Effects of the probiotic Saccharomyces boulardii CNCM I-745 and the antibiotic Amoxicillin on the gut microbiota of healthy volunteers

INTERVENTION: Trade Name: Ultra‐Levure® Product Name: Ultra‐Levure® Pharmaceutical Form: Capsule INN or Proposed INN: Saccharomyces boulardii Current Sponsor code: CNCM I‐745 Other descriptive name: SACCHAROMYCES BOULARDII Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 200‐ Trade Name: Clamoxyl® Product Name: Clamoxyl Pharmaceutical Form: Tablet INN or Proposed INN: Amoxycillin CAS Number: 26787‐78‐0 Current Sponsor code: Amoxycillin Other descriptive name: AMOXYCILLIN TRIHYDRATE ‐ EP Concentration unit: g gram(s) Concentration type: equal Concentration number: 1‐ CONDITION: Healthy volunteers ; MedDRA version: 19.1 Level: SOC Classification code 10017947 Term: Gastrointestinal disorders System Organ Class: 10017947 ‐ Gastrointestinal disorders Therapeutic area: Body processes [G] ‐ Digestive System and Oral Physiological Phenomena [G10] PRIMARY OUTCOME: Main Objective: The overall goals of this study are to characterize the changes in the human microbiota that result from the ingestion of the antibiotic Amoxicillin and to evaluate the ability of S. boulardii CNCM I‐745 to prevent, diminish or shorten these changes. ; ; The primary objective is to assess the preventive effects of S. boulardii CNCM I‐745 on the gut microbiota changes induced by Amoxicillin in the healthy volunteers.; Primary end point(s): The primary endpoint will be the change in the gut microbiota, using species richness, species diversity, PCA, and individual Operational Taxonomic Units (OTUs) frequencies.; Thus, communities will be described using species richness, species diversity, Principal Coordinate Analysis (PCA), and individual OTU frequencies. ANOVA and discriminant analyses will differentiate the microbiota according to the presence or absence of treatments. The frequencies of OTUs in this analysis will serve to indicate the resilience of microbial communities to antibiotic treatment, and the ability of probiotics to preserve or restore OTU frequencies to approximate those of the normal gut microbiota. Secondary Objective: The secondary objective is to describe the clinical characteristics of the subjects. Timepoint(s) of evaluation of this end point: (‐21 to ‐7 days), Day 0, Day3, Day 7, Day 10, Day 14, Day 21 SECONDARY OUTCOME: Secondary end point(s): The following population characteristics: physical examination, ECG, vital signs, safety blood and urinary laboratory tests, serology, alcohol breath test, drug screen Timepoint(s) of evaluation of this end point: The population characteristics will be described for all of the parameters collected at the screening ; The comparability of the treatment groups at baseline will be evaluated. INCLUSION CRITERIA: Subjects enrolled in the study will have to fulfill the following criteria: 1) Healthy volunteers aging from 18 to 65 years (male or female) 2) Physically and mentally healthy subjects as confirmed by an interview, medical history, clinical examination, laboratory tests and electrocardiogram (ECG) 3) With a body mass index (BMI) comprised between 18.5 and 30.0 kg/m2 and weight >50 kg at Screening 4) Able to comply with study requirements and to provide signed informed consent 5) No clinically relevant abnormalities in results of laboratory tests as per Investigator’s judgement 6) For women of childbearing potential o A negative urine pregnancy test immediately prior to starting the study treatment o Agreement to comply with approved methods of contraception during the whole study): unless they meet the criteria of post‐menopausal, i.e. 12 months of spontaneous amenorrhea, women of child‐bearing potential, defined as all women physiolo