The Safety, Tolerability, and Pharmacokinetics of Single and Multiple Ascending Doses of BWC0977 in Healthy Adult Volunteers

NCT05942820 | Terminated Phase 1 DMC

• 1 other identifier: C002-2023-001
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

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.

Conditions

Infectious Diseases; Bacterial Infections

Keywords

Safety; Tolerability; Pharmacokinetics; BWC0977

Outcome Measures

Primary Outcomes (1)

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

  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

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

Secondary Outcomes (18)

• 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

• 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

• 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]

Study Arms (2)

BWC0977

EXPERIMENTAL

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

Drug: BWC0977

Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo

Interventions

BWC0977 DRUG

SAD Cohorts: Double-blind dosing will occur. Six participants will receive single doses of BWC0977. The dose escalation steps may be altered following review of the safety data upon completion of each cohort. MAD Cohorts: Double blind dosing will occur. Six participants in each cohort will receive multiple doses of BWC0977. The dose escalation steps may be altered following review of the safety data upon completion of each cohort. Dosing will commence on the morning of Day 1. Dosing frequency to be confirmed based on safety, tolerability and PK data from SAD cohorts. Daily dosing will continue for a total of 10 consecutive days.

BWC0977

Placebo DRUG

SAD Cohorts: Two participants in each cohort will receive a matching placebo. MAD Cohorts: Two participants in each cohort will receive matching placebo. Other Names: • Compounded solution minus BWC0977

Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Gender Eligibility Details: Efforts will be made to randomize approximately equal numbers of males and females to either active or placebo in Part 1 and Part 2 (including both genders).
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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).
• Willing to refrain from prescription medications from Screening visit until follow-up; and over-the-counter (OTC) medications, vitamin preparations and other food supplements, from Day -1 up to follow-up.
• Have suitable venous access for drug administration and blood sampling.
• If female of child-bearing potential, must agree to and comply with:
• Using 1 barrier method (e.g., female condom or male partner using a condom) plus 1 other highly effective method of birth control (e.g., oral contraceptive, implant, injectable, indwelling intrauterine device, vasectomized partner), or double-barrier method (use of a condom by the male partner with use of a diaphragm by the female partner), from signing the consent form until 30 days after last study drug administration, or
• Sexual abstinence, for the duration of the study (from signing of consent to FU visit) and for 30 days after last study drug administration, plus

You may not qualify if:

• 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.
• 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.
• Documented hypersensitivity reaction or anaphylaxis to any medication.
• Smoker (including tobacco, e-cigarettes, or marijuana) or nicotine user within 1 month prior to dosing and have a negative test for cotinine at check in on Day -1 (may be repeated once, at the discretion of the Investigator, in the instance of a positive result).
• Positive urine drug/alcohol 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, in the instance of a positive result).
• Donation of blood or plasma within 30 days prior to randomization, or loss of whole blood of more than 500mL within 30 days prior to randomization, or receipt of a blood transfusion within 1 year of study enrollment.
• Previous participation in this study 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.

Sponsors & Collaborators

• Bugworks Research Inc.: lead
• Avance Clinical Pty Ltd.: collaborator

Study Sites (1)

CMAX Clinical Research

Adelaide, South Australia, 5000, Australia

Location

MeSH Terms

Conditions

Communicable Diseases; Bacterial Infections

Condition Hierarchy (Ancestors)

Infections; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Bacterial Infections and Mycoses

Study Officials

• Nicholas Farinola, BSc,BMBS

  CMAX Clinical Research ,Adelaide, SA, Australia, 5000

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Participants will be randomized in a 3:1 ratio of BWC0977 and Placebo. The following controls will be employed to maintain the double-blind status of the study Infusion solution containing active drug and placebo will be indistinguishable in appearance Randomization list will be provided to the study center pharmacist for dispensing purposes and kept in the pharmacy, accessible to the pharmacist and authorized personnel only PK results for the interim analyses between cohorts will be presented in a blinded fashion.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Randomized, double-blind, placebo-controlled, combined single and multiple ascending dose (SAD and MAD) trial

Study Record Dates

• First Submitted: July 5, 2023
• First Posted: July 12, 2023
• Study Start: August 30, 2023
• Primary Completion: January 30, 2024
• Study Completion: February 15, 2024
• Last Updated: March 20, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)