ADAPT-PO: 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)
Study Details
Study Description
Brief Summary
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).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 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. |
Drug: TBPM-PI-HBr
TBPM-PI-HBr tablets administered orally.
Other Names:
Drug: Dummy Infusion
Dummy intravenous infusion.
|
| Active Comparator: 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. |
Drug: Ertapenem
Antibiotic Therapy for cUTI.
Drug: Dummy tablets
Dummy tablets orally.
|
Outcome Measures
Primary Outcome Measures
- Overall Response (Combined Clinical Cure and Microbiological Eradication) at Test-of-Cure (TOC) in Micro Intent-to-Treat Population [Day 19 (TOC)]
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.
- Number of Participants With Treatment Emergent Adverse Events (TEAEs) in The Safety Population [From the first dose of administration up to Day 25 post-treatment ± 2 days (up to approximately 27 days)]
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.
Secondary Outcome Measures
- Overall Response (Combined Clinical Cure Plus Microbiological Eradication) At Test-Of-Cure (TOC) In The Microbiologically Evaluable (ME) - TOC Population [Day 19 (TOC)]
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.
- Clinical Cure at End-of-Treatment (EOT), TOC, and Sustained Clinical Cure at Late Follow-Up (LFU) Days in the Micro-ITT Populations [Days 15 (EOT), Day 19 (TOC) and Day 25 (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 participants who met criteria for clinical cure at TOC and remained free of signs and symptoms of cUTI or AP at LFU.
- Clinical Cure at EOT Days the Clinically Evaluable (CE-EOT) Populations [Day 15 (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.
- Clinical Cure at TOC in the CE-TOC Populations [Day 19 (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.
- Sustained Clinical Cure at LFU in the CE-LFU Populations [Day 25 (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.
- Clinical Cure at EOT in the ME-EOT Populations [Day 15 (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.
- Clinical Cure at TOC Days in the ME-TOC Populations [Day 19 (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.
- Sustained Clinical Cure at LFU in the ME-LFU Population [Day 25 (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 participants who met criteria for clinical cure at TOC and remained free of signs and symptoms of cUTI or AP at LFU.
- By-Patient Microbiological Eradication at EOT, TOC, and Sustained Microbiological Eradication at LFU Days in the Micro-ITT Population [Days 15 (EOT), 19 (TOC) and 25 (LFU)]
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.
- By-Pathogen Microbiological Eradication Rate at EOT in the Micro-ITT Population [Days 15 (EOT)]
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.
- By-Pathogen Microbiological Eradication Rate at TOC in the Micro-ITT Population [Day 19 (TOC)]
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.
- By-Pathogen Sustained Microbiological Eradication Rate at LFU in the Micro-ITT Population (m-ITT) [Day 25 (LFU)]
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.
- By-Patient Microbiological Eradication at EOT in the ME-EOT Populations [Day 15 (EOT)]
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.
- By-Patient Microbiological Eradication at TOC in the ME-TOC Population [Day 15 (TOC)]
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.
- By-Patient Sustained Microbiological Eradication at LFU Days in the ME-LFU Populations [Day 25 (LFU)]
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.
- By-pathogen Microbiological Eradication Rate in Participants at EOT in the ME-EOT Populations [Day 15 (EOT)]
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.
- By-pathogen Microbiological Eradication Rate in Participants at TOC in the ME-TOC Populations [Day 19 (TOC)]
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.
- By-pathogen Sustained Microbiological Eradication Rate in Participants at LFU in the ME-LFU Populations [Day 25 (LFU)]
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.
- Overall Response Rate (Combined Clinical Cure Plus Microbiological Eradication) In Subgroup Including: Stratified Infection Category [Day 19 (TOC)]
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.
- Overall Response Rate (Combined Clinical Cure Plus Microbiological Eradication) at TOC In Subgroup Stratified Age Category [Day 19 (TOC)]
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.
- Overall Response Rate (Combined Clinical Cure Plus Microbiological Eradication) at TOC In Subgroup Including Region [Day 25 (LFU)]
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 (Days) to Resolution or Improvement of Signs and Symptoms of cUTI and AP Present a Baseline in the Micro-ITT Populations [Day 25 (LFU)]
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 (Days) to Defervescence in Micro-ITT Population With a Documented Fever at Screening or Day 1 [Day 25 (LFU)]
Time to Defervescence (days) = date of first post-baseline temperature measure with maximum daily Temperature ≤38°C at the date of randomization.
- Rate of Clinical Relapse at the LFU Days in the Micro-ITT Population [Day 25 (LFU)]
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.
- Rates Of Superinfection And New Infection In The Micro-ITT Population [Day 25 (LFU)]
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.
- Apparent Volume of Distribution (Vss) at Steady State in TBPM-PI-HBr Recipients in the Pharmacokinetic (PK) Population [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 [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 [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 [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 [Predose and post-dose at 0.25h, 0.5h, 1h, 2h, and 8h on Days 1 and 3]
Eligibility Criteria
Criteria
Inclusion Criteria
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Male and female participants at least 18 years of age.
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Able to provide informed consent.
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Able to ingest oral tablets for the anticipated treatment duration. If present at baseline, nausea and/or vomiting should have been mild or well-controlled with antiemetic therapy, in order to tolerate oral study drug.
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Have a diagnosis of cUTI or AP as defined below:
- cUTI definition:
At least Two of the following signs and symptoms:
-
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])
-
Dysuria, urgency to void, or increased urinary frequency
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Nausea or vomiting, as reported by the participants
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Lower abdominal, suprapubic, or pelvic pain
And at least One of the following risk factors for cUTI:
-
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 contraindicated).
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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.
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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]).
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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.
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Urinary retention, including urinary retention in men due to previously diagnosed benign prostatic hyperplasia (BPH).
- 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:
-
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]).
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Peripheral white blood cell count (WBC) >10,000/mm3 or bandemia (≥15% immature polymorphonuclear neutrophils (PMNs), regardless of WBC count).
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Nausea or vomiting, as reported by the participants.
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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.
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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:
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At least 10 WBCs per high power field (hpf) in urine sediment.
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At least 10 WBCs per cubic millimeter (mm3) in unspun (non-centrifuged) urine.
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Positive leukocyte esterase (LE) on urinalysis. Note: Participants could be randomized and administered investigational product (IP) prior to knowledge of urine culture results.
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Expectation, in the judgment of the Investigator, that the participant would survive with effective antibiotic therapy and appropriate supportive care for the anticipated duration of the study.
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Willing to comply with all the study activities and procedures throughout the duration of the study.
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Participants were required to use a highly-effective method of birth control; male participants were required to use an effective barrier method of contraception from Screening through LFU and for 90 days following the last dose if sexually active with a female of childbearing potential (FOCP); female participants must not have been pregnant or nursing, and were required to commit to either sexual abstinence or use at least two medically accepted, effective methods of birth control (e.g., condom, spermicidal gel, oral contraceptive, indwelling intrauterine device, hormonal implant/patch, injections, approved cervical ring) from Screening through LFU and for 90 days following the last dose.
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:
-
Perinephric or renal corticomedullary abscess.
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Uncomplicated urinary tract infection (cUTI) - (acute cystitis that does not meet the cUTI disease definition, see Inclusion Criterion 4a).
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Polycystic kidney disease.
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Recent history of trauma to the pelvis or urinary tract.
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Confirmed or suspected acute or chronic bacterial prostatitis, orchitis, or epididymitis.
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Chronic vesicoureteral reflux.
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Previous or planned renal transplantation.
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Previous or planned cystectomy or ileal loop surgery.
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Known or suspected non-renal source of infection (e.g., infective endocarditis, osteomyelitis, meningitis, pneumonia).
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Confirmed or suspected infection that is caused by a pathogen that is resistant to either IP (e.g., carbapenem-resistant pathogen), including infection caused by fungi (e.g., candiduria) or mycobacteria (e.g., urogenital tuberculosis).
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Gross hematuria requiring intervention other than administration of IP or removal/placement of urinary tract instrumentation.
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Urinary tract surgery within 7 days prior to randomization or urinary tract surgery planned during the study period (except surgery required relieving an obstruction or placing urinary tract instrumentation).
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Creatinine clearance (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]).
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Anticipated concomitant use of non-study antibacterial drug therapy between randomization and the LFU Visit that would potentially effect outcome evaluations of cUTI/ AP, including but not limited to antibacterials with potential activity versus uropathogens, antibacterial drug prophylaxis, and antibacterial bladder irrigation.
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Anticipated concomitant use of gastric acid-reducing medications between randomization and end-of-treatment (EOT), including proton pump inhibitors, histamine-2 receptor antagonists, and antacids.
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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:
-
In the opinion of the Investigator they have failed the prior antibiotic therapy (e.g., have worsening signs and symptoms of cUTI/AP).
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Had a documented uropathogen (growth in urine culture >10^5 CFU/mL) that is resistant to the prior antibiotic therapy.
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Had a documented uropathogen that is carbapenem-susceptible.
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Received approval from the Medical Monitor to enroll the participants.
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Severe hepatic impairment at Screening, as evidenced by alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >5x upper limit of normal (ULN) or total bilirubin
3x ULN, or clinical signs of cirrhosis or end-stage hepatic disease (e.g., ascites, hepatic encephalopathy).
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Any signs of severe sepsis, including shock or profound hypotension defined as systolic blood pressure <90 mmHg or a decrease of >40 mmHg from baseline that is not responsive to fluid challenge.
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Pregnant or breastfeeding women.
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History of epilepsy or known seizure disorder (excluding a history of childhood febrile seizures).
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Receipt of any investigational medication during the last 30 days or 5 half-lives, whichever is longer, prior to randomization.
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Known history of human immunodeficiency virus (HIV) infection and or acquired immunodeficiency syndrome (AIDS)-defining illness, or known history of HIV infection and known CD4 count <200/mm^3 within the past year.
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Presence of immunodeficiency or an immunocompromised condition including neutropenia (<1,000 neutrophils/mm^3 obtained from the local laboratory at Screening), hematologic malignancy, bone marrow transplant, or receiving immunosuppressive therapy such as cancer chemotherapy, medications for the rejection of transplantation, and long-term use of systemic corticosteroids (e.g., ≥20 mg/day of prednisone or systemic equivalent for at least 2 weeks).
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A mean QT interval corrected using Fridericia's formula (QTcF) >480 msec based on triplicate ECGs at Screening.
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History of significant hypersensitivity or allergic reaction to β-lactam antibiotics (e.g., cephalosporins, penicillins, carbapenems), product excipients (mannitol, microcrystalline cellulose, crospovidone, magnesium stearate, colloidal silicon dioxide, and Opadry®) or any contraindication to the use of ertapenem.
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History of known genetic metabolism anomaly associated with carnitine deficiency (e.g., carnitine transporter defect, methylmalonic aciduria, propionic acidemia)
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Requirement for concomitant use of valproic acid, divalproex sodium, or probenecid between randomization and EOT.
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Unable or unwilling to comply with the protocol.
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An employee of the Investigator or study center with direct involvement in the proposed study or other studies under the direction of that Investigator or study center, as well as a family member of the employee or the Investigator.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Medical Facility | La Mesa | California | United States | 91942 |
| 2 | Medical Facility | Miami | Florida | United States | 33144 |
| 3 | Medical Facility | Blagoevgrad | Bulgaria | 2700 | |
| 4 | Medical Facility | Dobrich | Bulgaria | 9300 | |
| 5 | Medical Facility | Ruse | Bulgaria | 7000 | |
| 6 | Medical Facility | Shumen | Bulgaria | 9700 | |
| 7 | Medical Facility | Sofia | Bulgaria | 1431 | |
| 8 | Medical Facility | Sofia | Bulgaria | 1606 | |
| 9 | Medical Facility | Veliko Tarnovo | Bulgaria | 5000 | |
| 10 | Medical Facility | Karlovy Vary | Czechia | 360 66 | |
| 11 | Medical Facility | Liberec | Czechia | 460 63 | |
| 12 | Medical Facility | Prague | Czechia | 140 59 | |
| 13 | Medical Facility | Zlin | Czechia | 762 75 | |
| 14 | Medical Facility | Ústí Nad Labem | Czechia | 401 13 | |
| 15 | Medical Facility | Kohtla-Jarve | Estonia | 31025 | |
| 16 | Medical Facility | Tallinn | Estonia | 10617 | |
| 17 | Medical Facility | Voru | Estonia | 65526 | |
| 18 | Medical Facility | Tbilisi | Georgia | 0144 | |
| 19 | Medical Facility | Tbilisi | Georgia | 0159 | |
| 20 | Medical Facility | Tbilisi | Georgia | 0160 | |
| 21 | Medical Facility | Tbilisi | Georgia | 0172 | |
| 22 | Medical Facility | Zestap'oni | Georgia | 2000 | |
| 23 | Medical Facility | Budapest | Hungary | H-1082 | |
| 24 | Medical Facility | Budapest | Hungary | H-1204 | |
| 25 | Medical Facility | Nagykanizsa | Hungary | H-8800 | |
| 26 | Medical Facility | Nyíregyháza | Hungary | 4400 | |
| 27 | Medical Facility | Tatabánya | Hungary | 2800 | |
| 28 | Medical Facility | Riga | Latvia | LV-1002 | |
| 29 | Medical Facility | Riga | Latvia | LV-1038 | |
| 30 | Medical Facility | Valmiera | Latvia | LV-4201 | |
| 31 | Medical Facility | Chisinau | Moldova, Republic of | MD-2004 | |
| 32 | Medical Facility | Chisinau | Moldova, Republic of | MD2025 | |
| 33 | Medical Facility | Katowice | Poland | 40-211 | |
| 34 | Medical Facility | Kraków | Poland | 31-559 | |
| 35 | Medical Facility | Oswiecim | Poland | 32-600 | |
| 36 | Medical Facility | Wrocław | Poland | 51-162 | |
| 37 | Medical Facility | Łódź | Poland | 90-153 | |
| 38 | Medical Facility | Bucharest | Romania | 020125 | |
| 39 | Medical Facility | Bucharest | Romania | 021494 | |
| 40 | Medical Facility | Bucharest | Romania | 050659 | |
| 41 | Medical Facility | Craiova | Romania | 200642 | |
| 42 | Medical Facility | Iaşi | Romania | 700503 | |
| 43 | Medical Facility | Oradea | Romania | 410469 | |
| 44 | Medical Facility | Arkhangelsk | Russian Federation | 163001 | |
| 45 | Medical Facility | Lomonosov | Russian Federation | 198412 | |
| 46 | Medical Facility | Penza | Russian Federation | 440026 | |
| 47 | Medical Facility | Pyatigorsk | Russian Federation | 357500 | |
| 48 | Medical Facility | Saint Petersburg | Russian Federation | 191186 | |
| 49 | Medical Facility | Saint Petersburg | Russian Federation | 193312 | |
| 50 | Medical Facility | Saint Petersburg | Russian Federation | 194017 | |
| 51 | Medical Facility | Saint Petersburg | Russian Federation | 194044 | |
| 52 | Medical Facility | Saint Petersburg | Russian Federation | 194064 | |
| 53 | Medical Facility | Saint Petersburg | Russian Federation | 195009 | |
| 54 | Medical Facility | Saint Petersburg | Russian Federation | 195067 | |
| 55 | Medical Facility | Saint Petersburg | Russian Federation | 196247 | |
| 56 | Medical Facility | Saint Petersburg | Russian Federation | 197022 | |
| 57 | Medical Facility | Saint Petersburg | Russian Federation | 197374 | |
| 58 | Medical Facility | Saint Petersburg | Russian Federation | 198205 | |
| 59 | Medical facility | Saint Petersburg | Russian Federation | 199106 | |
| 60 | Medical Facility | Smolensk | Russian Federation | 214019 | |
| 61 | Medical Facility | Smolensk | Russian Federation | 214025 | |
| 62 | Medical Facility | Vsevolozhsk | Russian Federation | 188643 | |
| 63 | Medical Facility | Yaroslavl | Russian Federation | 150062 | |
| 64 | Medical Facility | Belgrade | Serbia | 11 000 | |
| 65 | Medical Facility | Belgrade | Serbia | 11080 | |
| 66 | Medical Facility | Kragujevac | Serbia | 34 000 | |
| 67 | Medical Facility | Novi Sad | Serbia | 21 000 | |
| 68 | Medical Facility | Vršac | Serbia | 26300 | |
| 69 | Medical Facility | Bratislava | Slovakia | 826 06 | |
| 70 | Medical Facility | Galanta | Slovakia | 924 22 | |
| 71 | Medical Facility | Lučenec | Slovakia | 984 01 | |
| 72 | Medical Facility | Martin | Slovakia | 03659 | |
| 73 | Medical Facility | Poprad | Slovakia | 05845 | |
| 74 | Medical Facility | Svidník | Slovakia | 089 01 | |
| 75 | Medical Facility | Benoni | South Africa | 1500 | |
| 76 | Medical Facility | Chatsworth | South Africa | 4092 | |
| 77 | Medical Facility | Durban | South Africa | 4001 | |
| 78 | Medical Facility | Johannesburg | South Africa | 2013 | |
| 79 | Medical Facility | Middelburg | South Africa | 1050 | |
| 80 | Medical Facility | Pretoria | South Africa | 0001 | |
| 81 | Medical Facility | Cherkasy | Ukraine | 18009 | |
| 82 | Medical Facility | Chernihiv | Ukraine | 14034 | |
| 83 | Medical Facility | Dnipro | Ukraine | 49027 | |
| 84 | Medical Facility | Ivano-Frankivs'k | Ukraine | 76008 | |
| 85 | Medical Facility | Ivano-Frankivs'k | Ukraine | 76018 | |
| 86 | Medical Facility | Kharkiv | Ukraine | 61037 | |
| 87 | Medical Facility | Kharkiv | Ukraine | 61103 | |
| 88 | Medical Facility | Lviv | Ukraine | 79010 | |
| 89 | Medical Facility | Lviv | Ukraine | 79059 | |
| 90 | Medical Facility | Mykolaiv | Ukraine | 54058 | |
| 91 | Medical Facility | Odesa | Ukraine | 65025 | |
| 92 | Medical Facility | Odesa | Ukraine | 65074 | |
| 93 | Medical Facility | Uzhhorod | Ukraine | 88000 | |
| 94 | Medical Facility | Vinnytsia | Ukraine | 21018 | |
| 95 | Medical Facility | Zaporizhia | Ukraine | 69600 | |
| 96 | Medical Facility | Zhytomyr | Ukraine | 10002 |
Sponsors and Collaborators
- Spero Therapeutics
Investigators
- Study Director: David Melnick, MD, Spero Therapeutics Inc
Study Documents (Full-Text)
More Information
Publications
None provided.- SPR994-301
- 2018-003671-35
Study Results
Participant Flow
| Recruitment Details | 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. |
|---|---|
| Pre-assignment Detail | 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. |
| Arm/Group Title | TBPM-PI-HBr 600 mg | Ertapenem 1 g |
|---|---|---|
| Arm/Group Description | 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 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. |
| Period Title: Overall Study | ||
| STARTED | 685 | 687 |
| Micro-Intent-to-Treat (ITT) Population | 449 | 419 |
| COMPLETED | 653 | 663 |
| NOT COMPLETED | 32 | 24 |
Baseline Characteristics
| Arm/Group Title | TBPM-PI-HBr 600 mg | Ertapenem 1 g | Total |
|---|---|---|---|
| Arm/Group Description | 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 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 of all reporting groups |
| Overall Participants | 685 | 687 | 1372 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
56.7
(18.68)
|
57.2
(18.23)
|
56.9
(18.45)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
368
53.7%
|
389
56.6%
|
757
55.2%
|
| Male |
317
46.3%
|
298
43.4%
|
615
44.8%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||
| Hispanic or Latino |
13
1.9%
|
5
0.7%
|
18
1.3%
|
| Not Hispanic or Latino |
672
98.1%
|
682
99.3%
|
1354
98.7%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
| Asian |
3
0.4%
|
4
0.6%
|
7
0.5%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
6
0.9%
|
6
0.9%
|
12
0.9%
|
| White |
676
98.7%
|
677
98.5%
|
1353
98.6%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
Outcome Measures
| Title | Overall Response (Combined Clinical Cure and Microbiological Eradication) at Test-of-Cure (TOC) in Micro Intent-to-Treat Population |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | TBPM-PI-HBr 600 mg | Ertapenem 1 g |
|---|---|---|
| Arm/Group Description | 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 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. |
| Measure Participants | 449 | 419 |
| Count of Participants [Participants] |
264
38.5%
|
258
37.6%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | TBPM-PI-HBr 600 mg, Ertapenem 1 g |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Non-Inferiority | |
| Comments | The non-inferiority hypothesis test was a 1-sided hypothesis test performed at the 2.5% level of significance. If the lower limit of the 95% CI for the difference in overall response was greater than -12.5%, non-inferiority was declared. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Risk Difference |
| Estimated Value | -3.3 | |
| Confidence Interval |
(2-Sided) 95% -9.7 to 3.2 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Number of Participants With Treatment Emergent Adverse Events (TEAEs) in The Safety Population |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety analysis population included all randomized participants who received any amount of study drug. |
| Arm/Group Title | TBPM-PI-HBr 600 mg | Ertapenem 1 g |
|---|---|---|
| Arm/Group Description | 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 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. |
| Measure Participants | 685 | 687 |
| Count of Participants [Participants] |
176
25.7%
|
176
25.6%
|
| Title | Overall Response (Combined Clinical Cure Plus Microbiological Eradication) At Test-Of-Cure (TOC) In The Microbiologically Evaluable (ME) - TOC Population |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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). |
| Arm/Group Title | TBPM-PI-HBr 600 mg | Ertapenem 1 g |
|---|---|---|
| Arm/Group Description | 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 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. |
| Measure Participants | 413 | 376 |
| Count of Participants [Participants] |
254
37.1%
|
247
36%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | TBPM-PI-HBr 600 mg, Ertapenem 1 g |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Risk Difference |
| Estimated Value | -4.7 | |
| Confidence Interval |
(2-Sided) 95% -11.3 to 1.9 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Clinical Cure at End-of-Treatment (EOT), TOC, and Sustained Clinical Cure at Late Follow-Up (LFU) Days in the Micro-ITT Populations |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | TBPM-PI-HBr 600 mg | Ertapenem 1 g |
|---|---|---|
| Arm/Group Description | 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 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. |
| Measure Participants | 449 | 419 |
| EOT |
446
65.1%
|
410
59.7%
|
| TOC |
418
61%
|
392
57.1%
|
| LFU |
398
58.1%
|
377
54.9%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | TBPM-PI-HBr 600 mg, Ertapenem 1 g |
|---|---|---|
| Comments | Statistical Analysis 1 (EOT) | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Risk Difference |
| Estimated Value | 1.4 | |
| Confidence Interval |
(2-Sided) 95% -0.1 to 3.4 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | TBPM-PI-HBr 600 mg, Ertapenem 1 g |
|---|---|---|
| Comments | Statistical Analysis 2 (TOC) | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Risk Difference |
| Estimated Value | -0.6 | |
| Confidence Interval |
(2-Sided) 95% -4 to 2.8 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | TBPM-PI-HBr 600 mg, Ertapenem 1 g |
|---|---|---|
| Comments | Statistical Analysis 3 (LFU) | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Risk Difference |
| Estimated Value | -1.5 | |
| Confidence Interval |
(2-Sided) 95% -5.7 to 2.6 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Clinical Cure at EOT Days the Clinically Evaluable (CE-EOT) Populations |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | TBPM-PI-HBr 600 mg | Ertapenem 1 g |
|---|---|---|
| Arm/Group Description | 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 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. |
| Measure Participants | 677 | 674 |
| Count of Participants [Participants] |
673
98.2%
|
665
96.8%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | TBPM-PI-HBr 600 mg, Ertapenem 1 g |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Risk Difference |
| Estimated Value | 0.7 | |
| Confidence Interval |
(2-Sided) 95% -0.3 to 2.0 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Clinical Cure at TOC in the CE-TOC Populations |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | TBPM-PI-HBr 600 mg | Ertapenem 1 g |
|---|---|---|
| Arm/Group Description | 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 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. |
| Measure Participants | 641 | 637 |
| Count of Participants [Participants] |
611
89.2%
|
617
89.8%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | TBPM-PI-HBr 600 mg, Ertapenem 1 g |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Risk Difference |
| Estimated Value | -1.6 | |
| Confidence Interval |
(2-Sided) 95% -3.8 to 0.6 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Sustained Clinical Cure at LFU in the CE-LFU Populations |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | TBPM-PI-HBr 600 mg | Ertapenem 1 g |
|---|---|---|
| Arm/Group Description | 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 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. |
| Measure Participants | 596 | 596 |
| Count of Participants [Participants] |
556
81.2%
|
559
81.4%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | TBPM-PI-HBr 600 mg, Ertapenem 1 g |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Risk Difference |
| Estimated Value | -0.5 | |
| Confidence Interval |
(2-Sided) 95% -3.3 to 2.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Clinical Cure at EOT in the ME-EOT Populations |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | TBPM-PI-HBr 600 mg | Ertapenem 1 g |
|---|---|---|
| Arm/Group Description | 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 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. |
| Measure Participants | 439 | 401 |
| Count of Participants [Participants] |
437
63.8%
|
394
57.4%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | TBPM-PI-HBr 600 mg, Ertapenem 1 g |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Risk Difference |
| Estimated Value | 1.3 | |
| Confidence Interval |
(2-Sided) 95% -0.2 to 3.2 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Clinical Cure at TOC Days in the ME-TOC Populations |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | TBPM-PI-HBr 600 mg | Ertapenem 1 g |
|---|---|---|
| Arm/Group Description | 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 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. |
| Measure Participants | 413 | 376 |
| Count of Participants [Participants] |
390
56.9%
|
363
52.8%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | TBPM-PI-HBr 600 mg, Ertapenem 1 g |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Risk Difference |
| Estimated Value | -2.2 | |
| Confidence Interval |
(2-Sided) 95% -5.3 to 0.8 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Sustained Clinical Cure at LFU in the ME-LFU Population |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | TBPM-PI-HBr 600 mg | Ertapenem 1 g |
|---|---|---|
| Arm/Group Description | 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 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. |
| Measure Participants | 391 | 353 |
| Count of Participants [Participants] |
360
52.6%
|
329
47.9%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | TBPM-PI-HBr 600 mg, Ertapenem 1 g |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Risk Difference |
| Estimated Value | -1.2 | |
| Confidence Interval |
(2-Sided) 95% -5.1 to 2.6 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | By-Patient Microbiological Eradication at EOT, TOC, and Sustained Microbiological Eradication at LFU Days in the Micro-ITT Population |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | TBPM-PI-HBr 600 mg | Ertapenem 1 g |
|---|---|---|
| Arm/Group Description | 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 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. |
| Measure Participants | 449 | 419 |
| EOT |
439
64.1%
|
403
58.7%
|
| TOC |
267
39%
|
266
38.7%
|
| LFU |
257
37.5%
|
244
35.5%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | TBPM-PI-HBr 600 mg, Ertapenem 1 g |
|---|---|---|
| Comments | Statistical Analysis 1 (EOT) | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Risk Difference |
| Estimated Value | 1.5 | |
| Confidence Interval |
(2-Sided) 95% -0.8 to 4.1 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | TBPM-PI-HBr 600 mg, Ertapenem 1 g |
|---|---|---|
| Comments | Statistical Analysis 2 (TOC) | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Risk Difference |
| Estimated Value | -4.5 | |
| Confidence Interval |
(2-Sided) 95% -10.8 to 1.9 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | TBPM-PI-HBr 600 mg, Ertapenem 1 g |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Risk Difference |
| Estimated Value | -1.5 | |
| Confidence Interval |
(2-Sided) 95% -7.9 to 5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | By-Pathogen Microbiological Eradication Rate at EOT in the Micro-ITT Population |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | TBPM-PI-HBr 600 mg | Ertapenem 1 g |
|---|---|---|
| Arm/Group Description | 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 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. |
| Measure Participants | 449 | 419 |
| Measure Pathogens | 493 | 455 |
| 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
|
| Title | By-Pathogen Microbiological Eradication Rate at TOC in the Micro-ITT Population |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | TBPM-PI-HBr 600 mg | Ertapenem 1 g |
|---|---|---|
| Arm/Group Description | 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 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. |
| Measure Participants | 449 | 419 |
| Measure Pathogens | 493 | 455 |
| 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
|
| Title | By-Pathogen Sustained Microbiological Eradication Rate at LFU in the Micro-ITT Population (m-ITT) |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | TBPM-PI-HBr 600 mg | Ertapenem 1 g |
|---|---|---|
| Arm/Group Description | 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 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. |
| Measure Participants | 449 | 419 |
| Measure Pathogens | 417 | 402 |
| 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
|
| Title | By-Patient Microbiological Eradication at EOT in the ME-EOT Populations |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | TBPM-PI-HBr 600 mg | Ertapenem 1 g |
|---|---|---|
| Arm/Group Description | 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 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. |
| Measure Participants | 439 | 401 |
| Count of Participants [Participants] |
436
63.6%
|
399
58.1%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | TBPM-PI-HBr 600 mg, Ertapenem 1 g |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Risk Difference |
| Estimated Value | -0.2 | |
| Confidence Interval |
(2-Sided) 95% -1.6 to 1.2 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | By-Patient Microbiological Eradication at TOC in the ME-TOC Population |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | TBPM-PI-HBr 600 mg | Ertapenem 1 g |
|---|---|---|
| Arm/Group Description | 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 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. |
| Measure Participants | 413 | 376 |
| Count of Participants [Participants] |
257
37.5%
|
254
37%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | TBPM-PI-HBr 600 mg, Ertapenem 1 g |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Risk Difference |
| Estimated Value | -5.9 | |
| Confidence Interval |
(2-Sided) 95% -12.4 to 0.7 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | By-Patient Sustained Microbiological Eradication at LFU Days in the ME-LFU Populations |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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 |
| Arm/Group Title | TBPM-PI-HBr 600 mg | Ertapenem 1 g |
|---|---|---|
| Arm/Group Description | 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 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. |
| Measure Participants | 391 | 353 |
| Count of Participants [Participants] |
234
34.2%
|
216
31.4%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | TBPM-PI-HBr 600 mg, Ertapenem 1 g |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Risk Difference (RD) |
| Estimated Value | -1.6 | |
| Confidence Interval |
(2-Sided) 95% -8.5 to 5.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | By-pathogen Microbiological Eradication Rate in Participants at EOT in the ME-EOT Populations |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | TBPM-PI-HBr | Ertapenem |
|---|---|---|
| Arm/Group Description | 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 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. |
| Measure Participants | 439 | 401 |
| Measure Pathogens | 481 | 436 |
| 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
|
| Title | By-pathogen Microbiological Eradication Rate in Participants at TOC in the ME-TOC Populations |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | TBPM-PI-HBr | Ertapenem |
|---|---|---|
| Arm/Group Description | 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 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. |
| Measure Participants | 413 | 376 |
| Measure Pathogens | 451 | 408 |
| 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
|
| Title | By-pathogen Sustained Microbiological Eradication Rate in Participants at LFU in the ME-LFU Populations |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | TBPM-PI-HBr 600 mg | Ertapenem 1 g |
|---|---|---|
| Arm/Group Description | 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 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. |
| Measure Participants | 391 | 353 |
| Measure Pathogens | 391 | 353 |
| 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
|
| Title | Overall Response Rate (Combined Clinical Cure Plus Microbiological Eradication) In Subgroup Including: Stratified Infection Category |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | TBPM-PI-HBr 600 mg | Ertapenem 1 g |
|---|---|---|
| Arm/Group Description | 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 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. |
| Measure Participants | 449 | 419 |
| AP |
65.9
9.6%
|
70.6
10.3%
|
| cUTI |
51.6
7.5%
|
53.2
7.7%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | TBPM-PI-HBr 600 mg, Ertapenem 1 g |
|---|---|---|
| Comments | Overall response for participants with AP | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Risk Difference |
| Estimated Value | -4.7 | |
| Confidence Interval |
(2-Sided) 95% -13.5 to 4.1 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | TBPM-PI-HBr 600 mg, Ertapenem 1 g |
|---|---|---|
| Comments | Overall response in participants with cUTI | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Risk Difference |
| Estimated Value | -1.6 | |
| Confidence Interval |
(2-Sided) 95% -11.0 to 7.7 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Overall Response Rate (Combined Clinical Cure Plus Microbiological Eradication) at TOC In Subgroup Stratified Age Category |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | TBPM-PI-HBr 600 mg | Ertapenem 1 g |
|---|---|---|
| Arm/Group Description | 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 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. |
| Measure Participants | 449 | 419 |
| ≥18 to <65 years |
66.7
9.7%
|
65.3
9.5%
|
| ≥65 to <75 years |
49.2
7.2%
|
57.6
8.4%
|
| ≥75 years |
49.4
7.2%
|
56.9
8.3%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | TBPM-PI-HBr 600 mg, Ertapenem 1 g |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Risk Difference |
| Estimated Value | 1.4 | |
| Confidence Interval |
(2-Sided) 95% -7.2 to 9.9 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | TBPM-PI-HBr 600 mg, Ertapenem 1 g |
|---|---|---|
| Comments | ≥65 to <75 years | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Risk Difference (RD) |
| Estimated Value | -8.4 | |
| Confidence Interval |
(2-Sided) 95% -20.6 to 3.8 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | TBPM-PI-HBr 600 mg, Ertapenem 1 g |
|---|---|---|
| Comments | ≥75 years | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Risk Difference (RD) |
| Estimated Value | -7.5 | |
| Confidence Interval |
(2-Sided) 95% -23.8 to 8.7 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Overall Response Rate (Combined Clinical Cure Plus Microbiological Eradication) at TOC In Subgroup Including Region |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | TBPM-PI-HBr 600 mg | Ertapenem 1 g |
|---|---|---|
| Arm/Group Description | 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 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. |
| Measure Participants | 449 | 419 |
| Central and Eastern Europe |
58.9
8.6%
|
62.0
9%
|
| South Africa |
100
14.6%
|
0.0
0%
|
| United States |
0.0
0%
|
50.0
7.3%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | TBPM-PI-HBr 600 mg, Ertapenem 1 g |
|---|---|---|
| Comments | Central and Eastern Europe | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Risk Difference |
| Estimated Value | -3.1 | |
| Confidence Interval |
(2-Sided) 95% -9.6 to 3.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Time (Days) to Resolution or Improvement of Signs and Symptoms of cUTI and AP Present a Baseline in the Micro-ITT Populations |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | TBPM-PI-HBr 600 mg | Ertapenem 1 g |
|---|---|---|
| Arm/Group Description | 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 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. |
| Measure Participants | 449 | 419 |
| Mean (Standard Deviation) [days] |
4.1
(3.85)
|
3.7
(3.26)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | TBPM-PI-HBr 600 mg, Ertapenem 1 g |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.044 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Title | Time (Days) to Defervescence in Micro-ITT Population With a Documented Fever at Screening or Day 1 |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | TBPM-PI-HBr 600 mg | Ertapenem 1 g |
|---|---|---|
| Arm/Group Description | 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 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. |
| Measure Participants | 226 | 193 |
| Mean (Standard Deviation) [days] |
2.2
(1.33)
|
2.2
(1.40)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | TBPM-PI-HBr 600 mg, Ertapenem 1 g |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.736 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Title | Rate of Clinical Relapse at the LFU Days in the Micro-ITT Population |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | TBPM-PI-HBr 600 mg | Ertapenem 1 g |
|---|---|---|
| Arm/Group Description | 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 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. |
| Measure Participants | 449 | 419 |
| Number [percentage of participants] |
2.7
0.4%
|
3.6
0.5%
|
| Title | Rates Of Superinfection And New Infection In The Micro-ITT Population |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | TBPM-PI-HBr 600 mg | Ertapenem 1 g |
|---|---|---|
| Arm/Group Description | 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 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. |
| Measure Participants | 449 | 419 |
| Superinfection |
0.2
0%
|
2.1
0.3%
|
| New Infection |
1.1
0.2%
|
1.9
0.3%
|
| Title | Apparent Volume of Distribution (Vss) at Steady State in TBPM-PI-HBr Recipients in the Pharmacokinetic (PK) Population |
|---|---|
| Description | |
| Time Frame | Predose and post-dose at 0.25h, 0.5h, 1h, 2h, and 8h on Days 1 and 3 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | TBPM-PI-HBr 600 mg |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 29 |
| Day 1 |
75.5
|
| Day 3 |
75.5
|
| Title | Cmax in TBPM-PI-HBr Recipients in the PK Population |
|---|---|
| Description | |
| Time Frame | Predose and post-dose at 0.25h, 0.5h, 1h, 2h, and 8h on Days 1 and 3 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | TBPM-PI-HBr 600 mg |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 29 |
| Day 1 |
7.01
|
| Day 3 |
7.21
|
| Title | Area Under Curve (AUC 0-24) in TBPM-PI-HBr Recipients in the PK Population |
|---|---|
| Description | |
| Time Frame | Predose and post-dose at 0.25h, 0.5h, 1h, 2h, and 8h on Days 1 and 3 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | TBPM-PI-HBr 600 mg |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 29 |
| Day 1 |
65.5
|
| Day 3 |
74.6
|
| Title | Minimum Concentration (Cmin) in TBPM-PI-HBr Recipients in the PK Population |
|---|---|
| Description | |
| Time Frame | Predose and post-dose at 0.25h, 0.5h, 1h, 2h, and 8h on Days 1 and 3 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | TBPM-PI-HBr 600 mg |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 29 |
| Day 1 |
0.706
|
| Day 3 |
1.17
|
| Title | Systemic Clearance (CL) in TBPM-PI-HBr Recipients in the PK Population |
|---|---|
| Description | |
| Time Frame | Predose and post-dose at 0.25h, 0.5h, 1h, 2h, and 8h on Days 1 and 3 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | TBPM-PI-HBr 600 mg |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 29 |
| Day 1 |
31.6
|
| Day 3 |
31.6
|
Adverse Events
| Time Frame | From the first dose of administration up to Day 25 post-treatment ± 2 days (up to approximately 27 days) | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | Safety analysis population included all randomized participants who received any amount of study drug. | |||
| Arm/Group Title | TBPM-PI-HBr 600 mg | Ertapenem 1 g | ||
| Arm/Group Description | 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 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. | ||
All Cause Mortality |
||||
| TBPM-PI-HBr 600 mg | Ertapenem 1 g | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/685 (0%) | 0/687 (0%) | ||
Serious Adverse Events |
||||
| TBPM-PI-HBr 600 mg | Ertapenem 1 g | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 14/685 (2%) | 12/687 (1.7%) | ||
| Cardiac disorders | ||||
| Myocardial ischaemia | 1/685 (0.1%) | 0/687 (0%) | ||
| Gastrointestinal disorders | ||||
| Duodenal ulcer hemorrhage | 0/685 (0%) | 1/687 (0.1%) | ||
| General disorders | ||||
| Pyrexia | 1/685 (0.1%) | 1/687 (0.1%) | ||
| Cyst | 0/685 (0%) | 1/687 (0.1%) | ||
| Infections and infestations | ||||
| Pyelonephritis acute | 1/685 (0.1%) | 2/687 (0.3%) | ||
| Clostridium difficile infection | 0/685 (0%) | 1/687 (0.1%) | ||
| Intervertebral discitis | 1/685 (0.1%) | 0/687 (0%) | ||
| Perirectal abscess | 1/685 (0.1%) | 0/687 (0%) | ||
| Retroperitoneal abscess | 1/685 (0.1%) | 0/687 (0%) | ||
| Urinary tract infection | 1/685 (0.1%) | 0/687 (0%) | ||
| Urinary tract infection enterococcal | 0/685 (0%) | 1/687 (0.1%) | ||
| Urosepsis | 1/685 (0.1%) | 0/687 (0%) | ||
| Injury, poisoning and procedural complications | ||||
| Procedural pneumothorax | 1/685 (0.1%) | 0/687 (0%) | ||
| Investigations | ||||
| Clostridium test positive | 0/685 (0%) | 1/687 (0.1%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Back pain | 0/685 (0%) | 1/687 (0.1%) | ||
| Osteochondrosis | 0/685 (0%) | 1/687 (0.1%) | ||
| Nervous system disorders | ||||
| Generalized tonic-clonic seizure | 1/685 (0.1%) | 0/687 (0%) | ||
| Radiculopathy | 0/685 (0%) | 1/687 (0.1%) | ||
| Renal and urinary disorders | ||||
| Renal colic | 1/685 (0.1%) | 0/687 (0%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Acute pulmonary edema | 1/685 (0.1%) | 0/687 (0%) | ||
| Acute respiratory failure | 1/685 (0.1%) | 0/687 (0%) | ||
| Pulmonary artery thrombosis | 0/685 (0%) | 1/687 (0.1%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Subcutaneous emphysema | 1/685 (0.1%) | 0/687 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| TBPM-PI-HBr 600 mg | Ertapenem 1 g | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 39/685 (5.7%) | 30/687 (4.4%) | ||
| Gastrointestinal disorders | ||||
| Diarrhoea | 39/685 (5.7%) | 30/687 (4.4%) | ||
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
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
Results Point of Contact
| Name/Title | Angela Talley |
|---|---|
| Organization | Senior Vice President Clinical Development |
| Phone | 857-242-1575 |
| atalley@sperotherapeutics.com |
- SPR994-301
- 2018-003671-35