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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05942820




Registration number
NCT05942820
Ethics application status
Date submitted
5/07/2023
Date registered
12/07/2023
Date last updated
20/03/2024

Titles & IDs
Public title
The Safety, Tolerability, and Pharmacokinetics of Single and Multiple Ascending Doses of BWC0977 in Healthy Adult Volunteers
Scientific title
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
Secondary ID [1] 0 0
C002-2023-001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Infectious Diseases 0 0
Bacterial Infections 0 0
Condition category
Condition code
Infection 0 0 0 0
Studies of infection and infectious agents
Infection 0 0 0 0
Other infectious diseases
Infection 0 0 0 0
Sexually transmitted infections

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - BWC0977
Treatment: Drugs - Placebo

Experimental: 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

Placebo comparator: 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.


Treatment: Drugs: BWC0977
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.

Treatment: Drugs: Placebo
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
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Incidence of treatment-emergent adverse events (TEAEs and serious adverse events (SAEs) overall and by intensity (Safety and tolerability).
Timepoint [1] 0 0
SAD: Up to 7 days; MAD: Up to 15 days
Secondary outcome [1] 0 0
AUC[0-t] of BWC0977 following single dose administration
Timepoint [1] 0 0
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
Secondary outcome [2] 0 0
AUC[0-inf]) of BWC0977 following single dose administration
Timepoint [2] 0 0
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
Secondary outcome [3] 0 0
AUC[0-8], AUC[0-12], AUC[0-24]) of BWC0977 following single dose administration
Timepoint [3] 0 0
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
Secondary outcome [4] 0 0
Cmax of BWC0977 following single dose administration
Timepoint [4] 0 0
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
Secondary outcome [5] 0 0
Cmax of BWC0977 following repeat dose administration
Timepoint [5] 0 0
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]
Secondary outcome [6] 0 0
Terminal half-life (T1/2)
Timepoint [6] 0 0
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
Secondary outcome [7] 0 0
Systemic clearance (CL) following single dose administration
Timepoint [7] 0 0
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
Secondary outcome [8] 0 0
Systemic clearance (CL) following repeat dose administration
Timepoint [8] 0 0
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]
Secondary outcome [9] 0 0
Volume of distribution at steady state (Vdss) following single dose administration
Timepoint [9] 0 0
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
Secondary outcome [10] 0 0
Pre-dose (trough) concentration (Ct) at the end of the dosing interval
Timepoint [10] 0 0
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]
Secondary outcome [11] 0 0
Observed accumulation ratio following repeat dose administration
Timepoint [11] 0 0
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
Secondary outcome [12] 0 0
Volume of distribution at steady state following repeat dose administration
Timepoint [12] 0 0
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
Secondary outcome [13] 0 0
Amount excreted in urine (Ae) following repeat dose administration
Timepoint [13] 0 0
Day 1 pre-dose, 0-8 hours post infusion start Day 10: 0-8 hours post infusion start
Secondary outcome [14] 0 0
Amount excreted in urine (Ae) following single dose administration
Timepoint [14] 0 0
Day 1 pre-dose, 0-2, 2-4, 4-8, 8-12, and 12-24 hours post infusion start
Secondary outcome [15] 0 0
Fraction of the dose excreted in urine (fe) following single dose administration
Timepoint [15] 0 0
Day 1 pre-dose, 0-2, 2-4, 4-8, 8-12, and 12-24 hours post infusion start
Secondary outcome [16] 0 0
Fraction of the dose excreted in urine (fe) following repeat dose administration
Timepoint [16] 0 0
Day 1 pre-dose, 0-8 hours post infusion start Day 10: 0-8 hours post infusion start
Secondary outcome [17] 0 0
Renal Clearance (CLr) following single dose administration
Timepoint [17] 0 0
Day 1 pre-dose, 0-2, 2-4, 4-8, 8-12, and 12-24 hours post infusion start
Secondary outcome [18] 0 0
Renal Clearance (CLr) following repeat dose administration
Timepoint [18] 0 0
Day 1 pre-dose, 0-8 hours post infusion start Day 10: 0-8 hours post infusion start

Eligibility
Key inclusion criteria
Each subject must meet all the following criteria to be eligible for study participation:

1. Healthy male or female 18 to 55 years of age, inclusive, at time of consent.
2. Body mass index (BMI) = 19.0 and = 30.0 (kg/m2) and weight between 55.0 and 100.0 kg (inclusive).
3. Medically healthy without clinically significant abnormalities at the screening visit, Day -1 or Day 1, including:

1. 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.
2. 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.
3. Clinically significant abnormalities in the screening clinical laboratory tests, as determined by the Investigator. Repeat testing could be performed at the Investigator's discretion.
4. Willing and able to provide written informed consent.
5. Agrees to be available for all study visits and cooperate fully with the requirements of the study protocol, including the schedule of events.
6. 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).
7. 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.
8. Have suitable venous access for drug administration and blood sampling.
9. If female of child-bearing potential, must agree to and comply with:

1. 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
2. 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
3. Females of child-bearing potential must also agree not to donate ova or oocytes (ie, human eggs) during the study, and for one menstrual cycle after completion of the study.
4. To be considered of non-childbearing potential, a female must have either a tubal ligation, hysterectomy, bilateral salpingo-oophorectomy (at least 6 weeks prior to screening), or menopause (last menstruation >12 months and FSH in menopausal range); provision of written documentation is not required for female sterilization and oral confirmation is adequate.
5. Female participants in same sex relationships do not need to utilize contraception.
10. Male volunteers, if sexually active with a female partner, must agree to and comply with using 1 barrier method of birth control (e.g., male condom) plus 1 other highly effective method of birth control in their partner (e.g., oral contraceptive; implant, injectable, indwelling intrauterine device), or double-barrier method (use of a condom by the male partner with use of a diaphragm by the female partner, or sexual abstinence, and must not donate sperm, for the duration of the study (from signing of consent) and for 90 days after last study drug administration.

To be considered surgically sterile, male participants must have had a vasectomy at least 3 months prior to screening with appropriate documentation of the absence of sperm in the ejaculate.

Male participants in same sex relationships do not need to utilize contraception.
Minimum age
18 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Volunteers who meet any of the following criteria will be excluded from the study:

1. Women who are pregnant and/or lactating.
2. 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.
3. 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.
4. History of photosensitivity to quinolones.
5. History of known or suspected Clostridium difficile infection.
6. Any condition that necessitated hospitalization within the 3 months prior to Day -1 or is likely to require so during the study.
7. Positive test for HbsAg, anti-HCV antibodies, or antibodies to HIV-1, HIV-2 at screening.
8. 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.
9. Documented hypersensitivity reaction or anaphylaxis to any medication.
10. 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).
11. 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).
12. 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.
13. 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.
14. Consumption of red wine, Seville oranges, grapefruit, or grapefruit juice, pummelos, other citrus fruits, grapefruit hybrids or fruit juices containing such products from 7 days prior to the first dose of study medication.
15. Employee or family member of an employee of the Sponsor, clinical research unit, or clinical research organization at which the study will be conducted.
16. 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.
17. Any disease or condition (medical or surgical) that, by the determination of the Investigator, precludes the subject's participation in the study or would place the subject at risk as a result of participation in the study.

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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
30/08/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
15/02/2024
Sample size
Target
Accrual to date
Final
4
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 0 0
CMAX Clinical Research - Adelaide
Recruitment postcode(s) [1] 0 0
5000 - Adelaide

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Bugworks Research Inc.
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Avance Clinical Pty Ltd.
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT05942820
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Nicholas Farinola, BSc,BMBS
Address 0 0
CMAX Clinical Research ,Adelaide, SA, Australia, 5000
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT05942820