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

NCT06727136 | Completed Phase 1 FDA Drug

• 1 other identifier: SPR994-110
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy Participants

Outcome Measures

Primary Outcomes (9)

• 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 Outcomes (8)

• 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

Study Arms (3)

Part A: Cohort 1

EXPERIMENTAL

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

Part A: Cohort 2 (Fasted/Fed)

EXPERIMENTAL

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

Part B: Cohort 3

EXPERIMENTAL

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

Interventions

TBP-PI-HBr DRUG

TBP-PI-HBr film-coated immediate-release tablets

Also known as: SPR994

Part A: Cohort 1; Part A: Cohort 2 (Fasted/Fed); Part B: Cohort 3

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Spero Therapeutics: lead
• GlaxoSmithKline: collaborator

Study Sites (1)

Medical Facility, Salt Lake City

Salt Lake City, Utah, 84124, United States

Location

MeSH Terms

Interventions

tebipenem

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The study involves 2 parts (A and B) and 3 cohorts (Cohort 1, 2 and 3) of which Cohort 2 has a crossover design.

Study Record Dates

• First Submitted: December 6, 2024
• First Posted: December 10, 2024
• Study Start: November 20, 2024
• Primary Completion: April 22, 2025
• Study Completion: April 22, 2025
• Last Updated: May 20, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)