A Clinical Study to Evaluate the Safety and Tolerability of BioPB-01 in Healthy Adults

Study Overview
=================
Brief Summary
-----------------
The present study is a randomized, placebo-controlled, parallel-group, double-blind clinical study. Seventy-eight individuals will be screened, and considering a screening failure rate of 20%, approximately 64 participants will be randomized in a ratio of 1:1 to receive either BioPB-01 or Placebo

Official Title
-----------------
A Pilot Randomized, Double-blind, Placebo-controlled, Parallel-group Clinical Study to Evaluate the Safety and Tolerability of BioPB-01 in Healthy Adults

Conditions
-----------------
Metabolic Syndrome

Intervention / Treatment
-----------------
* Other: BioPB-01
* Other: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Participants who are 25 to 55 years of age (inclusive) at the time ofsigning the informed consent form. Participants having good general health (no active or uncontrolled diseases, infections, or conditions). BMI within the range of 24.9 to 34.9 kg/m2 (inclusive). Random blood glucose level <140 mg/dL. Concurrent metformin use is acceptable for indications other than diabetes. (However, the subject and investigator must not change metformin dosing during the three weeks of the study). Non-pregnant and non-lactating females of childbearing potential who agree to use adequate contraception/sexual abstinence throughout the study period. Willing and able to agree to the requirements and restrictions of this study, be willing to give voluntary consent, be able to understand and read the questionnaires, and carry out all study-related procedures. Individuals with access to a digital device to fill out the questionnaires. Exclusion Criteria: Participant has a history of uncontrolled hypertension (i.e., ≥150 mmHg systolic and/or ≥110 mmHg diastolic). Participant with history of post-prandial hypoglycemia (occurring 2-5 hours after food intake) of unknown cause. Abnormal thyroid-stimulating hormone (TSH) levels (<0.4 or > 4.2 μIU/ml). Known case of Type 1 or 2 diabetes. Participant has a history of heart disease and/or cardiovascular disease, kidney disease (dialysis or renal failure), and/or hepatic impairment or disease. Participant has a history of previously diagnosed major affective disorder, psychiatric disorder that required hospitalization in the year prior to screening, immune disorder (i.e., HIV/AIDS), or a history of cancer (except localized skin cancer without metastases or in situ cervical cancer) within 5 years prior to the screening visit. Received a vaccine for COVID-19 or any other vaccination in the 2 weeks prior to screening or planned during the study period, currentCOVID-19 infections, or currently have the post COVID-19 condition as defined by the World Health Organization (WHO) (i.e., individuals with a history of probable or confirmed SARS-CoV-2 infection, usually 3 months from the onset of COVID-19 with symptoms that last for at least 2 months and cannot be explained by an alternative diagnosis). Have a known intolerance, sensitivity, or allergy to any of the study products, their ingredients, or any excipients used in the formulation. Individuals who have a known history of diverticulitis. Have a known intolerance, sensitivity, or allergy to milk or soy. Any condition or abnormality that, in the opinion of the Investigator, would compromise the safety of the participant or the quality of the study data. Currently taking dietary supplements other than vitamins and minerals. Taking any other prescription medication at the time of randomization that is known to impact blood sugar and or blood sugar metabolism, as per the Principal Investigator's (PI) discretion. History of smoking, alcohol (heavy drinking as defined by NIAAA [National Institute on Alcohol Abuse and Alcoholism], USA), or substance abuse in the 12 months prior to screening. Receipt or use of an investigational product in another research study within 30 days prior to baseline/Visit 2.

Ages Eligible for Study
-----------------
Minimum Age: 25 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: randomized, double-blind, placebo-controlled, parallel-group
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: BioPB-01<br>2 sachets/day, one to be taken orally with (4±1 mins prior) at breakfast and one (4±1 mins prior) at dinner. | Other: BioPB-01<br>* 2 sachets/day, one to be taken orally with (4±1 mins prior) at breakfast and one (4±1 mins prior) at dinner<br>|
| Placebo Comparator: Placebo<br>2 sachets/day, one to be taken orally with (4±1 mins prior) at breakfast and one (4±1 mins prior) at dinner. | Other: Placebo<br>* 2 sachets/day, one to be taken orally with (4±1 mins prior) at breakfast and one (4±1 mins prior) at dinner<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the safety of 21 days of BioPB-01 administration on | The gastrointestinal (GI) health assessed using a modified Gastrointestinal Symptom Questionnaire (GSQ) compared to baseline and placebo | Day 21 | 
| To evaluate the safety of 21 days of BioPB-01 administration on | The gastrointestinal (GI) health assessed using a modified Gastrointestinal Symptom Questionnaire (GSQ) compared to baseline and placebo | Day 14 | 
| To evaluate the safety of 21 days of BioPB-01 administration on | The gastrointestinal (GI) health assessed using a modified Gastrointestinal Symptom Questionnaire (GSQ) compared to baseline and placebo | Day 7 | 
| To evaluate the safety of 21 days of BioPB-01 administration on | Stool consistency using Bristol stool form scale (BSFS) compared to baseline and placebo.This scale is a 7 point ordinal scale of stool types. The participants will be asked to rate their stool consistency and frequency daily to assess abnormal stools, defined as alteration in the frequency or consistency type 1, 2, 6, or 7. | Day 21 | 
| To evaluate the safety of 21 days of BioPB-01 administration on | Stool consistency using Bristol stool form scale (BSFS) compared to baseline and placebo. The participants will be asked to rate their stool consistency and frequency daily to assess abnormal stools, defined as alteration in the frequency or consistency type 1, 2, 6, or 7. | Day 14 | 
| To evaluate the safety of 21 days of BioPB-01 administration on | Stool consistency using Bristol stool form scale (BSFS) compared to baseline and placebo. The participants will be asked to rate their stool consistency and frequency daily to assess abnormal stools, defined as alteration in the frequency or consistency type 1, 2, 6, or 7. | Day 7 | 
| To evaluate the safety of 21 days of BioPB-01 administration on | Liver function biomarkers Alanine transaminase (ALT) Reference range: Females: 9-52 U/L Males: 21-72 U/L | Day 21 | 
| To evaluate the safety of 21 days of BioPB-01 administration on | Liver function biomarkers Aspartate aminotransferase (AST) Reference range: Females: 14-36 U/L Males: 17-59 U/L | Day 21 | 
| To evaluate the safety of 21 days of BioPB-01 administration on | Renal function biomarker blood urea nitrogen (BUN) - Female: 7-17 mg/dL or 2.5-6.1 mmol/L Male: 9-20 mg/dL or 3.2-7.1 mmol/L | Day 21 | 
| To evaluate the safety of 21 days of BioPB-01 administration on | Renal function biomarker Creatinine Reference range: Female: 0.52-1.04 mg/dL or 46-92 μmol/L Male: 0.66-1.25 mg/dL or 58-110 μmol/L | Day 21 | 
| To evaluate the safety of 21 days of BioPB-01 administration on | Serum electrolytes (sodium) : 137-145 mmol/L | Day 21 | 
| To evaluate the safety of 21 days of BioPB-01 administration on | Serum electrolytes (potassium): 3.5-5.1 mmol/L | Day 21 | 
| To evaluate the safety of 21 days of BioPB-01 administration on | Vitals - Blood pressure : Both Systolic and Diastolic pressure will be measured | Day 21 | 
| To evaluate the safety of 21 days of BioPB-01 administration on | Vitals - Pulse rate | Day 21 | 
| To evaluate the safety of 21 days of BioPB-01 administration on | The number and percentage of participants having adverse product reaction (as per CTCAE V5.0) | Throughout the study (an average of 21 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the efficacy of BioPB-01 after 21 days of administration by assessing the metabolic health | As assessed by the serum lipid profile (Triglycerides (TG), Total cholesterol (TC), low-density lipoprotein (LDL), and high-density lipoprotein (HDL)) level from Baseline | Day 21 | 
| To evaluate the efficacy of BioPB-01 after 21 days of administration by assessing | The insulin sensitivity as assessed by HOMA-IR from baseline | Day 21 | 
| To evaluate the efficacy of BioPB-01 after 21 days of administration by assessing | The post-prandial insulin response by net incremental area-under-the-curve (AUC) for post-prandial glucose and insulin (30, 60, 90, and 120 min. after standardised meal) from baseline. | Day 21 | 
| To evaluate the efficacy of BioPB-01 after 21 days of administration by assessing | Inflammation by serum C-reactive protein (CRP) level from Baseline | Day 21 | 
| To evaluate the efficacy of BioPB-01 after 21 days of administration by assessing | Satiety using the Appetite/Satiety - using Visual Analog Scale (VAS) from Baseline. The scale comprises of 4 main domains: 1) Hunger, 2) Fullness after meals, 3) Thoughts of food, 4) Cravings. The appetite will be analysed based on these four domains on a 100 mm VAS. Reduction in scores as compared to day 0 and placebo will indicate improvement in the appetite/satiety and efficacy of the IP on the appetite/satiety. | Day 21 | 
| To evaluate the efficacy of BioPB-01 after 21 days of administration by assessing | Body weight from baseline. | Day 21 | 
| To evaluate the efficacy of BioPB-01 after 21 days of administration by assessing Fecal short chain fatty acids (SCFA) | Namely acetate, propionate, and butyrate from Baseline. The samples will be analysed using liquid chromatography tandem mass spectrometry (LC-MS/MS). | Day 21 |