Trial Outcomes & Findings for Study to Assess the Efficacy, Safety and Pharmacokinetics of Orally Administered Tebipenem Pivoxil Hydrobromide (SPR994) Compared to Intravenous Ertapenem in Participants With Complicated Urinary Tract Infection (cUTI) or Acute Pyelonephritis (AP) (NCT NCT03788967)

NCT ID: NCT03788967

Last Updated: 2022-07-25

Results Overview

Overall response is participants with combined clinical cure and microbiological eradication. Clinical cure is defined as 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 antimicrobial therapy is warranted. Microbiological eradication is defined as reduction of baseline urine pathogen(s) to \<10\^3 colony forming unit/milliliter (CFU/mL) and negative repeated blood culture if blood culture was positive for uropathogen growth at baseline.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 1372 participants
• Primary outcome timeframe: Day 19 (TOC)
• Results posted on: 2022-07-25

Participant Flow

Participants took part in the study at 95 study centers in Bulgaria, Czech Republic, Estonia, Georgia, Hungary, Latvia, Moldova, Poland, Romania, Russia, Serbia, Slovakia, South Africa, Ukraine, and the United States from 03 June 2019 to 27 May 2020.

Participants with diagnosis of complicated Urinary Tract Infection (cUTI) or Acute Pyelonephritis (AP) were enrolled to receive tebipenem pivoxil hydrobromide (TBPM-PI-HBr) and ertapenem.

Participant milestones

Measure	TBPM-PI-HBr 600 mg TBPM-PI-HBr 600 mg (300 mg×2 ) film-coated tablets, administered orally three times per day (every 8 hours \[q8h\] ± 0.5 h) plus a single dummy IV infusion over 30 minutes (min) once daily (every 24 hours \[q24h\] ± 0.5 h) up to Day 15; participants with moderate renal insufficiency (creatinine clearance \[CrCl\] \>30 to ≤50 mL/min) required TBPM-PI-HBr dosage adjustment to 300 mg (one tablet) q8h ± 0.5 h.	Ertapenem 1 g Ertapenem for IV injection, administered as a 1-gram IV infusion over 30 min once daily (q24h ± 0.5 h) plus dummy placebo tablets administered orally q8h (±0.5 h) up to Day 14; no dose adjustment of ertapenem was required for participants with renal insufficiency.
Overall Study STARTED	685	687
Overall Study Micro-Intent-to-Treat (ITT) Population	449	419
Overall Study COMPLETED	653	663
Overall Study NOT COMPLETED	32	24

Reasons for withdrawal

Measure	TBPM-PI-HBr 600 mg TBPM-PI-HBr 600 mg (300 mg×2 ) film-coated tablets, administered orally three times per day (every 8 hours \[q8h\] ± 0.5 h) plus a single dummy IV infusion over 30 minutes (min) once daily (every 24 hours \[q24h\] ± 0.5 h) up to Day 15; participants with moderate renal insufficiency (creatinine clearance \[CrCl\] \>30 to ≤50 mL/min) required TBPM-PI-HBr dosage adjustment to 300 mg (one tablet) q8h ± 0.5 h.	Ertapenem 1 g Ertapenem for IV injection, administered as a 1-gram IV infusion over 30 min once daily (q24h ± 0.5 h) plus dummy placebo tablets administered orally q8h (±0.5 h) up to Day 14; no dose adjustment of ertapenem was required for participants with renal insufficiency.
Overall Study Lost to Follow-up	14	10
Overall Study Participant Non-Compliance/Uncooperativeness	3	6
Overall Study Participant Withdrawal of Consent	13	5
Overall Study Adverse Event	1	1
Overall Study COVID-19	1	2

Baseline Characteristics

Study to Assess the Efficacy, Safety and Pharmacokinetics of Orally Administered Tebipenem Pivoxil Hydrobromide (SPR994) Compared to Intravenous Ertapenem in Participants With Complicated Urinary Tract Infection (cUTI) or Acute Pyelonephritis (AP)

Baseline characteristics by cohort

Measure	TBPM-PI-HBr 600 mg n=685 Participants TBPM-PI-HBr 600 mg (300 mg×2 ) film-coated tablets, administered orally three times per day (every 8 hours \[q8h\] ± 0.5 h) plus a single dummy IV infusion over 30 minutes (min) once daily (every 24 hours \[q24h\] ± 0.5 h) up to Day 15; participants with moderate renal insufficiency (creatinine clearance \[CrCl\] \>30 to ≤50 mL/min) required TBPM-PI-HBr dosage adjustment to 300 mg (one tablet) q8h ± 0.5 h.	Ertapenem 1 g n=687 Participants Ertapenem for IV injection, administered as a 1-gram IV infusion over 30 min once daily (q24h ± 0.5 h) plus dummy placebo tablets administered orally q8h (±0.5 h) up to Day 14; no dose adjustment of ertapenem was required for participants with renal insufficiency.	Total n=1372 Participants Total of all reporting groups
Age, Continuous	56.7 years STANDARD_DEVIATION 18.68 • n=5 Participants	57.2 years STANDARD_DEVIATION 18.23 • n=7 Participants	56.9 years STANDARD_DEVIATION 18.45 • n=5 Participants
Sex: Female, Male Female	368 Participants n=5 Participants	389 Participants n=7 Participants	757 Participants n=5 Participants
Sex: Female, Male Male	317 Participants n=5 Participants	298 Participants n=7 Participants	615 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	13 Participants n=5 Participants	5 Participants n=7 Participants	18 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	672 Participants n=5 Participants	682 Participants n=7 Participants	1354 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	3 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	6 Participants n=5 Participants	6 Participants n=7 Participants	12 Participants n=5 Participants
Race (NIH/OMB) White	676 Participants n=5 Participants	677 Participants n=7 Participants	1353 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Day 19 (TOC)

Population: Microbiological intent-to-treat population (Micro-ITT) included all randomized participants with a confirmed diagnosis of cUTI or AP and a positive Screening urine culture defined as growth of one or two uropathogens at ≥10\^5 CFU/mL and/or positive Screening blood culture with isolation of one or more uropathogens.

Overall response is participants with combined clinical cure and microbiological eradication. Clinical cure is defined as 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 antimicrobial therapy is warranted. Microbiological eradication is defined as reduction of baseline urine pathogen(s) to <10^3 colony forming unit/milliliter (CFU/mL) and negative repeated blood culture if blood culture was positive for uropathogen growth at baseline.

Outcome measures

Measure	TBPM-PI-HBr 600 mg n=449 Participants TBPM-PI-HBr 600 mg (300 mg×2 ) film-coated tablets, administered orally three times per day (every 8 hours \[q8h\] ± 0.5 h) plus a single dummy IV infusion over 30 minutes (min) once daily (every 24 hours \[q24h\] ± 0.5 h) up to Day 15; participants with moderate renal insufficiency (creatinine clearance \[CrCl\] \>30 to ≤50 mL/min) required TBPM-PI-HBr dosage adjustment to 300 mg (one tablet) q8h ± 0.5 h.	Ertapenem 1 g n=419 Participants Ertapenem for IV injection, administered as a 1-gram IV infusion over 30 min once daily (q24h ± 0.5 h) plus dummy placebo tablets administered orally q8h (±0.5 h) up to Day 14; no dose adjustment of ertapenem was required for participants with renal insufficiency.
Overall Response (Combined Clinical Cure and Microbiological Eradication) at Test-of-Cure (TOC) in Micro Intent-to-Treat Population	264 Participants	258 Participants

PRIMARY outcome

Timeframe: From the first dose of administration up to Day 25 post-treatment ± 2 days (up to approximately 27 days)

Population: Safety analysis population included all randomized participants who received any amount of study drug.

An Adverse Event (AE) was defined as any untoward medical occurrence in a subject 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.

Outcome measures

Measure	TBPM-PI-HBr 600 mg n=685 Participants TBPM-PI-HBr 600 mg (300 mg×2 ) film-coated tablets, administered orally three times per day (every 8 hours \[q8h\] ± 0.5 h) plus a single dummy IV infusion over 30 minutes (min) once daily (every 24 hours \[q24h\] ± 0.5 h) up to Day 15; participants with moderate renal insufficiency (creatinine clearance \[CrCl\] \>30 to ≤50 mL/min) required TBPM-PI-HBr dosage adjustment to 300 mg (one tablet) q8h ± 0.5 h.	Ertapenem 1 g n=687 Participants Ertapenem for IV injection, administered as a 1-gram IV infusion over 30 min once daily (q24h ± 0.5 h) plus dummy placebo tablets administered orally q8h (±0.5 h) up to Day 14; no dose adjustment of ertapenem was required for participants with renal insufficiency.
Number of Participants With Treatment Emergent Adverse Events (TEAEs) in The Safety Population	176 Participants	176 Participants

SECONDARY outcome

Timeframe: Day 19 (TOC)

Population: Microbiologically evaluable (ME) - TOC is a subset which included participants who met the definitions of both the micro-ITT Population and CE Population and were defined for each visit for the analyses in the ME Population at each respective visit as outlined in the evaluability review plan (ERP).

Overall response is participants with combined clinical cure and microbiological eradication. Clinical cure is defined as complete resolution or significant improvement of signs and symptoms of cUTI or acute pyelonephritis (AP) that were present at baseline and no new symptoms, such that no further antimicrobial therapy is warranted. Microbiological eradication is defined as reduction of baseline urine pathogen(s) to <10^3 CFU/mL and negative repeated blood culture if blood culture was positive for uropathogen growth at baseline.

Outcome measures

Measure	TBPM-PI-HBr 600 mg n=413 Participants TBPM-PI-HBr 600 mg (300 mg×2 ) film-coated tablets, administered orally three times per day (every 8 hours \[q8h\] ± 0.5 h) plus a single dummy IV infusion over 30 minutes (min) once daily (every 24 hours \[q24h\] ± 0.5 h) up to Day 15; participants with moderate renal insufficiency (creatinine clearance \[CrCl\] \>30 to ≤50 mL/min) required TBPM-PI-HBr dosage adjustment to 300 mg (one tablet) q8h ± 0.5 h.	Ertapenem 1 g n=376 Participants Ertapenem for IV injection, administered as a 1-gram IV infusion over 30 min once daily (q24h ± 0.5 h) plus dummy placebo tablets administered orally q8h (±0.5 h) up to Day 14; no dose adjustment of ertapenem was required for participants with renal insufficiency.
Overall Response (Combined Clinical Cure Plus Microbiological Eradication) At Test-Of-Cure (TOC) In The Microbiologically Evaluable (ME) - TOC Population	254 Participants	247 Participants

SECONDARY outcome

Timeframe: Days 15 (EOT), Day 19 (TOC) and Day 25 (LFU)

Population: Microbiological intent-to-treat population (Micro-ITT) included all randomized participants with a confirmed diagnosis of cUTI or AP and a positive Screening urine culture defined as growth of one or two uropathogens at ≥10\^5 CFU/mL and/or positive Screening blood culture with isolation of one or more uropathogens.

Clinical cure is defined as number of participants with 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 antimicrobial therapy is warranted. Sustained clinical cure is defined as participants who met criteria for clinical cure at TOC and remained free of signs and symptoms of cUTI or AP at LFU.

Outcome measures

Measure	TBPM-PI-HBr 600 mg n=449 Participants TBPM-PI-HBr 600 mg (300 mg×2 ) film-coated tablets, administered orally three times per day (every 8 hours \[q8h\] ± 0.5 h) plus a single dummy IV infusion over 30 minutes (min) once daily (every 24 hours \[q24h\] ± 0.5 h) up to Day 15; participants with moderate renal insufficiency (creatinine clearance \[CrCl\] \>30 to ≤50 mL/min) required TBPM-PI-HBr dosage adjustment to 300 mg (one tablet) q8h ± 0.5 h.	Ertapenem 1 g n=419 Participants Ertapenem for IV injection, administered as a 1-gram IV infusion over 30 min once daily (q24h ± 0.5 h) plus dummy placebo tablets administered orally q8h (±0.5 h) up to Day 14; no dose adjustment of ertapenem was required for participants with renal insufficiency.
Clinical Cure at End-of-Treatment (EOT), TOC, and Sustained Clinical Cure at Late Follow-Up (LFU) Days in the Micro-ITT Populations EOT	446 Participants	410 Participants
Clinical Cure at End-of-Treatment (EOT), TOC, and Sustained Clinical Cure at Late Follow-Up (LFU) Days in the Micro-ITT Populations TOC	418 Participants	392 Participants
Clinical Cure at End-of-Treatment (EOT), TOC, and Sustained Clinical Cure at Late Follow-Up (LFU) Days in the Micro-ITT Populations LFU	398 Participants	377 Participants

SECONDARY outcome

Timeframe: Day 15 (EOT)

Population: CE-EOT population is a subset which included participants who meet the definition for the ITT population, have no important protocol deviations that would affect the assessment of efficacy, and had an outcome assessed as clinical cure or clinical failure at EOT.

Clinical cure is defined as number of participants with 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 antimicrobial therapy is warranted.

Outcome measures

Measure	TBPM-PI-HBr 600 mg n=677 Participants TBPM-PI-HBr 600 mg (300 mg×2 ) film-coated tablets, administered orally three times per day (every 8 hours \[q8h\] ± 0.5 h) plus a single dummy IV infusion over 30 minutes (min) once daily (every 24 hours \[q24h\] ± 0.5 h) up to Day 15; participants with moderate renal insufficiency (creatinine clearance \[CrCl\] \>30 to ≤50 mL/min) required TBPM-PI-HBr dosage adjustment to 300 mg (one tablet) q8h ± 0.5 h.	Ertapenem 1 g n=674 Participants Ertapenem for IV injection, administered as a 1-gram IV infusion over 30 min once daily (q24h ± 0.5 h) plus dummy placebo tablets administered orally q8h (±0.5 h) up to Day 14; no dose adjustment of ertapenem was required for participants with renal insufficiency.
Clinical Cure at EOT Days the Clinically Evaluable (CE-EOT) Populations	673 Participants	665 Participants

SECONDARY outcome

Timeframe: Day 19 (TOC)

Population: CE-TOC population is a subset which included participants who meet the definition for the ITT population, have no important protocol deviations that would affect the assessment of efficacy, and had an outcome assessed as clinical cure or clinical failure at TOC.

Clinical cure is defined as number of participants with 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 antimicrobial therapy is warranted.

Outcome measures

Measure	TBPM-PI-HBr 600 mg n=641 Participants TBPM-PI-HBr 600 mg (300 mg×2 ) film-coated tablets, administered orally three times per day (every 8 hours \[q8h\] ± 0.5 h) plus a single dummy IV infusion over 30 minutes (min) once daily (every 24 hours \[q24h\] ± 0.5 h) up to Day 15; participants with moderate renal insufficiency (creatinine clearance \[CrCl\] \>30 to ≤50 mL/min) required TBPM-PI-HBr dosage adjustment to 300 mg (one tablet) q8h ± 0.5 h.	Ertapenem 1 g n=637 Participants Ertapenem for IV injection, administered as a 1-gram IV infusion over 30 min once daily (q24h ± 0.5 h) plus dummy placebo tablets administered orally q8h (±0.5 h) up to Day 14; no dose adjustment of ertapenem was required for participants with renal insufficiency.
Clinical Cure at TOC in the CE-TOC Populations	611 Participants	617 Participants

SECONDARY outcome

Timeframe: Day 25 (LFU)

Population: CE-LFU population is a subset which included participants who meet the definition for the ITT population, have no important protocol deviations that would affect the assessment of efficacy, and had an outcome assessed as clinical cure or clinical failure at LFU.

Clinical cure is defined as number of participants with 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 antimicrobial therapy is warranted. Sustained clinical cure is defined as number of participants who met criteria for clinical cure at TOC and remained free of signs and symptoms of cUTI or AP at LFU.

Outcome measures

Measure	TBPM-PI-HBr 600 mg n=596 Participants TBPM-PI-HBr 600 mg (300 mg×2 ) film-coated tablets, administered orally three times per day (every 8 hours \[q8h\] ± 0.5 h) plus a single dummy IV infusion over 30 minutes (min) once daily (every 24 hours \[q24h\] ± 0.5 h) up to Day 15; participants with moderate renal insufficiency (creatinine clearance \[CrCl\] \>30 to ≤50 mL/min) required TBPM-PI-HBr dosage adjustment to 300 mg (one tablet) q8h ± 0.5 h.	Ertapenem 1 g n=596 Participants Ertapenem for IV injection, administered as a 1-gram IV infusion over 30 min once daily (q24h ± 0.5 h) plus dummy placebo tablets administered orally q8h (±0.5 h) up to Day 14; no dose adjustment of ertapenem was required for participants with renal insufficiency.
Sustained Clinical Cure at LFU in the CE-LFU Populations	556 Participants	559 Participants

SECONDARY outcome

Timeframe: Day 15 (EOT)

Population: ME-EOT population is a subset which included participants who met the definitions of both the micro-ITT Population and CE Population and were defined for each visit for the analyses in the ME Population at each respective visit as outlined in the ERP.

Clinical cure is defined as number of participants with 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 antimicrobial therapy is warranted.

Outcome measures

Measure	TBPM-PI-HBr 600 mg n=439 Participants TBPM-PI-HBr 600 mg (300 mg×2 ) film-coated tablets, administered orally three times per day (every 8 hours \[q8h\] ± 0.5 h) plus a single dummy IV infusion over 30 minutes (min) once daily (every 24 hours \[q24h\] ± 0.5 h) up to Day 15; participants with moderate renal insufficiency (creatinine clearance \[CrCl\] \>30 to ≤50 mL/min) required TBPM-PI-HBr dosage adjustment to 300 mg (one tablet) q8h ± 0.5 h.	Ertapenem 1 g n=401 Participants Ertapenem for IV injection, administered as a 1-gram IV infusion over 30 min once daily (q24h ± 0.5 h) plus dummy placebo tablets administered orally q8h (±0.5 h) up to Day 14; no dose adjustment of ertapenem was required for participants with renal insufficiency.
Clinical Cure at EOT in the ME-EOT Populations	437 Participants	394 Participants

SECONDARY outcome

Timeframe: Day 19 (TOC)

Population: ME-TOC population is a subset which included participants who met the definitions of both the micro-ITT Population and CE Population and were defined for each visit for the analyses in the ME Population at each respective visit as outlined in the ERP.

Clinical cure is defined as number of participants with 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 antimicrobial therapy is warranted.

Outcome measures

Measure	TBPM-PI-HBr 600 mg n=413 Participants TBPM-PI-HBr 600 mg (300 mg×2 ) film-coated tablets, administered orally three times per day (every 8 hours \[q8h\] ± 0.5 h) plus a single dummy IV infusion over 30 minutes (min) once daily (every 24 hours \[q24h\] ± 0.5 h) up to Day 15; participants with moderate renal insufficiency (creatinine clearance \[CrCl\] \>30 to ≤50 mL/min) required TBPM-PI-HBr dosage adjustment to 300 mg (one tablet) q8h ± 0.5 h.	Ertapenem 1 g n=376 Participants Ertapenem for IV injection, administered as a 1-gram IV infusion over 30 min once daily (q24h ± 0.5 h) plus dummy placebo tablets administered orally q8h (±0.5 h) up to Day 14; no dose adjustment of ertapenem was required for participants with renal insufficiency.
Clinical Cure at TOC Days in the ME-TOC Populations	390 Participants	363 Participants

SECONDARY outcome

Timeframe: Day 25 (LFU)

Population: ME-LFU population is a subset which included participants who met the definitions of both the micro-ITT Population and CE Population and were defined for each visit for the analyses in the ME Population at each respective visit as outlined in the ERP.

Clinical cure is defined as number of participants with 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 antimicrobial therapy is warranted. Sustained clinical cure is defined as participants who met criteria for clinical cure at TOC and remained free of signs and symptoms of cUTI or AP at LFU.

Outcome measures

Measure	TBPM-PI-HBr 600 mg n=391 Participants TBPM-PI-HBr 600 mg (300 mg×2 ) film-coated tablets, administered orally three times per day (every 8 hours \[q8h\] ± 0.5 h) plus a single dummy IV infusion over 30 minutes (min) once daily (every 24 hours \[q24h\] ± 0.5 h) up to Day 15; participants with moderate renal insufficiency (creatinine clearance \[CrCl\] \>30 to ≤50 mL/min) required TBPM-PI-HBr dosage adjustment to 300 mg (one tablet) q8h ± 0.5 h.	Ertapenem 1 g n=353 Participants Ertapenem for IV injection, administered as a 1-gram IV infusion over 30 min once daily (q24h ± 0.5 h) plus dummy placebo tablets administered orally q8h (±0.5 h) up to Day 14; no dose adjustment of ertapenem was required for participants with renal insufficiency.
Sustained Clinical Cure at LFU in the ME-LFU Population	360 Participants	329 Participants

SECONDARY outcome

Timeframe: Days 15 (EOT), 19 (TOC) and 25 (LFU)

Population: Micro-ITT include all randomized participants with a confirmed diagnosis of cUTI or AP and a positive Screening urine culture defined as growth of one or two uropathogens at ≥10\^5 CFU/mL and/or positive Screening blood culture with isolation of one or more uropathogens.

Microbiological eradication is defined as reduction of baseline urine pathogen(s) to <10^3 CFU/mL and negative repeated blood culture if blood culture was positive for uropathogen growth at baseline. Microbiological eradication is defined as number of participants with reduction of Baseline urine pathogen(s) to <10^3 CFU/mL and negative repeated blood culture if blood culture was positive for uropathogen growth at Baseline. Sustained Microbiological Eradication is defined as number of participants with microbiologic eradication at the TOC and no subsequent urine culture after TOC demonstrating recurrence of the original baseline uropathogen at ≥10^5 CFU/mL.

Outcome measures

Measure	TBPM-PI-HBr 600 mg n=449 Participants TBPM-PI-HBr 600 mg (300 mg×2 ) film-coated tablets, administered orally three times per day (every 8 hours \[q8h\] ± 0.5 h) plus a single dummy IV infusion over 30 minutes (min) once daily (every 24 hours \[q24h\] ± 0.5 h) up to Day 15; participants with moderate renal insufficiency (creatinine clearance \[CrCl\] \>30 to ≤50 mL/min) required TBPM-PI-HBr dosage adjustment to 300 mg (one tablet) q8h ± 0.5 h.	Ertapenem 1 g n=419 Participants Ertapenem for IV injection, administered as a 1-gram IV infusion over 30 min once daily (q24h ± 0.5 h) plus dummy placebo tablets administered orally q8h (±0.5 h) up to Day 14; no dose adjustment of ertapenem was required for participants with renal insufficiency.
By-Patient Microbiological Eradication at EOT, TOC, and Sustained Microbiological Eradication at LFU Days in the Micro-ITT Population EOT	439 Participants	403 Participants
By-Patient Microbiological Eradication at EOT, TOC, and Sustained Microbiological Eradication at LFU Days in the Micro-ITT Population TOC	267 Participants	266 Participants
By-Patient Microbiological Eradication at EOT, TOC, and Sustained Microbiological Eradication at LFU Days in the Micro-ITT Population LFU	257 Participants	244 Participants

SECONDARY outcome

Timeframe: Days 15 (EOT)

Population: Micro-ITT-all randomized participants with confirmed diagnosis of cUTI/AP and positive Screening urine culture defined as growth of one or two uropathogens at ≥10\^5 CFU/mL and/or positive Screening blood culture with isolation of one or more uropathogens. Overall Number of Units Analyzed=number of pathogens available for analysis at given timepoint. Participant may have had more than 1 pathogen. Multiple isolates of same species/category from same participant are counted only once towards total.

Microbiological eradication is defined as reduction of baseline urine pathogen(s) to <10^3 CFU/mL and negative repeated blood culture if blood culture was positive for uropathogen growth at baseline. Microbiological eradication rate is the percentage of pathogens being eradicated from the overall number of pathogens analyzed.

Outcome measures

Measure	TBPM-PI-HBr 600 mg n=493 Pathogens TBPM-PI-HBr 600 mg (300 mg×2 ) film-coated tablets, administered orally three times per day (every 8 hours \[q8h\] ± 0.5 h) plus a single dummy IV infusion over 30 minutes (min) once daily (every 24 hours \[q24h\] ± 0.5 h) up to Day 15; participants with moderate renal insufficiency (creatinine clearance \[CrCl\] \>30 to ≤50 mL/min) required TBPM-PI-HBr dosage adjustment to 300 mg (one tablet) q8h ± 0.5 h.	Ertapenem 1 g n=455 Pathogens Ertapenem for IV injection, administered as a 1-gram IV infusion over 30 min once daily (q24h ± 0.5 h) plus dummy placebo tablets administered orally q8h (±0.5 h) up to Day 14; no dose adjustment of ertapenem was required for participants with renal insufficiency.
By-Pathogen Microbiological Eradication Rate at EOT in the Micro-ITT Population Enterobacterales, Citrobacter braakii	—	100 percentage of pathogen eradication
By-Pathogen Microbiological Eradication Rate at EOT in the Micro-ITT Population Enterobacterales, Citrobacter freundii	75.0 percentage of pathogen eradication	66.7 percentage of pathogen eradication
By-Pathogen Microbiological Eradication Rate at EOT in the Micro-ITT Population Enterobacterales, Citrobacter koseri	100 percentage of pathogen eradication	100 percentage of pathogen eradication
By-Pathogen Microbiological Eradication Rate at EOT in the Micro-ITT Population Enterobacterales, Enterobacter amnigenus	—	100 percentage of pathogen eradication
By-Pathogen Microbiological Eradication Rate at EOT in the Micro-ITT Population Enterobacterales, Enterobacter asburiae	—	100 percentage of pathogen eradication
By-Pathogen Microbiological Eradication Rate at EOT in the Micro-ITT Population Enterobacterales, Enterobacter bugandensis	—	100 percentage of pathogen eradication
By-Pathogen Microbiological Eradication Rate at EOT in the Micro-ITT Population Enterobacterales, Enterobacter cloacae	90.9 percentage of pathogen eradication	100 percentage of pathogen eradication
By-Pathogen Microbiological Eradication Rate at EOT in the Micro-ITT Population Enterobacterales, Escherichia coli	98.3 percentage of pathogen eradication	96.7 percentage of pathogen eradication
By-Pathogen Microbiological Eradication Rate at EOT in the Micro-ITT Population Enterobacterales, Klebsiella aerogenes	100 percentage of pathogen eradication	0.0 percentage of pathogen eradication
By-Pathogen Microbiological Eradication Rate at EOT in the Micro-ITT Population Enterobacterales, Klebsiella oxytoca	100 percentage of pathogen eradication	100 percentage of pathogen eradication
By-Pathogen Microbiological Eradication Rate at EOT in the Micro-ITT Population Enterobacterales, Klebsiella pneumoniae	98.1 percentage of pathogen eradication	98.6 percentage of pathogen eradication
By-Pathogen Microbiological Eradication Rate at EOT in the Micro-ITT Population Enterobacterales, Klebsiella variicola	100 percentage of pathogen eradication	100 percentage of pathogen eradication
By-Pathogen Microbiological Eradication Rate at EOT in the Micro-ITT Population Enterobacterales, Morganella morganii	100 percentage of pathogen eradication	100 percentage of pathogen eradication
By-Pathogen Microbiological Eradication Rate at EOT in the Micro-ITT Population Enterobacterales, Proteus hauseri	100 percentage of pathogen eradication	—
By-Pathogen Microbiological Eradication Rate at EOT in the Micro-ITT Population Enterobacterales, Proteus mirabilis	97.1 percentage of pathogen eradication	100 percentage of pathogen eradication
By-Pathogen Microbiological Eradication Rate at EOT in the Micro-ITT Population Enterobacterales, Proteus penneri	—	100 percentage of pathogen eradication
By-Pathogen Microbiological Eradication Rate at EOT in the Micro-ITT Population Enterobacterales, Proteus vulgaris	—	100 percentage of pathogen eradication
By-Pathogen Microbiological Eradication Rate at EOT in the Micro-ITT Population Enterobacterales, Providencia rettgeri	100 percentage of pathogen eradication	100 percentage of pathogen eradication
By-Pathogen Microbiological Eradication Rate at EOT in the Micro-ITT Population Enterobacterales, Providencia stuartii	100 percentage of pathogen eradication	100 percentage of pathogen eradication
By-Pathogen Microbiological Eradication Rate at EOT in the Micro-ITT Population Enterobacterales, Raoultella ornithinolytica	100 percentage of pathogen eradication	—
By-Pathogen Microbiological Eradication Rate at EOT in the Micro-ITT Population Enterobacterales, Serratia liquefaciens	—	100 percentage of pathogen eradication
By-Pathogen Microbiological Eradication Rate at EOT in the Micro-ITT Population Enterobacterales, Serratia marcescens	100 percentage of pathogen eradication	100 percentage of pathogen eradication
By-Pathogen Microbiological Eradication Rate at EOT in the Micro-ITT Population Gram Positive, Enterococcus faecalis	94.8 percentage of pathogen eradication	91.7 percentage of pathogen eradication
By-Pathogen Microbiological Eradication Rate at EOT in the Micro-ITT Population Gram Positive, Enterococcus faecium	100 percentage of pathogen eradication	100 percentage of pathogen eradication
By-Pathogen Microbiological Eradication Rate at EOT in the Micro-ITT Population Gram Positive, Enterococcus hirae	100 percentage of pathogen eradication	—
By-Pathogen Microbiological Eradication Rate at EOT in the Micro-ITT Population Gram Positive, Staphylococcus aureus	100 percentage of pathogen eradication	75.0 percentage of pathogen eradication
By-Pathogen Microbiological Eradication Rate at EOT in the Micro-ITT Population Gram Positive, Staphylococcus lugdunensis	100 percentage of pathogen eradication	100 percentage of pathogen eradication
By-Pathogen Microbiological Eradication Rate at EOT in the Micro-ITT Population Gram Positive, Staphylococcus saprophyticus	100 percentage of pathogen eradication	100 percentage of pathogen eradication
By-Pathogen Microbiological Eradication Rate at EOT in the Micro-ITT Population Gram Positive, Streptococcus gallolyticus	100 percentage of pathogen eradication	—

SECONDARY outcome

Timeframe: Day 19 (TOC)

Population: Micro-ITT included all randomized participants with a confirmed diagnosis of cUTI or AP and a positive Screening urine culture defined as growth of one or two uropathogens at ≥10\^5 CFU/mL and/or positive Screening blood culture with isolation of one or more uropathogens. Number analyzed are the number of pathogens available for analysis at the given timepoint.

Microbiological eradication is defined as reduction of baseline urine pathogen(s) to <10^3 CFU/mL and negative repeated blood culture if blood culture was positive for uropathogen growth at baseline. Microbiological eradication rate is the percentage of pathogens being eradicated from the overall number of pathogens analyzed.

Outcome measures

Measure	TBPM-PI-HBr 600 mg n=493 Pathogens TBPM-PI-HBr 600 mg (300 mg×2 ) film-coated tablets, administered orally three times per day (every 8 hours \[q8h\] ± 0.5 h) plus a single dummy IV infusion over 30 minutes (min) once daily (every 24 hours \[q24h\] ± 0.5 h) up to Day 15; participants with moderate renal insufficiency (creatinine clearance \[CrCl\] \>30 to ≤50 mL/min) required TBPM-PI-HBr dosage adjustment to 300 mg (one tablet) q8h ± 0.5 h.	Ertapenem 1 g n=455 Pathogens Ertapenem for IV injection, administered as a 1-gram IV infusion over 30 min once daily (q24h ± 0.5 h) plus dummy placebo tablets administered orally q8h (±0.5 h) up to Day 14; no dose adjustment of ertapenem was required for participants with renal insufficiency.
By-Pathogen Microbiological Eradication Rate at TOC in the Micro-ITT Population Enterobacterales, Citrobacter braakii	—	100 percentage of pathogen eradication
By-Pathogen Microbiological Eradication Rate at TOC in the Micro-ITT Population Enterobacterales, Citrobacter freundii	50.0 percentage of pathogen eradication	100 percentage of pathogen eradication
By-Pathogen Microbiological Eradication Rate at TOC in the Micro-ITT Population Enterobacterales, Citrobacter koseri	66.7 percentage of pathogen eradication	50.0 percentage of pathogen eradication
By-Pathogen Microbiological Eradication Rate at TOC in the Micro-ITT Population Enterobacterales, Enterobacter amnigenus	—	100 percentage of pathogen eradication
By-Pathogen Microbiological Eradication Rate at TOC in the Micro-ITT Population Enterobacterales, Enterobacter asburiae	—	100 percentage of pathogen eradication
By-Pathogen Microbiological Eradication Rate at TOC in the Micro-ITT Population Enterobacterales, Enterobacter bugandensis	—	100 percentage of pathogen eradication
By-Pathogen Microbiological Eradication Rate at TOC in the Micro-ITT Population Enterobacterales, Enterobacter cloacae	54.5 percentage of pathogen eradication	50.0 percentage of pathogen eradication
By-Pathogen Microbiological Eradication Rate at TOC in the Micro-ITT Population Enterobacterales, Escherichia coli	62.7 percentage of pathogen eradication	65.2 percentage of pathogen eradication
By-Pathogen Microbiological Eradication Rate at TOC in the Micro-ITT Population Enterobacterales, Klebsiella aerogenes	0.0 percentage of pathogen eradication	0.0 percentage of pathogen eradication
By-Pathogen Microbiological Eradication Rate at TOC in the Micro-ITT Population Enterobacterales, Klebsiella oxytoca	75.0 percentage of pathogen eradication	33.3 percentage of pathogen eradication
By-Pathogen Microbiological Eradication Rate at TOC in the Micro-ITT Population Enterobacterales, Klebsiella pneumoniae	45.3 percentage of pathogen eradication	63.4 percentage of pathogen eradication
By-Pathogen Microbiological Eradication Rate at TOC in the Micro-ITT Population Enterobacterales, Klebsiella variicola	50.0 percentage of pathogen eradication	75.0 percentage of pathogen eradication
By-Pathogen Microbiological Eradication Rate at TOC in the Micro-ITT Population Enterobacterales, Morganella morganii	100 percentage of pathogen eradication	100 percentage of pathogen eradication
By-Pathogen Microbiological Eradication Rate at TOC in the Micro-ITT Population Enterobacterales, Proteus hauseri	100 percentage of pathogen eradication	—
By-Pathogen Microbiological Eradication Rate at TOC in the Micro-ITT Population Enterobacterales, Proteus mirabilis	48.6 percentage of pathogen eradication	69.6 percentage of pathogen eradication
By-Pathogen Microbiological Eradication Rate at TOC in the Micro-ITT Population Enterobacterales, Proteus penneri	—	100 percentage of pathogen eradication
By-Pathogen Microbiological Eradication Rate at TOC in the Micro-ITT Population Enterobacterales, Proteus vulgaris	—	100 percentage of pathogen eradication
By-Pathogen Microbiological Eradication Rate at TOC in the Micro-ITT Population Enterobacterales, Providencia rettgeri	100 percentage of pathogen eradication	100 percentage of pathogen eradication
By-Pathogen Microbiological Eradication Rate at TOC in the Micro-ITT Population Enterobacterales, Providencia stuartii	0.0 percentage of pathogen eradication	100 percentage of pathogen eradication
By-Pathogen Microbiological Eradication Rate at TOC in the Micro-ITT Population Enterobacterales, Raoultella ornithinolytica	100 percentage of pathogen eradication	—
By-Pathogen Microbiological Eradication Rate at TOC in the Micro-ITT Population Enterobacterales, Serratia liquefaciens	—	100 percentage of pathogen eradication
By-Pathogen Microbiological Eradication Rate at TOC in the Micro-ITT Population Enterobacterales, Serratia marcescens	50.0 percentage of pathogen eradication	100 percentage of pathogen eradication
By-Pathogen Microbiological Eradication Rate at TOC in the Micro-ITT Population Gram Positive, Enterococcus faecalis	67.2 percentage of pathogen eradication	55.6 percentage of pathogen eradication
By-Pathogen Microbiological Eradication Rate at TOC in the Micro-ITT Population Gram Positive, Enterococcus faecium	100 percentage of pathogen eradication	100 percentage of pathogen eradication
By-Pathogen Microbiological Eradication Rate at TOC in the Micro-ITT Population Gram Positive, Enterococcus hirae	100 percentage of pathogen eradication	—
By-Pathogen Microbiological Eradication Rate at TOC in the Micro-ITT Population Gram Positive, Staphylococcus aureus	100 percentage of pathogen eradication	37.5 percentage of pathogen eradication
By-Pathogen Microbiological Eradication Rate at TOC in the Micro-ITT Population Gram Positive, Staphylococcus lugdunensis	100 percentage of pathogen eradication	100 percentage of pathogen eradication
By-Pathogen Microbiological Eradication Rate at TOC in the Micro-ITT Population Gram Positive, Staphylococcus saprophyticus	100 percentage of pathogen eradication	83.3 percentage of pathogen eradication
By-Pathogen Microbiological Eradication Rate at TOC in the Micro-ITT Population Gram Positive, Streptococcus gallolyticus	100 percentage of pathogen eradication	—

SECONDARY outcome

Timeframe: Day 25 (LFU)

Population: mITT-all randomized participants with confirmed diagnosis of cUTI/AP \& positive Screening urine culture defined as growth of one/two uropathogens at ≥10\^5 CFU/mL and/or positive Screening blood culture with isolation of one or more uropathogens. Overall Number of Units Analyzed are number of enterobacterale pathogens. Participant may have more than 1 pathogen. Multiple isolates of same species/category from same participants are counted once towards total.

Microbiological eradication is defined as reduction of baseline urine pathogen(s) to <10^3 CFU/mL and negative repeated blood culture if blood culture was positive for uropathogen growth at baseline. Sustained Microbiological Eradication is defined as microbiologic eradication at the TOC and no subsequent urine culture after TOC demonstrating recurrence of the original baseline uropathogen at ≥10^5 CFU/mL. Microbiological eradication rate is the percentage of pathogens being eradicated from the overall number of pathogen analyzed.

Outcome measures

Measure	TBPM-PI-HBr 600 mg n=417 Pathogens TBPM-PI-HBr 600 mg (300 mg×2 ) film-coated tablets, administered orally three times per day (every 8 hours \[q8h\] ± 0.5 h) plus a single dummy IV infusion over 30 minutes (min) once daily (every 24 hours \[q24h\] ± 0.5 h) up to Day 15; participants with moderate renal insufficiency (creatinine clearance \[CrCl\] \>30 to ≤50 mL/min) required TBPM-PI-HBr dosage adjustment to 300 mg (one tablet) q8h ± 0.5 h.	Ertapenem 1 g n=402 Pathogens Ertapenem for IV injection, administered as a 1-gram IV infusion over 30 min once daily (q24h ± 0.5 h) plus dummy placebo tablets administered orally q8h (±0.5 h) up to Day 14; no dose adjustment of ertapenem was required for participants with renal insufficiency.
By-Pathogen Sustained Microbiological Eradication Rate at LFU in the Micro-ITT Population (m-ITT) Citrobacter braakii	—	100 percentage of pathogen eradication
By-Pathogen Sustained Microbiological Eradication Rate at LFU in the Micro-ITT Population (m-ITT) Citrobacter freundii	50.0 percentage of pathogen eradication	100 percentage of pathogen eradication
By-Pathogen Sustained Microbiological Eradication Rate at LFU in the Micro-ITT Population (m-ITT) Citrobacter koseri	66.7 percentage of pathogen eradication	50.0 percentage of pathogen eradication
By-Pathogen Sustained Microbiological Eradication Rate at LFU in the Micro-ITT Population (m-ITT) Enterobacter amnigenus	—	100 percentage of pathogen eradication
By-Pathogen Sustained Microbiological Eradication Rate at LFU in the Micro-ITT Population (m-ITT) Enterobacter asburiae	—	0 percentage of pathogen eradication
By-Pathogen Sustained Microbiological Eradication Rate at LFU in the Micro-ITT Population (m-ITT) Enterobacter bugandensis	—	100 percentage of pathogen eradication
By-Pathogen Sustained Microbiological Eradication Rate at LFU in the Micro-ITT Population (m-ITT) Enterobacter cloacae	54.5 percentage of pathogen eradication	37.5 percentage of pathogen eradication
By-Pathogen Sustained Microbiological Eradication Rate at LFU in the Micro-ITT Population (m-ITT) Enterococcus faecalis	63.8 percentage of pathogen eradication	50.0 percentage of pathogen eradication
By-Pathogen Sustained Microbiological Eradication Rate at LFU in the Micro-ITT Population (m-ITT) Enterococcus faecium	100 percentage of pathogen eradication	100 percentage of pathogen eradication
By-Pathogen Sustained Microbiological Eradication Rate at LFU in the Micro-ITT Population (m-ITT) Enterococcus hirae	100 percentage of pathogen eradication	—
By-Pathogen Sustained Microbiological Eradication Rate at LFU in the Micro-ITT Population (m-ITT) Escherichia coli	59.9 percentage of pathogen eradication	60.0 percentage of pathogen eradication
By-Pathogen Sustained Microbiological Eradication Rate at LFU in the Micro-ITT Population (m-ITT) Klebsiella aerogenes	0.0 percentage of pathogen eradication	0.0 percentage of pathogen eradication
By-Pathogen Sustained Microbiological Eradication Rate at LFU in the Micro-ITT Population (m-ITT) Klebsiella oxytoca	75.0 percentage of pathogen eradication	33.3 percentage of pathogen eradication
By-Pathogen Sustained Microbiological Eradication Rate at LFU in the Micro-ITT Population (m-ITT) Klebsiella pneumoniae	43.4 percentage of pathogen eradication	60.6 percentage of pathogen eradication
By-Pathogen Sustained Microbiological Eradication Rate at LFU in the Micro-ITT Population (m-ITT) Klebsiella variicola	50.0 percentage of pathogen eradication	75.0 percentage of pathogen eradication
By-Pathogen Sustained Microbiological Eradication Rate at LFU in the Micro-ITT Population (m-ITT) Morganella morganii	100 percentage of pathogen eradication	100 percentage of pathogen eradication
By-Pathogen Sustained Microbiological Eradication Rate at LFU in the Micro-ITT Population (m-ITT) Proteus hauseri	100 percentage of pathogen eradication	—
By-Pathogen Sustained Microbiological Eradication Rate at LFU in the Micro-ITT Population (m-ITT) Proteus mirabilis	48.6 percentage of pathogen eradication	60.9 percentage of pathogen eradication
By-Pathogen Sustained Microbiological Eradication Rate at LFU in the Micro-ITT Population (m-ITT) Proteus penneri	—	100 percentage of pathogen eradication
By-Pathogen Sustained Microbiological Eradication Rate at LFU in the Micro-ITT Population (m-ITT) Proteus vulgaris	—	100 percentage of pathogen eradication
By-Pathogen Sustained Microbiological Eradication Rate at LFU in the Micro-ITT Population (m-ITT) Providencia rettgeri	100 percentage of pathogen eradication	100 percentage of pathogen eradication
By-Pathogen Sustained Microbiological Eradication Rate at LFU in the Micro-ITT Population (m-ITT) Providencia stuartii	0.0 percentage of pathogen eradication	100 percentage of pathogen eradication
By-Pathogen Sustained Microbiological Eradication Rate at LFU in the Micro-ITT Population (m-ITT) Raoultella ornithinolytica	100 percentage of pathogen eradication	—
By-Pathogen Sustained Microbiological Eradication Rate at LFU in the Micro-ITT Population (m-ITT) Serratia liquefaciens	—	100 percentage of pathogen eradication
By-Pathogen Sustained Microbiological Eradication Rate at LFU in the Micro-ITT Population (m-ITT) Serratia marcescens	50.0 percentage of pathogen eradication	100 percentage of pathogen eradication
By-Pathogen Sustained Microbiological Eradication Rate at LFU in the Micro-ITT Population (m-ITT) Staphylococcus aureus	100 percentage of pathogen eradication	37.5 percentage of pathogen eradication
By-Pathogen Sustained Microbiological Eradication Rate at LFU in the Micro-ITT Population (m-ITT) Staphylococcus lugdunensis	100 percentage of pathogen eradication	100 percentage of pathogen eradication
By-Pathogen Sustained Microbiological Eradication Rate at LFU in the Micro-ITT Population (m-ITT) Staphylococcus saprophyticus	100 percentage of pathogen eradication	83.3 percentage of pathogen eradication
By-Pathogen Sustained Microbiological Eradication Rate at LFU in the Micro-ITT Population (m-ITT) Staphylococcus gallolyticus	100 percentage of pathogen eradication	—

SECONDARY outcome

Timeframe: Day 15 (EOT)

Population: ME-EOT population is a subset which included participants who met the definitions of both the micro-ITT Population and CE Population and were defined for each visit for the analyses in the ME Population at each respective visit as outlined in the ERP.

Microbiological eradication is defined as reduction of baseline urine pathogen(s) to <10^3 CFU/mL and negative repeated blood culture if blood culture was positive for uropathogen growth at baseline.

Outcome measures

Measure	TBPM-PI-HBr 600 mg n=439 Participants TBPM-PI-HBr 600 mg (300 mg×2 ) film-coated tablets, administered orally three times per day (every 8 hours \[q8h\] ± 0.5 h) plus a single dummy IV infusion over 30 minutes (min) once daily (every 24 hours \[q24h\] ± 0.5 h) up to Day 15; participants with moderate renal insufficiency (creatinine clearance \[CrCl\] \>30 to ≤50 mL/min) required TBPM-PI-HBr dosage adjustment to 300 mg (one tablet) q8h ± 0.5 h.	Ertapenem 1 g n=401 Participants Ertapenem for IV injection, administered as a 1-gram IV infusion over 30 min once daily (q24h ± 0.5 h) plus dummy placebo tablets administered orally q8h (±0.5 h) up to Day 14; no dose adjustment of ertapenem was required for participants with renal insufficiency.
By-Patient Microbiological Eradication at EOT in the ME-EOT Populations	436 Participants	399 Participants

SECONDARY outcome

Timeframe: Day 15 (TOC)

Population: ME-TOC population included participants who met the definitions of both the micro-ITT Population and CE Population and were defined for each visit for the analyses in the ME Population at each respective visit as outlined in the ERP.

Microbiological eradication is defined as number of participants with reduction of baseline urine pathogen(s) to <10^3 CFU/mL and negative repeated blood culture if blood culture was positive for uropathogen growth at baseline. Microbiological eradication rate is the percentage of pathogens being eradicated from the overall number of pathogens analyzed.

Outcome measures

Measure	TBPM-PI-HBr 600 mg n=413 Participants TBPM-PI-HBr 600 mg (300 mg×2 ) film-coated tablets, administered orally three times per day (every 8 hours \[q8h\] ± 0.5 h) plus a single dummy IV infusion over 30 minutes (min) once daily (every 24 hours \[q24h\] ± 0.5 h) up to Day 15; participants with moderate renal insufficiency (creatinine clearance \[CrCl\] \>30 to ≤50 mL/min) required TBPM-PI-HBr dosage adjustment to 300 mg (one tablet) q8h ± 0.5 h.	Ertapenem 1 g n=376 Participants Ertapenem for IV injection, administered as a 1-gram IV infusion over 30 min once daily (q24h ± 0.5 h) plus dummy placebo tablets administered orally q8h (±0.5 h) up to Day 14; no dose adjustment of ertapenem was required for participants with renal insufficiency.
By-Patient Microbiological Eradication at TOC in the ME-TOC Population	257 Participants	254 Participants

SECONDARY outcome

Timeframe: Day 25 (LFU)

Population: ME-LFU population included participants who met the definitions of both the micro-ITT Population and CE Population and were defined for each visit for the analyses in the ME Population at each respective visit as outlined in the ERP

Microbiological eradication is defined as number of participants with reduction of baseline urine pathogen(s) to <10^3 colony forming unit/milliliter (CFU/mL) and negative repeated blood culture if blood culture was positive for uropathogen growth at baseline. Sustained Microbiological Eradication is defined participants with microbiologic eradication at the TOC and no subsequent urine culture after TOC demonstrating recurrence of the original baseline uropathogen at ≥10^5 CFU/mL.

Outcome measures

Measure	TBPM-PI-HBr 600 mg n=391 Participants TBPM-PI-HBr 600 mg (300 mg×2 ) film-coated tablets, administered orally three times per day (every 8 hours \[q8h\] ± 0.5 h) plus a single dummy IV infusion over 30 minutes (min) once daily (every 24 hours \[q24h\] ± 0.5 h) up to Day 15; participants with moderate renal insufficiency (creatinine clearance \[CrCl\] \>30 to ≤50 mL/min) required TBPM-PI-HBr dosage adjustment to 300 mg (one tablet) q8h ± 0.5 h.	Ertapenem 1 g n=353 Participants Ertapenem for IV injection, administered as a 1-gram IV infusion over 30 min once daily (q24h ± 0.5 h) plus dummy placebo tablets administered orally q8h (±0.5 h) up to Day 14; no dose adjustment of ertapenem was required for participants with renal insufficiency.
By-Patient Sustained Microbiological Eradication at LFU Days in the ME-LFU Populations	234 Participants	216 Participants

SECONDARY outcome

Timeframe: Day 15 (EOT)

Population: ME-EOT population included participants who met the definitions of both the micro-ITT Population and CE Population and were defined for each visit for the analyses in the ME Population at each respective visit as outlined in the ERP. Number analyzed are the number of pathogens available for analysis at the given timepoint.

Microbiological eradication is defined as number of participants with reduction of baseline urine pathogen(s) to <10^3 CFU/mL and negative repeated blood culture if blood culture was positive for uropathogen growth at baseline. Microbiological eradication rate is the percentage of pathogens being eradicated from the overall number of pathogens analyzed.

Outcome measures

Measure	TBPM-PI-HBr 600 mg n=481 Pathogens TBPM-PI-HBr 600 mg (300 mg×2 ) film-coated tablets, administered orally three times per day (every 8 hours \[q8h\] ± 0.5 h) plus a single dummy IV infusion over 30 minutes (min) once daily (every 24 hours \[q24h\] ± 0.5 h) up to Day 15; participants with moderate renal insufficiency (creatinine clearance \[CrCl\] \>30 to ≤50 mL/min) required TBPM-PI-HBr dosage adjustment to 300 mg (one tablet) q8h ± 0.5 h.	Ertapenem 1 g n=436 Pathogens Ertapenem for IV injection, administered as a 1-gram IV infusion over 30 min once daily (q24h ± 0.5 h) plus dummy placebo tablets administered orally q8h (±0.5 h) up to Day 14; no dose adjustment of ertapenem was required for participants with renal insufficiency.
By-pathogen Microbiological Eradication Rate in Participants at EOT in the ME-EOT Populations Enterobacterales, Citrobacter braakii	—	100 percentage of pathogen eradication
By-pathogen Microbiological Eradication Rate in Participants at EOT in the ME-EOT Populations Enterobacterales, Citrobacter freundii	100 percentage of pathogen eradication	100 percentage of pathogen eradication
By-pathogen Microbiological Eradication Rate in Participants at EOT in the ME-EOT Populations Enterobacterales, Citrobacter koseri	100 percentage of pathogen eradication	100 percentage of pathogen eradication
By-pathogen Microbiological Eradication Rate in Participants at EOT in the ME-EOT Populations Enterobacterales, Enterobacter amnigenus	—	100 percentage of pathogen eradication
By-pathogen Microbiological Eradication Rate in Participants at EOT in the ME-EOT Populations Enterobacterales, Enterobacter asburiae	—	100 percentage of pathogen eradication
By-pathogen Microbiological Eradication Rate in Participants at EOT in the ME-EOT Populations Enterobacterales, Enterobacter bugandensis	—	100 percentage of pathogen eradication
By-pathogen Microbiological Eradication Rate in Participants at EOT in the ME-EOT Populations Enterobacterales, Enterobacter cloacae	90.9 percentage of pathogen eradication	100 percentage of pathogen eradication
By-pathogen Microbiological Eradication Rate in Participants at EOT in the ME-EOT Populations Enterobacterales, Escherichia coli	99.6 percentage of pathogen eradication	100 percentage of pathogen eradication
By-pathogen Microbiological Eradication Rate in Participants at EOT in the ME-EOT Populations Enterobacterales, Klebsiella aerogenes	100 percentage of pathogen eradication	—
By-pathogen Microbiological Eradication Rate in Participants at EOT in the ME-EOT Populations Enterobacterales, Klebsiella oxytoca	100 percentage of pathogen eradication	100 percentage of pathogen eradication
By-pathogen Microbiological Eradication Rate in Participants at EOT in the ME-EOT Populations Enterobacterales, Klebsiella pneumoniae	100 percentage of pathogen eradication	100 percentage of pathogen eradication
By-pathogen Microbiological Eradication Rate in Participants at EOT in the ME-EOT Populations Enterobacterales, Klebsiella variicola	100 percentage of pathogen eradication	100 percentage of pathogen eradication
By-pathogen Microbiological Eradication Rate in Participants at EOT in the ME-EOT Populations Enterobacterales, Morganella morganii	100 percentage of pathogen eradication	100 percentage of pathogen eradication
By-pathogen Microbiological Eradication Rate in Participants at EOT in the ME-EOT Populations Enterobacterales, Proteus hauseri	100 percentage of pathogen eradication	—
By-pathogen Microbiological Eradication Rate in Participants at EOT in the ME-EOT Populations Enterobacterales, Proteus mirabilis	100 percentage of pathogen eradication	100 percentage of pathogen eradication
By-pathogen Microbiological Eradication Rate in Participants at EOT in the ME-EOT Populations Enterobacterales, Proteus penneri	—	100 percentage of pathogen eradication
By-pathogen Microbiological Eradication Rate in Participants at EOT in the ME-EOT Populations Enterobacterales, Proteus vulgaris	—	100 percentage of pathogen eradication
By-pathogen Microbiological Eradication Rate in Participants at EOT in the ME-EOT Populations Enterobacterales, Providencia rettgeri	100 percentage of pathogen eradication	100 percentage of pathogen eradication
By-pathogen Microbiological Eradication Rate in Participants at EOT in the ME-EOT Populations Enterobacterales, Providencia stuartii	100 percentage of pathogen eradication	100 percentage of pathogen eradication
By-pathogen Microbiological Eradication Rate in Participants at EOT in the ME-EOT Populations Enterobacterales, Raoultella ornithinolytica	100 percentage of pathogen eradication	—
By-pathogen Microbiological Eradication Rate in Participants at EOT in the ME-EOT Populations Enterobacterales, Serratia liquefaciens	—	100 percentage of pathogen eradication
By-pathogen Microbiological Eradication Rate in Participants at EOT in the ME-EOT Populations Enterobacterales, Serratia marcescens	100 percentage of pathogen eradication	100 percentage of pathogen eradication
By-pathogen Microbiological Eradication Rate in Participants at EOT in the ME-EOT Populations Gram Positive, Enterococcus faecalis	98.1 percentage of pathogen eradication	97.1 percentage of pathogen eradication
By-pathogen Microbiological Eradication Rate in Participants at EOT in the ME-EOT Populations Gram Positive, Enterococcus faecium	100 percentage of pathogen eradication	100 percentage of pathogen eradication
By-pathogen Microbiological Eradication Rate in Participants at EOT in the ME-EOT Populations Gram Positive, Enterococcus hirae	100 percentage of pathogen eradication	—
By-pathogen Microbiological Eradication Rate in Participants at EOT in the ME-EOT Populations Gram Positive, Staphylococcus aureus	100 percentage of pathogen eradication	85.7 percentage of pathogen eradication
By-pathogen Microbiological Eradication Rate in Participants at EOT in the ME-EOT Populations Gram Positive, Staphylococcus lugdunensis	100 percentage of pathogen eradication	100 percentage of pathogen eradication
By-pathogen Microbiological Eradication Rate in Participants at EOT in the ME-EOT Populations Gram Positive,Staphylococcus saprophyticus	100 percentage of pathogen eradication	100 percentage of pathogen eradication
By-pathogen Microbiological Eradication Rate in Participants at EOT in the ME-EOT Populations Gram Positive, Streptococcus gallolyticus	100 percentage of pathogen eradication	—

SECONDARY outcome

Timeframe: Day 19 (TOC)

Population: ME-EOT population included participants who met the definitions of both the micro-ITT Population and CE Population and were defined for each visit for the analyses in the ME Population at each respective visit as outlined in the ERP. Number analyzed are the number of pathogens available for analysis at the given timepoint. A participant may have had more than 1 pathogen. Multiple isolates of the same species/category from the same participants are counted only once towards total.

Microbiological eradication is defined as number of participants with reduction of baseline urine pathogen(s) to <10^3 CFU/mL and negative repeated blood culture if blood culture was positive for uropathogen growth at baseline. Microbiological eradication rate is the percentage of pathogens being eradicated from the overall number of participants analyzed.

Outcome measures

Measure	TBPM-PI-HBr 600 mg n=451 Pathogens TBPM-PI-HBr 600 mg (300 mg×2 ) film-coated tablets, administered orally three times per day (every 8 hours \[q8h\] ± 0.5 h) plus a single dummy IV infusion over 30 minutes (min) once daily (every 24 hours \[q24h\] ± 0.5 h) up to Day 15; participants with moderate renal insufficiency (creatinine clearance \[CrCl\] \>30 to ≤50 mL/min) required TBPM-PI-HBr dosage adjustment to 300 mg (one tablet) q8h ± 0.5 h.	Ertapenem 1 g n=408 Pathogens Ertapenem for IV injection, administered as a 1-gram IV infusion over 30 min once daily (q24h ± 0.5 h) plus dummy placebo tablets administered orally q8h (±0.5 h) up to Day 14; no dose adjustment of ertapenem was required for participants with renal insufficiency.
By-pathogen Microbiological Eradication Rate in Participants at TOC in the ME-TOC Populations Gram Positive, Streptococcus gallolyticus	100 percentage of pathogen eradication	—
By-pathogen Microbiological Eradication Rate in Participants at TOC in the ME-TOC Populations Enterobacterales, Citrobacter braakii	—	100 percentage of pathogen eradication
By-pathogen Microbiological Eradication Rate in Participants at TOC in the ME-TOC Populations Enterobacterales, Citrobacter freundii	66.7 percentage of pathogen eradication	100 percentage of pathogen eradication
By-pathogen Microbiological Eradication Rate in Participants at TOC in the ME-TOC Populations Enterobacterales, Citrobacter koseri	66.7 percentage of pathogen eradication	66.7 percentage of pathogen eradication
By-pathogen Microbiological Eradication Rate in Participants at TOC in the ME-TOC Populations Enterobacterales, Enterobacter amnigenus	—	100 percentage of pathogen eradication
By-pathogen Microbiological Eradication Rate in Participants at TOC in the ME-TOC Populations Enterobacterales, Enterobacter asburiae	—	100 percentage of pathogen eradication
By-pathogen Microbiological Eradication Rate in Participants at TOC in the ME-TOC Populations Enterobacterales, Enterobacter bugandensis	—	100 percentage of pathogen eradication
By-pathogen Microbiological Eradication Rate in Participants at TOC in the ME-TOC Populations Enterobacterales, Enterobacter cloacae	54.5 percentage of pathogen eradication	50.0 percentage of pathogen eradication
By-pathogen Microbiological Eradication Rate in Participants at TOC in the ME-TOC Populations Enterobacterales, Escherichia coli	65.8 percentage of pathogen eradication	68.3 percentage of pathogen eradication
By-pathogen Microbiological Eradication Rate in Participants at TOC in the ME-TOC Populations Enterobacterales, Klebsiella aerogenes	0.0 percentage of pathogen eradication	—
By-pathogen Microbiological Eradication Rate in Participants at TOC in the ME-TOC Populations Enterobacterales, Klebsiella oxytoca	100 percentage of pathogen eradication	50.0 percentage of pathogen eradication
By-pathogen Microbiological Eradication Rate in Participants at TOC in the ME-TOC Populations Enterobacterales, Klebsiella pneumoniae	49.0 percentage of pathogen eradication	71.0 percentage of pathogen eradication
By-pathogen Microbiological Eradication Rate in Participants at TOC in the ME-TOC Populations Enterobacterales, Klebsiella variicola	50.0 percentage of pathogen eradication	75.0 percentage of pathogen eradication
By-pathogen Microbiological Eradication Rate in Participants at TOC in the ME-TOC Populations Enterobacterales, Morganella morganii	100 percentage of pathogen eradication	100 percentage of pathogen eradication
By-pathogen Microbiological Eradication Rate in Participants at TOC in the ME-TOC Populations Enterobacterales, Proteus hauseri	100 percentage of pathogen eradication	—
By-pathogen Microbiological Eradication Rate in Participants at TOC in the ME-TOC Populations Enterobacterales, Proteus mirabilis	51.6 percentage of pathogen eradication	76.2 percentage of pathogen eradication
By-pathogen Microbiological Eradication Rate in Participants at TOC in the ME-TOC Populations Enterobacterales, Proteus penneri	—	100 percentage of pathogen eradication
By-pathogen Microbiological Eradication Rate in Participants at TOC in the ME-TOC Populations Enterobacterales, Proteus vulgaris	—	100 percentage of pathogen eradication
By-pathogen Microbiological Eradication Rate in Participants at TOC in the ME-TOC Populations Enterobacterales, Providencia rettgeri	100 percentage of pathogen eradication	100 percentage of pathogen eradication
By-pathogen Microbiological Eradication Rate in Participants at TOC in the ME-TOC Populations Enterobacterales, Providencia stuartii	0.0 percentage of pathogen eradication	100 percentage of pathogen eradication
By-pathogen Microbiological Eradication Rate in Participants at TOC in the ME-TOC Populations Enterobacterales, Raoultella ornithinolytica	100 percentage of pathogen eradication	—
By-pathogen Microbiological Eradication Rate in Participants at TOC in the ME-TOC Populations Enterobacterales, Serratia liquefaciens	—	100 percentage of pathogen eradication
By-pathogen Microbiological Eradication Rate in Participants at TOC in the ME-TOC Populations Enterobacterales, Serratia marcescens	66.7 percentage of pathogen eradication	100 percentage of pathogen eradication
By-pathogen Microbiological Eradication Rate in Participants at TOC in the ME-TOC Populations Gram Positive, Enterococcus faecalis	69.8 percentage of pathogen eradication	57.6 percentage of pathogen eradication
By-pathogen Microbiological Eradication Rate in Participants at TOC in the ME-TOC Populations Gram Positive, Enterococcus faecium	100 percentage of pathogen eradication	100 percentage of pathogen eradication
By-pathogen Microbiological Eradication Rate in Participants at TOC in the ME-TOC Populations Gram Positive, Enterococcus hirae	100 percentage of pathogen eradication	—
By-pathogen Microbiological Eradication Rate in Participants at TOC in the ME-TOC Populations Gram Positive, Staphylococcus aureus	100 percentage of pathogen eradication	50.0 percentage of pathogen eradication
By-pathogen Microbiological Eradication Rate in Participants at TOC in the ME-TOC Populations Gram Positive, Staphylococcus lugdunensis	100 percentage of pathogen eradication	100 percentage of pathogen eradication
By-pathogen Microbiological Eradication Rate in Participants at TOC in the ME-TOC Populations Gram Positive,Staphylococcus saprophyticus	100 percentage of pathogen eradication	83.3 percentage of pathogen eradication

SECONDARY outcome

Timeframe: Day 25 (LFU)

Population: ME-LFU population included participants who met the definitions of both the micro-ITT Population and CE Population and were defined for each visit for the analyses in the ME Population at each respective visit as outlined in the ERP. Overall Number of Units Analyzed are the number of enterobacteral pathogens. A participant may have had more than 1 pathogen. Multiple isolates of the same species/category from the same participants are counted only once towards total.

Microbiological eradication is defined as number of participants with reduction of baseline urine pathogen(s) to <10^3 CFU/mL and negative repeated blood culture if blood culture was positive for uropathogen growth at baseline. Sustained Microbiological Eradication is defined participants with microbiologic eradication at the TOC and no subsequent urine culture after TOC demonstrating recurrence of the original baseline uropathogen at ≥10^5 CFU/mL.Microbiological eradication rate is the percentage of pathogens being eradicated from the overall number of pathogen analyzed.

Outcome measures

Measure	TBPM-PI-HBr 600 mg n=391 Pathogens TBPM-PI-HBr 600 mg (300 mg×2 ) film-coated tablets, administered orally three times per day (every 8 hours \[q8h\] ± 0.5 h) plus a single dummy IV infusion over 30 minutes (min) once daily (every 24 hours \[q24h\] ± 0.5 h) up to Day 15; participants with moderate renal insufficiency (creatinine clearance \[CrCl\] \>30 to ≤50 mL/min) required TBPM-PI-HBr dosage adjustment to 300 mg (one tablet) q8h ± 0.5 h.	Ertapenem 1 g n=353 Pathogens Ertapenem for IV injection, administered as a 1-gram IV infusion over 30 min once daily (q24h ± 0.5 h) plus dummy placebo tablets administered orally q8h (±0.5 h) up to Day 14; no dose adjustment of ertapenem was required for participants with renal insufficiency.
By-pathogen Sustained Microbiological Eradication Rate in Participants at LFU in the ME-LFU Populations Citrobacter braakii	—	100 percentage of pathogens eradications
By-pathogen Sustained Microbiological Eradication Rate in Participants at LFU in the ME-LFU Populations Citrobacter freundii	66.7 percentage of pathogens eradications	100 percentage of pathogens eradications
By-pathogen Sustained Microbiological Eradication Rate in Participants at LFU in the ME-LFU Populations Citrobacter koseri	100 percentage of pathogens eradications	66.7 percentage of pathogens eradications
By-pathogen Sustained Microbiological Eradication Rate in Participants at LFU in the ME-LFU Populations Enterobacter amnigenus	—	100 percentage of pathogens eradications
By-pathogen Sustained Microbiological Eradication Rate in Participants at LFU in the ME-LFU Populations Enterobacter asburiae	—	0 percentage of pathogens eradications
By-pathogen Sustained Microbiological Eradication Rate in Participants at LFU in the ME-LFU Populations Enterobacter bugandensis	—	100 percentage of pathogens eradications
By-pathogen Sustained Microbiological Eradication Rate in Participants at LFU in the ME-LFU Populations Enterobacter cloacae	55.6 percentage of pathogens eradications	33.3 percentage of pathogens eradications
By-pathogen Sustained Microbiological Eradication Rate in Participants at LFU in the ME-LFU Populations Enterococcus faecalis	66.7 percentage of pathogens eradications	52.9 percentage of pathogens eradications
By-pathogen Sustained Microbiological Eradication Rate in Participants at LFU in the ME-LFU Populations Enterococcus faecium	100 percentage of pathogens eradications	100 percentage of pathogens eradications
By-pathogen Sustained Microbiological Eradication Rate in Participants at LFU in the ME-LFU Populations Enterococcus hirae	100 percentage of pathogens eradications	—
By-pathogen Sustained Microbiological Eradication Rate in Participants at LFU in the ME-LFU Populations Escherichia coli	62.4 percentage of pathogens eradications	61.8 percentage of pathogens eradications
By-pathogen Sustained Microbiological Eradication Rate in Participants at LFU in the ME-LFU Populations Klebsiella aerogenes	0 percentage of pathogens eradications	—
By-pathogen Sustained Microbiological Eradication Rate in Participants at LFU in the ME-LFU Populations Klebsiella oxytoca	100 percentage of pathogens eradications	50.0 percentage of pathogens eradications
By-pathogen Sustained Microbiological Eradication Rate in Participants at LFU in the ME-LFU Populations Klebsiella pneumoniae	46.7 percentage of pathogens eradications	68.4 percentage of pathogens eradications
By-pathogen Sustained Microbiological Eradication Rate in Participants at LFU in the ME-LFU Populations Klebsiella variicola	50.0 percentage of pathogens eradications	66.7 percentage of pathogens eradications
By-pathogen Sustained Microbiological Eradication Rate in Participants at LFU in the ME-LFU Populations Morganella morganii	100 percentage of pathogens eradications	100 percentage of pathogens eradications
By-pathogen Sustained Microbiological Eradication Rate in Participants at LFU in the ME-LFU Populations Proteus hauseri	100 percentage of pathogens eradications	—
By-pathogen Sustained Microbiological Eradication Rate in Participants at LFU in the ME-LFU Populations Proteus mirabilis	51.7 percentage of pathogens eradications	70.0 percentage of pathogens eradications
By-pathogen Sustained Microbiological Eradication Rate in Participants at LFU in the ME-LFU Populations Proteus penneri	—	100 percentage of pathogens eradications
By-pathogen Sustained Microbiological Eradication Rate in Participants at LFU in the ME-LFU Populations Proteus vulgaris	—	100 percentage of pathogens eradications
By-pathogen Sustained Microbiological Eradication Rate in Participants at LFU in the ME-LFU Populations Providencia rettgeri	100 percentage of pathogens eradications	100 percentage of pathogens eradications
By-pathogen Sustained Microbiological Eradication Rate in Participants at LFU in the ME-LFU Populations Providencia stuartii	0.0 percentage of pathogens eradications	100 percentage of pathogens eradications
By-pathogen Sustained Microbiological Eradication Rate in Participants at LFU in the ME-LFU Populations Raoultella ornithinolytica	100 percentage of pathogens eradications	—
By-pathogen Sustained Microbiological Eradication Rate in Participants at LFU in the ME-LFU Populations Serratia liquefaciens	—	100 percentage of pathogens eradications
By-pathogen Sustained Microbiological Eradication Rate in Participants at LFU in the ME-LFU Populations Serratia marcescens	66.7 percentage of pathogens eradications	100 percentage of pathogens eradications
By-pathogen Sustained Microbiological Eradication Rate in Participants at LFU in the ME-LFU Populations Staphylococcus aureus	100 percentage of pathogens eradications	50.0 percentage of pathogens eradications
By-pathogen Sustained Microbiological Eradication Rate in Participants at LFU in the ME-LFU Populations 1Staphylococcus lugdunensis	100 percentage of pathogens eradications	100 percentage of pathogens eradications
By-pathogen Sustained Microbiological Eradication Rate in Participants at LFU in the ME-LFU Populations Staphylococcus saprophyticus	100 percentage of pathogens eradications	80.0 percentage of pathogens eradications
By-pathogen Sustained Microbiological Eradication Rate in Participants at LFU in the ME-LFU Populations Staphylococcus gallolyticus	100 percentage of pathogens eradications	—

SECONDARY outcome

Timeframe: Day 19 (TOC)

Population: Micro-ITT population included all randomized participants with a confirmed diagnosis of cUTI or AP and a positive Screening urine culture defined as growth of one or two uropathogens at ≥10\^5 CFU/mL and/or positive Screening blood culture with isolation of one or more uropathogens. Number analyzed are the number of participants with data available for analysis.

Overall response rate is percentage of participants with combined clinical cure plus microbiological eradication. Clinical cure is defined as 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 antimicrobial therapy is warranted. Microbiological eradication is defined as reduction of baseline urine pathogen(s) to <10^3 colony forming unit/milliliter (CFU/mL) and negative repeated blood culture if blood culture was positive for uropathogen growth at baseline.

Outcome measures

Measure	TBPM-PI-HBr 600 mg n=449 Participants TBPM-PI-HBr 600 mg (300 mg×2 ) film-coated tablets, administered orally three times per day (every 8 hours \[q8h\] ± 0.5 h) plus a single dummy IV infusion over 30 minutes (min) once daily (every 24 hours \[q24h\] ± 0.5 h) up to Day 15; participants with moderate renal insufficiency (creatinine clearance \[CrCl\] \>30 to ≤50 mL/min) required TBPM-PI-HBr dosage adjustment to 300 mg (one tablet) q8h ± 0.5 h.	Ertapenem 1 g n=419 Participants Ertapenem for IV injection, administered as a 1-gram IV infusion over 30 min once daily (q24h ± 0.5 h) plus dummy placebo tablets administered orally q8h (±0.5 h) up to Day 14; no dose adjustment of ertapenem was required for participants with renal insufficiency.
Overall Response Rate (Combined Clinical Cure Plus Microbiological Eradication) In Subgroup Including: Stratified Infection Category AP	65.9 percentage of participants	70.6 percentage of participants
Overall Response Rate (Combined Clinical Cure Plus Microbiological Eradication) In Subgroup Including: Stratified Infection Category cUTI	51.6 percentage of participants	53.2 percentage of participants

SECONDARY outcome

Timeframe: Day 19 (TOC)

Population: Micro-ITT population included all randomized participants with a confirmed diagnosis of cUTI or AP and a positive Screening urine culture defined as growth of one or two uropathogens at ≥10\^5 CFU/mL and/or positive Screening blood culture with isolation of one or more uropathogens. Number analyzed is number of participants with data available for analysis.

Overall response rate is percentage of participants with combined clinical cure plus microbiological eradication. Clinical cure is defined as 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 antimicrobial therapy is warranted. Microbiological eradication is defined as reduction of baseline urine pathogen(s) to <10^3 CFU/mL and negative repeated blood culture if blood culture was positive for uropathogen growth at baseline.

Outcome measures

Measure	TBPM-PI-HBr 600 mg n=449 Participants TBPM-PI-HBr 600 mg (300 mg×2 ) film-coated tablets, administered orally three times per day (every 8 hours \[q8h\] ± 0.5 h) plus a single dummy IV infusion over 30 minutes (min) once daily (every 24 hours \[q24h\] ± 0.5 h) up to Day 15; participants with moderate renal insufficiency (creatinine clearance \[CrCl\] \>30 to ≤50 mL/min) required TBPM-PI-HBr dosage adjustment to 300 mg (one tablet) q8h ± 0.5 h.	Ertapenem 1 g n=419 Participants Ertapenem for IV injection, administered as a 1-gram IV infusion over 30 min once daily (q24h ± 0.5 h) plus dummy placebo tablets administered orally q8h (±0.5 h) up to Day 14; no dose adjustment of ertapenem was required for participants with renal insufficiency.
Overall Response Rate (Combined Clinical Cure Plus Microbiological Eradication) at TOC In Subgroup Stratified Age Category ≥18 to <65 years	66.7 percentage of participants	65.3 percentage of participants
Overall Response Rate (Combined Clinical Cure Plus Microbiological Eradication) at TOC In Subgroup Stratified Age Category ≥65 to <75 years	49.2 percentage of participants	57.6 percentage of participants
Overall Response Rate (Combined Clinical Cure Plus Microbiological Eradication) at TOC In Subgroup Stratified Age Category ≥75 years	49.4 percentage of participants	56.9 percentage of participants

SECONDARY outcome

Timeframe: Day 25 (LFU)

Population: Micro-ITT included all randomized participants with a confirmed diagnosis of cUTI or AP and a positive Screening urine culture defined as growth of one or two uropathogens at ≥10\^5 CFU/mL and/or positive Screening blood culture with isolation of one or more uropathogens. Number analyzed is number of participants with data available for analysis.

Overall response rate is percentage of participants with combined clinical cure plus microbiological eradication. Clinical cure is defined as 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 antimicrobial therapy is warranted. Microbiological eradication is defined as reduction of baseline urine pathogen(s) to <10^3 colony forming unit/milliliter (CFU/mL) and negative repeated blood culture if blood culture was positive for uropathogen growth at baseline. The point estimate and confidence interval (CI) is presented for Central and eastern Europe subgroup.

Outcome measures

Measure	TBPM-PI-HBr 600 mg n=449 Participants TBPM-PI-HBr 600 mg (300 mg×2 ) film-coated tablets, administered orally three times per day (every 8 hours \[q8h\] ± 0.5 h) plus a single dummy IV infusion over 30 minutes (min) once daily (every 24 hours \[q24h\] ± 0.5 h) up to Day 15; participants with moderate renal insufficiency (creatinine clearance \[CrCl\] \>30 to ≤50 mL/min) required TBPM-PI-HBr dosage adjustment to 300 mg (one tablet) q8h ± 0.5 h.	Ertapenem 1 g n=419 Participants Ertapenem for IV injection, administered as a 1-gram IV infusion over 30 min once daily (q24h ± 0.5 h) plus dummy placebo tablets administered orally q8h (±0.5 h) up to Day 14; no dose adjustment of ertapenem was required for participants with renal insufficiency.
Overall Response Rate (Combined Clinical Cure Plus Microbiological Eradication) at TOC In Subgroup Including Region Central and Eastern Europe	58.9 percentage of participants	62.0 percentage of participants
Overall Response Rate (Combined Clinical Cure Plus Microbiological Eradication) at TOC In Subgroup Including Region South Africa	100 percentage of participants	0.0 percentage of participants
Overall Response Rate (Combined Clinical Cure Plus Microbiological Eradication) at TOC In Subgroup Including Region United States	0.0 percentage of participants	50.0 percentage of participants

SECONDARY outcome

Timeframe: Day 25 (LFU)

Population: Micro-ITT population included all randomized participants with a confirmed diagnosis of cUTI or AP and a positive Screening urine culture defined as growth of one or two uropathogens at ≥105 CFU/mL and/or positive Screening blood culture with isolation of one or more uropathogens.

Time (days) to resolution or improvement of signs and symptoms of cUTI and AP present at baseline was defined as follows: date of the first visit at which all baseline signs/symptoms have improved by at least 1 grade with worsening of none and development of no new signs/symptoms of the index infection minus the date of randomization.

Outcome measures

Measure	TBPM-PI-HBr 600 mg n=449 Participants TBPM-PI-HBr 600 mg (300 mg×2 ) film-coated tablets, administered orally three times per day (every 8 hours \[q8h\] ± 0.5 h) plus a single dummy IV infusion over 30 minutes (min) once daily (every 24 hours \[q24h\] ± 0.5 h) up to Day 15; participants with moderate renal insufficiency (creatinine clearance \[CrCl\] \>30 to ≤50 mL/min) required TBPM-PI-HBr dosage adjustment to 300 mg (one tablet) q8h ± 0.5 h.	Ertapenem 1 g n=419 Participants Ertapenem for IV injection, administered as a 1-gram IV infusion over 30 min once daily (q24h ± 0.5 h) plus dummy placebo tablets administered orally q8h (±0.5 h) up to Day 14; no dose adjustment of ertapenem was required for participants with renal insufficiency.
Time (Days) to Resolution or Improvement of Signs and Symptoms of cUTI and AP Present a Baseline in the Micro-ITT Populations	4.1 days Standard Deviation 3.85	3.7 days Standard Deviation 3.26

SECONDARY outcome

Timeframe: Day 25 (LFU)

Population: Micro-ITT population included all randomized participants with a confirmed diagnosis of cUTI or AP and a positive Screening urine culture defined as growth of one or two uropathogens at ≥10\^5 CFU/mL and/or positive Screening blood culture with isolation of one or more uropathogens. Overall number of participants analyzed are the participants with data available for analysis.

Time to Defervescence (days) = date of first post-baseline temperature measure with maximum daily Temperature ≤38°C at the date of randomization.

Outcome measures

Measure	TBPM-PI-HBr 600 mg n=226 Participants TBPM-PI-HBr 600 mg (300 mg×2 ) film-coated tablets, administered orally three times per day (every 8 hours \[q8h\] ± 0.5 h) plus a single dummy IV infusion over 30 minutes (min) once daily (every 24 hours \[q24h\] ± 0.5 h) up to Day 15; participants with moderate renal insufficiency (creatinine clearance \[CrCl\] \>30 to ≤50 mL/min) required TBPM-PI-HBr dosage adjustment to 300 mg (one tablet) q8h ± 0.5 h.	Ertapenem 1 g n=193 Participants Ertapenem for IV injection, administered as a 1-gram IV infusion over 30 min once daily (q24h ± 0.5 h) plus dummy placebo tablets administered orally q8h (±0.5 h) up to Day 14; no dose adjustment of ertapenem was required for participants with renal insufficiency.
Time (Days) to Defervescence in Micro-ITT Population With a Documented Fever at Screening or Day 1	2.2 days Standard Deviation 1.33	2.2 days Standard Deviation 1.40

SECONDARY outcome

Timeframe: Day 25 (LFU)

Population: Micro-ITT population included all randomized participants with a confirmed diagnosis of cUTI or AP and a positive Screening urine culture defined as growth of one or two uropathogens at ≥10\^5 CFU/mL and/or positive Screening blood culture with isolation of one or more uropathogens.

Clinical relapse is participants who met criteria for clinical cure at TOC, but new signs and symptoms of cUTI or AP are present at the LFU Visit and the subject requires antibiotic therapy for the cUT. Clinical cure is defined as 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 antimicrobial therapy is warranted.

Outcome measures

Measure	TBPM-PI-HBr 600 mg n=449 Participants TBPM-PI-HBr 600 mg (300 mg×2 ) film-coated tablets, administered orally three times per day (every 8 hours \[q8h\] ± 0.5 h) plus a single dummy IV infusion over 30 minutes (min) once daily (every 24 hours \[q24h\] ± 0.5 h) up to Day 15; participants with moderate renal insufficiency (creatinine clearance \[CrCl\] \>30 to ≤50 mL/min) required TBPM-PI-HBr dosage adjustment to 300 mg (one tablet) q8h ± 0.5 h.	Ertapenem 1 g n=419 Participants Ertapenem for IV injection, administered as a 1-gram IV infusion over 30 min once daily (q24h ± 0.5 h) plus dummy placebo tablets administered orally q8h (±0.5 h) up to Day 14; no dose adjustment of ertapenem was required for participants with renal insufficiency.
Rate of Clinical Relapse at the LFU Days in the Micro-ITT Population	2.7 percentage of participants	3.6 percentage of participants

SECONDARY outcome

Timeframe: Day 25 (LFU)

Population: Micro-ITT population included all randomized participants with a confirmed diagnosis of cUTI or AP and a positive Screening urine culture defined as growth of one or two uropathogens at ≥10\^5 CFU/mL and/or positive Screening blood culture with isolation of one or more uropathogens.

Superinfection was isolation of a new uropathogen at ≥105 CFU/mL (other than the original Baseline pathogen[s] from blood and/or urine) from a urine culture that was accompanied by clinical signs and symptoms of infection requiring alternative antimicrobial therapy (e.g., the participant was assessed by the investigator as a clinical failure) during the period up to and including EOT. New infection was isolation of a new uropathogen at ≥105 CFU/mL (other than the original baseline pathogen[s] from blood and/or urine) from a urine culture that was accompanied by clinical signs and symptoms of infection requiring alternative antimicrobial therapy (e.g., the participant was assessed by the Investigator as a clinical failure) in the period after EOT.

Outcome measures

Measure	TBPM-PI-HBr 600 mg n=449 Participants TBPM-PI-HBr 600 mg (300 mg×2 ) film-coated tablets, administered orally three times per day (every 8 hours \[q8h\] ± 0.5 h) plus a single dummy IV infusion over 30 minutes (min) once daily (every 24 hours \[q24h\] ± 0.5 h) up to Day 15; participants with moderate renal insufficiency (creatinine clearance \[CrCl\] \>30 to ≤50 mL/min) required TBPM-PI-HBr dosage adjustment to 300 mg (one tablet) q8h ± 0.5 h.	Ertapenem 1 g n=419 Participants Ertapenem for IV injection, administered as a 1-gram IV infusion over 30 min once daily (q24h ± 0.5 h) plus dummy placebo tablets administered orally q8h (±0.5 h) up to Day 14; no dose adjustment of ertapenem was required for participants with renal insufficiency.
Rates Of Superinfection And New Infection In The Micro-ITT Population Superinfection	0.2 percentage of participants	2.1 percentage of participants
Rates Of Superinfection And New Infection In The Micro-ITT Population New Infection	1.1 percentage of participants	1.9 percentage of participants

SECONDARY outcome

Timeframe: Predose and post-dose at 0.25h, 0.5h, 1h, 2h, and 8h on Days 1 and 3

Population: PK population included participants treated with at least 1 dose of TBPM-PI-HBr with at least 1 analyzable plasma or urine PK sample. The data is reported only for TBPM-PI-HBr arm.

Outcome measures

Measure	TBPM-PI-HBr 600 mg n=29 Participants TBPM-PI-HBr 600 mg (300 mg×2 ) film-coated tablets, administered orally three times per day (every 8 hours \[q8h\] ± 0.5 h) plus a single dummy IV infusion over 30 minutes (min) once daily (every 24 hours \[q24h\] ± 0.5 h) up to Day 15; participants with moderate renal insufficiency (creatinine clearance \[CrCl\] \>30 to ≤50 mL/min) required TBPM-PI-HBr dosage adjustment to 300 mg (one tablet) q8h ± 0.5 h.	Ertapenem 1 g Ertapenem for IV injection, administered as a 1-gram IV infusion over 30 min once daily (q24h ± 0.5 h) plus dummy placebo tablets administered orally q8h (±0.5 h) up to Day 14; no dose adjustment of ertapenem was required for participants with renal insufficiency.
Apparent Volume of Distribution (Vss) at Steady State in TBPM-PI-HBr Recipients in the Pharmacokinetic (PK) Population Day 1	75.5 Liters (L) Interval 49.5 to 89.9	—
Apparent Volume of Distribution (Vss) at Steady State in TBPM-PI-HBr Recipients in the Pharmacokinetic (PK) Population Day 3	75.5 Liters (L) Interval 49.5 to 89.9	—

SECONDARY outcome

Timeframe: Predose and post-dose at 0.25h, 0.5h, 1h, 2h, and 8h on Days 1 and 3

Population: PK population included participants treated with at least 1 dose of TBPM-PI-HBr with at least 1 analyzable plasma or urine PK sample. The data is reported only for TBPM-PI-HBr arm.

Outcome measures

Measure	TBPM-PI-HBr 600 mg n=29 Participants TBPM-PI-HBr 600 mg (300 mg×2 ) film-coated tablets, administered orally three times per day (every 8 hours \[q8h\] ± 0.5 h) plus a single dummy IV infusion over 30 minutes (min) once daily (every 24 hours \[q24h\] ± 0.5 h) up to Day 15; participants with moderate renal insufficiency (creatinine clearance \[CrCl\] \>30 to ≤50 mL/min) required TBPM-PI-HBr dosage adjustment to 300 mg (one tablet) q8h ± 0.5 h.	Ertapenem 1 g Ertapenem for IV injection, administered as a 1-gram IV infusion over 30 min once daily (q24h ± 0.5 h) plus dummy placebo tablets administered orally q8h (±0.5 h) up to Day 14; no dose adjustment of ertapenem was required for participants with renal insufficiency.
Cmax in TBPM-PI-HBr Recipients in the PK Population Day 1	7.01 microgram per milliliter (μg/mL) Interval 2.05 to 17.2	—
Cmax in TBPM-PI-HBr Recipients in the PK Population Day 3	7.21 microgram per milliliter (μg/mL) Interval 2.11 to 18.8	—

SECONDARY outcome

Timeframe: Predose and post-dose at 0.25h, 0.5h, 1h, 2h, and 8h on Days 1 and 3

Population: PK population included participants treated with at least 1 dose of TBPM-PI-HBr with at least 1 analyzable plasma or urine PK sample. The data is reported only for TBPM-PI-HBr arm.

Outcome measures

Measure	TBPM-PI-HBr 600 mg n=29 Participants TBPM-PI-HBr 600 mg (300 mg×2 ) film-coated tablets, administered orally three times per day (every 8 hours \[q8h\] ± 0.5 h) plus a single dummy IV infusion over 30 minutes (min) once daily (every 24 hours \[q24h\] ± 0.5 h) up to Day 15; participants with moderate renal insufficiency (creatinine clearance \[CrCl\] \>30 to ≤50 mL/min) required TBPM-PI-HBr dosage adjustment to 300 mg (one tablet) q8h ± 0.5 h.	Ertapenem 1 g Ertapenem for IV injection, administered as a 1-gram IV infusion over 30 min once daily (q24h ± 0.5 h) plus dummy placebo tablets administered orally q8h (±0.5 h) up to Day 14; no dose adjustment of ertapenem was required for participants with renal insufficiency.
Area Under Curve (AUC 0-24) in TBPM-PI-HBr Recipients in the PK Population Day 1	65.5 microgram.hour per milliliter (μg•h/mL) Interval 27.6 to 243.0	—
Area Under Curve (AUC 0-24) in TBPM-PI-HBr Recipients in the PK Population Day 3	74.6 microgram.hour per milliliter (μg•h/mL) Interval 27.6 to 318.0	—

SECONDARY outcome

Timeframe: Predose and post-dose at 0.25h, 0.5h, 1h, 2h, and 8h on Days 1 and 3

Population: PK population included subjects treated with at least 1 dose of TBPM-PI-HBr with at least 1 analyzable plasma or urine PK sample. The data is reported only for TBPM-PI-HBr arm.

Outcome measures

Measure	TBPM-PI-HBr 600 mg n=29 Participants TBPM-PI-HBr 600 mg (300 mg×2 ) film-coated tablets, administered orally three times per day (every 8 hours \[q8h\] ± 0.5 h) plus a single dummy IV infusion over 30 minutes (min) once daily (every 24 hours \[q24h\] ± 0.5 h) up to Day 15; participants with moderate renal insufficiency (creatinine clearance \[CrCl\] \>30 to ≤50 mL/min) required TBPM-PI-HBr dosage adjustment to 300 mg (one tablet) q8h ± 0.5 h.	Ertapenem 1 g Ertapenem for IV injection, administered as a 1-gram IV infusion over 30 min once daily (q24h ± 0.5 h) plus dummy placebo tablets administered orally q8h (±0.5 h) up to Day 14; no dose adjustment of ertapenem was required for participants with renal insufficiency.
Minimum Concentration (Cmin) in TBPM-PI-HBr Recipients in the PK Population Day 1	0.706 μg/mL Interval 0.000913 to 4.89	—
Minimum Concentration (Cmin) in TBPM-PI-HBr Recipients in the PK Population Day 3	1.17 μg/mL Interval 0.000877 to 8.44	—

SECONDARY outcome

Timeframe: Predose and post-dose at 0.25h, 0.5h, 1h, 2h, and 8h on Days 1 and 3

Population: PK population included subjects treated with at least 1 dose of TBPM-PI-HBr with at least 1 analyzable plasma or urine PK sample. The data is reported only for TBPM-PI-HBr arm.

Outcome measures

Measure	TBPM-PI-HBr 600 mg n=29 Participants TBPM-PI-HBr 600 mg (300 mg×2 ) film-coated tablets, administered orally three times per day (every 8 hours \[q8h\] ± 0.5 h) plus a single dummy IV infusion over 30 minutes (min) once daily (every 24 hours \[q24h\] ± 0.5 h) up to Day 15; participants with moderate renal insufficiency (creatinine clearance \[CrCl\] \>30 to ≤50 mL/min) required TBPM-PI-HBr dosage adjustment to 300 mg (one tablet) q8h ± 0.5 h.	Ertapenem 1 g Ertapenem for IV injection, administered as a 1-gram IV infusion over 30 min once daily (q24h ± 0.5 h) plus dummy placebo tablets administered orally q8h (±0.5 h) up to Day 14; no dose adjustment of ertapenem was required for participants with renal insufficiency.
Systemic Clearance (CL) in TBPM-PI-HBr Recipients in the PK Population Day 1	31.6 Litre per hour (L/h) Interval 5.65 to 65.3	—
Systemic Clearance (CL) in TBPM-PI-HBr Recipients in the PK Population Day 3	31.6 Litre per hour (L/h) Interval 5.65 to 65.3	—

Adverse Events

TBPM-PI-HBr 600 mg

Serious events: 14 serious events

Other events: 39 other events

Deaths: 0 deaths

Ertapenem 1 g

Serious events: 12 serious events

Other events: 30 other events

Deaths: 0 deaths

Serious adverse events

Measure	TBPM-PI-HBr 600 mg n=685 participants at risk TBPM-PI-HBr 600 mg (300 mg×2 ) film-coated tablets, administered orally three times per day (every 8 hours \[q8h\] ± 0.5 h) plus a single dummy IV infusion over 30 minutes (min) once daily (every 24 hours \[q24h\] ± 0.5 h) up to Day 15; participants with moderate renal insufficiency (creatinine clearance \[CrCl\] \>30 to ≤50 mL/min) required TBPM-PI-HBr dosage adjustment to 300 mg (one tablet) q8h ± 0.5 h.	Ertapenem 1 g n=687 participants at risk Ertapenem for IV injection, administered as a 1-gram IV infusion over 30 min once daily (q24h ± 0.5 h) plus dummy placebo tablets administered orally q8h (±0.5 h) up to Day 14; no dose adjustment of ertapenem was required for participants with renal insufficiency.
Cardiac disorders Myocardial ischaemia	0.15% 1/685 • From the first dose of administration up to Day 25 post-treatment ± 2 days (up to approximately 27 days) Safety analysis population included all randomized participants who received any amount of study drug.	0.00% 0/687 • From the first dose of administration up to Day 25 post-treatment ± 2 days (up to approximately 27 days) Safety analysis population included all randomized participants who received any amount of study drug.
Gastrointestinal disorders Duodenal ulcer hemorrhage	0.00% 0/685 • From the first dose of administration up to Day 25 post-treatment ± 2 days (up to approximately 27 days) Safety analysis population included all randomized participants who received any amount of study drug.	0.15% 1/687 • From the first dose of administration up to Day 25 post-treatment ± 2 days (up to approximately 27 days) Safety analysis population included all randomized participants who received any amount of study drug.
General disorders Pyrexia	0.15% 1/685 • From the first dose of administration up to Day 25 post-treatment ± 2 days (up to approximately 27 days) Safety analysis population included all randomized participants who received any amount of study drug.	0.15% 1/687 • From the first dose of administration up to Day 25 post-treatment ± 2 days (up to approximately 27 days) Safety analysis population included all randomized participants who received any amount of study drug.
General disorders Cyst	0.00% 0/685 • From the first dose of administration up to Day 25 post-treatment ± 2 days (up to approximately 27 days) Safety analysis population included all randomized participants who received any amount of study drug.	0.15% 1/687 • From the first dose of administration up to Day 25 post-treatment ± 2 days (up to approximately 27 days) Safety analysis population included all randomized participants who received any amount of study drug.
Infections and infestations Pyelonephritis acute	0.15% 1/685 • From the first dose of administration up to Day 25 post-treatment ± 2 days (up to approximately 27 days) Safety analysis population included all randomized participants who received any amount of study drug.	0.29% 2/687 • From the first dose of administration up to Day 25 post-treatment ± 2 days (up to approximately 27 days) Safety analysis population included all randomized participants who received any amount of study drug.
Infections and infestations Clostridium difficile infection	0.00% 0/685 • From the first dose of administration up to Day 25 post-treatment ± 2 days (up to approximately 27 days) Safety analysis population included all randomized participants who received any amount of study drug.	0.15% 1/687 • From the first dose of administration up to Day 25 post-treatment ± 2 days (up to approximately 27 days) Safety analysis population included all randomized participants who received any amount of study drug.
Infections and infestations Intervertebral discitis	0.15% 1/685 • From the first dose of administration up to Day 25 post-treatment ± 2 days (up to approximately 27 days) Safety analysis population included all randomized participants who received any amount of study drug.	0.00% 0/687 • From the first dose of administration up to Day 25 post-treatment ± 2 days (up to approximately 27 days) Safety analysis population included all randomized participants who received any amount of study drug.
Infections and infestations Perirectal abscess	0.15% 1/685 • From the first dose of administration up to Day 25 post-treatment ± 2 days (up to approximately 27 days) Safety analysis population included all randomized participants who received any amount of study drug.	0.00% 0/687 • From the first dose of administration up to Day 25 post-treatment ± 2 days (up to approximately 27 days) Safety analysis population included all randomized participants who received any amount of study drug.
Infections and infestations Retroperitoneal abscess	0.15% 1/685 • From the first dose of administration up to Day 25 post-treatment ± 2 days (up to approximately 27 days) Safety analysis population included all randomized participants who received any amount of study drug.	0.00% 0/687 • From the first dose of administration up to Day 25 post-treatment ± 2 days (up to approximately 27 days) Safety analysis population included all randomized participants who received any amount of study drug.
Infections and infestations Urinary tract infection	0.15% 1/685 • From the first dose of administration up to Day 25 post-treatment ± 2 days (up to approximately 27 days) Safety analysis population included all randomized participants who received any amount of study drug.	0.00% 0/687 • From the first dose of administration up to Day 25 post-treatment ± 2 days (up to approximately 27 days) Safety analysis population included all randomized participants who received any amount of study drug.
Infections and infestations Urinary tract infection enterococcal	0.00% 0/685 • From the first dose of administration up to Day 25 post-treatment ± 2 days (up to approximately 27 days) Safety analysis population included all randomized participants who received any amount of study drug.	0.15% 1/687 • From the first dose of administration up to Day 25 post-treatment ± 2 days (up to approximately 27 days) Safety analysis population included all randomized participants who received any amount of study drug.
Infections and infestations Urosepsis	0.15% 1/685 • From the first dose of administration up to Day 25 post-treatment ± 2 days (up to approximately 27 days) Safety analysis population included all randomized participants who received any amount of study drug.	0.00% 0/687 • From the first dose of administration up to Day 25 post-treatment ± 2 days (up to approximately 27 days) Safety analysis population included all randomized participants who received any amount of study drug.
Injury, poisoning and procedural complications Procedural pneumothorax	0.15% 1/685 • From the first dose of administration up to Day 25 post-treatment ± 2 days (up to approximately 27 days) Safety analysis population included all randomized participants who received any amount of study drug.	0.00% 0/687 • From the first dose of administration up to Day 25 post-treatment ± 2 days (up to approximately 27 days) Safety analysis population included all randomized participants who received any amount of study drug.
Investigations Clostridium test positive	0.00% 0/685 • From the first dose of administration up to Day 25 post-treatment ± 2 days (up to approximately 27 days) Safety analysis population included all randomized participants who received any amount of study drug.	0.15% 1/687 • From the first dose of administration up to Day 25 post-treatment ± 2 days (up to approximately 27 days) Safety analysis population included all randomized participants who received any amount of study drug.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/685 • From the first dose of administration up to Day 25 post-treatment ± 2 days (up to approximately 27 days) Safety analysis population included all randomized participants who received any amount of study drug.	0.15% 1/687 • From the first dose of administration up to Day 25 post-treatment ± 2 days (up to approximately 27 days) Safety analysis population included all randomized participants who received any amount of study drug.
Musculoskeletal and connective tissue disorders Osteochondrosis	0.00% 0/685 • From the first dose of administration up to Day 25 post-treatment ± 2 days (up to approximately 27 days) Safety analysis population included all randomized participants who received any amount of study drug.	0.15% 1/687 • From the first dose of administration up to Day 25 post-treatment ± 2 days (up to approximately 27 days) Safety analysis population included all randomized participants who received any amount of study drug.
Nervous system disorders Generalized tonic-clonic seizure	0.15% 1/685 • From the first dose of administration up to Day 25 post-treatment ± 2 days (up to approximately 27 days) Safety analysis population included all randomized participants who received any amount of study drug.	0.00% 0/687 • From the first dose of administration up to Day 25 post-treatment ± 2 days (up to approximately 27 days) Safety analysis population included all randomized participants who received any amount of study drug.
Nervous system disorders Radiculopathy	0.00% 0/685 • From the first dose of administration up to Day 25 post-treatment ± 2 days (up to approximately 27 days) Safety analysis population included all randomized participants who received any amount of study drug.	0.15% 1/687 • From the first dose of administration up to Day 25 post-treatment ± 2 days (up to approximately 27 days) Safety analysis population included all randomized participants who received any amount of study drug.
Renal and urinary disorders Renal colic	0.15% 1/685 • From the first dose of administration up to Day 25 post-treatment ± 2 days (up to approximately 27 days) Safety analysis population included all randomized participants who received any amount of study drug.	0.00% 0/687 • From the first dose of administration up to Day 25 post-treatment ± 2 days (up to approximately 27 days) Safety analysis population included all randomized participants who received any amount of study drug.
Respiratory, thoracic and mediastinal disorders Acute pulmonary edema	0.15% 1/685 • From the first dose of administration up to Day 25 post-treatment ± 2 days (up to approximately 27 days) Safety analysis population included all randomized participants who received any amount of study drug.	0.00% 0/687 • From the first dose of administration up to Day 25 post-treatment ± 2 days (up to approximately 27 days) Safety analysis population included all randomized participants who received any amount of study drug.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.15% 1/685 • From the first dose of administration up to Day 25 post-treatment ± 2 days (up to approximately 27 days) Safety analysis population included all randomized participants who received any amount of study drug.	0.00% 0/687 • From the first dose of administration up to Day 25 post-treatment ± 2 days (up to approximately 27 days) Safety analysis population included all randomized participants who received any amount of study drug.
Respiratory, thoracic and mediastinal disorders Pulmonary artery thrombosis	0.00% 0/685 • From the first dose of administration up to Day 25 post-treatment ± 2 days (up to approximately 27 days) Safety analysis population included all randomized participants who received any amount of study drug.	0.15% 1/687 • From the first dose of administration up to Day 25 post-treatment ± 2 days (up to approximately 27 days) Safety analysis population included all randomized participants who received any amount of study drug.
Skin and subcutaneous tissue disorders Subcutaneous emphysema	0.15% 1/685 • From the first dose of administration up to Day 25 post-treatment ± 2 days (up to approximately 27 days) Safety analysis population included all randomized participants who received any amount of study drug.	0.00% 0/687 • From the first dose of administration up to Day 25 post-treatment ± 2 days (up to approximately 27 days) Safety analysis population included all randomized participants who received any amount of study drug.

Other adverse events

Measure	TBPM-PI-HBr 600 mg n=685 participants at risk TBPM-PI-HBr 600 mg (300 mg×2 ) film-coated tablets, administered orally three times per day (every 8 hours \[q8h\] ± 0.5 h) plus a single dummy IV infusion over 30 minutes (min) once daily (every 24 hours \[q24h\] ± 0.5 h) up to Day 15; participants with moderate renal insufficiency (creatinine clearance \[CrCl\] \>30 to ≤50 mL/min) required TBPM-PI-HBr dosage adjustment to 300 mg (one tablet) q8h ± 0.5 h.	Ertapenem 1 g n=687 participants at risk Ertapenem for IV injection, administered as a 1-gram IV infusion over 30 min once daily (q24h ± 0.5 h) plus dummy placebo tablets administered orally q8h (±0.5 h) up to Day 14; no dose adjustment of ertapenem was required for participants with renal insufficiency.
Gastrointestinal disorders Diarrhoea	5.7% 39/685 • From the first dose of administration up to Day 25 post-treatment ± 2 days (up to approximately 27 days) Safety analysis population included all randomized participants who received any amount of study drug.	4.4% 30/687 • From the first dose of administration up to Day 25 post-treatment ± 2 days (up to approximately 27 days) Safety analysis population included all randomized participants who received any amount of study drug.

Additional Information

Angela Talley

Senior Vice President Clinical Development

Phone: 857-242-1575

Email: atalley@sperotherapeutics.com

Results disclosure agreements

• Principal investigator is a sponsor employee No publication related to study results will be published prior to publication of a multi-center report submitted for publication within 18 months after conclusion or termination of a study at all study sites. Results publications will be submitted to sponsor for review 60 days in advance of publication. Sponsor can require removal of confidential information unrelated to study results. Sponsor can embargo a proposed publication for another 45 days to preserve intellectual property
• Publication restrictions are in place

Restriction type: OTHER