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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) (ADAPT-PO)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03788967
Recruitment Status : Completed
First Posted : December 28, 2018
Results First Posted : July 25, 2022
Last Update Posted : July 25, 2022
Sponsor:
Information provided by (Responsible Party):
Spero Therapeutics

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
Complicated Urinary Tract Infection Acute Pyelonephritis Drug: TBPM-PI-HBr Drug: Ertapenem Drug: Dummy Infusion Drug: Dummy tablets Phase 3

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1372 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 3, Randomized, Double-blind, Double-dummy, Multicenter, Prospective Study to Assess the Efficacy, Safety and Pharmacokinetics of Orally Administered Tebipenem Pivoxil Hydrobromide (SPR994) Compared to Intravenous Ertapenem in Patients With Complicated Urinary Tract Infection (cUTI) or Acute Pyelonephritis (AP)
Actual Study Start Date : June 3, 2019
Actual Primary Completion Date : May 20, 2020
Actual Study Completion Date : May 27, 2020


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 Name: SPR994

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.




Primary Outcome Measures :
  1. Overall Response (Combined Clinical Cure and Microbiological Eradication) at Test-of-Cure (TOC) in Micro Intent-to-Treat Population [ Time Frame: 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.

  2. Number of Participants With Treatment Emergent Adverse Events (TEAEs) in The Safety Population [ Time Frame: 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 :
  1. Overall Response (Combined Clinical Cure Plus Microbiological Eradication) At Test-Of-Cure (TOC) In The Microbiologically Evaluable (ME) - TOC Population [ Time Frame: 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.

  2. Clinical Cure at End-of-Treatment (EOT), TOC, and Sustained Clinical Cure at Late Follow-Up (LFU) Days in the Micro-ITT Populations [ Time Frame: 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.

  3. Clinical Cure at EOT Days the Clinically Evaluable (CE-EOT) Populations [ Time Frame: 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.

  4. Clinical Cure at TOC in the CE-TOC Populations [ Time Frame: 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.

  5. Sustained Clinical Cure at LFU in the CE-LFU Populations [ Time Frame: 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.

  6. Clinical Cure at EOT in the ME-EOT Populations [ Time Frame: 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.

  7. Clinical Cure at TOC Days in the ME-TOC Populations [ Time Frame: 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.

  8. Sustained Clinical Cure at LFU in the ME-LFU Population [ Time Frame: 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.

  9. By-Patient Microbiological Eradication at EOT, TOC, and Sustained Microbiological Eradication at LFU Days in the Micro-ITT Population [ Time Frame: 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.

  10. By-Pathogen Microbiological Eradication Rate at EOT in the Micro-ITT Population [ Time Frame: 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.

  11. By-Pathogen Microbiological Eradication Rate at TOC in the Micro-ITT Population [ Time Frame: 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.

  12. By-Pathogen Sustained Microbiological Eradication Rate at LFU in the Micro-ITT Population (m-ITT) [ Time Frame: 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.

  13. By-Patient Microbiological Eradication at EOT in the ME-EOT Populations [ Time Frame: 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.

  14. By-Patient Microbiological Eradication at TOC in the ME-TOC Population [ Time Frame: 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.

  15. By-Patient Sustained Microbiological Eradication at LFU Days in the ME-LFU Populations [ Time Frame: 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.

  16. By-pathogen Microbiological Eradication Rate in Participants at EOT in the ME-EOT Populations [ Time Frame: 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.

  17. By-pathogen Microbiological Eradication Rate in Participants at TOC in the ME-TOC Populations [ Time Frame: 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.

  18. By-pathogen Sustained Microbiological Eradication Rate in Participants at LFU in the ME-LFU Populations [ Time Frame: 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.

  19. Overall Response Rate (Combined Clinical Cure Plus Microbiological Eradication) In Subgroup Including: Stratified Infection Category [ Time Frame: 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.

  20. Overall Response Rate (Combined Clinical Cure Plus Microbiological Eradication) at TOC In Subgroup Stratified Age Category [ Time Frame: 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.

  21. Overall Response Rate (Combined Clinical Cure Plus Microbiological Eradication) at TOC In Subgroup Including Region [ Time Frame: 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.

  22. Time (Days) to Resolution or Improvement of Signs and Symptoms of cUTI and AP Present a Baseline in the Micro-ITT Populations [ Time Frame: 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.

  23. Time (Days) to Defervescence in Micro-ITT Population With a Documented Fever at Screening or Day 1 [ Time Frame: 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.

  24. Rate of Clinical Relapse at the LFU Days in the Micro-ITT Population [ Time Frame: 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.

  25. Rates Of Superinfection And New Infection In The Micro-ITT Population [ Time Frame: 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.

  26. Apparent Volume of Distribution (Vss) at Steady State in TBPM-PI-HBr Recipients in the Pharmacokinetic (PK) Population [ Time Frame: Predose and post-dose at 0.25h, 0.5h, 1h, 2h, and 8h on Days 1 and 3 ]
  27. Cmax in TBPM-PI-HBr Recipients in the PK Population [ Time Frame: Predose and post-dose at 0.25h, 0.5h, 1h, 2h, and 8h on Days 1 and 3 ]
  28. Area Under Curve (AUC 0-24) in TBPM-PI-HBr Recipients in the PK Population [ Time Frame: Predose and post-dose at 0.25h, 0.5h, 1h, 2h, and 8h on Days 1 and 3 ]
  29. Minimum Concentration (Cmin) in TBPM-PI-HBr Recipients in the PK Population [ Time Frame: Predose and post-dose at 0.25h, 0.5h, 1h, 2h, and 8h on Days 1 and 3 ]
  30. Systemic Clearance (CL) in TBPM-PI-HBr Recipients in the PK Population [ Time Frame: Predose and post-dose at 0.25h, 0.5h, 1h, 2h, and 8h on Days 1 and 3 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  1. Male and female participants at least 18 years of age.
  2. Able to provide informed consent.
  3. 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.
  4. Have a diagnosis of cUTI or AP as defined below:

    a. cUTI definition:

    At least Two of the following signs and symptoms:

    i. Chills, rigors, or fever; fever must be observed and documented by a health care provider (oral, tympanic, rectal or core temperature >38.0°C [>100.4°F])

    ii. Dysuria, urgency to void, or increased urinary frequency

    iii. Nausea or vomiting, as reported by the participants

    iv. Lower abdominal, suprapubic, or pelvic pain

    And at least One of the following risk factors for cUTI:

    i. Implanted urinary tract instrumentation (e.g., nephrostomy tube, ureteric stents, or other urinary tract prosthetic material), ongoing intermittent bladder catheterization, or presence of an indwelling bladder catheter (Note: bladder catheters that have been in place for >24 hours prior to Screening must be removed or replaced prior to collection of the Screening urine for urinalysis and culture, unless removal or replacement is considered unsafe or contraindicated).

    ii. Current known functional or anatomical abnormality of the urogenital tract, including anatomic abnormalities of the urinary tract, neurogenic bladder, or post-void residual urine volume of ≥ 100 mL within the past 6 months.

    iii. Complete or partial obstructive uropathy (e.g., nephrolithiasis, tumor, fibrosis, urethral stricture) that is expected to be medically or surgically treated during study drug therapy (prior to end of the treatment [EOT]).

    iv. Known intrinsic renal disease with blood urea nitrogen (BUN) >20 mg/deciliter (dL), or blood urea >42.8 mg/dL, or serum creatinine (Cr) >1.4 mg/dL.

    v. Urinary retention, including urinary retention in men due to previously diagnosed benign prostatic hyperplasia (BPH).

    b. AP definition: Acute flank pain (onset within 7 days prior to randomization) or costovertebral angle tenderness on physical examination.

    And at least One of the following signs and symptoms:

    i. Chills, rigors, or fever; fever must be observed and documented by a health care provider (oral, tympanic, rectal or core temperature >38.0°C [>100.4°F]).

    ii. Peripheral white blood cell count (WBC) >10,000/mm3 or bandemia (≥15% immature polymorphonuclear neutrophils (PMNs), regardless of WBC count).

    iii. Nausea or vomiting, as reported by the participants.

    iv. Dysuria, urgency to void, or increased urinary frequency.

    Note: Participants who meet the definition for cUTI (Inclusion Criterion 4a) and also have flank pain or costovertebral tenderness should be randomized as cUTI rather than AP.

  5. 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:

    1. At least 10 WBCs per high power field (hpf) in urine sediment.
    2. At least 10 WBCs per cubic millimeter (mm3) in unspun (non-centrifuged) urine.
    3. Positive leukocyte esterase (LE) on urinalysis. Note: Participants could be randomized and administered investigational product (IP) prior to knowledge of urine culture results.
  6. 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.
  7. Willing to comply with all the study activities and procedures throughout the duration of the study.
  8. 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

  1. 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:

    1. Perinephric or renal corticomedullary abscess.
    2. Uncomplicated urinary tract infection (cUTI) - (acute cystitis that does not meet the cUTI disease definition, see Inclusion Criterion 4a).
    3. Polycystic kidney disease.
    4. Recent history of trauma to the pelvis or urinary tract.
    5. Confirmed or suspected acute or chronic bacterial prostatitis, orchitis, or epididymitis.
    6. Chronic vesicoureteral reflux.
    7. Previous or planned renal transplantation.
    8. Previous or planned cystectomy or ileal loop surgery.
    9. Known or suspected non-renal source of infection (e.g., infective endocarditis, osteomyelitis, meningitis, pneumonia).
    10. 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).
  2. Gross hematuria requiring intervention other than administration of IP or removal/placement of urinary tract instrumentation.
  3. Urinary tract surgery within 7 days prior to randomization or urinary tract surgery planned during the study period (except surgery required relieving an obstruction or placing urinary tract instrumentation).
  4. 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]).

  5. 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.
  6. 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.
  7. 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:

    1. In the opinion of the Investigator they have failed the prior antibiotic therapy (e.g., have worsening signs and symptoms of cUTI/AP).
    2. Had a documented uropathogen (growth in urine culture >10^5 CFU/mL) that is resistant to the prior antibiotic therapy.
    3. Had a documented uropathogen that is carbapenem-susceptible.
    4. Received approval from the Medical Monitor to enroll the participants.
  8. 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).
  9. 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.
  10. Pregnant or breastfeeding women.
  11. History of epilepsy or known seizure disorder (excluding a history of childhood febrile seizures).
  12. Receipt of any investigational medication during the last 30 days or 5 half-lives, whichever is longer, prior to randomization.
  13. 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.
  14. 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).
  15. A mean QT interval corrected using Fridericia's formula (QTcF) >480 msec based on triplicate ECGs at Screening.
  16. 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.
  17. History of known genetic metabolism anomaly associated with carnitine deficiency (e.g., carnitine transporter defect, methylmalonic aciduria, propionic acidemia)
  18. Requirement for concomitant use of valproic acid, divalproex sodium, or probenecid between randomization and EOT.
  19. Unable or unwilling to comply with the protocol.
  20. 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03788967


Locations
Show Show 96 study locations
Sponsors and Collaborators
Spero Therapeutics
Investigators
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Study Director: David Melnick, MD Spero Therapeutics Inc
  Study Documents (Full-Text)

Documents provided by Spero Therapeutics:
Study Protocol  [PDF] May 26, 2020
Statistical Analysis Plan  [PDF] September 3, 2020

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Spero Therapeutics
ClinicalTrials.gov Identifier: NCT03788967    
Other Study ID Numbers: SPR994-301
2018-003671-35 ( EudraCT Number )
First Posted: December 28, 2018    Key Record Dates
Results First Posted: July 25, 2022
Last Update Posted: July 25, 2022
Last Verified: June 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Spero Therapeutics:
Complicated Urinary Tract Infection
Acute Pyelonephritis
Additional relevant MeSH terms:
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Infections
Communicable Diseases
Urinary Tract Infections
Pyelonephritis
Disease Attributes
Pathologic Processes
Urologic Diseases
Nephritis, Interstitial
Nephritis
Kidney Diseases
Pyelitis
Ertapenem
Anti-Bacterial Agents
Anti-Infective Agents