Study Title

A prospective, randomized, double blind, placebo-controlled, parallel-group, comparative three arm study to evaluate the efficacy and safety of two probiotic formulations in subjects with functional intestinal gas symptoms.

Study Rationale

The study is designed to study two formulations of probiotics on gastro intestinal gas symptoms.

Investigational Product

1)      Formulation of Bacillus coagulans manufactured by Sanzyme  Biologics

Arm 1: SNZ-1969 [Each capsule contains NLT 2 Billion CFU of Bacillus coagulans].

2)      Formulation of a probiotic

Arm 2: SNZ-TRIBAC [Each capsule contains NLT 2 Billion CFU of Bacillus coagulans (SNZ-1969), Bacillus clausii (SNZ-1971), Bacillus subtilis (SNZ-1972)].

3)      Placebo

Arm 3: Placebo capsule of Calcium carbonate.

One capsule of investigational probiotic formulations or placebo will be self-administered by the subject once daily (OD) after a major meal at roughly the same time of the day for a period of 30 days.

Study Objective(s)

Primary Objective

Efficacy- To compare the efficacy of two probiotic formulations with placebo as therapy in subject with complaints of abdominal distress symptoms, in the absence of specific pathologies.

Secondary Objective

Safety-The secondary objective of the study is to identify and evaluate adverse events occurring during the use of the formulations, and compare the same with the use of placebo.

Approximate Duration of Study

The entire study duration will be approximately 12 months. This includes the enrollment period.

Sample size

It was determined that 25 analyzable subjects per treatment arm would provide 80% power to obtain a significant result for a 0.8- sigma effect size. A 15% drop out rate was considered possible based on experience at the chosen sites and hence a total of 30 subjects were recruited in each group. An alpha level of 0.05 was assumed (p ≤ 0.05 considered significant).

Study Design

The subject will be given a detailed description of the nature and purpose of the study. Only that subjects who are willing to participate in the study and have signed the Informed consent would be considered for the trial.

At screening visit/visit 1 (-7 days), Informed consent will be obtained from the subject. Thereafter, the subject will be evaluated for demographics, medical history, prior medication, physical examination, vital signs, height, body weight, haemogram, liver function tests (ALT, AST and total bilirubin), renal function tests (BUN, Sr. Creatinine) GSRS, SODA Scale, VAS Scale and QoL questionnaire (QoLSF-36 v2). Eligible subject will be requested to visit site on visit 2.

On visit 2/ randomization visit (Day 0±2 Days), subject will be randomized on the basis of their OPD (or PRN) using a fixed randomization table. IP will be dispensed to the subject. One capsule of investigational probiotic formulations or placebo will be self-administered by the subject  once daily after a major meal at roughly the same time of the day for a period of 30 days

On visit 3 (Day 15±2 Days), subject will visit site and evaluated for GSRS, SODA Scale, VAS scale and QoL questionnaire.

On visit 4 (Day 30±2 Days), subject will visit site and evaluated for GSRS, SODA Scale, VAS scale and QoL questionnaire

Follow up visit/visit 5/ EOS (Day 37±2 Days) subject will visit site and evaluated for haemogram, liver function tests (ALT, AST and total bilirubin), renal function tests (BUN, Sr  Creatinine) GSRS, SODA Scale, VAS scale and QoL questionnaire.

Statistical/Data Analysis

Statistical analyses will be performed using statistical software (SPSS/SAS). The change in severity of assessment will be compared intragroup using a paired student t-test and intergroup using ANOVA.

Ethical Issues

The study will commence only after a written approval is obtained from ethics committee. Informed consent will be signed by patients with abdominal distress. The trial will be conducted as per the [Schedule Y of CDSCO (Central Drug Standards Control Organization), Ministry of Health and Family Welfare, Government of India], [Ethical guidelines for biomedical research on human participant, ICMR (Indian Council of Medical Research (2017)],

[ICH (International Conference on Harmonization) E6 (R2) “Guideline for Good Clinical Practice”], Declaration of Helsinki (Ethical principles for Medical Research involving Human subjects, revised by WMA General Assembly, Fortaleza, Brazil October 2013) and JCDC’s standard operating procedures.