Oral Tebipenem vs IV Imipenem for Urinary Tract Infections

(PIVOT-PO Trial)

Recruiting at 83 trial locations

Overseen By Lori Muir

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Spero Therapeutics

Must not be taking: Valproic acid, Probenecid

Disqualifiers: Seizure disorder, HIV, Pregnancy, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

The primary purpose of this study is to assess the efficacy of oral TBP-PI-HBr as compared with intravenous (IV) imipenem-cilastatin with respect to the overall response (combined clinical cure plus microbiological eradication) at the Test-of-Cure (TOC) visit in hospitalized adult participants (≥18 years of age) with cUTI or AP.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but you cannot use certain drugs like valproic acid, divalproex sodium, or probenecid during the study. Also, you should not have taken any effective antimicrobial drugs within 72 hours before joining the trial.

What data supports the effectiveness of the drug Tebipenem Pivoxil Hydrobromide for urinary tract infections?

Research shows that Tebipenem Pivoxil Hydrobromide is effective against multidrug-resistant bacteria causing urinary tract infections, including strains resistant to other antibiotics. It is an oral drug that works similarly to intravenous carbapenems, making it a promising option for treating serious infections without the need for hospitalization. ^{1 2 3 4 5}

How does the drug Tebipenem Pivoxil Hydrobromide differ from other drugs for urinary tract infections?

Tebipenem Pivoxil Hydrobromide is unique because it is an oral medication, unlike many other treatments for urinary tract infections that require intravenous administration, such as Imipenem-cilastatin. This oral route can make it more convenient for patients to take at home. ^{6 7 8 9 10}

Research Team

David Hong, MD

Principal Investigator

Spero Therapeutics

Eligibility Criteria

Adults diagnosed with complicated urinary tract infection (cUTI) or acute pyelonephritis (AP), showing signs of infection in urine tests. Participants must be expected to survive the treatment duration with proper care. People are excluded if they don't meet these health criteria.

Inclusion Criteria

My recent urine test shows signs of infection.

Expectation, in the judgment of the Investigator, that the participant will survive with effective antimicrobial therapy and appropriate supportive care for the anticipated duration of the study

I have been diagnosed with a complicated urinary tract infection or acute pyelonephritis.

Exclusion Criteria

I have severe blood in my urine that needs treatment beyond study drugs or urinary tools.

I expect to use antibiotics not part of the study that could affect my treatment results.

I haven't taken more than one dose of a strong antibiotic within the last 3 days.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either oral TBP-PI-HBr or intravenous imipenem-cilastatin every 6 hours from Days 1 through 10

10 days

Daily visits (in-person)

Test-of-Cure (TOC)

Assessment of overall response including clinical cure and microbiological eradication

Day 17

1 visit (in-person)

Follow-up

Participants are monitored for sustained clinical and microbiological response

28 days

Visits on Days 10, 17, and 28

Treatment Details

Interventions

• Imipenem-cilastatin (Carbapenem)
• Tebipenem Pivoxil Hydrobromide (Carbapenem)

Trial Overview The trial is testing oral TBP-PI-HBr against IV imipenem-cilastatin for treating cUTI or AP. The goal is to see which treatment better clears the infection and symptoms at a follow-up visit after therapy.

Participant Groups

Group I: TBP-PI-HBr 600 mg + Dummy Infusion Experimental Treatment 2 Interventions

Participants will receive TBP-PI-HBr 600 mg, orally and dummy infusion IV, every 6 hours from Days 1 through 10.

Group II: Imipenem-cilastatin 500 mg + Dummy Tablets Active Control 2 Interventions

Participants will receive imipenem-cilastatin 500 mg, IV and matched dummy tablets, orally, every 6 hours from Days 1 through 10.

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 (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 (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, 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

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

2. 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]

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

Population Pharmacokinetic Analyses for Tebipenem after Oral Administration of Pro-Drug Tebipenem Pivoxil Hydrobromide. [2023]

4. 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]

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

Oral Tebipenem Pivoxil Hydrobromide in Complicated Urinary Tract Infection. [2022]

6. Japan pubmed.ncbi.nlm.nih.gov

[A case of complete response in a patient with invasive bladder cancer due to intermittent intraarterial infusion chemotherapy using the alteration of blood flow]. [2014]

7. Japan pubmed.ncbi.nlm.nih.gov

[The intravesical recurrence after 3-day consecutive intravesical instillation of pirarubicine hydrochloride (THP) following transurethral resection of bladder tumor (TURBT) for non-muscle-invasive bladder cancer]. [2019]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Patterns of Bladder Preservation Therapy Utilization for Muscle-Invasive Bladder Cancer. [2020]

9. Japan pubmed.ncbi.nlm.nih.gov

[The study on intravesical instillation of THP in the treatment of in-situ and superficial bladder cancers]. [2014]

10. Germany pubmed.ncbi.nlm.nih.gov

Prospective randomized controlled trial of postoperative early intravesical chemotherapy with pirarubicin (THP) for solitary non-muscle invasive bladder cancer comparing single and two-time instillation. [2019]