A 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)

ClinicalTrials.gov processed this data on November 14, 2024. Link to the current ClinicalTrials.gov record.

Recruitment Status

RECRUITING (See Contacts and Locations)
Verified November 2024 by Spero Therapeutics, GlaxoSmithKline

Sponsor

Spero Therapeutics

Information Provided by (Responsible Party)

Spero Therapeutics

Clinicaltrials.gov Identifier

NCT06059846
Other Study ID Numbers: SPR994-305
First Submitted: September 22, 2023
First Posted: September 29, 2023
Last Update Posted: November 15, 2024
Last Verified: November 2024
History of Changes

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Study Description

Not Provided
Condition or Disease Intervention/Treatment
  • Urinary Tract Infection
  • Acute Pyelonephritis
  • Drug: TBP-PI-HBr
  • Drug: Imipenem-cilastatin
  • Drug: Dummy Infusion
  • Drug: Dummy Tablets

Study Design

Study TypeInterventional
Anticipated Enrollment2648 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 21, 2023
Anticipated Primary Completion DateNovember 2025
Anticipated Study Completion DateNovember 2025

Groups and Cohorts

Group/ CohortIntervention/ Treatment
  • TBP-PI-HBr 600 mg + Dummy Infusion
    • Participants will receive TBP-PI-HBr 600 mg, orally and dummy infusion IV, every 6 hours from Days 1 through 10.
  • Drug: TBP-PI-HBr
    • TBP-PI-HBr film-coated immediate-release tablets.
  • Drug: Dummy Infusion
    • Imipenem-cilastatin 500 mg + Dummy Tablets
      • Participants will receive imipenem-cilastatin 500 mg, IV and matched dummy tablets, orally, every 6 hours from Days 1 through 10.
    • Drug: Imipenem-cilastatin
      • Drug: Dummy Tablets

        Outcome Measures

        Primary Outcome Measures

        1. Number of Participants With Overall Response at the Test-of-Cure (TOC) Visit [Day 17]
          Overall response includes combination of clinical cure and favorable microbiological response. Clinical cure is defined as a complete resolution or significant improvement of signs and symptoms of cUTI or AP that were present at Baseline and no new symptoms, such that no further antibacterial therapy is warranted, and participant is alive. Favorable microbiological response (microbiological eradication) is defined as a reduction of Baseline uropathogens to <10^3 colony forming unit per milliliter (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 in the Microbiologically Evaluable Population With Overall Response at the TOC Visit [Day 17]
          Overall response includes combination of clinical cure and favorable microbiological response. Clinical cure is defined as a complete resolution or significant improvement of signs and symptoms of cUTI or AP that were present at Baseline and no new symptoms, such that no further antibacterial therapy is warranted, and participant is alive. Favorable microbiological response (microbiological eradication) is defined as a reduction of Baseline uropathogens to <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 [Days 10 and 28]
          Overall response includes combination of clinical cure and favorable microbiological response. Clinical cure is defined as a complete resolution or significant improvement of signs and symptoms of cUTI or AP that were present at Baseline and no new symptoms, such that no further antibacterial therapy is warranted, and participant is alive. Favorable microbiological response (microbiological eradication) is defined as a reduction of Baseline uropathogens to <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 Clinical Response at the EOT, TOC and LFU Visits [Days 10, 17, and 28]
          Participants will be 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.
        4. Number of Participants With Microbiological Response at the EOT, TOC and LFU Visits [Days 10, 17, and 28]
          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 ≥10^3 CFU/mL;Persistence, including microbiologic recurrence, i.e.,isolation from urine culture at ≥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.
        5. Number of Participants With Overall Response at the EOT, TOC, and LFU Visits in Participants With Drug-resistant Enterobacterales [Days 10, 17, and 28]
          Overall response includes combination of clinical cure and favorable microbiological response. Clinical cure is defined as a complete resolution or significant improvement of signs and symptoms of cUTI or AP that were present at Baseline and no new symptoms, such that no further antibacterial therapy is warranted, and participant is alive. Favorable microbiological response (microbiological eradication) is defined as a reduction of Baseline uropathogens to <10^3 CFU/mL and negative repeated blood culture if blood culture was positive for uropathogen growth at Baseline and participant is alive.
        6. Number of Participants With Clinical Response at the EOT, TOC, and LFU Visits in Participants With Drug-resistant Enterobacterales [Days 10, 17, and 28]
          Participants will be 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.
        7. Number of Participants With Microbiological Response at the EOT, TOC, and LFU Visits in Participants With Drug-resistant Enterobacterales [Days 10, 17, and 28]
          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 ≥10^3 CFU/mL;Persistence, including microbiologic recurrence, i.e.,isolation from urine culture at ≥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.
        8. Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [From first dose of study drug (Day 1) up to Day 28]
        9. Plasma Concentration of Tebipenem [At multiple time points post dose on Day 2]

        Eligibility Criteria

        Ages Eligible for Study 18 Years and Older (Adult, Older Adult)
        Sexes Eligible for Study All
        Accepts Healthy Volunteers No
        Inclusion Criteria
        • Have a diagnosis of cUTI or AP.
        • 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:
        • at least 10 white blood cells (WBCs) per high power field (HPF) in urine sediment
        • at least 10 WBCs per millimeters cubed (mm^3) in unspun urine
        • 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.
        • 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
        • Presence of any known or suspected disease or condition that may confound the assessment of efficacy.
        • Gross hematuria requiring intervention other than administration of study drug or removal/placement of urinary tract instrumentation.
        • Urinary tract surgery within 7 days prior to randomization or urinary tract surgery planned during the study period.
        • Creatinine clearance (CrCl) of ≤30 milliliters per minute (mL/min), as estimated by the Cockcroft-Gault formula.
        • Anticipated concomitant use of non-study antimicrobial drug therapy between randomization and the LFU visit that would potentially effect outcome evaluations of cUTI/AP.
        • Receipt of a potentially effective antimicrobial within 72 hours prior to study randomization.
        • 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).
        • Pregnant or lactating women.
        • History of epilepsy or known seizure disorder (excluding a history of childhood febrile seizures).
        • History of proven or suspected Clostridioides difficile associated diarrhea.
        • History of human immunodeficiency virus (HIV) infection.
        • QT interval corrected using Fridericia's formula (QTcF) >480 milliseconds (msec) based on screening ECG.
        • History of known genetic metabolism anomaly associated with carnitine deficiency.
        • 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 Collaborators Spero Therapeutics, GlaxoSmithKline
        GlaxoSmithKline
        Locations
        • Medical facility | Miami, Florida, United States, 33144
        • Medical Facility | Miami, Florida, United States, 33176
        • Medical Facility | Buenos Aires, Argentina,
        • Medical Facility | Cordoba, 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 | Sao Jose 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 | Ruse, Bulgaria,
        • Medical facility | Shumen, Bulgaria,
        • Medical Facility | Sliven, Bulgaria,
        • Medical facility | Sofia, Bulgaria,
        • Medical Facility | Varna, Bulgaria,
        • Medical Facility | Slavonski Brod, Croatia,
        • Medical Facility | Split, Croatia,
        • Medical Facility | Zagreb, Croatia,
        • Medical Facility | Čakovec, Croatia,
        • Medical Facility | Kohtla-Jarve, Estonia,
        • Medical Facility | Parnu, Estonia,
        • Medical Facility | Tallinn, Estonia,
        • Medical Facility | Voru, Estonia,
        • Medical facility | Tbilisi, Georgia,
        • Medical facility | Tbilisi, Georgia,
        • Medical Facility | Alexandroupolis, Greece,
        • Medical Facility | Athens, Greece,
        • Medical Facility | Ioánnina, Greece,
        • Medical Facility | Patras, Greece,
        • Medical Facility | Thessaloníki, Greece,
        • Medical Facility | Budapest, Hungary,
        • Medical Facility | Eger, Hungary,
        • Medical Facility | Kistarcsa, Hungary,
        • Medical Facility | Nyiregyhaza, Hungary,
        • Medical Facility | Varanasi, Uttar Pradesh, India,
        • Medical Facility | Bangalore, India,
        • Medical Facility | Belgaum, India,
        • Medical Facility | Jaipur, India,
        • Medical Facility | Lucknow, India,
        • Medical Facility | Daugavpils, Latvia,
        • Medical Facility | Liepaja, Latvia,
        • Medical Facility | Riga, Latvia,
        • Medical Facility | Valmiera, Latvia,
        • Medical Facility | Chisinau, Moldova, Republic of,
        • Medical Facility | Krakow, Poland,
        • Medical Facility | Leczna, Poland,
        • Medical Facility | Lodz, Poland,
        • Medical Facility | Warsaw, Poland,
        • Medical Facility | Brasov, Romania,
        • Medical facility | Bucharest, Romania,
        • Medical facility | Craiova, Romania,
        • Medical Facility | Iasi, Romania,
        • Medical Facility | Oradea, Romania,
        • Medical Facility | Timisoara, Romania,
        • Medical facility | Belgrade, Serbia,
        • Medical facility | Kragujevac, Serbia,
        • Medical facility | Nis, 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,
        • Medical Facility | Diyarbakir, Turkey,
        • Medical Facility | Istanbul, Turkey,
        • Medical Facility | Izmir, Turkey,
        • Medical Facility | Samsun, Turkey,
        Investigators

          More Information

          Additional Relevant MeSH Terms

          • Infections
          • Communicable Diseases
          • Urinary Tract Infections
          • Pyelonephritis
          • Disease Attributes
          • Pathologic Processes
          • Urologic Diseases
          • Female Urogenital Diseases
          • Female Urogenital Diseases and Pregnancy Complications
          • Urogenital Diseases
          • Male Urogenital Diseases
          • Nephritis, Interstitial
          • Nephritis
          • Kidney Diseases
          • Pyelitis