Overview

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)

Status:
Recruiting
Trial end date:
2025-12-01
Target enrollment:
0
Participant gender:
All
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.
Phase:
Phase 3
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Spero Therapeutics
Collaborator:
GlaxoSmithKline
Treatments:
Cilastatin
Cilastatin, Imipenem Drug Combination
Imipenem
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, in the opinion of the
Investigator, 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 more than a single dose 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.