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)

NCT06059846 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: SPR994-3052023-503785-22-00
• Study Type: interventional
• Target: 1,690
• Locations: 19 countries
• Sites: 85

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 (greater than or equal to (≥)18 years of age) with cUTI or AP.

Conditions

Urinary Tract Infection; Acute Pyelonephritis

Outcome Measures

Primary Outcomes (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 \<10\^3 CFU/mL and negative repeated blood culture if blood culture was positive for uropathogen growth at baseline and participant is alive.

  At Day 17 (TOC)

Secondary Outcomes (19)

• 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

  At Day 17 (TOC)

• Number of Participants With Overall Response at the End-of-Treatment (EOT) and Late Follow-Up (LFU) Visits in the Micro-ITT Population

  At Day 10 (EOT) and Day 28 (LFU)

• Number of Participants With Overall Response at EOT and LFU Visits in the ME Population

  At Day 10 (EOT) and Day 28 (LFU)

• Number of Participants With Clinical Response at EOT, TOC and LFU Visits in the Micro-ITT Population

  At Day 10 (EOT), Day 17 (TOC), and Day 28 (LFU)

• Number of Participants With Clinical Response at EOT, TOC and LFU Visits in the CE Population

  At Day 10 (EOT), Day 17 (TOC), and Day 28 (LFU)

Study Arms (2)

TBP-PI-HBr

EXPERIMENTAL

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; Drug: Dummy Infusion

Imipenem-cilastatin

ACTIVE COMPARATOR

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; Drug: Dummy Tablets

Interventions

TBP-PI-HBr DRUG

TBP-PI-HBr film-coated immediate-release tablets.

Also known as: SPR994

TBP-PI-HBr

Imipenem-cilastatin DRUG

Sterile powder for reconstitution administered as IV.

Imipenem-cilastatin

Dummy Infusion DRUG

0.9% sodium chloride administered as IV infusion.

TBP-PI-HBr

Dummy Tablets DRUG

TBP-PI-HBr matching dummy tablets.

Imipenem-cilastatin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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 diarrhoea.
• 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.

Sponsors & Collaborators

• GlaxoSmithKline: collaborator
• Spero Therapeutics: lead

Study Sites (85)

Medical facility

Miami, Florida, 33144, United States

Location

Medical Facility

Miami, Florida, 33176, United States

Location

Medical Facility

Buenos Aires, Argentina

Location

Medical Facility

Córdoba, Argentina

Location

Medical Facility

La Plata, Argentina

Location

Medical Facility

Mendoza, Argentina

Location

Medical Facility

San Miguel de Tucumán, Argentina

Location

Medical Facility

Villa Regina, Argentina

Location

Medical Facility

Banja Luka, Bosnia and Herzegovina

Location

Medical Facility

Sarajevo, Bosnia and Herzegovina

Location

Medical Facility

Tuzla, Bosnia and Herzegovina

Location

Medical Facility

Barueri, Brazil

Location

Medical Facility

Campinas, Brazil

Location

Medical Facility

Curitiba, Brazil

Location

Medical Facility

Porto Alegre, Brazil

Location

Medical Facility

São José do Rio Preto, Brazil

Location

Medical Facility

Blagoevgrad, Bulgaria

Location

Medical Facility

Dobrich, Bulgaria

Location

Medical Facility

Gabrovo, Bulgaria

Location

Medical facility

Lom, Bulgaria

Location

Medical Facility

Pleven, Bulgaria

Location

Medical Facility

Plovdiv, Bulgaria

Location

Medical facility

Rousse, Bulgaria

Location

Medical facility

Shumen, Bulgaria

Location

Medical Facility

Sliven, Bulgaria

Location

Medical facility

Sofia, Bulgaria

Location

Medical Facility

Varna, Bulgaria

Location

Medical Facility

Čakovec, Croatia

Location

Medical Facility

Slavonski Brod, Croatia

Location

Medical Facility

Split, Croatia

Location

Medical Facility

Zagreb, Croatia

Location

Medical Facility

Kohtla-Järve, Estonia

Location

Medical Facility

Pärnu, Estonia

Location

Medical Facility

Tallinn, Estonia

Location

Medical Facility

Tartu, 50406, Estonia

Location

Medical Facility

Võru, Estonia

Location

Medical facility

Tbilisi, Georgia

Location

Medical Facility

Alexandroupoli, Greece

Location

Medical Facility

Athens, Greece

Location

Medical Facility

Ioannina, Greece

Location

Medical Facility

Pátrai, Greece

Location

Medical Facility

Thessaloniki, Greece

Location

Medical Facility

Budapest, Hungary

Location

Medical Facility

Eger, Hungary

Location

Medical Facility

Kistarcsa, Hungary

Location

Medical Facility

Nyíregyháza, Hungary

Location

Medical Facility

Belagavi, Karnataka, 590010, India

Location

Medical Facility

Bangalore, India

Location

Medical Facility

Jaipur, India

Location

Medical Facility

Lucknow, India

Location

Medical Facility

Varanasi, India

Location

Medical Facility

Daugavpils, Latvia

Location

Medical Facility

Liepāja, Latvia

Location

Medical Facility

Riga, Latvia

Location

Medical Facility

Valmiera, Latvia

Location

Medical Facility

Chisinau, Moldova

Location

Medical Facility

Krakow, Poland

Location

Medical Facility

Lodz, Poland

Location

Medical Facility

Warsaw, Poland

Location

Medical Facility

Łęczna, Poland

Location

Medical Facility

Brasov, Romania

Location

Medical facility

Bucharest, Romania

Location

Medical facility

Craiova, Romania

Location

Medical Facility

Iași, Romania

Location

Medical Facility

Oradea, Romania

Location

Medical Facility

Timișoara, Romania

Location

Medical facility

Belgrade, Serbia

Location

Medical facility

Kragujevac, Serbia

Location

Medical facility

Niš, Serbia

Location

Medical facility

Novi Sad, Serbia

Location

Medical Facility

Bratislava, Slovakia

Location

Medical Facility

Galanta, Slovakia

Location

Medical Facility

Lučenec, Slovakia

Location

Medical Facility

Malacky, Slovakia

Location

Medical Facility

Poprad, Slovakia

Location

Medical facility

Benoni, South Africa

Location

Medical facility

Durban, South Africa

Location

Medical Facility

Pretoria, South Africa

Location

Medical Facility

Tongaat, South Africa

Location

Medical Facility

Umhlanga, South Africa

Location

Medical Facility

Ankara, Turkey (Türkiye)

Location

Medical Facility

Diyarbakır, Turkey (Türkiye)

Location

Medical Facility

Istanbul, Turkey (Türkiye)

Location

Medical Facility

Izmir, Turkey (Türkiye)

Location

Medical Facility

Samsun, Turkey (Türkiye)

Location

MeSH Terms

Conditions

Urinary Tract Infections

Interventions

tebipenem; Cilastatin, Imipenem Drug Combination

Condition Hierarchy (Ancestors)

Infections; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Imipenem; Thienamycins; Carbapenems; beta-Lactams; Lactams; Amides; Organic Chemicals; Cilastatin; Cyclopropanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Fatty Acids, Monounsaturated; Fatty Acids, Unsaturated; Fatty Acids; Lipids; Drug Combinations; Pharmaceutical Preparations

Results Point of Contact

• Title: David Hong
• Organization: Senior Vice President Clinical Development

dhong@sperotherapeutics.com

857-242-1583

Study Officials

• David Hong, MD

  Spero Therapeutics

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 22, 2023
• First Posted: September 29, 2023
• Study Start: December 21, 2023
• Primary Completion: January 27, 2025
• Study Completion: February 6, 2025
• Last Updated: March 10, 2026
• Results First Posted: March 10, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

ES (5); BR (5); PL (4); IN (5); AR (6); ZA (5); TU (5); BO (3); CR (4); SL (5); US (2); BU (11); RO (6); GE (1); LA (4); GR (5); HU (4); SE (4); MO (1)