Clinical trial NCT06059846: 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)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Urinary Tract Infection
Acute Pyelonephritis
Lead sponsor: Spero Therapeutics
Sponsor class: INDUSTRY
Collaborators: name: GlaxoSmithKline
First posted: 2023-09-29
Enrollment: 2648
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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 diarrhea.
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.

Primary outcomes:
measure: Number of Participants With Overall Response at the Test-of-Cure (TOC) Visit
timeFrame: Day 17
Secondary outcomes:
measure: Number of Participants in the Microbiologically Evaluable Population With Overall Response at the TOC Visit
timeFrame: Day 17
measure: Number of Participants With Overall Response at the End-of-Treatment (EOT) and Late Follow-Up (LFU) Visits
timeFrame: Days 10 and 28
measure: Number of Participants With Clinical Response at the EOT, TOC and LFU Visits
timeFrame: Days 10, 17, and 28
measure: Number of Participants With Microbiological Response at the EOT, TOC and LFU Visits
timeFrame: Days 10, 17, and 28
measure: Number of Participants With Overall Response at the EOT, TOC, and LFU Visits in Participants With Drug-resistant Enterobacterales
timeFrame: Days 10, 17, and 28
measure: Number of Participants With Clinical Response at the EOT, TOC, and LFU Visits in Participants With Drug-resistant Enterobacterales
timeFrame: Days 10, 17, and 28
measure: Number of Participants With Microbiological Response at the EOT, TOC, and LFU Visits in Participants With Drug-resistant Enterobacterales
timeFrame: Days 10, 17, and 28
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
timeFrame: From first dose of study drug (Day 1) up to Day 28
measure: Plasma Concentration of Tebipenem
timeFrame: At multiple time points post dose on Day 2
Other outcomes:
Locations:
city: Miami
country: United States
facility: Medical facility
state: Florida
city: Miami
country: United States
facility: Medical Facility
state: Florida
city: Buenos Aires
country: Argentina
facility: Medical Facility
city: Cordoba
country: Argentina
facility: Medical Facility
city: Córdoba
country: Argentina
facility: Medical Facility
city: La Plata
country: Argentina
facility: Medical Facility
city: Mendoza
country: Argentina
facility: Medical Facility
city: San Miguel De Tucumán
country: Argentina
facility: Medical Facility
city: Villa Regina
country: Argentina
facility: Medical Facility
city: Banja Luka
country: Bosnia and Herzegovina
facility: Medical Facility
city: Sarajevo
country: Bosnia and Herzegovina
facility: Medical Facility
city: Tuzla
country: Bosnia and Herzegovina
facility: Medical Facility
city: Barueri
country: Brazil
facility: Medical Facility
city: Campinas
country: Brazil
facility: Medical Facility
city: Curitiba
country: Brazil
facility: Medical Facility
city: Porto Alegre
country: Brazil
facility: Medical Facility
city: Sao Jose do Rio Preto
country: Brazil
facility: Medical Facility
city: Blagoevgrad
country: Bulgaria
facility: Medical Facility
city: Dobrich
country: Bulgaria
facility: Medical Facility
city: Gabrovo
country: Bulgaria
facility: Medical Facility
city: Lom
country: Bulgaria
facility: Medical facility
city: Pleven
country: Bulgaria
facility: Medical Facility
city: Plovdiv
country: Bulgaria
facility: Medical Facility
city: Ruse
country: Bulgaria
facility: Medical facility
city: Shumen
country: Bulgaria
facility: Medical facility
city: Sliven
country: Bulgaria
facility: Medical Facility
city: Sofia
country: Bulgaria
facility: Medical facility
city: Varna
country: Bulgaria
facility: Medical Facility
city: Slavonski Brod
country: Croatia
facility: Medical Facility
city: Split
country: Croatia
facility: Medical Facility
city: Zagreb
country: Croatia
facility: Medical Facility
city: Čakovec
country: Croatia
facility: Medical Facility
city: Kohtla-Jarve
country: Estonia
facility: Medical Facility
city: Parnu
country: Estonia
facility: Medical Facility
city: Tallinn
country: Estonia
facility: Medical Facility
city: Voru
country: Estonia
facility: Medical Facility
city: Tbilisi
country: Georgia
facility: Medical facility
city: Tbilisi
country: Georgia
facility: Medical facility
city: Alexandroupolis
country: Greece
facility: Medical Facility
city: Athens
country: Greece
facility: Medical Facility
city: Ioánnina
country: Greece
facility: Medical Facility
city: Patras
country: Greece
facility: Medical Facility
city: Thessaloníki
country: Greece
facility: Medical Facility
city: Budapest
country: Hungary
facility: Medical Facility
city: Eger
country: Hungary
facility: Medical Facility
city: Kistarcsa
country: Hungary
facility: Medical Facility
city: Nyiregyhaza
country: Hungary
facility: Medical Facility
city: Varanasi
country: India
facility: Medical Facility
state: Uttar Pradesh
city: Bangalore
country: India
facility: Medical Facility
city: Belgaum
country: India
facility: Medical Facility
city: Jaipur
country: India
facility: Medical Facility
city: Lucknow
country: India
facility: Medical Facility
city: Daugavpils
country: Latvia
facility: Medical Facility
city: Liepaja
country: Latvia
facility: Medical Facility
city: Riga
country: Latvia
facility: Medical Facility
city: Valmiera
country: Latvia
facility: Medical Facility
city: Chisinau
country: Moldova, Republic of
facility: Medical Facility
city: Krakow
country: Poland
facility: Medical Facility
city: Leczna
country: Poland
facility: Medical Facility
city: Lodz
country: Poland
facility: Medical Facility
city: Warsaw
country: Poland
facility: Medical Facility
city: Brasov
country: Romania
facility: Medical Facility
city: Bucharest
country: Romania
facility: Medical facility
city: Craiova
country: Romania
facility: Medical facility
city: Iasi
country: Romania
facility: Medical Facility
city: Oradea
country: Romania
facility: Medical Facility
city: Timisoara
country: Romania
facility: Medical Facility
city: Belgrade
country: Serbia
facility: Medical facility
city: Kragujevac
country: Serbia
facility: Medical facility
city: Nis
country: Serbia
facility: Medical facility
city: Novi Sad
country: Serbia
facility: Medical facility
city: Bratislava
country: Slovakia
facility: Medical Facility
city: Galanta
country: Slovakia
facility: Medical Facility
city: Lučenec
country: Slovakia
facility: Medical Facility
city: Malacky
country: Slovakia
facility: Medical Facility
city: Poprad
country: Slovakia
facility: Medical Facility
city: Benoni
country: South Africa
facility: Medical facility
city: Durban
country: South Africa
facility: Medical facility
city: Pretoria
country: South Africa
facility: Medical Facility
city: Tongaat
country: South Africa
facility: Medical Facility
city: Umhlanga
country: South Africa
facility: Medical Facility
city: Ankara
country: Turkey
facility: Medical Facility
city: Diyarbakir
country: Turkey
facility: Medical Facility
city: Istanbul
country: Turkey
facility: Medical Facility
city: Izmir
country: Turkey
facility: Medical Facility
city: Samsun
country: Turkey
facility: Medical Facility
Study officials:
affiliation: Spero Therapeutics
name: David Hong, MD
role: STUDY_DIRECTOR
References: