro-resistant capsule with radio-labelled non-mucoadhesive formulation is administered to subject in fasted state | Drug: Metronidazole Benzoate gastro-resistant capsule with radio-labelled non-mucoadhesive formulation<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Scintigraphic analysis of time of capsule disintegration |  | 3 days | 
| Scintigraphic analysis of location of capsule disintegration |  | 3 days | 
| Transit time of the released granules after capsule disintegration |  | 3 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximal plasma concentration (Cmax) |  | 3 days | 
| Time to reach Cmax (Tmax) |  | 3 days | 
| Area under the concentration-time curve |  | 3 days | 
| Elimination rate constant (k) |  | 3 days | 
| Apparent terminal half-live (t½) |  | 3 days | 
| Lag time (t-lag) |  | 3 days | 
| Time of first measurable concentration after dosing |  | 3 days |