Tebipenem for Healthy Subjects

Overseen By Aubri Hutchins

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Spero Therapeutics

Must not be taking: Herbal medications

Disqualifiers: Cardiovascular, Respiratory, Hepatic, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 5 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests how the antibiotic tebipenem is processed in the body and excreted through urine in healthy individuals. Researchers aim to understand how different doses of this drug, taken under various conditions such as with or without food, affect the body. Healthy individuals with no major ongoing health issues and who have not recently taken certain medications may be suitable for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new drug.

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.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research shows that tebipenem pivoxil hydrobromide, the treatment under study, is generally safe. Studies have found that the most common side effects are mild, including diarrhea, headache, and nausea. A small number of patients, usually less than 3%, reported these side effects, and most experienced them only briefly. This suggests the treatment is relatively safe and manageable for most people. Prospective participants might find this information helpful in understanding what to expect regarding safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Tebipenem-Pivoxil-Hydrobromide (TBP-PI-HBr) is unique because it is an oral carbapenem, which could offer a more convenient alternative to the current intravenous carbapenems used to treat bacterial infections. Unlike typical treatments that require hospital admission for IV administration, TBP-PI-HBr can be taken as a tablet, making it potentially more accessible for patients. Researchers are excited about its ability to provide effective treatment without the need for hospital stays, which could improve patient quality of life and reduce healthcare costs. Additionally, its flexible dosing under both fasted and fed conditions could enhance patient compliance and treatment outcomes.

What evidence suggests that tebipenem-pivoxil-hydrobromide could be effective?

Research shows that tebipenem pivoxil hydrobromide (TBP-PI-HBr) could be a promising oral treatment for complicated urinary tract infections. Studies have found it to be as effective as intravenous ertapenem, a commonly used antibiotic. Tebipenem HBr achieved a clinical cure rate of 93.5%, close to the 95.2% rate of imipenem-cilastatin. It also demonstrated a microbiological response rate of 60.3%. These results suggest tebipenem could be a strong alternative to current treatments, with the added convenience of oral administration. Participants in this trial will receive different dosages and conditions of TBP-PI-HBr to further evaluate its effectiveness and safety. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

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

Exclusion Criteria

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

QTc >450 msec

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Tebipenem-Pivoxil-Hydrobromide

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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 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]

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 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]

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]

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 (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]

Citations

1. gsk.com gsk.com/en-gb/media/press-releases/positive-pivot-po-phase-iii-data-show-tebipenem-hbr-s-potential-as-the-first-oral-carbapenem-antibiotic-for-patients-with-complicated-urinary-tract-infections-cutis/

Positive PIVOT-PO phase III data show tebipenem HBr's ... Tebipenem HBr (oral, 600 mg) achieved a 58.5% overall success rate (261/446 participants) compared to 60.2% overall success rate (291/483 ...

2. firstwordpharma.com firstwordpharma.com/story/6327647

PIVOT-PO Phase 3 Data Show Tebipenem HBr's Potential ... Tebipenem HBr (oral, 600 mg) achieved a 58.5% overall success rate (261/446 participants) compared to 60.2% overall success rate (291/483 ...

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa2105462

Oral Tebipenem Pivoxil Hydrobromide in Complicated ... Oral tebipenem pivoxil hydrobromide was noninferior to intravenous ertapenem in the treatment of complicated urinary tract infection and acute pyelonephritis.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10112213/

Tebipenem Pivoxil Hydrobromide (TBP-PI-HBr) in Healthy ... At least 90% of the TBP-PI radioactive dose was recovered in the urine or feces within 48 h in rats and monkeys (data on file, Spero ...

5. contagionlive.com contagionlive.com/view/oral-carbapenem-tebipenem-hbr-demonstrates-non-inferiority-to-iv-therapy-in-phase-iii-pivot-po-trial

Oral Carbapenem Tebipenem HBr Demonstrates Non- ... Clinical cure rates were 93.5% for tebipenem HBr and 95.2% for imipenem-cilastatin, while microbiological response rates were 60.3% and 61.3%, ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31262768/

Safety, Pharmacokinetics, and Food Effect of Tebipenem ... TBPM-PI-HBr was well tolerated; mild, transient diarrhea was the most commonly reported adverse event. TBPM-PI-HBr provides an orally ...

7. accpjournals.onlinelibrary.wiley.com accpjournals.onlinelibrary.wiley.com/doi/10.1002/phar.2614

Tebipenem pivoxil hydrobromide—No PICC, no problem! The most common adverse effects associated with TBP-PI-HBr are diarrhea, headache, and nausea. TBP-PI-HBr will be particularly useful in ...

8. sperotherapeutics.com sperotherapeutics.com/pipeline/tebipenem-hbr

Tebipenem Hbr | Oral Carbapenem | Spero Therapuetics Tebipenem HBr is an investigational oral carbapenem for cUTI and AP, potentially reducing hospitalizations and inpatient therapy duration.