A Phase I Study to assess Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single and Multiple Oral Ascending Doses of BioE-1115 in Healthy Adult Volunteers

INTERVENTION: This first in human (FIH) Phase 1 study to assess safety, tolerability, PK and PD of BioE‐1115. The study is conducted in two parts a single ascending dose (SAD) where subjects receive only one dose of BioE‐1115, and a multiple ascending dose (MAD) where subjects receive multiple daily dose of BioE‐1115 for up to 7 days. Mode of administration of BioE‐1115: Oral Capsules A total of approximately up to 121 subjects from both parts are expected to be enrolled in this study. Each subject will be allowed to participate in either the SAD cohort or MAD cohort, but not both. The SAD and MAD studies of BioE‐1115 vs. placebo will be conducted in 2 parts of 5 × SAD and 4 × MAD dose cohorts. Part A (SAD): o Each cohort will consist of 8 subjects (2 receiving placebo and 6 receiving BioE‐1115, in fasting state). One cohort may be called back to be redosed in a fed state after a washout period. The dose of BioE‐1115 administered in each cohort and/or the ascending schedule between cohorts of Part A (SAD): The study drug will be administered on Day 1. 5 dose levels in the range of 50 to 1000 mg/day are planned to be administered to the 5 cohorts. The starting dose will be 50 mg and subsequent higher dose levels will be determined by the Safety Review Committee (SRC) based on safety data and blinded PK data, evaluated up to and including Day 7, from the previous cohort(s). It is estimated that the dose levels will be approximately 50mg/day, 150mg/day, 450mg/day, 750mg/day and 1000mg/day. All study doses will be administered an overnight fast of at least 10 hours. In the fed cohort, the IMP will be administered within 30 minutes after the start of a standardized meal. Part B (MAD): o Each MAD cohort will consist of 15 subjects, (3 receiving placebo and 12 receiving BioE‐1115) in a fasted state. The dose of BioE‐1115 administered in each cohort and/or the ascending schedule between cohorts of Part B (MAD): The study drug will be administered da CONDITION: Non‐alcoholic fatty liver disease (NAFLD); ; Non‐alcoholic fatty liver disease (NAFLD) Oral and Gastrointestinal ‐ Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon PRIMARY OUTCOME: To assess safety and tolerability of BioE‐1115 following escalating single and multiple doses of BioE‐1115 in healthy volunteers.[The safety and tolerability will be evaluated by targeted physical examination including Adverse Events (AEs) reporting, Weight, Vital signs (blood pressure, heart rate, body temperature, respiration rate), 12‐lead electrocardiogram (ECG) monitoring, Ambulatory arrhythmia monitoring (telemetry), Blood and urine sampling for haematology, clinical chemistry including Creatinine Phosphokinase (CPK) and cardiac troponins and coagulation; ] SECONDARY OUTCOME: To assess the Pharmacodynamic (PD) effects of ; BioE‐1115 assessed as fructose‐stimulated de‐novo lipogenesis (FS‐DNL) and resting metabolic rate (RMR) of multiple ascending doses (MAD) of BioE‐1115.[FS‐DNL will be measured using sodium [1‐13C1] acetate at approximately 1 week prior to the initiation of dosing and at the end of dosing. Subjects will undergo measurement of RMR along with the FS‐DNL measurement. RMR will be measured by indirect calorimetry. ; ; On Day 5, blood samples for PK analysis will be collected at pre‐dose (within 5 minutes prior to IMP administration) only ; ; ; ; ] INCLUSION CRITERIA: 1. Healthy males and females aged 18‐55 years, inclusive, at the time of signing the informed consent 2. Body Mass Index (BMI) greater than or equal to 18 kg/m2 and lesser than or equal to 30 kg/m2 and body weight greater than or equal to 50 kg and lesser than or equal to 100 kg at screening 3. Subjects have not used any nicotine product from 12 weeks prior to screening ; ] To assess the PK effects of BioE‐1115 assessed as fructose‐stimulated de‐novo lipogenesis (FS‐DNL) and resting metabolic rate (RMR) of multiple ascending doses (MAD) of BioE‐1115.[Part B (MAD): ; FS‐DNL will be measured using sodium [1‐13C1] acetate at approximately 1 week prior to the initiation of dosing and at the end of dosing. Subjects will undergo measurement of RMR along with the FS‐DNL measurement. ; Blood samples for PK analysis will be collected on Day 1 at pre‐dose (within 5 minutes prior to IMP administration) and post‐dose at 20 minutes, 40 minutes, 60 minutes, 90 minutes, 120 minutes, 180 minutes, 4 hours, 6 hours, 9 hours, 12 hours and 18 hours; on Day 2 (24 hours post Day 1 dosing time) and on Day 3 (48 hours post Day 2 dosing time) ; Blood samples for PK analysis will again be collected on Day 7 at pre‐dose (within 5 minutes prior to IMP administration) and post‐dose at 20 minutes, 40 minutes, 60 minutes, 90 minutes, 120 minutes, 180 minutes, 4 hours, 6 hours, 9 hours, 12 hours and 18 hours; on Day 8 (24 hours post Day 7 dosing time) and on Day 9 (48 hours post Day 7 dosing time). ; Urine sampling for PK will be collected at 0 to 2 hours, 2 to 4 hours, 4 to 9 hours, 9 to 24 hours post Day 1 and Day 7 dosing time. Urine samples will also be collected at 24‐36 and 36‐48 hr time points post the last dose on Day 7. ] To determine pharmacokinetics (PK), including the effects on PK in fed vs. fasting states, of single ascending doses (SAD) of BioE‐1115. ; PK parameters‐ Area under the plasma concentration time curve (AUC), maximum concentration (Cmax), time to maximum concentration (Tmax). The PK concentrations by nominal time profile data will be presented graphically on linear and log‐linear scales. Individual subject profiles (spaghetti or overlay plots) will be presented for each dosing group. The mean and median concentrations over time will also be presented. PK concentrations will be assessed using both plasma and urinalysis.[Part A (SAD): ; PK analysis will be collected on Day 1 at pre‐dose (within 5 minutes prior to IMP administration) and post‐dose at 20 minutes, 40 minutes, 60 minutes, 90 minutes, 120 minutes, 180 minutes, 4 hours, 6 hours, 9 hours, 12 hours and 18 hours; on Day 2 (24 hours post dosing on Day 1) and on Day 3 (48 hours post dosing on Day 1) 4. No significant medical condition, and normal physical findings, vital signs (systolic blood pressure [BP]: 90‐ 140 mm Hg, diastolic BP: 40‐90 mm Hg, pulse:40‐100 beats per minute, respiratory rate: 10‐22 breaths per minute, body temperature: 35.5‐37.5 degree Celsius) and laboratory values at the time of screening, as judged by the Investigator 5. Normal 12‐lead electrocardiogram (ECG) or 1 with abnormalities that are considered clinically insignificant by the Investigator 6. Normal renal function (estimated glomerular filtration rate calculated using the Cockcroft‐G