A Study to Characterize Single and Repeat Dose Pharmacokinetics of Tebipenem-Pivoxil-Hydrobromide (TBP-PI-HBr) and Its Major Metabolite (SPR1349) in Healthy Participants

A Phase 1, Open-label Study to Characterize Single and Repeat Dose Pharmacokinetics (Including Food Effect) of Tebipenem-pivoxil-hydrobromide and Its Major Metabolite (SPR1349) in Healthy Participants

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.

Study Overview

• Status: Completed
• Conditions: Healthy Participants
• Intervention / Treatment: Drug: TBP-PI-HBr

• Study Type: Interventional
• Enrollment (Actual): 39
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Utah
    • Salt Lake City, Utah, United States, 84124
      • Medical Facility, Salt Lake City

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria

• Participants who are healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and electrocardiogram (ECG).
• Body weight considering body mass index (BMI) within the range of 18 to 32 kilogram per meter square (kg/m^2), inclusive.
• Participant must be 18 (or the legal age of consent in the jurisdiction in which the study is taking place) to 55 years of age inclusive, at the time of signing the informed consent.

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A: Cohort 1; Participants will receive TBP-PI-HBr, 900 milligrams (mg) tablets orally, as a single dose under fasted condition on Day 1.	Drug: TBP-PI-HBr; TBP-PI-HBr film-coated immediate-release tablets; Other Names: SPR994
Experimental: Part A: Cohort 2 (Fasted/Fed); 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.	Drug: TBP-PI-HBr; TBP-PI-HBr film-coated immediate-release tablets; Other Names: SPR994
Experimental: Part B: Cohort 3; 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).	Drug: TBP-PI-HBr; TBP-PI-HBr film-coated immediate-release tablets; Other Names: SPR994

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: Spero Therapeutics
• Collaborators: GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start (Actual): November 20, 2024
• Primary Completion (Actual): April 22, 2025
• Study Completion (Actual): April 22, 2025

Study Registration Dates

• First Submitted: December 6, 2024
• First Submitted That Met QC Criteria: December 6, 2024
• First Posted (Actual): December 10, 2024

Study Record Updates

• Last Update Posted (Estimated): May 20, 2025
• Last Update Submitted That Met QC Criteria: May 19, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Other Study ID Numbers: SPR994-110

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No