A Randomized, Double-blind, Placebo-controlled, Phase 1 Study of the Safety, Tolerability, and Pharmacokinetics of Single and Multiple Ascending Doses of BWC0977 in Healthy Adult Volunteers

Bugworks Research Inc.1 site in 1 country4 target enrollmentAugust 30, 2023

ConditionsInfectious Diseases Bacterial Infections

InterventionsBWC0977 Placebo

DrugsBWC0977 Placebo

Overview

Phase: Phase 1
Intervention: BWC0977
Conditions: Infectious Diseases
Sponsor: Bugworks Research Inc.
Enrollment: 4
Locations: 1
Primary Endpoint: Incidence of treatment-emergent adverse events (TEAEs and serious adverse events (SAEs) overall and by intensity (Safety and tolerability).
Status: Terminated
Last Updated: 2 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

The purpose of this study is to assess the safety, tolerability and pharmacokinetics of single and multiple intravenous doses of BWC0977 when administered to healthy adult volunteers.

Detailed Description

This Phase 1 study is designed to assess the safety, tolerabilty and pharmacokinetics of single and multiple intravenous doses of BWC0977 when administered to healthy adult volunteers. This is a randomized double-blind, placebo-controlled, ascending dose, multi-cohort trial. A total of 56 healthy volunteers are expected to be enrolled into 7 Cohorts. The study will be conducted in two phases: A multiple ascending dose (MAD) phase , followed by A single ascending dose (SAD) phase. In SAD, participants in Cohorts 1 - 2 will receive one dose of BWC0977 or placebo. In MAD, participants in Cohorts 6 - 8 will receive multiple doses of BWC0977 or placebo for 10 consecutive days at a dose deemed safe and tolerable as determined in the preceding SAD Cohorts. In both parts sequential cohorts will be exposed to increasing doses of BWC0977.

Registry

clinicaltrials.gov

Start Date

August 30, 2023

End Date

February 15, 2024

Last Updated

2 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Bugworks Research Inc.

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Each subject must meet all the following criteria to be eligible for study participation:
•Healthy male or female 18 to 55 years of age, inclusive, at time of consent.
•Body mass index (BMI) ≥ 19.0 and ≤ 30.0 (kg/m2) and weight between 55.0 and 100.0 kg (inclusive).
•Medically healthy without clinically significant abnormalities at the screening visit, Day -1 or Day 1, including:
•No findings in Physical examination or vital signs (including temperature, HR, respiratory rate, and blood pressure) that the Investigator determines would interfere with interpretation of study results.
•Electrocardiograms (ECGs) without clinically significant abnormalities, including a QTcF interval duration ≤450 msec (for males), and ≤470 msec (for females) obtained as an average from the triplicate screening ECGs after at least 5 minutes in a supine quiet-rest position.
•Clinically significant abnormalities in the screening clinical laboratory tests, as determined by the Investigator. Repeat testing could be performed at the Investigator's discretion.
•Willing and able to provide written informed consent.
•Agrees to be available for all study visits and cooperate fully with the requirements of the study protocol, including the schedule of events.
•Willing to refrain from strenuous physical activity that could cause muscle aches or injury, including contact sports, at any time from 4 days prior to admission in the clinical research unit (CRU) until completion of the study (follow-up \[FU\] visit).

Exclusion Criteria

•Volunteers who meet any of the following criteria will be excluded from the study:
•Women who are pregnant and/or lactating.
•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.
•A serum creatinine value on Day -1 (check-in) that increased by more than 0.2 mg/Dl (or 15.25 μmol/L) from the Screening value. Note: the serum creatinine test may be repeated prior to confirming exclusion.
•History of photosensitivity to quinolones.
•History of known or suspected Clostridium difficile infection.
•Any condition that necessitated hospitalization within the 3 months prior to Day -1 or is likely to require so during the study.
•Positive test for HbsAg, anti-HCV antibodies, or antibodies to HIV-1, HIV-2 at screening.
•Exposure to any prescription medications (small molecules, biologics, and vaccines, including influenza and/or COVID-19 vaccines) or, systemically administered OTC drugs, dietary supplements, or herbal remedies, within 14 days or 5 half-lives (if known), whichever is longer, prior to Day 1 (first dose). Participants should not receive any vaccinations (including influenza and/or COVID-19 vaccines) until after study completion. 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 and a limited amount of paracetamol (a maximum of 4 doses per day of 500-mg paracetamol, and no more than 3 g per week) for the treatment of headache or any other pain.

Arms & Interventions

BWC0977

MAD Cohorts: Subjects will receive multiple doses of 240mg BID 7 days, 750mg BID 10 days,1250mg BID 10 days and 1000mg TID 10 days BWC0977 via IV infusion over 2 hours in the first 4 cohorts. The dose for the A5 cohort will be determined based on safety and tolerability data from the previous cohorts Up to five dose groups will be studied. SAD Cohorts: Subjects will receive single doses of BWC0977 via IV infusion over 2 hours. The planned dose to be studied are 1500mg. Upto 2 cohorts will be studied

Intervention: BWC0977

Placebo

Compounded solution minus BWC0977 The placebo used during this study is 5% Dextrose for injection. SAD Cohorts: Subjects will receive single infusions of placebo (Compounded solution minus BWC0977) over two hours. MAD Cohorts: Subjects will receive multiple infusions of placebo over 2 hours for 7 or 10 consecutive days.

Intervention: Placebo

Outcomes

Primary Outcomes

Incidence of treatment-emergent adverse events (TEAEs and serious adverse events (SAEs) overall and by intensity (Safety and tolerability).

Time Frame: SAD: Up to 7 days; MAD: Up to 15 days

This outcome combines the measure of the number of participants experiencing adverse events (AEs), the nature and severity of those AEs and their relationship to the study treatment

Secondary Outcomes

Systemic clearance (CL) following single dose administration(Day 1 pre-dose, 5, 10,15, 20, 30, 45, 60, 75, and 90 minutes and 2, 2.5, 3, 4, 6, 8, 10, 12, 24 and 48 hours post infusion start)
Renal Clearance (CLr) following single dose administration(Day 1 pre-dose, 0-2, 2-4, 4-8, 8-12, and 12-24 hours post infusion start)
AUC[0-inf]) of BWC0977 following single dose administration(Day 1 pre-dose, 5, 10,15, 20, 30, 45, 60, 75, and 90 minutes and 2, 2.5, 3, 4, 6, 8, 10, 12, 24 and 48 hours post infusion start)
AUC[0-8], AUC[0-12], AUC[0-24]) of BWC0977 following single dose administration(Day 1 pre-dose, 5, 10,15, 20, 30, 45, 60, 75, and 90 minutes and 2, 2.5, 3, 4, 6, 8, 10, 12, 24 and 48 hours post infusion start)
Cmax of BWC0977 following single dose administration(Day 1 pre-dose, 5, 10,15, 20, 30, 45, 60, 75, and 90 minutes and 2, 2.5, 3, 4, 6, 8, 10, 12, 24 and 48 hours post infusion start)
Systemic clearance (CL) following repeat dose administration(Day 1 pre-dose, 30, 60, 75, and 90 minutes and 2, 2.5, 3, 4, 6, and 8 hours post infusion start Days 5, 6, 7, 8, and 9: pre-dose Day 10 pre-dose, 30, 60, 75, and 90 minutes and 2, 2.5, 3, 4, 6, 8, 10, 12 and 24 hours post infusion start])
Fraction of the dose excreted in urine (fe) following single dose administration(Day 1 pre-dose, 0-2, 2-4, 4-8, 8-12, and 12-24 hours post infusion start)
Pre-dose (trough) concentration (Cτ) at the end of the dosing interval(Day 1 pre-dose, 30, 60, 75, and 90 minutes and 2, 2.5, 3, 4, 6, and 8 hours post infusion start Days 5, 6, 7, 8, and 9: pre-dose Day 10 pre-dose, 30, 60, 75, and 90 minutes and 2, 2.5, 3, 4, 6, 8, 10, 12 and 24 hours post infusion start])
Observed accumulation ratio following repeat dose administration(Day 1 pre-dose, 30, 60, 75, and 90 minutes and 2, 2.5, 3, 4, 6, and 8 hours post infusion start Days 5, 6, 7, 8, and 9: pre-dose Day 10 pre-dose, 30, 60, 75, and 90 minutes and 2, 2.5, 3, 4, 6, 8, 10, 12 and 24 hours post infusion start)
Amount excreted in urine (Ae) following single dose administration(Day 1 pre-dose, 0-2, 2-4, 4-8, 8-12, and 12-24 hours post infusion start)
Fraction of the dose excreted in urine (fe) following repeat dose administration(Day 1 pre-dose, 0-8 hours post infusion start Day 10: 0-8 hours post infusion start)
AUC[0-t] of BWC0977 following single dose administration(Day 1 pre-dose, 5, 10,15, 20, 30, 45, 60, 75, and 90 minutes and 2, 2.5, 3, 4, 6, 8, 10, 12, 24 and 48 hours post infusion start)
Volume of distribution at steady state (Vdss) following single dose administration(Day 1 pre-dose, 5, 10,15, 20, 30, 45, 60, 75, and 90 minutes and 2, 2.5, 3, 4, 6, 8, 10, 12, 24 and 48 hours post infusion start)
Volume of distribution at steady state following repeat dose administration(Day 1 pre-dose, 30, 60, 75, and 90 minutes and 2, 2.5, 3, 4, 6, and 8 hours post infusion start Days 5, 6, 7, 8, and 9: pre-dose Day 10 pre-dose, 30, 60, 75, and 90 minutes and 2, 2.5, 3, 4, 6, 8, 10, 12 and 24 hours post infusion start)
Amount excreted in urine (Ae) following repeat dose administration(Day 1 pre-dose, 0-8 hours post infusion start Day 10: 0-8 hours post infusion start)
Cmax of BWC0977 following repeat dose administration(Day 1 pre-dose, 30, 60, 75, and 90 minutes and 2, 2.5, 3, 4, 6, and 8 hours post infusion start Days 5, 6, 7, 8, and 9: pre-dose Day 10 pre-dose, 30, 60, 75, and 90 minutes and 2, 2.5, 3, 4, 6, 8, 10, 12 and 24 hours post infusion start])
Terminal half-life (T1/2)(Day 1 pre-dose, 5, 10,15, 20, 30, 45, 60, 75, and 90 minutes and 2, 2.5, 3, 4, 6, 8, 10, 12, 24 and 48 hours post infusion start)
Renal Clearance (CLr) following repeat dose administration(Day 1 pre-dose, 0-8 hours post infusion start Day 10: 0-8 hours post infusion start)