Study of the Safety and Tolerability of the Broad-spectrum Probiotic Medicine "AS-Probionorm"
Condition: Intestinal Infections; Dysbacteriosis
MeSH terms: Infections; Dysbiosis
Study type: Interventional
Phase: Phase 1

Summary: 
      The subject of this clinical trial is the medicine "AS-Probionorm". Pharmacological group -
      Antidiarrheal drugs. Antidiarrheal microorganisms. Microorganisms that produce lactic acid.

      The investigational probiotic medicine "AS-Probionorm" was created on the basis of an
      association of lactic acid bacteria with targeted action for oral use for the treatment of
      inflammatory and infectious diseases of the human gastrointestinal tract.

      The first phase of a clinical trial is the first test of a medicine conducted on healthy
      volunteers to establish tolerability and safety.

      According to the goal and objectives of the phase I clinical trial, the main parameter is to
      study the safety and tolerability of the medicine throughout the entire study period.

      Phase I of the clinical trial of the medicine included 20 healthy subjects of both sexes aged
      18-50 years. Clinical and laboratory parameters to characterize the safety of the medicine:
      medical history, physical examination, ECG, general and biochemical blood tests, urine and
      stool tests.

      Selection and Exclusion of Subjects: Prior to inclusion in a clinical trial, each trial
      subject must first sign an Informed Consent Form for Participation in the Study, followed by
      a screening examination of each subject, including a variety of procedures, medical history,
      and physical examination. Each subject participating in the survey will be assigned an
      identification number.

      Study design: open-label, single-center, phase I of clinical trial. Dosage regimen - 1 sachet
      (1 g) 2 times a day with an interval of 12 hours. The total duration of study subjects'
      participation in the study is 21 days. Tolerability of the study drug: Tolerability of the
      drug will be assessed based on subjective symptoms and sensations reported by patients and
      objective data obtained by the investigator during the study. The frequency of occurrence and
      nature of adverse reactions are also taken into account.

      The degree of tolerability of the study drug will be determined in three gradations:
      intolerance, absence of undesirable drug reactions (side reactions), undesirable drug
      reactions (side effects) not classified as serious.

      Ethical and Legal Issues in Clinical Research: This clinical trial will be conducted in
      accordance with the principles set forth by the 18th World Medical Assembly (Helsinki, 1964)
      and the ICH guidelines for good clinical practice (GCP), and in accordance with all
      international and national laws and regulations.
    

Detailed description: 
      Dosage form of the medicine "AS-Probionorm" (powder for the preparation of solution for oral
      administration) - 1 g in a sachet.

      Pharmacological group - Antidiarrheal drugs. Antidiarrheal microorganisms. Microorganisms
      that produce lactic acid.

      Introduction:

      Acute intestinal infections (AII) are one of the pressing health problems in all countries.
      The complexity of their treatment is associated with the massive irrational use of
      antibiotics and chemotherapeutic drugs, which has led to the development of multidrug
      resistance in pathogens. Therefore, the modern strategy for the treatment of acute intestinal
      infections gives priority to therapeutic measures aimed at correcting intestinal
      microbiocenosis to eliminate the source of infection localized in the intestine.

      The main idea is to conduct clinical studies of the domestic medicinal probiotic medicine
      "AS-Probionorm" based on the association of lactic acid bacteria of targeted action for oral
      use for the treatment of inflammatory and infectious diseases of the human gastrointestinal
      tract.

      During preclinical trials, it was established that the drug exhibits high antimicrobial
      activity, therapeutic and prophylactic effectiveness, as well as safety during use.

      The purpose of the study was to study the safety and tolerability of the study medicine
      "AS-Probionorm" in healthy study subjects.

      Phase I of the clinical trial of the drug included 20 healthy subjects of both sexes aged
      18-50 years. Clinical and laboratory parameters to characterize the safety of the drug:
      medical history, physical examination, ECG, general and biochemical blood tests, urine and
      stool tests.

      Study design: open-label, single-center, phase I clinical trial. Dosage regimen: 1 sachet (1
      g) 2 times a day with an interval of 12 hours. The study drug should be used 15-20 minutes
      before meals in the morning and evening. Before use, the medicine is mixed with 30-50 ml of
      boiled water at room temperature, resulting in a cream-colored suspension. The resulting
      water suspension should be drunk. The duration of taking is 7 days.

      The study will be carried out on an outpatient basis. The total duration of study subjects'
      participation in the study is 21 days. On days 1, 8, 15, 21, a medical examination and
      laboratory tests will be carried out.

      The duration of the study course of 21 days is determined by studying the possibility of
      developing local toxic and allergic reactions at the dosages recommended to identify the
      therapeutic effect.

      Tolerability of the drug will be assessed based on subjective symptoms and sensations
      reported by patients and objective data obtained by the investigator during the study. The
      frequency of occurrence and nature of adverse reactions are also taken into account. The
      degree of tolerability of the study drug will be determined by three gradations: intolerance,
      absence of undesirable drug reactions (side reactions), undesirable drug reactions (side
      effects) not classified as serious.

      Statistical analysis of data is carried out based on the results of collecting anamnestic,
      clinical data, as well as data from laboratory and instrumental studies. The volume of
      consultations, examinations and concomitant treatment carried out before the study is also
      recorded. Data collection will be carried out using an approved form - Individual
      Registration Card.

      Ethical and legal issues in clinical research Ethical principles: The clinical trial will be
      conducted in accordance with the principles formulated by the 18th World Medical Assembly
      (Helsinki, 1964) and the ICH guidelines for good clinical practice (GCP).

      Laws and Regulations: The clinical trial will be conducted in accordance with all
      international laws and guidelines, as well as national laws and regulations in accordance
      with any applicable guidelines.

      Data collection, maintenance and storage of records. Data collection will be carried out
      electronically and, partially, in paper form.

      The Investigator must maintain all research documentation (electronic and paper) in
      confidence and take steps to prevent accidental or premature destruction of this
      documentation.

      The Investigator must retain all study documentation for a minimum of fifteen (15) years
      after completion or premature termination of the clinical trial.

      However, if a longer period is required, applicable legal requirements must be taken into
      account.

      The investigator must notify the sponsor before destroying any important study documents
      following completion or premature termination of a clinical trial.

      Financing and insurance. All financing and insurance issues will be determined in the
      agreement concluded between the Sponsor and the Contractor.

      Publications. The Investigator agrees not to publish or report the study and/or its results
      without the prior written permission of the study sponsor, noting that the sponsor will not
      withhold such permission without reasonable cause. The researcher will not use the sponsor's
      name in any promotional material or publication without the sponsor's prior written consent.
      The sponsor will not use the name of the investigator and/or his/her collaborators in
      promotional materials or publications without first obtaining his/their written consent. The
      sponsor has the right to publish the study results at any time.
    

Intervention name(s): "AS-Probionorm"
Intervention type(s): Drug
Intervention description(s): Dosage form - powder for the preparation of a solution for oral administration. Dosage regimen -1 sachet (1 g) take 2 times a day with an interval of 12 hours. Apply 15-20 minutes before meals in the morning and evening. Before use, the medicine is mixed with 30-50 ml of boiled water at room temperature, resulting in a cream-colored suspension. The resulting aqueous suspension should be drunk without achieving complete dissolution. The diluted drug cannot be stored. The duration of taking the medicine is 7 days. The study is carried out on an outpatient basis.
The total duration of each subject's participation in the clinical trial is no more than 21 ± 1 days. Throughout the entire study period, the research subject has the opportunity to contact the research team on all questions relating to the nature of this study. After completion of the entire observation period of 21 days, there is no follow-up of study subjects under the trial protocol.
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Intervention model description: Objectives of the study: Determine the safety and tolerability of the study medicine "AS-Probionorm" (powder 1 g in a sachet) in healthy study subjects.
The study included the following stages:
Stage 1 of the study (introductory stage) included recruitment and screening of healthy volunteers - study participants, signing of informed consent, medical examination and laboratory tests.
Stage 2 of the study (baseline control stage) included clinical measurements before the start of the study (baseline measurements) on each subject to obtain baseline data, which were then compared with the results after the end of the study.
Stage 3 of the study (the stage of dynamic observation of the treatment effect and safety monitoring after the study) included clinical observations in each subject daily during the use of the study medicine and a week after the last use (21 days in total).
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: probiotic; intestinal infections; dysbiosis; lactic acid bacteria; phase 1 of clinical trial