A Phase 3 interventional study of TBPM-PI-HBr and Ertapenem in Complicated Urinary Tract Infection and Acute Pyelonephritis, sponsored by Spero Therapeutics. Completed at 96 sites in 15 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2022-07-25.
Sponsored by Spero Therapeutics · Phase 3, Interventional, and Treatment
The key purpose of this study is to evaluate the efficacy, safety and pharmacokinetics (PK) of tebipenem pivoxil hydrobromide (TBPM-PI-HBr) compared to intravenous (IV) ertapenem, in participants with complicated Urinary Tract Infection (cUTI) or Acute Pyelonephritis (AP).
79 studies on the registry are indexed under Pyelonephritis; 12 are open to participants now.
This study's enrollment of 1,372 is above the median of 175 across 62 interventional studies indexed under Pyelonephritis.
Browse Pyelonephritis studies →Spero Therapeutics is the lead sponsor of 22 studies on the registry; none are open to participants now.
Of its 15 completed or terminated interventional studies of FDA-regulated products, 3 (20%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Have a diagnosis of cUTI or AP as defined below:
a. cUTI definition:
At least Two of the following signs and symptoms:
i. Chills, rigors, or fever; fever must be observed and documented by a health care provider (oral, tympanic, rectal or core temperature >38.0°C [>100.4°F])
ii. Dysuria, urgency to void, or increased urinary frequency
iii. Nausea or vomiting, as reported by the participants
iv. Lower abdominal, suprapubic, or pelvic pain
And at least One of the following risk factors for cUTI:
i. Implanted urinary tract instrumentation (e.g., nephrostomy tube, ureteric stents, or other urinary tract prosthetic material), ongoing intermittent bladder catheterization, or presence of an indwelling bladder catheter (Note: bladder catheters that have been in place for >24 hours prior to Screening must be removed or replaced prior to collection of the Screening urine for urinalysis and culture, unless removal or replacement is considered unsafe or ).
ii. Current known functional or anatomical abnormality of the urogenital tract, including anatomic abnormalities of the urinary tract, neurogenic bladder, or post-void residual urine volume of ≥ 100 mL within the past 6 months.
iii. Complete or partial obstructive uropathy (e.g., nephrolithiasis, tumor, fibrosis, urethral stricture) that is expected to be medically or surgically treated during study drug therapy (prior to end of the treatment [EOT]).
iv. Known intrinsic renal disease with blood urea nitrogen (BUN) >20 mg/deciliter (dL), or blood urea >42.8 mg/dL, or serum creatinine (Cr) >1.4 mg/dL.
v. Urinary retention, including urinary retention in men due to previously diagnosed benign prostatic hyperplasia (BPH).
b. AP definition: Acute flank pain (onset within 7 days prior to randomization) or costovertebral angle tenderness on physical examination.
And at least One of the following signs and symptoms:
i. Chills, rigors, or fever; fever must be observed and documented by a health care provider (oral, tympanic, rectal or core temperature >38.0°C [>100.4°F]).
ii. Peripheral white blood cell count (WBC) >10,000/mm3 or bandemia (≥15% immature polymorphonuclear neutrophils (PMNs), regardless of WBC count).
iii. Nausea or vomiting, as reported by the participants.
iv. Dysuria, urgency to void, or increased urinary frequency.
Note: Participants who meet the definition for cUTI (Inclusion Criterion 4a) and also have flank pain or costovertebral tenderness should be randomized as cUTI rather than AP.
Have an adequate urine specimen for evaluation and culture obtained within 24 h prior to randomization with evidence of pyuria that includes at least one of the following:
Exclusion Criteria
Presence of any known or suspected disease or condition that, in the opinion of the Investigator, may have confounded the assessment of efficacy, including but not limited to the following:
(CrCl) of ≤30 mL/min, as estimated by the Cockcroft-Gault formula:
estimated Creatinine Clearance (eC_Cr) [mL/min]=((140-Age [yrs]) × Body Weight [kg] × [0.85 if Female])/(72 × Serum Creatinine [mg⁄dL]).
Receipt of more than a single dose of a short-acting potentially effective antibiotic started within 72 h prior to randomization.
Exception: Participants who received more than a single dose of short-acting potentially effective antibiotic within 72 h prior to randomization may be eligible for enrollment if they meet all of the following criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
The number of CD4 cells, a type of white blood cell, in a given amount of blood. It is used to follow how well the immune system is doing in HIV.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Creatinine clearance (CrCl)
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Bilirubin
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
CD4 count
The number of CD4 cells, a type of white blood cell, in a given amount of blood. It is used to follow how well the immune system is doing in HIV.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
QT and QTc
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Excipients
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
Drug: TBPM-PI-HBr · Drug: Dummy Infusion
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.
Drug: Ertapenem · Drug: Dummy tablets
TBPM-PI-HBr tablets administered orally.
Also known as: SPR994
Antibiotic Therapy for cUTI.
Dummy intravenous infusion.
Dummy tablets orally.
Overall Response (Combined Clinical Cure and Microbiological Eradication) at Test-of-Cure (TOC) in Micro Intent-to-Treat Population
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.
Time frame: Day 19 (TOC)
Number of Participants With Treatment Emergent Adverse Events (TEAEs) in The Safety Population
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.
Time frame: From the first dose of administration up to Day 25 post-treatment ± 2 days (up to approximately 27 days)
Overall Response (Combined Clinical Cure Plus Microbiological Eradication) At Test-Of-Cure (TOC) In The Microbiologically Evaluable (ME) - TOC Population
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.
Time frame: Day 19 (TOC)
Clinical Cure at End-of-Treatment (EOT), TOC, and Sustained Clinical Cure at Late Follow-Up (LFU) Days in the Micro-ITT Populations
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.
Time frame: Days 15 (EOT), Day 19 (TOC) and Day 25 (LFU)
Clinical Cure at EOT Days the Clinically Evaluable (CE-EOT) Populations
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.
Time frame: Day 15 (EOT)
Clinical Cure at TOC in the CE-TOC Populations
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.
Time frame: Day 19 (TOC)
Sustained Clinical Cure at LFU in the CE-LFU Populations
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.
Time frame: Day 25 (LFU)
Clinical Cure at EOT in the ME-EOT Populations
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.
Time frame: Day 15 (EOT)
Clinical Cure at TOC Days in the ME-TOC Populations
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.
Time frame: Day 19 (TOC)
Sustained Clinical Cure at LFU in the ME-LFU Population
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.
Time frame: Day 25 (LFU)
By-Patient Microbiological Eradication at EOT, TOC, and Sustained Microbiological Eradication at LFU Days in the Micro-ITT Population
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.
Time frame: Days 15 (EOT), 19 (TOC) and 25 (LFU)
By-Pathogen Microbiological Eradication Rate at EOT in the Micro-ITT Population
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.
Time frame: Days 15 (EOT)
By-Pathogen Microbiological Eradication Rate at TOC in the Micro-ITT Population
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.
Time frame: Day 19 (TOC)
By-Pathogen Sustained Microbiological Eradication Rate at LFU in the Micro-ITT Population (m-ITT)
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.
Time frame: Day 25 (LFU)
By-Patient Microbiological Eradication at EOT in the ME-EOT Populations
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.
Time frame: Day 15 (EOT)
By-Patient Microbiological Eradication at TOC in the ME-TOC Population
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.
Time frame: Day 15 (TOC)
By-Patient Sustained Microbiological Eradication at LFU Days in the ME-LFU Populations
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.
Time frame: Day 25 (LFU)
By-pathogen Microbiological Eradication Rate in Participants at EOT in the ME-EOT Populations
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.
Time frame: Day 15 (EOT)
By-pathogen Microbiological Eradication Rate in Participants at TOC in the ME-TOC Populations
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.
Time frame: Day 19 (TOC)
By-pathogen Sustained Microbiological Eradication Rate in Participants at LFU in the ME-LFU Populations
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.
Time frame: Day 25 (LFU)
Overall Response Rate (Combined Clinical Cure Plus Microbiological Eradication) In Subgroup Including: Stratified Infection Category
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.
Time frame: Day 19 (TOC)
Overall Response Rate (Combined Clinical Cure Plus Microbiological Eradication) at TOC In Subgroup Stratified Age Category
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.
Time frame: Day 19 (TOC)
Overall Response Rate (Combined Clinical Cure Plus Microbiological Eradication) at TOC In Subgroup Including Region
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.
Time frame: Day 25 (LFU)
Time (Days) to Resolution or Improvement of Signs and Symptoms of cUTI and AP Present a Baseline in the Micro-ITT Populations
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.
Time frame: Day 25 (LFU)
Time (Days) to Defervescence in Micro-ITT Population With a Documented Fever at Screening or Day 1
Time to Defervescence (days) = date of first post-baseline temperature measure with maximum daily Temperature ≤38°C at the date of randomization.
Time frame: Day 25 (LFU)
Rate of Clinical Relapse at the LFU Days in the Micro-ITT Population
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.
Time frame: Day 25 (LFU)
Rates Of Superinfection And New Infection In The Micro-ITT Population
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.
Time frame: Day 25 (LFU)
Apparent Volume of Distribution (Vss) at Steady State in TBPM-PI-HBr Recipients in the Pharmacokinetic (PK) Population
Time frame: Predose and post-dose at 0.25h, 0.5h, 1h, 2h, and 8h on Days 1 and 3
Cmax in TBPM-PI-HBr Recipients in the PK Population
Time frame: Predose and post-dose at 0.25h, 0.5h, 1h, 2h, and 8h on Days 1 and 3
Area Under Curve (AUC 0-24) in TBPM-PI-HBr Recipients in the PK Population
Time frame: Predose and post-dose at 0.25h, 0.5h, 1h, 2h, and 8h on Days 1 and 3
Minimum Concentration (Cmin) in TBPM-PI-HBr Recipients in the PK Population
Time frame: Predose and post-dose at 0.25h, 0.5h, 1h, 2h, and 8h on Days 1 and 3
Systemic Clearance (CL) in TBPM-PI-HBr Recipients in the PK Population
Time frame: Predose and post-dose at 0.25h, 0.5h, 1h, 2h, and 8h on Days 1 and 3
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.
| Milestone | TBPM-PI-HBr 600 mg | Ertapenem 1 g |
|---|---|---|
| Started | 685 | 687 |
| Micro-intent-to-treat (itt) population | 449 | 419 |
| Completed | 653 | 663 |
| Not completed | 32 | 24 |
| Withdrew: Lost to follow-up | 14 | 10 |
| Withdrew: Participant non-compliance/uncooperativeness | 3 | 6 |
| Withdrew: Participant withdrawal of consent | 13 | 5 |
| Withdrew: Adverse event | 1 | 1 |
| Withdrew: Covid-19 | 1 | 2 |
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.
| Participants | TBPM-PI-HBr 600 mg | Ertapenem 1 g |
|---|---|---|
| Overall Response (Combined Clinical Cure and Microbiological Eradication) at Test-of-Cure (TOC) in Micro Intent-to-Treat Population | 264 | 258 |
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.
| Participants | TBPM-PI-HBr 600 mg | Ertapenem 1 g |
|---|---|---|
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) in The Safety Population | 176 | 176 |
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.
| Participants | TBPM-PI-HBr 600 mg | Ertapenem 1 g |
|---|---|---|
| Overall Response (Combined Clinical Cure Plus Microbiological Eradication) At Test-Of-Cure (TOC) In The Microbiologically Evaluable (ME) - TOC Population | 254 | 247 |
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.
| Participants | TBPM-PI-HBr 600 mg | Ertapenem 1 g |
|---|---|---|
| EOT | 446 | 410 |
| TOC | 418 | 392 |
| LFU | 398 | 377 |
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.
| Participants | TBPM-PI-HBr 600 mg | Ertapenem 1 g |
|---|---|---|
| Clinical Cure at EOT Days the Clinically Evaluable (CE-EOT) Populations | 673 | 665 |
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.
| Participants | TBPM-PI-HBr 600 mg | Ertapenem 1 g |
|---|---|---|
| Clinical Cure at TOC in the CE-TOC Populations | 611 | 617 |
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.
| Participants | TBPM-PI-HBr 600 mg | Ertapenem 1 g |
|---|---|---|
| Sustained Clinical Cure at LFU in the CE-LFU Populations | 556 | 559 |
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.
| Participants | TBPM-PI-HBr 600 mg | Ertapenem 1 g |
|---|---|---|
| Clinical Cure at EOT in the ME-EOT Populations | 437 | 394 |
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.
| Participants | TBPM-PI-HBr 600 mg | Ertapenem 1 g |
|---|---|---|
| Clinical Cure at TOC Days in the ME-TOC Populations | 390 | 363 |
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.
| Participants | TBPM-PI-HBr 600 mg | Ertapenem 1 g |
|---|---|---|
| Sustained Clinical Cure at LFU in the ME-LFU Population | 360 | 329 |
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.
| Participants | TBPM-PI-HBr 600 mg | Ertapenem 1 g |
|---|---|---|
| EOT | 439 | 403 |
| TOC | 267 | 266 |
| LFU | 257 | 244 |
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.
| percentage of pathogen eradication | TBPM-PI-HBr 600 mg | Ertapenem 1 g |
|---|---|---|
| Enterobacterales, Citrobacter braakii | — | 100 |
| Enterobacterales, Citrobacter freundii | 75.0 | 66.7 |
| Enterobacterales, Citrobacter koseri | 100 | 100 |
| Enterobacterales, Enterobacter amnigenus | — | 100 |
| Enterobacterales, Enterobacter asburiae | — | 100 |
| Enterobacterales, Enterobacter bugandensis | — | 100 |
| Enterobacterales, Enterobacter cloacae | 90.9 | 100 |
| Enterobacterales, Escherichia coli | 98.3 | 96.7 |
| Enterobacterales, Klebsiella aerogenes | 100 | 0.0 |
| Enterobacterales, Klebsiella oxytoca | 100 | 100 |
| Enterobacterales, Klebsiella pneumoniae | 98.1 | 98.6 |
| Enterobacterales, Klebsiella variicola | 100 | 100 |
| Enterobacterales, Morganella morganii | 100 | 100 |
| Enterobacterales, Proteus hauseri | 100 | — |
| Enterobacterales, Proteus mirabilis | 97.1 | 100 |
| Enterobacterales, Proteus penneri | — | 100 |
| Enterobacterales, Proteus vulgaris | — | 100 |
| Enterobacterales, Providencia rettgeri | 100 | 100 |
| Enterobacterales, Providencia stuartii | 100 | 100 |
| Enterobacterales, Raoultella ornithinolytica | 100 | — |
| Enterobacterales, Serratia liquefaciens | — | 100 |
| Enterobacterales, Serratia marcescens | 100 | 100 |
| Gram Positive, Enterococcus faecalis | 94.8 | 91.7 |
| Gram Positive, Enterococcus faecium | 100 | 100 |
| Gram Positive, Enterococcus hirae | 100 | — |
| Gram Positive, Staphylococcus aureus | 100 | 75.0 |
| Gram Positive, Staphylococcus lugdunensis | 100 | 100 |
| Gram Positive, Staphylococcus saprophyticus | 100 | 100 |
| Gram Positive, Streptococcus gallolyticus | 100 | — |
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.
| percentage of pathogen eradication | TBPM-PI-HBr 600 mg | Ertapenem 1 g |
|---|---|---|
| Enterobacterales, Citrobacter braakii | — | 100 |
| Enterobacterales, Citrobacter freundii | 50.0 | 100 |
| Enterobacterales, Citrobacter koseri | 66.7 | 50.0 |
| Enterobacterales, Enterobacter amnigenus | — | 100 |
| Enterobacterales, Enterobacter asburiae | — | 100 |
| Enterobacterales, Enterobacter bugandensis | — | 100 |
| Enterobacterales, Enterobacter cloacae | 54.5 | 50.0 |
| Enterobacterales, Escherichia coli | 62.7 | 65.2 |
| Enterobacterales, Klebsiella aerogenes | 0.0 | 0.0 |
| Enterobacterales, Klebsiella oxytoca | 75.0 | 33.3 |
| Enterobacterales, Klebsiella pneumoniae | 45.3 | 63.4 |
| Enterobacterales, Klebsiella variicola | 50.0 | 75.0 |
| Enterobacterales, Morganella morganii | 100 | 100 |
| Enterobacterales, Proteus hauseri | 100 | — |
| Enterobacterales, Proteus mirabilis | 48.6 | 69.6 |
| Enterobacterales, Proteus penneri | — | 100 |
| Enterobacterales, Proteus vulgaris | — | 100 |
| Enterobacterales, Providencia rettgeri | 100 | 100 |
| Enterobacterales, Providencia stuartii | 0.0 | 100 |
| Enterobacterales, Raoultella ornithinolytica | 100 | — |
| Enterobacterales, Serratia liquefaciens | — | 100 |
| Enterobacterales, Serratia marcescens | 50.0 | 100 |
| Gram Positive, Enterococcus faecalis | 67.2 | 55.6 |
| Gram Positive, Enterococcus faecium | 100 | 100 |
| Gram Positive, Enterococcus hirae | 100 | — |
| Gram Positive, Staphylococcus aureus | 100 | 37.5 |
| Gram Positive, Staphylococcus lugdunensis | 100 | 100 |
| Gram Positive, Staphylococcus saprophyticus | 100 | 83.3 |
| Gram Positive, Streptococcus gallolyticus | 100 | — |
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.
| percentage of pathogen eradication | TBPM-PI-HBr 600 mg | Ertapenem 1 g |
|---|---|---|
| Citrobacter braakii | — | 100 |
| Citrobacter freundii | 50.0 | 100 |
| Citrobacter koseri | 66.7 | 50.0 |
| Enterobacter amnigenus | — | 100 |
| Enterobacter asburiae | — | 0 |
| Enterobacter bugandensis | — | 100 |
| Enterobacter cloacae | 54.5 | 37.5 |
| Enterococcus faecalis | 63.8 | 50.0 |
| Enterococcus faecium | 100 | 100 |
| Enterococcus hirae | 100 | — |
| Escherichia coli | 59.9 | 60.0 |
| Klebsiella aerogenes | 0.0 | 0.0 |
| Klebsiella oxytoca | 75.0 | 33.3 |
| Klebsiella pneumoniae | 43.4 | 60.6 |
| Klebsiella variicola | 50.0 | 75.0 |
| Morganella morganii | 100 | 100 |
| Proteus hauseri | 100 | — |
| Proteus mirabilis | 48.6 | 60.9 |
| Proteus penneri | — | 100 |
| Proteus vulgaris | — | 100 |
| Providencia rettgeri | 100 | 100 |
| Providencia stuartii | 0.0 | 100 |
| Raoultella ornithinolytica | 100 | — |
| Serratia liquefaciens | — | 100 |
| Serratia marcescens | 50.0 | 100 |
| Staphylococcus aureus | 100 | 37.5 |
| Staphylococcus lugdunensis | 100 | 100 |
| Staphylococcus saprophyticus | 100 | 83.3 |
| Staphylococcus gallolyticus | 100 | — |
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.
| Participants | TBPM-PI-HBr 600 mg | Ertapenem 1 g |
|---|---|---|
| By-Patient Microbiological Eradication at EOT in the ME-EOT Populations | 436 | 399 |
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.
| Participants | TBPM-PI-HBr 600 mg | Ertapenem 1 g |
|---|---|---|
| By-Patient Microbiological Eradication at TOC in the ME-TOC Population | 257 | 254 |
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.
| Participants | TBPM-PI-HBr 600 mg | Ertapenem 1 g |
|---|---|---|
| By-Patient Sustained Microbiological Eradication at LFU Days in the ME-LFU Populations | 234 | 216 |
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.
| percentage of pathogen eradication | TBPM-PI-HBr | Ertapenem |
|---|---|---|
| Enterobacterales, Citrobacter braakii | — | 100 |
| Enterobacterales, Citrobacter freundii | 100 | 100 |
| Enterobacterales, Citrobacter koseri | 100 | 100 |
| Enterobacterales, Enterobacter amnigenus | — | 100 |
| Enterobacterales, Enterobacter asburiae | — | 100 |
| Enterobacterales, Enterobacter bugandensis | — | 100 |
| Enterobacterales, Enterobacter cloacae | 90.9 | 100 |
| Enterobacterales, Escherichia coli | 99.6 | 100 |
| Enterobacterales, Klebsiella aerogenes | 100 | — |
| Enterobacterales, Klebsiella oxytoca | 100 | 100 |
| Enterobacterales, Klebsiella pneumoniae | 100 | 100 |
| Enterobacterales, Klebsiella variicola | 100 | 100 |
| Enterobacterales, Morganella morganii | 100 | 100 |
| Enterobacterales, Proteus hauseri | 100 | — |
| Enterobacterales, Proteus mirabilis | 100 | 100 |
| Enterobacterales, Proteus penneri | — | 100 |
| Enterobacterales, Proteus vulgaris | — | 100 |
| Enterobacterales, Providencia rettgeri | 100 | 100 |
| Enterobacterales, Providencia stuartii | 100 | 100 |
| Enterobacterales, Raoultella ornithinolytica | 100 | — |
| Enterobacterales, Serratia liquefaciens | — | 100 |
| Enterobacterales, Serratia marcescens | 100 | 100 |
| Gram Positive, Enterococcus faecalis | 98.1 | 97.1 |
| Gram Positive, Enterococcus faecium | 100 | 100 |
| Gram Positive, Enterococcus hirae | 100 | — |
| Gram Positive, Staphylococcus aureus | 100 | 85.7 |
| Gram Positive, Staphylococcus lugdunensis | 100 | 100 |
| Gram Positive,Staphylococcus saprophyticus | 100 | 100 |
| Gram Positive, Streptococcus gallolyticus | 100 | — |
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.
| percentage of pathogen eradication | TBPM-PI-HBr | Ertapenem |
|---|---|---|
| Enterobacterales, Citrobacter braakii | — | 100 |
| Enterobacterales, Citrobacter freundii | 66.7 | 100 |
| Enterobacterales, Citrobacter koseri | 66.7 | 66.7 |
| Enterobacterales, Enterobacter amnigenus | — | 100 |
| Enterobacterales, Enterobacter asburiae | — | 100 |
| Enterobacterales, Enterobacter bugandensis | — | 100 |
| Enterobacterales, Enterobacter cloacae | 54.5 | 50.0 |
| Enterobacterales, Escherichia coli | 65.8 | 68.3 |
| Enterobacterales, Klebsiella aerogenes | 0.0 | — |
| Enterobacterales, Klebsiella oxytoca | 100 | 50.0 |
| Enterobacterales, Klebsiella pneumoniae | 49.0 | 71.0 |
| Enterobacterales, Klebsiella variicola | 50.0 | 75.0 |
| Enterobacterales, Morganella morganii | 100 | 100 |
| Enterobacterales, Proteus hauseri | 100 | — |
| Enterobacterales, Proteus mirabilis | 51.6 | 76.2 |
| Enterobacterales, Proteus penneri | — | 100 |
| Enterobacterales, Proteus vulgaris | — | 100 |
| Enterobacterales, Providencia rettgeri | 100 | 100 |
| Enterobacterales, Providencia stuartii | 0.0 | 100 |
| Enterobacterales, Raoultella ornithinolytica | 100 | — |
| Enterobacterales, Serratia liquefaciens | — | 100 |
| Enterobacterales, Serratia marcescens | 66.7 | 100 |
| Gram Positive, Enterococcus faecalis | 69.8 | 57.6 |
| Gram Positive, Enterococcus faecium | 100 | 100 |
| Gram Positive, Enterococcus hirae | 100 | — |
| Gram Positive, Staphylococcus aureus | 100 | 50.0 |
| Gram Positive, Staphylococcus lugdunensis | 100 | 100 |
| Gram Positive,Staphylococcus saprophyticus | 100 | 83.3 |
| Gram Positive, Streptococcus gallolyticus | 100 | — |
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.
| percentage of pathogens eradications | TBPM-PI-HBr 600 mg | Ertapenem 1 g |
|---|---|---|
| Citrobacter braakii | — | 100 |
| Citrobacter freundii | 66.7 | 100 |
| Citrobacter koseri | 100 | 66.7 |
| Enterobacter amnigenus | — | 100 |
| Enterobacter asburiae | — | 0 |
| Enterobacter bugandensis | — | 100 |
| Enterobacter cloacae | 55.6 | 33.3 |
| Enterococcus faecalis | 66.7 | 52.9 |
| Enterococcus faecium | 100 | 100 |
| Enterococcus hirae | 100 | — |
| Escherichia coli | 62.4 | 61.8 |
| Klebsiella aerogenes | 0 | — |
| Klebsiella oxytoca | 100 | 50.0 |
| Klebsiella pneumoniae | 46.7 | 68.4 |
| Klebsiella variicola | 50.0 | 66.7 |
| Morganella morganii | 100 | 100 |
| Proteus hauseri | 100 | — |
| Proteus mirabilis | 51.7 | 70.0 |
| Proteus penneri | — | 100 |
| Proteus vulgaris | — | 100 |
| Providencia rettgeri | 100 | 100 |
| Providencia stuartii | 0.0 | 100 |
| Raoultella ornithinolytica | 100 | — |
| Serratia liquefaciens | — | 100 |
| Serratia marcescens | 66.7 | 100 |
| Staphylococcus aureus | 100 | 50.0 |
| 1Staphylococcus lugdunensis | 100 | 100 |
| Staphylococcus saprophyticus | 100 | 80.0 |
| Staphylococcus gallolyticus | 100 | — |
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.
| percentage of participants | TBPM-PI-HBr 600 mg | Ertapenem 1 g |
|---|---|---|
| AP | 65.9 | 70.6 |
| cUTI | 51.6 | 53.2 |
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.
| percentage of participants | TBPM-PI-HBr 600 mg | Ertapenem 1 g |
|---|---|---|
| ≥18 to <65 years | 66.7 | 65.3 |
| ≥65 to <75 years | 49.2 | 57.6 |
| ≥75 years | 49.4 | 56.9 |
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.
| percentage of participants | TBPM-PI-HBr 600 mg | Ertapenem 1 g |
|---|---|---|
| Central and Eastern Europe | 58.9 | 62.0 |
| South Africa | 100 | 0.0 |
| United States | 0.0 | 50.0 |
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.
| days | TBPM-PI-HBr 600 mg | Ertapenem 1 g |
|---|---|---|
| Time (Days) to Resolution or Improvement of Signs and Symptoms of cUTI and AP Present a Baseline in the Micro-ITT Populations | 4.1 ± 3.85 | 3.7 ± 3.26 |
Time to Defervescence (days) = date of first post-baseline temperature measure with maximum daily Temperature ≤38°C at the date of randomization.
| days | TBPM-PI-HBr 600 mg | Ertapenem 1 g |
|---|---|---|
| Time (Days) to Defervescence in Micro-ITT Population With a Documented Fever at Screening or Day 1 | 2.2 ± 1.33 | 2.2 ± 1.40 |
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.
| percentage of participants | TBPM-PI-HBr 600 mg | Ertapenem 1 g |
|---|---|---|
| Rate of Clinical Relapse at the LFU Days in the Micro-ITT Population | 2.7 | 3.6 |
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.
| percentage of participants | TBPM-PI-HBr 600 mg | Ertapenem 1 g |
|---|---|---|
| Superinfection | 0.2 | 2.1 |
| New Infection | 1.1 | 1.9 |
| Liters (L) | TBPM-PI-HBr 600 mg |
|---|---|
| Day 1 | 75.5 (49.5 to 89.9) |
| Day 3 | 75.5 (49.5 to 89.9) |
| microgram per milliliter (μg/mL) | TBPM-PI-HBr 600 mg |
|---|---|
| Day 1 | 7.01 (2.05 to 17.2) |
| Day 3 | 7.21 (2.11 to 18.8) |
| microgram.hour per milliliter (μg•h/mL) | TBPM-PI-HBr 600 mg |
|---|---|
| Day 1 | 65.5 (27.6 to 243) |
| Day 3 | 74.6 (27.6 to 318) |
| μg/mL | TBPM-PI-HBr 600 mg |
|---|---|
| Day 1 | 0.706 (0.000913 to 4.89) |
| Day 3 | 1.17 (0.000877 to 8.44) |
| Litre per hour (L/h) | TBPM-PI-HBr 600 mg |
|---|---|
| Day 1 | 31.6 (5.65 to 65.3) |
| Day 3 | 31.6 (5.65 to 65.3) |
Collected over From the first dose of administration up to Day 25 post-treatment ± 2 days (up to approximately 27 days). Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| TBPM-PI-HBr 600 mg | 0/685 (0%) | 14/685 (2%) | 39/685 (5.7%) |
| Ertapenem 1 g | 0/687 (0%) | 12/687 (1.7%) | 30/687 (4.4%) |
| Event | TBPM-PI-HBr 600 mg | Ertapenem 1 g |
|---|---|---|
| Pyelonephritis acuteInfections and infestations | 1/685 | 2/687 |
| Myocardial ischaemiaCardiac disorders | 1/685 | 0/687 |
| PyrexiaGeneral disorders | 1/685 | 1/687 |
| Intervertebral discitisInfections and infestations | 1/685 | 0/687 |
| Perirectal abscessInfections and infestations | 1/685 | 0/687 |
| Retroperitoneal abscessInfections and infestations | 1/685 | 0/687 |
| Urinary tract infectionInfections and infestations | 1/685 | 0/687 |
| UrosepsisInfections and infestations | 1/685 | 0/687 |
| Procedural pneumothoraxInjury, poisoning and procedural complications | 1/685 | 0/687 |
| Generalized tonic-clonic seizureNervous system disorders | 1/685 | 0/687 |
| Event | TBPM-PI-HBr 600 mg | Ertapenem 1 g |
|---|---|---|
| DiarrhoeaGastrointestinal disorders | 39/685 | 30/687 |
Safety population included all randomized participants who received any amount of study drug.
| Age, Continuous(years) | TBPM-PI-HBr 600 mg | Ertapenem 1 g | Total |
|---|---|---|---|
| Mean | 56.7 ± 18.68 | 57.2 ± 18.23 | 56.9 ± 18.45 |
| Sex: Female, Male(Participants) | TBPM-PI-HBr 600 mg | Ertapenem 1 g | Total |
|---|---|---|---|
| Female | 368 | 389 | 757 |
| Male | 317 | 298 | 615 |
| Ethnicity (NIH/OMB)(Participants) | TBPM-PI-HBr 600 mg | Ertapenem 1 g | Total |
|---|---|---|---|
| Hispanic or Latino | 13 | 5 | 18 |
| Not Hispanic or Latino | 672 | 682 | 1354 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Race (NIH/OMB)(Participants) | TBPM-PI-HBr 600 mg | Ertapenem 1 g | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 3 | 4 | 7 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 6 | 6 | 12 |
| White | 676 | 677 | 1353 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 0 |
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: No
Ran from Jun 2019 to primary completion in May 2020, 11 months.
Results were first posted in Jul 2022, 2 years 2 months after primary completion. A results delay was requested in May 2021.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in Jun 2022. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Studies of the drug tested here: Tebipenem