This is a Phase 1, single-center, multi-arm, open-label, randomized, three-period, crossover study to evaluate the drug-drug interaction, pharmacokinetics, safety, and tolerability of a single dose of SPR741 combined with each of 3 different partner antibiotics (ceftazidime or piperacillin/tazobactam or aztreonam) in healthy volunteers. Participants will be administered single doses of SPR741 alone, a single dose of SPR741 in combination with 1 of 3 different partner antibiotics, and the partner antibiotic alone in a randomized sequence. Twenty-seven (27) adult male and female normal healthy participants 18 to 55 years of age are planned to participate in the study. Women of childbearing potential will not be eligible to participate.
This is a Phase 1, single-center, multi-arm, open-label, randomized, three-period crossover study to evaluate the drug-drug interaction, pharmacokinetics, safety, and tolerability of a single dose of SPR741 combined with each of 3 different partner antibiotics (ceftazidime, piperacillin/tazobactam, and aztreonam) in healthy volunteers. Participants will be administered a single dose of SPR741 alone, a single dose of SPR741 in combination with 1 of the 3 different partner antibiotics, and a single dose of the partner antibiotic alone in a randomized sequence. Twenty-seven (27) adult male and female normal healthy participants 18 to 55 years of age are planned to participate in the study. Women of childbearing potential will not be eligible to participate. The study will consist of 3 phases: a screening phase, a treatment phase, and a follow-up phase. The 3 treatment arms will be enrolled and dosed in parallel or in a staggered manner, as needed for scheduling. All participants in the study will be monitored for safety after administration of the last dose of investigational product.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
27
400 mg IV over 1 hour
1.0 gram IV over 1 hour
4.5 grams IV over 1 hour
1.0 gram IV over 1 hour
Simbec Research, Ltd.
Merthyr Tydfil, Mid Glamorgan, United Kingdom
Pharmacokinetics: Maximum concentration (Cmax)
Blood draws will be taken pre-dose (within 10 minutes), 30 minutes following the start of infusion, end of infusion and at 75, 90, 105, and 120 minutes, 4, 8, 12, and 24 hours following start of infusion.
Time frame: Days 1 to 2, Days 4 to 5, Days 7 to 8
Pharmacokinetics: Area under the concentration-time curve from time 0 to last measurable time-point (AUC0-t)
Blood draws will be taken pre-dose (within 10 minutes), 30 minutes following the start of infusion, end of infusion and at 75, 90, 105, and 120 minutes, 4, 8, 12, and 24 hours following start of infusion.
Time frame: Days 1 to 2, Days 4 to 5, Days 7 to 8
Pharmacokinetics: Area under the concentration-time curve from time 0 to infinity (AUC0-inf)
Blood draws will be taken pre-dose (within 10 minutes), 30 minutes following the start of infusion, end of infusion and at 75, 90, 105, and 120 minutes, 4, 8, 12, and 24 hours following start of infusion.
Time frame: Days 1 to 2, Days 4 to 5, Days 7 to 8
Pharmacokinetics: Time to maximum concentration (Tmax)
Blood draws will be taken pre-dose (within 10 minutes), 30 minutes following the start of infusion, end of infusion and at 75, 90, 105, and 120 minutes, 4, 8, 12, and 24 hours following start of infusion.
Time frame: Days 1 to 2, Days 4 to 5, Days 7 to 8
Pharmacokinetics: Terminal Elimination Rate Constant (kel)
Blood draws will be taken pre-dose (within 10 minutes), 30 minutes following the start of infusion, end of infusion and at 75, 90, 105, and 120 minutes, 4, 8, 12, and 24 hours following start of infusion.
Time frame: Days 1 to 2, Days 4 to 5, Days 7 to 8
Pharmacokinetics: Terminal half-life (t1/2)
Blood draws will be taken pre-dose (within 10 minutes), 30 minutes following the start of infusion, end of infusion and at 75, 90, 105, and 120 minutes, 4, 8, 12, and 24 hours following start of infusion.
Time frame: Days 1 to 2, Days 4 to 5, Days 7 to 8
Pharmacokinetics: Terminal clearance (CL)
Blood draws will be taken pre-dose (within 10 minutes), 30 minutes following the start of infusion, end of infusion and at 75, 90, 105, and 120 minutes, 4, 8, 12, and 24 hours following start of infusion.
Time frame: Days 1 to 2, Days 4 to 5, Days 7 to 8
Pharmacokinetics: Volume of distribution (Vd)
Blood draws will be taken pre-dose (within 10 minutes), 30 minutes following the start of infusion, end of infusion and at 75, 90, 105, and 120 minutes, 4, 8, 12, and 24 hours following start of infusion.
Time frame: Days 1 to 2, Days 4 to 5, Days 7 to 8
Safety measures: adverse events (AEs)
The types and frequency of AEs
Time frame: Day -1 to Day 9
Safety measures: Summary of type and frequency of concomitant medication
The type and frequency of medications used will be summarized
Time frame: Day -1 to Day 9
Safety measures: change in temperature (C/F)
Change from baseline to end of study
Time frame: Day -1 to Day 9
Safety measures: change in blood pressure (mmHg)
Change from baseline to end of study
Time frame: Day -1 to Day 9
Safety measures: change in heart rate (beats per minute)
Change from baseline to end of study
Time frame: Day -1 to Day 9
Safety measures: abnormal, clinically significant physical exam findings
Change from baseline to end of study
Time frame: Day -1 to Day 9
Safety measures: abnormal, clinically significant changes in electrocardiogram parameter (RR Interval)
Change from baseline to end of study
Time frame: Day -1 to Day 9
Safety measures: abnormal, clinically significant changes in electrocardiogram parameter (P wave)
Change from baseline to end of study
Time frame: Day -1 to Day 9
Safety measures: abnormal, clinically significant changes in electrocardiogram parameter (PR Interval)
Change from baseline to end of study
Time frame: Day -1 to Day 9
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Safety measures: abnormal, clinically significant changes in electrocardiogram parameter (QRS)
Change from baseline to end of study
Time frame: Day -1 to Day 9
Safety measures: abnormal, clinically significant changes in electrocardiogram parameter (ST Segment)
Change from baseline to end of study
Time frame: Day -1 to Day 9
Safety measures: abnormal, clinically significant changes in electrocardiogram parameter (T Wave)
Change from baseline to end of study
Time frame: Day -1 to Day 9
Safety measures:abnormal, clinically significant changes in urinalysis from baseline to end of study
Change from baseline to end of study
Time frame: Day -1 to Day 9
Safety measures: abnormal, clinically significant hematology changes from baseline to end of study
Change from baseline to end of study
Time frame: Day -1 to Day 9
Safety measures: abnormal, clinically significant serum chemistry changes from baseline to end of study
Change from baseline to end of study
Time frame: Day -1 to Day 9