A Study to Characterize Single and Repeat Dose Pharmacokinetics of Tebipenem-Pivoxil-Hydrobromide (TBP-PI-HBr) and Its Major Metabolite (SPR1349) in Healthy Participants
- Registration Number
- NCT06727136
- Lead Sponsor
- Spero Therapeutics
- Brief Summary
The main purpose of the study is to characterize the systemic pharmacokinetic (PK) parameters (plasma, whole blood) of tebipenem (TBP) pharmacologically active moiety of tebipenem-pivoxil-hydrobromide (TBP-PI-HBr) and its urinary excretion at different dose levels in healthy participants. The study also aims to assess the plasma and urine PK parameters of SPR1349, a major metabolite of TBP.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 39
Inclusion Criteria
Not provided
Exclusion Criteria
- History or presence of/significant history of or current cardiovascular (CV), respiratory, hepatic, renal, gastrointestinal, endocrine, hematologic, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study intervention or study procedures or interfering with the interpretation of data.
- Past or intended use of over-the-counter or prescription medication including herbal medications within 28 days prior to dosing, with the exception of supplemental vitamins, hormonal medications (contraceptives or hormone-replacement therapy), or occasional oral acetaminophen (not to exceeding 2 g total daily dose).
- Current enrollment or past participation in another investigational/observational clinical study in which an investigational intervention (e.g., drug, vaccine, invasive device) was administered within the last 30 days, or 5 half-lives whichever is longer.
- Positive COVID-19 screening test using PCR or antigen assay at Day -1
- Donation of, or significant blood loss of, more than 500 mL of blood within 56 days prior to dosing.
- Receipt of a blood transfusion within 1 year prior to enrollment or plasma donation within 7 days prior to dosing.
- QTc >450 msec.
Note: Other inclusion/exclusion criteria may also apply
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part B: Cohort 3 TBP-PI-HBr Participants will receive TBP-PI-HBr, 600 mg, orally as a single dose on Day 1, followed by 9 doses every 6 hours from Day 3 through Day 5. (first and ninth dose will be given under fasted conditions). Part A: Cohort 1 TBP-PI-HBr Participants will receive TBP-PI-HBr, 900 milligrams (mg) tablets orally, as a single dose under fasted condition on Day 1. Part A: Cohort 2 (Fasted/Fed) TBP-PI-HBr Participants will receive TBP-PI-HBr, 1200 mg, tablets, orally, as a single dose under fasted and fed conditions on Day 1 and Day 3, as per the assigned crossover sequence.
- Primary Outcome Measures
Name Time Method Part A and B: Maximum Observed Concentration (Cmax) of TBP in Plasma and Blood Cohort 1: Pre-dose and at multiple timepoints post-dose up to Day 3; Cohort 2: Pre-dose and at multiple timepoints post-dose up to Day 5; Cohort 3: pre-dose and at multiple timepoints post-dose up to Day 7 Part A and B: Time to Cmax (Tmax) of TBP in Plasma and Blood Cohort 1: Pre-dose and at multiple timepoints post-dose up to Day 3; Cohort 2: Pre-dose and at multiple timepoints post-dose up to Day 5; Cohort 3: pre-dose and at multiple timepoints post-dose up to Day 7 Part A and B: Area Under the Concentration-Time Curve (AUC) Extrapolated to Infinity [AUC(0-inf)] of TBP in Plasma and Blood Cohort 1: Pre-dose and at multiple timepoints post-dose up to Day 3; Cohort 2: Pre-dose and at multiple timepoints post-dose up to Day 5; Cohort 3: pre-dose and at multiple timepoints post-dose up to Day 7 Part A and B: AUC From Time Zero to the Time of the Last Evaluable Concentration [AUC(0-t)] of TBP in Plasma and Blood Cohort 1: Pre-dose and at multiple timepoints post-dose up to Day 3; Cohort 2: Pre-dose and at multiple timepoints post-dose up to Day 5; Cohort 3: pre-dose and at multiple timepoints post-dose up to Day 7 Part A and B: Amount Excreted in Urine (Ae) of TBP Cohort 1: Pre-dose and at multiple timepoints post-dose up to Day 3; Cohort 2: Pre-dose and at multiple timepoints post-dose up to Day 5; Cohort 3: pre-dose and at multiple timepoints post-dose up to Day 7 Part A and B: Fraction of Dose Excreted in Urine (Fe) of TBP Cohort 1: Pre-dose and at multiple timepoints post-dose up to Day 3; Cohort 2: Pre-dose and at multiple timepoints post-dose up to Day 5; Cohort 3: pre-dose and at multiple timepoints post-dose up to Day 7 Part B: AUC From Time Zero to 6 Hours Post-dose AUC(0-6) of TBP in Plasma and Blood Pre-dose and at multiple timepoints post-dose up to Day 7 Part B: Ae of SPR1349 Pre-dose and at multiple timepoints post-dose up to Day 7 Part B: Fe of SPR1349 Pre-dose and at multiple timepoints post-dose up to Day 7
- Secondary Outcome Measures
Name Time Method Part B: Tmax of SPR1349 in Plasma Pre-dose and at multiple timepoints post-dose up to Day 7 Part B: Cmax of SPR1349 in Plasma Pre-dose and at multiple timepoints post-dose up to Day 7 Part B: AUC(0-inf) of SPR1349 in Plasma Pre-dose and at multiple timepoints post-dose up to Day 7 Part B: AUC(0-t) of SPR1349 in Plasma Pre-dose and at multiple timepoints post-dose up to Day 7 Part B: AUC(0-6) of SPR1349 in Plasma Pre-dose and at multiple timepoints post-dose up to Day 7 Part B: Plasma AUC Ratio of SPR1349 to TBP Pre-dose and at multiple timepoints post-dose up to Day 7 Part B: Ae Ratio of SPR1349 to TBP Pre-dose and at multiple timepoints post-dose up to Day 7 Parts A and B: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Day 1 to Day 21
Related Research Topics
Explore scientific publications, clinical data analysis, treatment approaches, and expert-compiled information related to the mechanisms and outcomes of this trial. Click any topic for comprehensive research insights.
What is the enzymatic conversion mechanism of TBP-PI-HBr to SPR1349 and its role in antibacterial activity?
How does TBP-PI-HBr's PK profile compare to meropenem in treating carbapenem-resistant pathogens?
Which biomarkers correlate with SPR1349 urinary excretion rates in beta-lactam antibiotic trials?
What are the safety profiles of TBP-PI-HBr versus other beta-lactam prodrugs in Phase 1 studies?
How do beta-lactamase inhibitors synergize with TBP-PI-HBr against Gram-negative infections?
Trial Locations
- Locations (1)
Medical Facility, Salt Lake City
🇺🇸Salt Lake City, Utah, United States