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.
This Phase 1 study is designed to assess the safety, tolerability, 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 64 healthy volunteers are expected to be enrolled in 8 Cohorts. The study will be conducted in two phases: A single ascending dose (SAD) phase, followed by a multiple ascending dose (MAD) phase. In SAD, participants in Cohorts 1 - 2 will receive one dose of BWC0977 or placebo. In MAD, participants in cohorts 3 - 7 will receive multiple doses of BWC0977 or placebo for 7-10 consecutive days (as per the schedule). In both parts, sequential cohorts will be exposed to increasing doses of BWC0977.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
48
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 and previous MAD cohorts. Daily dosing will continue for a total of 7-10 consecutive days (as per schedule).
SAD Cohorts: Two participants in each cohort will receive a matching placebo. MAD Cohorts: Two participants in each cohort will receive a matching placebo.
Nucleus Network
Melbourne, Victoria, Australia
RECRUITINGIncidence of treatment-emergent adverse events (TEAEs and serious adverse events (SAEs) overall and by intensity (Safety and tolerability).
Description: 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.
Time frame: SAD: Up to 8 days MAD: Up to 16 days
AUC[0-t] of BWC0977 following single dose administration
Area under the plasma concentration curve from time zero to last time of quantifiable concentration (AUC0-t) of BWC0977 following single dose administration
Time frame: Immediately before (within 60 minutes before) the start of infusion of the study drug and 5, 10,15, 20, 30, 45, 60, 75, and 90 minutes, 2, 2.5, 3, 4, 6, 8, 10, 12, 24 and 48 hours after the start of study drug infusion.
AUC[0-inf] of BWC0977 following single dose administration
Area under the plasma concentration curve from time zero to infinity (AUC0-inf) of BWC0977 following single dose administration
Time frame: Immediately before (within 60 minutes before) the start of infusion of the study drug and 5, 10,15, 20, 30, 45, 60, 75, and 90 minutes, 2, 2.5, 3, 4, 6, 8, 10, 12, 24 and 48 hours after the start of study drug infusion.
AUC[0-8], AUC[0-12], AUC[0-24] of BWC0977 following single dose administration
AUC from time zero to 8, 12, and 24 hours (AUC\[0-8\], AUC\[0-12\], AUC\[0-24\]) of BWC0977 following single dose administration
Time frame: Immediately before (within 60 minutes before) the start of infusion of the study drug and 5, 10,15, 20, 30, 45, 60, 75, and 90 minutes, 2, 2.5, 3, 4, 6, 8, 10, 12, 24 and 48 hours after the start of study drug infusion.
Cmax of BWC0977 following single dose administration
Maximum observed plasma concentration (Cmax) of BWC0977 following single dose administration
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Time frame: Immediately before (within 60 minutes before) the start of infusion of the study drug and 5, 10,15, 20, 30, 45, 60, 75, and 90 minutes, 2, 2.5, 3, 4, 6, 8, 10, 12, 24 and 48 hours after the start of study drug infusion.
Cmax of BWC0977 following repeated dose administration
Maximum observed plasma concentration (Cmax) of BWC0977 following repeat dose administration
Time frame: Immediately before (within 60 minutes before) the start of the first infusion and at 5,15, 30, 60, 75, and 90 minutes, 2, 4, 6, and 8, 12, 24 hours after the start of the last infusion on Day 1 and 7 (MAD 1 cohort) or 10 (For MAD2 -MAD4 cohort).
Termianl Half life (T1/2) of BWC0977 following single dose administration
Terminal half-life (T1/2) of BWC0977 following single dose administration
Time frame: Immediately before (within 60 minutes before) the start of infusion of the study drug and 5, 10,15, 20, 30, 45, 60, 75, and 90 minutes, 2, 2.5, 3, 4, 6, 8, 10, 12, 24 and 48 hours after the start of study drug infusion.
Systemic clearance (CL) following single dose administration
Systemic clearance (CL) of BWC0977 following single dose administration
Time frame: Immediately before (within 60 minutes before) the start of infusion of the study drug and 5, 10,15, 20, 30, 45, 60, 75, and 90 minutes, 2, 2.5, 3, 4, 6, 8, 10, 12, 24 and 48 hours after the start of study drug infusion.
Volume of distribution at steady state (Vdss) following single dose administration
Volume of distribution at steady state (Vdss) of BWC0977 following single dose
Time frame: Immediately before (within 60 minutes before) the start of infusion of the study drug and 5, 10,15, 20, 30, 45, 60, 75, and 90 minutes, 2, 2.5, 3, 4, 6, 8, 10, 12, 24 and 48 hours after the start of study drug infusion.
Pre-dose (trough) concentration (Ct) at the end of the dosing interval
Pre-dose (trough) concentration (Ct) at the end of the dosing interval of BWC0977 following repeat dose administration
Time frame: Immediately before (within 60 minutes before) the start of the first infusion and at 5,15, 30, 60, 75, and 90 minutes, 2, 4, 6, and 8, 12, 24 hours after the start of the last infusion on Day 1 and 7 (MAD 1 cohort) or 10 (For MAD2 -MAD4 cohort).
Volume of distribution at steady state following repeat dose administration
Volume of distribution at steady state (Vdss) of BWC0977 following repeat dose
Time frame: Immediately before (within 60 minutes before) the start of the first infusion and at 5,15, 30, 60, 75, and 90 minutes, 2, 4, 6, and 8, 12, 24 hours after the start of the last infusion on Day 1 and 7 (MAD 1 cohort) or 10 (For MAD2 -MAD4 cohort).
Observed accumulation ratio following repeat dose administration
Observed accumulation ratio (Ro) of BWC0977 following repeat dose administration
Time frame: Immediately before (within 60 minutes before) the start of the first infusion and at 5,15, 30, 60, 75, and 90 minutes, 2, 4, 6, and 8, 12, 24 hours after the start of the last infusion on Day 1 and 7 (MAD 1 cohort) or 10 (For MAD2 -MAD4 cohort).
Amount excreted in urine (Ae) following repeat dose administration
Amount excreted in urine (Ae) of BWC0977 following repeat dose administration
Time frame: Day 1 pre-dose, 0-8 hours post infusion start Day 7 (MAD1 Cohort): 0-12 hours post infusion start Day 10 (MAD 2-3 cohort): 0-12 hours post infusion start Day 10 (MAD 4 Cohort): 0-8 hours post infusion start
Amount excreted in urine (Ae) following single dose administration
Amount excreted in urine (Ae) of BWC0977 following single dose administration
Time frame: 0-4, 4-8, >8-12, >12-24 hours (Days 1-2), >24-36, and >36-48 hours (Days 2-3) after the start of the study drug infusion.
Fraction of the dose excreted in urine (fe) following single dose administration
Fraction of the dose excreted in urine (fe) of BWC0977 following single dose administration
Time frame: 0-4, 4-8, >8-12, >12-24 hours (Days 1-2), >24-36, and >36-48 hours (Days 2-3) after the start of the study drug infusion.
Fraction of the dose excreted in urine (fe) following repeat dose administration
Fraction of the dose excreted in urine (fe) of BWC0977 following repeat dose administration
Time frame: Day 1 pre-dose, 0-8 hours post infusion start Day 7 (MAD1 Cohort): 0-12 hours post infusion start Day 10 (MAD 2-3 cohort): 0-12 hours post infusion start Day 10 (MAD 4 Cohort): 0-8 hours post infusion start
Renal Clearance (CLr) following single dose administration
Renal Clearance (CLr) of BWC0977 following single dose administration
Time frame: 0-4, 4-8, >8-12, >12-24 hours (Days 1-2), >24-36, and >36-48 hours (Days 2-3) after the start of the study drug infusion.
Renal Clearance (CLr) following repeat dose administration
Renal Clearance (CLr) of BWC0977 following repeat dose administration
Time frame: Day 1 pre-dose, 0-8 hours post infusion start Day 7 (MAD1 Cohort): 0-12 hours post infusion start Day 10 (MAD 2-3 cohort): 0-12 hours post infusion start Day 10 (MAD 4 Cohort): 0-8 hours post infusion start