A Study of Oral Tebipenem Pivoxil Hydrobromide (TBP-PI-HBr) Compared to Intravenous Imipenem-cilastatin in Participants With Complicated Urinary Tract Infection (cUTI) or Acute Pyelonephritis (AP)

Recruitment Status
COMPLETED - HAS RESULTS
(See Contacts and Locations)Verified February 2026 by Spero Therapeutics
Sponsor
Spero Therapeutics
Information Provided by (Responsible Party)
Spero Therapeutics
Clinicaltrials.gov Identifier
NCT06059846
Other Study ID Numbers:
SPR994-305
First Submitted
September 21, 2023
First Posted
September 28, 2023
Results First Posted
January 22, 2026
Last Update Posted
March 9, 2026
Last Verified
February 2026

ClinicalTrials.gov processed this data on March 2026. Link to the current ClinicalTrials.gov record .

History of Changes

Study Details

Study Description

The study included a pre-planned interim analysis with stopping criteria for efficacy and futility that was performed by an independent data monitoring committee (IDMC). For full details please refer to the protocol and statistical analysis plan.

Condition or DiseaseIntervention/Treatment
Urinary Tract InfectionAcute Pyelonephritis
Drug: TBP-PI-HBrDrug: Imipenem-cilastatin

Study Design

Study TypeInterventional
Actual Enrollment1690 participants
Design AllocationRandomized
Interventional ModelParallel Assignment
MaskingTriple
Primary PurposeTreatment
Official TitleA Phase 3, Randomized, Double-blind, Double-dummy, Multicenter, Multinational Study to Assess the Efficacy and Safety of Orally Administered Tebipenem Pivoxil Hydrobromide (TBP-PI-HBr) Compared to Intravenously Administered Imipenem-cilastatin in Patients With Complicated Urinary Tract Infection (cUTI) or Acute Pyelonephritis (AP)
Study Start DateDecember 20, 2023
Actual Primary Completion DateJanuary 26, 2025
Actual Study Completion DateFebruary 5, 2025

Groups and Cohorts

Group/CohortIntervention/Treatment
TBP-PI-HBr
Participants received TBP-PI-HBr 600 milligrams (mg), two x 300mg film-coated tablets, orally (PO) and a dummy infusion intravenously (IV), every 6 hours (q6h) from Day 1 through Day 10. Participants with estimated baseline creatinine clearance (CrCl) greater than (\>) 30 millilitres per minute (mL/min) and less than or equal to (≤) 50 mL/min received TBP-PI-HBr 300 mg q6h.
Drug: TBP-PI-HBr
TBP-PI-HBr film-coated immediate-release tablets.
Imipenem-cilastatin
Participants received imipenem-cilastatin 500 mg, IV and matched dummy tablets, PO, q6h from Day 1 through Day 10. Dose adjustments for imipenem-cilastatin were made for participants with estimated baseline CrCl less than (\<) 90mL/min per approved imipenem-cilastatin package insert. Participants with baseline CrCl levels greater than or equal to (≥) 60 to \< 90 mL/min were administered imipenem-cilastatin, 400 mg IV q6h and participants with baseline CrCl levels \>30 to \<60 mL/min, were administered 300mg IV, q6h.
Drug: Imipenem-cilastatin
Sterile powder for reconstitution administered as IV.

Outcome Measures

Primary Outcome Measures
  1. Number of Participants With Overall Response at the Test-of-Cure (TOC) Visit in the Microbiological Intent-to-Treat (Micro-ITT) Population
    Overall response includes combined clinical cure plus microbiological eradication. Clinical cure is defined as a complete resolution or significant improvement of signs and symptoms of cUTI or AP present at baseline and no new symptoms, such that no further antibacterial therapy is warranted, and participant is alive. Microbiological eradication (favorable microbiological response) is defined as a reduction of baseline uropathogens to \&lt;10\^3 CFU/mL and negative repeated blood culture if blood culture was positive for uropathogen growth at baseline and participant is alive.
Secondary Outcome Measures
  1. Number of Participants With Overall Response (Combined Per-Participant Clinical Cure and Favorable Microbiological Response) at the TOC Visit in the Microbiologically Evaluable (ME) Population
    Overall response includes combined clinical cure plus microbiological eradication. Clinical cure is defined as a complete resolution or significant improvement of signs and symptoms of cUTI or AP present at baseline and no new symptoms, such that no further antibacterial therapy is warranted, and participant is alive. Microbiological eradication (favorable microbiological response) is defined as a reduction of baseline uropathogens to \&lt;10\^3 CFU/mL and negative repeated blood culture if blood culture was positive for uropathogen growth at baseline and participant is alive.
  2. Number of Participants With Overall Response at the End-of-Treatment (EOT) and Late Follow-Up (LFU) Visits in the Micro-ITT Population
    Overall response includes combined clinical cure plus microbiological eradication. Clinical cure is defined as a complete resolution or significant improvement of signs and symptoms of cUTI or AP present at baseline and no new symptoms, such that no further antibacterial therapy is warranted, and participant is alive. Microbiological eradication (favorable microbiological response) is defined as a reduction of baseline uropathogens to \&lt;10\^3 CFU/mL and negative repeated blood culture if blood culture was positive for uropathogen growth at baseline and participant is alive.
  3. Number of Participants With Overall Response at EOT and LFU Visits in the ME Population
    Overall response includes combined clinical cure plus microbiological eradication. Clinical cure is defined as a complete resolution or significant improvement of signs and symptoms of cUTI or AP present at baseline and no new symptoms, such that no further antibacterial therapy is warranted, and participant is alive. Microbiological eradication (favorable microbiological response) is defined as a reduction of baseline uropathogens to \&lt;10\^3 CFU/mL and negative repeated blood culture if blood culture was positive for uropathogen growth at baseline and participant is alive.
  4. Number of Participants With Clinical Response at EOT, TOC and LFU Visits in the Micro-ITT Population
    Clinical response at EOT and TOC is based on the Investigator&#039;s assessment of changes in baseline cUTI/AP signs and symptoms. Clinical cure: complete resolution or marked improvement of baseline symptoms with no new symptoms and no need for additional antimicrobial therapy. Clinical failure: baseline symptoms not fully resolved, new symptoms occur requiring non-study antibiotics, or death. Clinical indeterminate: insufficient data to classify response (e.g., lost to follow-up or missing data). Clinical response at LFU is based on change from baseline. Cure, including sustained clinical cure: met cure criteria at TOC and remained free of new or recurrent cUTI/AP symptoms at LFU with no need for further antibiotics. Failure, including clinical relapse: met cure criteria at TOC but developed new cUTI/AP symptoms at LFU requiring antibiotics. Clinical indeterminate: insufficient data to classify as sustained cure or relapse.
  5. Number of Participants With Clinical Response at EOT, TOC and LFU Visits in the CE Population
    Clinical response at EOT and TOC is based on the Investigator&#039;s assessment of changes in baseline cUTI/AP signs and symptoms. Clinical cure: complete resolution or marked improvement of baseline symptoms with no new symptoms and no need for additional antimicrobial therapy. Clinical failure: baseline symptoms not fully resolved, new symptoms occur requiring non-study antibiotics, or death. Clinical indeterminate: insufficient data to classify response (e.g., lost to follow-up or missing data). Clinical response at LFU is based on change from baseline. Cure, including sustained clinical cure: met cure criteria at TOC and remained free of new or recurrent cUTI/AP symptoms at LFU with no need for further antibiotics. Failure, including clinical relapse: met cure criteria at TOC but developed new cUTI/AP symptoms at LFU requiring antibiotics. Clinical indeterminate: insufficient data to classify as sustained cure or relapse.
  6. Number of Participants With Clinical Response at EOT, TOC and LFU Visits in the ME Population
    Clinical response at EOT and TOC is based on the Investigator&#039;s assessment of changes in baseline cUTI/AP signs and symptoms. Clinical cure: complete resolution or marked improvement of baseline symptoms with no new symptoms and no need for additional antimicrobial therapy. Clinical failure: baseline symptoms not fully resolved, new symptoms occur requiring non-study antibiotics, or death. Clinical indeterminate: insufficient data to classify response (e.g., lost to follow-up or missing data). Clinical response at LFU is based on change from baseline. Cure, including sustained clinical cure: met cure criteria at TOC and remained free of new or recurrent cUTI/AP symptoms at LFU with no need for further antibiotics. Failure, including clinical relapse: met cure criteria at TOC but developed new cUTI/AP symptoms at LFU requiring antibiotics. Clinical indeterminate: insufficient data to classify as sustained cure or relapse.
  7. Number of Participants With Microbiological Response at EOT, TOC and LFU Visits in the Micro-ITT Population
    Participants were evaluated for microbiological response based on blood and urine cultures as: Eradication, defined as reduction of Baseline uropathogens to \&lt;10\^3 CFU/mL on urine culture and negative repeated blood culture (if blood culture was positive at Baseline) ;Persistence, defined as Isolation from urine culture of &ge;10\^3 CFU/mL or from blood of any of the Baseline uropathogen(s) identified at study entry; Indeterminate: no follow-up urine culture is available, or urine culture results are missing, or follow-up urine culture cannot be interpreted for any reason.
  8. Number of Participants With Microbiological Response at EOT, TOC and LFU Visits in the ME Population
    Participants were evaluated for microbiological response based on blood and urine cultures as: Eradication, defined as reduction of baseline uropathogens to \&lt;10\^3 CFU/mL on urine culture and negative repeated blood culture (if blood culture was positive at Baseline); Persistence, defined as Isolation from urine culture of &ge;10\^3 CFU/mL or from blood of any of the Baseline uropathogen(s) identified at study entry; Indeterminate: no follow-up urine culture is available, or urine culture results are missing, or follow-up urine culture cannot be interpreted for any reason.
  9. Number of Participants With Overall Response at EOT, TOC, and LFU Visits in Participants With Drug-Resistant Enterobacterales in Micro-ITT Population
    Overall response includes combined clinical cure plus microbiological eradication. Clinical cure is defined as a complete resolution or significant improvement of signs and symptoms of cUTI or AP present at baseline and no new symptoms, such that no further antibacterial therapy is warranted, and participant is alive. Microbiological eradication (favorable microbiological response) is defined as a reduction of baseline uropathogens to \&lt;10\^3 CFU/mL and negative repeated blood culture if blood culture was positive for uropathogen growth at baseline and participant is alive.
  10. Number of Participants With Overall Response at EOT, TOC, and LFU Visits in Participants With Drug-Resistant Enterobacterales in the ME Population
    Overall response includes combined clinical cure plus microbiological eradication. Clinical cure is defined as a complete resolution or significant improvement of signs and symptoms of cUTI or AP present at baseline and no new symptoms, such that no further antibacterial therapy is warranted, and participant is alive. Microbiological eradication (favorable microbiological response) is defined as a reduction of baseline uropathogens to \&lt;10\^3 CFU/mL and negative repeated blood culture if blood culture was positive for uropathogen growth at baseline and participant is alive.
  11. Number of Participants With Clinical Response at the EOT and TOC Visits in Participants With Drug-resistant Enterobacterales in the Micro-ITT Population
    Participants were evaluated for clinical response outcome based on assessment of signs and symptoms as: Cure, including sustained clinical cure (defined as met criteria for clinical cure at TOC, and remained free of new or recurrent signs and symptoms of cUTI or AP at LFU visit such that no further antibacterial therapy is warranted); Failure, including clinical relapse (defined as met criteria for clinical cure at TOC, but new signs and symptoms of cUTI or AP are present at LFU visit and participant requires antibacterial therapy for cUTI); or Clinical indeterminate: insufficient data are available to determine if participant is a sustained clinical cure or clinical relapse. If a participant is assessed as a clinical failure at EOT, participant is automatically considered a failure at TOC and LFU visits. If a participant is assessed as a clinical failure at TOC, participant is automatically considered a failure at LFU visit.
  12. Number of Participants With Clinical Response at the LFU Visit in Participants With Drug-resistant Enterobacterales in the Micro-ITT Population
    Participants were evaluated for clinical response outcome based on assessment of signs and symptoms as: Cure, including sustained clinical cure (defined as met criteria for clinical cure at TOC, and remained free of new or recurrent signs and symptoms of cUTI or AP at LFU visit such that no further antibacterial therapy is warranted); Failure, including clinical relapse (defined as met criteria for clinical cure at TOC, but new signs and symptoms of cUTI or AP are present at LFU visit and participant requires antibacterial therapy for cUTI); or Clinical indeterminate: insufficient data are available to determine if participant is a sustained clinical cure or clinical relapse. If a participant is assessed as a clinical failure at EOT, participant is automatically considered a failure at TOC and LFU visits. If a participant is assessed as a clinical failure at TOC, participant is automatically considered a failure at LFU visit.
  13. Number of Participants With Clinical Response at the EOT, TOC and LFU Visits in Participants With Drug-resistant Enterobacterales in the ME Population
    Participants were evaluated for clinical response outcome based on assessment of signs and symptoms as: Cure, including sustained clinical cure: Sustained clinical cure is defined as met criteria for clinical cure at TOC, and remained free of new or recurrent signs and symptoms of cUTI or AP at LFU visit such that no further antibacterial therapy is warranted; Failure, including clinical relapse: Clinical relapse is defined as met criteria for clinical cure at TOC, but new signs and symptoms of cUTI or AP are present at LFU visit and participant requires antibacterial therapy for cUTI; Clinical indeterminate: insufficient data are available to determine if participant is a sustained clinical cure or clinical relapse. If a participant is assessed as a clinical failure at EOT, participant is automatically considered a failure at TOC and LFU visits. If a participant is assessed as a clinical failure at TOC, participant is automatically considered a failure at LFU visit.
  14. Number of Participants With Microbiological Response at the EOT and TOC Visits in Participants With Drug-resistant Enterobacterales in the Micro-ITT Population
    Participants were evaluated for microbiological response based on blood and urine cultures as: Eradication, including sustained microbiologic eradication, i.e.,microbiologic eradication at TOC and no subsequent urine culture after TOC demonstrating recurrence of original Baseline uropathogen at &ge;10\^3 CFU/mL;Persistence, including microbiologic recurrence, i.e.,isolation from urine culture at &ge;10\^3 CFU/mL or blood culture of any of Baseline uropathogen(s) at any time after documented eradication at TOC visit up to and including LFU visit; Microbiologic indeterminate: no follow-up urine culture is available, or urine culture results are missing, or follow-up urine culture cannot be interpreted for any reason. If a participant is assessed as a microbiological persistence at EOT, participant is automatically considered persistent at TOC and LFU. If assessed as persistent at TOC, participant is automatically considered a persistent at LFU.
  15. Number of Participants With Microbiological Response at the LFU Visit in Participants With Drug-resistant Enterobacterales in the Micro-ITT Population
    Participants were evaluated for clinical response outcome based on assessment of signs and symptoms as: Cure, including sustained clinical cure: Sustained clinical cure is defined as met criteria for clinical cure at TOC, and remained free of new or recurrent signs and symptoms of cUTI or AP at LFU visit such that no further antibacterial therapy is warranted; Failure, including clinical relapse: Clinical relapse is defined as met criteria for clinical cure at TOC, but new signs and symptoms of cUTI or AP are present at LFU visit and participant requires antibacterial therapy for cUTI; Clinical indeterminate: insufficient data are available to determine if participant is a sustained clinical cure or clinical relapse. If a participant is assessed as a clinical failure at EOT, participant is automatically considered a failure at TOC and LFU visits. If a participant is assessed as a clinical failure at TOC, participant is automatically considered a failure at LFU visit.
  16. Number of Participants With Microbiological Response at the EOT and TOC Visits in Participants With Drug-resistant Enterobacterales in the ME Population
    Participants were evaluated for microbiological response based on blood and urine cultures as: Eradication, including sustained microbiologic eradication, i.e.,microbiologic eradication at TOC and no subsequent urine culture after TOC demonstrating recurrence of original Baseline uropathogen at &ge;10\^3 CFU/mL;Persistence, including microbiologic recurrence, i.e.,isolation from urine culture at &ge;10\^3 CFU/mL or blood culture of any of Baseline uropathogen(s) at any time after documented eradication at TOC visit up to and including LFU visit; Microbiologic indeterminate: no follow-up urine culture is available, or urine culture results are missing, or follow-up urine culture cannot be interpreted for any reason. If a participant is assessed as a microbiological persistence at EOT, participant is automatically considered persistent at TOC and LFU. If assessed as persistent at TOC, participant is automatically considered a persistent at LFU.
  17. Number of Participants With Microbiological Response at the LFU Visit in Participants With Drug-resistant Enterobacterales in the ME Population
    Participants will be evaluated for microbiological response based on blood and urine cultures as :Eradication, including sustained microbiologic eradication, i.e., microbiologic eradication at TOC and no subsequent urine culture after TOC demonstrating recurrence of original Baseline uropathogen at &ge;10\^3 CFU/mL;Persistence, including microbiologic recurrence, i.e.,isolation from urine culture at &ge;10\^3 CFU/mL or blood culture of any of Baseline uropathogen(s) at any time after documented eradication at TOC visit up to and including LFU visit; Microbiologic indeterminate:no follow-up urine culture is available, or urine culture results are missing, or follow-up urine culture cannot be interpreted for any reason. If a participant is assessed as a microbiological persistence at EOT,participant is automatically considered persistent at TOC and LFU. If assessed as persistent at TOC, participant is automatically considered a persistent at LFU.
  18. Number of Participants With at Least One Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events
    An Adverse Event (AE) was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product, which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal investigational/experimental) product, whether or not related to this product. Serious Adverse Event (SAE) is any AE occurring at any dose and regardless of causality that results in death, is life threatening, requires immediate or prolongation of hospitalization, results in significant disability, congenital anomaly and is a medically important reaction. TEAEs are defined as events that are newly occurring or worsening from the time of the first dose of IP through LFU.
  19. Plasma Concentrations of TBP-PI-HBr

Eligibility Criteria

Ages Eligible for Study(Adult, Older Adult)
Sexes Eligible for StudyAll
Accepts Healthy VolunteersNo
Inclusion Criteria
1. Have a diagnosis of cUTI or AP. 2. Have an adequate urine specimen for evaluation and culture obtained within 24 hours prior to randomization with evidence of pyuria that includes at least one of the following: 1. at least 10 white blood cells (WBCs) per high power field (HPF) in urine sediment 2. at least 10 WBCs per millimeters cubed (mm\^3) in unspun urine 3. positive leukocyte esterase (LE) on urinalysis Note: Participants may be randomized and administered study drug prior to knowledge of urine culture results, but pyuria must be documented. 3. 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.
Exclusion Criteria
1. Presence of any known or suspected disease or condition that may confound the assessment of efficacy. 2. Gross hematuria requiring intervention other than administration of study drug or removal/placement of urinary tract instrumentation. 3. Urinary tract surgery within 7 days prior to randomization or urinary tract surgery planned during the study period. 4. Creatinine clearance (CrCl) of ≤30 milliliters per minute (mL/min), as estimated by the Cockcroft-Gault formula. 5. Anticipated concomitant use of non-study antimicrobial drug therapy between randomization and the LFU visit that would potentially effect outcome evaluations of cUTI/AP. 6. Receipt of a potentially effective antimicrobial within 72 hours prior to study randomization. 7. Severe hepatic impairment at Screening, as evidenced by alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>5×upper limit of normal (ULN) or total bilirubin \>3×ULN, or clinical signs of cirrhosis or end-stage hepatic disease (e.g., ascites, hepatic encephalopathy). 8. Pregnant or lactating women. 9. History of epilepsy or known seizure disorder (excluding a history of childhood febrile seizures). 10. History of proven or suspected Clostridioides difficile associated diarrhoea. 11. History of human immunodeficiency virus (HIV) infection. 12. QT interval corrected using Fridericia's formula (QTcF) \>480 milliseconds (msec) based on screening ECG. 13. History of known genetic metabolism anomaly associated with carnitine deficiency. 14. Requirement for concomitant use of valproic acid, divalproex sodium, or probenecid between randomization and EOT. Note: Other inclusion and exclusion criteria as per protocol may apply.

Contacts and Locations

Sponsors and CollaboratorsSpero Therapeutics
Locations
Medical facility | Miami Florida, United States, 33144Medical Facility | Miami Florida, United States, 33176Medical Facility | Buenos Aires , Argentina, Medical Facility | Córdoba , Argentina, Medical Facility | La Plata , Argentina, Medical Facility | Mendoza , Argentina, Medical Facility | San Miguel de Tucumán , Argentina, Medical Facility | Villa Regina , Argentina, Medical Facility | Banja Luka , Bosnia and Herzegovina, Medical Facility | Sarajevo , Bosnia and Herzegovina, Medical Facility | Tuzla , Bosnia and Herzegovina, Medical Facility | Barueri , Brazil, Medical Facility | Campinas , Brazil, Medical Facility | Curitiba , Brazil, Medical Facility | Porto Alegre , Brazil, Medical Facility | São José do Rio Preto , Brazil, Medical Facility | Blagoevgrad , Bulgaria, Medical Facility | Dobrich , Bulgaria, Medical Facility | Gabrovo , Bulgaria, Medical facility | Lom , Bulgaria, Medical Facility | Pleven , Bulgaria, Medical Facility | Plovdiv , Bulgaria, Medical facility | Rousse , Bulgaria, Medical facility | Shumen , Bulgaria, Medical Facility | Sliven , Bulgaria, Medical facility | Sofia , Bulgaria, Medical Facility | Varna , Bulgaria, Medical Facility | Čakovec , Croatia, Medical Facility | Slavonski Brod , Croatia, Medical Facility | Split , Croatia, Medical Facility | Zagreb , Croatia, Medical Facility | Kohtla-Järve , Estonia, Medical Facility | Pärnu , Estonia, Medical Facility | Tallinn , Estonia, Medical Facility | Tartu , Estonia, 50406Medical Facility | Võru , Estonia, Medical facility | Tbilisi , Georgia, Medical Facility | Alexandroupoli , Greece, Medical Facility | Athens , Greece, Medical Facility | Ioannina , Greece, Medical Facility | Pátrai , Greece, Medical Facility | Thessaloniki , Greece, Medical Facility | Budapest , Hungary, Medical Facility | Eger , Hungary, Medical Facility | Kistarcsa , Hungary, Medical Facility | Nyíregyháza , Hungary, Medical Facility | Belagavi Karnataka, India, 590010Medical Facility | Bangalore , India, Medical Facility | Jaipur , India, Medical Facility | Lucknow , India, Medical Facility | Varanasi , India, Medical Facility | Daugavpils , Latvia, Medical Facility | Liepāja , Latvia, Medical Facility | Riga , Latvia, Medical Facility | Valmiera , Latvia, Medical Facility | Chisinau , Moldova, Medical Facility | Krakow , Poland, Medical Facility | Lodz , Poland, Medical Facility | Warsaw , Poland, Medical Facility | Łęczna , Poland, Medical Facility | Brasov , Romania, Medical facility | Bucharest , Romania, Medical facility | Craiova , Romania, Medical Facility | Iași , Romania, Medical Facility | Oradea , Romania, Medical Facility | Timișoara , Romania, Medical facility | Belgrade , Serbia, Medical facility | Kragujevac , Serbia, Medical facility | Niš , Serbia, Medical facility | Novi Sad , Serbia, Medical Facility | Bratislava , Slovakia, Medical Facility | Galanta , Slovakia, Medical Facility | Lučenec , Slovakia, Medical Facility | Malacky , Slovakia, Medical Facility | Poprad , Slovakia, Medical facility | Benoni , South Africa, Medical facility | Durban , South Africa, Medical Facility | Pretoria , South Africa, Medical Facility | Tongaat , South Africa, Medical Facility | Umhlanga , South Africa, Medical Facility | Ankara , Turkey (Türkiye), Medical Facility | Diyarbakır , Turkey (Türkiye), Medical Facility | Istanbul , Turkey (Türkiye), Medical Facility | Izmir , Turkey (Türkiye), Medical Facility | Samsun , Turkey (Türkiye),
Investigators
Study Director: David Hong, MD, Spero Therapeutics
Study Documents (Full Text)
Documents provided by Spero Therapeutics: Study Protocol  August 25, 2024Documents provided by Spero Therapeutics: Statistical Analysis Plan  March 16, 2025