A Phase 1 Study of the Safety and Tolerability of Single and Multiple Ascending Doses of BWC0977 in Healthy Volunteers

Exclusion Criteria

• •* 1\) Pregnancy and Lactation: Women who are pregnant and/or lactating. 2) Significant Medical History: History or presence of significant cardiovascular (including QT prolongation, clinically significant hypokalemia, or other proarrhythmic conditions), pulmonary, hepatic, renal, hematological, gastrointestinal, endocrine (including glucose intolerance, diabetes mellitus), immunologic (including asthma or seasonal allergies \[that require intermittent use of steroids or other medication\]), musculoskeletal (including tendinopathy), dermatologic, or neurological disease (including seizure disorders, psychiatric disorders), including any acute illness or surgery within the past 3 months, as determined by the Investigator to be clinically relevant.
• •1. History of any kidney disease or current or chronic history of impaired renal function as indicated by a calculated creatinine clearance (Cockcroft-Gault formula) \<80 milliliter per minute (mL/min).
• •2. Current or chronic history of liver disease or known hepatic or biliary abnormalities (except for Gilbert syndrome or asymptomatic gallstones) 3) Laboratory abnormalities
• •a) Clinically significant abnormal findings in serum chemistry, hematology, coagulation or urinalysis results obtained at screening or check-in (Day-1) b) Alanine aminotransferase (ALT) more than (\>)1 upper limit of normal (ULN) at screening or check-in (Day-1) c) Aspartate aminotransferase (AST) \> ULN at screening or check-in (Day-1)d) Bilirubin \>ULN at screening or check-in (Day-1) e) Serum creatinine \> ULN at screening or check-in (Day-1). The serum creatinine or any laboratory test may be repeated prior to confirming exclusion, at the PI's discretion.
• •4\) Electrocardiographic abnormalities: Baseline QTcF of \>450 msec (for males), and \>470 msec (for females) at screening or check-in (Day-1) 5) Photosensitivity: History of photosensitivity to quinolones 6) Clostridium Difficile: History of known or suspected Clostridium difficile infection 7) Hospitalization History: Any condition that necessitated hospitalization within the 3 months prior to Day -1 or is likely to require so during the study 8) Antibiotic History: No systemic antibiotic use within 5 days before dosing. 9) Infection History: Positive test for hepatitis B virus surface antigen (HBsAg), hepatitis C virus antibody (anti-HCV antibodies), or human immunodeficiency virus antibody (antibodies to HIV-1, HIV-2) at screening.
• •10\) Recent Medications: Exclude participants receiving all prescription and OTC medications (except hormonal contraception and Paracetamol) 14 days or 5 half-lives, whichever is longer, prior to IP dosing.Discussion between the PI and the Sponsor Medical Monitor is encouraged regarding prior use of any medications during the pre-dose period. Note: An exception is made for hormonal contraceptives, paracetamol (a maximum of 4 doses per day of 500 mg, and no more than 3 g per week) for the treatment of headache or any other pain as per the PI's judgement.
• •11\) Hypersensitivity: DocumentedHistory of significant hypersensitivity reaction or anaphylaxis to any medication, as determined by the Medical Officer.
• •12\) Tobacco and Nicotine Use: Smoker (including tobacco, e-cigarettes, or marijuana) or nicotine user within 1 month prior to dosing and have a positive test for cotinine at check in on Day -1 (may be repeated once, at the discretion of the Investigator or Medical officer, in the instance of a positive result).
• •13\) Drug/Alcohol Abuse: Positive urine drug/alcohol breath testing at screening or check-in (Day -1), or history of substance abuse or alcohol abuse (defined as greater than 2 standard drinks on average each and every day, where one standard drink is defined as containing 10 g of alcohol and is equivalent to 1 can or stubby of mid-strength beer, 30 ml nip spirits, or 100 ml wine) within the previous 5 years (may be repeated once per timepoint, at the discretion of the Investigator or Medical officer, in the instance of a positive result).
• •14\) Blood/Plasma Donation: Donation of blood within 30 days or plasma within 7 days prior to randomization, or loss of whole blood of more than 500 mL within 30 days prior to randomization, or receipt of a blood transfusion within 1 year of study enrollment.
• •15\) Previous Study Participation: Previous participation in this study, i.e., who has already completed earlier cohorts or previous participation in another study within 5 half-lives (if known) of the agent, or 30 days, whichever is longer, of Day 1.
• •Note: prior participation at any time in non-invasive methodology trials in which no drugs were given is acceptable. Those who were screen failures or not dosed in this study may will be considered for re-screening in subsequent cohorts.
• •16\) Food Restrictions: Consumption of red wine, Seville oranges, grapefruit, or grapefruit juice, pummelos, exotic citrus fruits, grapefruit hybrids, or fruit juices containing such products from 7 days prior to the first dose of study medication.(Note: Lemon and lime, including their juice or zest, are permitted as they are not known to significantly affect cytochrome P450 (CYP3A4) enzyme activity) 17) Sponsor Relationships: Employee or family member of an employee of the Sponsor, CRU, or clinical research organization at which the study will be conducted.
• •18\) Non-compliance: Unable to cooperate fully with the requirements of the study protocol, including the schedule of events, or likely to be non-compliant with any study requirements.
• •19\) Other Medical Conditions: Any other disease or condition that, in the opinion of the Investigator, would preclude the subject's participation in the study or place them at risk as a result of study participation.
• •Note: Volunteers should refrain from consumption of any foods containing poppy seeds within 48 hours (2 days) prior to screening and prior to Day -1 to avoid false positive drug screen results. Examples of foods to avoid include: poppy seed bagels, muffins, pastries, salad dressings, or any baked goods or dishes that list poppy seeds as an ingredient.