Tebipenem for Healthy Subjects

Overseen By Aubri Hutchins

Age: 18 - 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Spero Therapeutics

Must not be taking: Herbal medications

Disqualifiers: Cardiovascular, Respiratory, Hepatic, others

No Placebo Group

Approved in 1 Jurisdiction

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

Yes, you will need to stop taking any over-the-counter or prescription medications, including herbal medications, at least 28 days before the trial starts, except for vitamins, hormonal medications, or occasional acetaminophen.

What data supports the effectiveness of the drug Tebipenem pivoxil hydrobromide?

Tebipenem pivoxil hydrobromide is an oral drug that has shown effectiveness against multidrug-resistant bacterial infections, similar to intravenous carbapenems like meropenem. It is being developed for treating complicated urinary tract infections and has demonstrated comparable activity to other carbapenems in both laboratory and animal studies. ^{1 2 3 4 5}

Is Tebipenem safe for healthy humans?

Tebipenem pivoxil hydrobromide was well tolerated in healthy adults, with mild and temporary diarrhea being the most common side effect reported. ^{1 3 5 6 7}

Eligibility Criteria

This trial is for healthy individuals who want to participate in a study assessing the behavior of a drug called Tebipenem-Pivoxil-Hydrobromide (TBP-PI-HBr) and its major metabolite in the body. Specific eligibility criteria are not provided, but typically participants must meet certain health standards.

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

I am between 18 and 55 years old.

Exclusion Criteria

I do not have major health issues that could affect drug processing or pose risks in the study.

QTc >450 msec

I have not taken any medication except vitamins, hormonal meds, or occasional acetaminophen in the last 28 days.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive TBP-PI-HBr in different dosing regimens to assess pharmacokinetics

5 days

Daily visits for dosing and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

1-2 weeks

Treatment Details

Interventions

• Tebipenem-Pivoxil-Hydrobromide (Anti-bacterial agent)

Trial Overview The study is testing how TBP-PI-HBr, an active drug form of tebipenem, and its major metabolite SPR1349 behave in the bloodstream and urine after single and repeated doses. The goal is to understand how these substances are processed by the body at different dose levels.

Participant Groups

Group I: Part B: Cohort 3 Experimental Treatment 1 Intervention

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).

Group II: Part A: Cohort 2 (Fasted/Fed) Experimental Treatment 1 Intervention

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.

Group III: Part A: Cohort 1 Experimental Treatment 1 Intervention

Participants will receive TBP-PI-HBr, 900 milligrams (mg) tablets orally, as a single dose under fasted condition on Day 1.

Tebipenem-Pivoxil-Hydrobromide is already approved in Japan for the following indications:

Approved in Japan as Orapenem for:

• Paediatric infections limited to pneumonia, otitis media and sinusitis

Who Is Running the Clinical Trial?

Spero Therapeutics

Lead Sponsor

Trials

24

Recruited

4,900+

GlaxoSmithKline

Industry Sponsor

Trials

4,834

Recruited

8,389,000+

Headquarters

London, UK

Known For

Vaccines & Medicines

Top Products

**Advair (salmeterol, fluticasone propionate)**, **Shingrix (shingles vaccine)**, **Augmentin (amoxicillin/clavulanate potassium)**, **Ventolin (salbutamol sulfate)

Dame Emma Walmsley

GlaxoSmithKline

Chief Executive Officer since 2017

MA in Classics and Modern Languages from Oxford University

Dr. Hal Barron

GlaxoSmithKline

Chief Medical Officer since 2018

MD from Harvard Medical School

Findings from Research

Tebipenem pivoxil hydrobromide (TBPM-PI-HBr) is an orally available prodrug that effectively treats multidrug-resistant Gram-negative infections, showing linear and dose-proportional pharmacokinetics in healthy adults across a range of doses (100 to 900 mg).

The drug was well tolerated with mild diarrhea as the most common side effect, indicating its safety profile, and it has the potential to reduce reliance on intravenous antibiotics for serious infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, Pharmacokinetics, and Food Effect of Tebipenem Pivoxil Hydrobromide after Single and Multiple Ascending Oral Doses in Healthy Adult Subjects. Eckburg, PB., Jain, A., Walpole, S., et al.[2020]

Tebipenem pivoxil hydrobromide (tebipenem-PI-HBr) is an orally available prodrug of tebipenem that shows effectiveness against multidrug-resistant Gram-negative bacteria, making it a promising option for treating complicated urinary tract infections (cUTI).

In laboratory tests and mouse infection models, tebipenem demonstrated equivalent efficacy to intravenous carbapenems like meropenem, indicating its potential as a valuable oral antibiotic for infections requiring strong carbapenem activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In Vitro and In Vivo Characterization of Tebipenem, an Oral Carbapenem. Cotroneo, N., Rubio, A., Critchley, IA., et al.[2021]

Tebipenem pivoxil hydrobromide, when crushed and administered via nasogastric tube (NGT), showed bioequivalence to whole tablet oral administration in terms of plasma concentration and overall exposure, indicating it can be effectively delivered in alternative forms.

The study, involving 12 healthy subjects, demonstrated that both crushed tebipenem with and without enteral feeds were well tolerated, supporting flexible administration methods based on patient needs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relative bioavailability of crushed tebipenem administered through a nasogastric tube with and without enteral feeding. Fouad, A., Quintiliani, R., Nicolau, DP., et al.[2023]

The study confirmed the bioequivalence of two formulations of tebipenem pivoxil hydrobromide (TBP-PI-HBr) in 36 healthy adults, showing that both formulations have similar pharmacokinetic profiles, which is important for ensuring consistent therapeutic effects.

Food intake did not significantly affect the pharmacokinetics of TBP, allowing for flexible dosing without dietary restrictions, and the treatment was well-tolerated with only mild adverse events reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bioequivalence of two oral formulations of tebipenem pivoxil hydrobromide in healthy subjects. Gupta, VK., Patel, G., Gasink, L., et al.[2022]

Tebipenem pivoxil HBr (TBPM-PI-HBr) is a new oral carbapenem antibiotic that has shown effective pharmacodynamics against complicated urinary tract infections (cUTI) in a murine model, with a specific focus on its action against Enterobacteriaceae strains.

The study established that a certain level of drug exposure (fAUC0-24/MIC) is necessary to achieve bacterial stasis and suppress resistance, providing critical data for designing future clinical trials in adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacodynamics of Tebipenem: New Options for Oral Treatment of Multidrug-Resistant Gram-Negative Infections. McEntee, L., Johnson, A., Farrington, N., et al.[2020]

A new ultra-high-performance liquid chromatography method was developed to identify and separate 23 related impurities in the oral formulation of tebipenem pivoxil (TBPM-PI), ensuring its safety for pediatric use.

The study revealed that some impurities could form from reactions between excipients and existing impurities, highlighting the importance of thorough impurity analysis in pharmaceutical formulations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identification of related impurities in an oral pharmaceutical formulation of tebipenem pivoxil using ultra-high-performance liquid chromatography/electrospray ionization quadrupole time-of-flight tandem mass spectrometry. Xi, P., Cao, W., Li, L., et al.[2022]

Tebipenem pivoxil hydrobromide, a novel oral carbapenem, showed effective distribution into skin and soft tissue in both healthy subjects and patients with diabetic foot infections, indicating its potential for treating infections in these areas.

The pharmacokinetics revealed that tebipenem achieved similar tissue concentrations in both populations, with a penetration ratio of 107% in healthy subjects and 90% in infected patients, suggesting good efficacy in delivering the drug to the site of infection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and soft-tissue distribution of tebipenem pivoxil hydrobromide using microdialysis: a study in healthy subjects and patients with diabetic foot infections. Abouelhassan, Y., Fratoni, AJ., Shepard, AK., et al.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

Safety, Pharmacokinetics, and Food Effect of Tebipenem Pivoxil Hydrobromide after Single and Multiple Ascending Oral Doses in Healthy Adult Subjects. [2020]

2. United States pubmed.ncbi.nlm.nih.gov

In Vitro and In Vivo Characterization of Tebipenem, an Oral Carbapenem. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Relative bioavailability of crushed tebipenem administered through a nasogastric tube with and without enteral feeding. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Bioequivalence of two oral formulations of tebipenem pivoxil hydrobromide in healthy subjects. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Pharmacodynamics of Tebipenem: New Options for Oral Treatment of Multidrug-Resistant Gram-Negative Infections. [2020]

6. England pubmed.ncbi.nlm.nih.gov

Identification of related impurities in an oral pharmaceutical formulation of tebipenem pivoxil using ultra-high-performance liquid chromatography/electrospray ionization quadrupole time-of-flight tandem mass spectrometry. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and soft-tissue distribution of tebipenem pivoxil hydrobromide using microdialysis: a study in healthy subjects and patients with diabetic foot infections. [2023]