A Phase 2 interventional study of Relebactam 250 mg and Relebactam 125 mg in Urinary Tract Infections and Pyelonephritis, sponsored by Merck Sharp & Dohme LLC. Completed. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2019-05-24.
Sponsored by Merck Sharp & Dohme LLC (part of Merck & Co., Inc) · Phase 2, Interventional, and Treatment
The purpose of this study is to evaluate the efficacy, safety and tolerability of adding 125 mg or 250 mg doses of MK-7655 (relebactam) to imipenem/cilastatin in adults 18 years or older with complicated urinary tract infection (cUTI). The primary hypothesis is that the relebactam + imipenem/cilastatin treatment regimen is non-inferior to imipenem/cilastatin with respect to the proportion of participants with a favorable microbiological response at completion of intravenous (IV) study therapy.
803 studies on the registry are indexed under Urinary Tract Infections; 133 are open to participants now.
This study's enrollment of 302 is above the median of 131 across 560 interventional studies indexed under Urinary Tract Infections.
Browse Urinary Tract Infections studies →Merck Sharp & Dohme LLC is the lead sponsor of 2,166 studies on the registry; 132 are open to participants now.
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pyelonephritis judged by the investigator to be serious (requiring hospitalization and treatment with IV antibiotic therapy)
(indwelling or straight catheter) urine specimen with greater than or equal to 10 white blood cells (WBCs) per high-power field (hpf) on standard examination of urine sediment or greater than or equal to 10 WBCs/mm3 in unspun urine
Exclusion Criteria:
permanent indwelling urinary catheter or instrumentation), a known ileal loop, or intractable vesico-ureteral reflux
serious reaction to carbapenem antibiotics, any cephalosporins, penicillins, or other beta (β)-lactam agents
valproic acid in the 2 weeks prior to screening.
during the study
ciprofloxacin) within the timeframe of treatment specified in this protocol is
considered unlikely.
the study antibiotics
designated in the various study treatment groups (use of vancomycin, daptomycin, or linezolid is allowed for certain infections)
confound the results of the study or pose additional risk in administering the study drug
involving the administration of or experimental medication (not
licensed by regulatory agencies) at the time of presentation or during the previous 30 days prior to screening or is anticipated to participate in such a clinical study during the course of this trial
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Creatinine clearance (CrCl)
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Relebactam 250 mg IV co-administered with 500 mg of imipenem/cilastatin once every 6 hours for a minimum of 96 hours. After 96 hours of IV treatment, participants may be switched to 500 mg ciprofloxacin (as optional oral therapy following minimum duration of IV study drug), administered orally, twice daily for the remainder of the study. Antibiotic therapy (IV and oral combined) should not exceed 14 days.
Drug: Relebactam 250 mg · Drug: imipenem/cilastatin 500 mg · Drug: Ciprofloxacin
Relebactam 125 mg IV co-administered with 500 mg of imipenem/cilastatin once every 6 hours for a minimum of 96 hours. After 96 hours of IV treatment, participants may be switched to 500 mg ciprofloxacin (as optional oral therapy following minimum duration of IV study drug), administered orally, twice daily for the remainder of the study. Antibiotic therapy (IV and oral combined) should not exceed 14 days.
Drug: Relebactam 125 mg · Drug: imipenem/cilastatin 500 mg · Drug: Ciprofloxacin
Matching placebo for relebactam (0.9% normal saline) IV co-administered with 500 mg dose of imipenem/cilastatin once every 6 hours for a minimum of 96 hours. After 96 hours of IV treatment, participants may be switched to 500 mg ciprofloxacin (as optional oral therapy following minimum duration of IV study drug), administered orally, twice daily for the remainder of the study. Antibiotic therapy (IV and oral combined) should not exceed 14 days.
Drug: imipenem/cilastatin 500 mg · Drug: Placebo to relebactam · Drug: Ciprofloxacin
Participants randomized to receive relebactam 250 mg will be administered a 250 mg dose of relebactam IV in a blinded fashion once every 6 hours with each dose infused over a 30-minute interval.
Also known as: MK-7655
Participants randomized to receive relebactam 125 mg will be administered a 125 mg dose of relebactam IV in a blinded-treatment fashion once every 6 hours with each dose infused over a 30-minute interval.
Also known as: MK-7655
Drug pages: Imipenem · Cilastatin
A 500 mg dose of imipenem/cilastatin will be administered IV in an open-label fashion once every 6 hours with each dose infused over a 30-minute interval.
Also known as: PRIMAXIN®, TIENAM®
Participants randomized to receive imipenem/cilastatin alone will receive a placebo-matching infusion of IV normal saline (0.9%) once every 6 hours.
After at least 96 hours of IV treatment, participants may be switched, at the discretion of the investigator, to 500 mg ciprofloxacin, administered orally, twice daily
Percentage of Participants With a Favorable Microbiological Response at Completion of IV Study Therapy
Microbiological response (MR) was assessed based on results of bacterial cultures obtained at completion of IV study medication relative to cultures obtained at baseline. A favorable microbiological response was defined as eradication of all pathogens identified at baseline. Microbiological response was assessed separately for each participant and pathogen identified in the Microbiologically Evaluable (ME) population that included participants with a urine culture confirmed to be positive for at least 1 gram-negative and/or anaerobic pathogen(s) commonly isolated in UTI. The overall microbiological response was determined as "favorable" if all pathogens isolated from a participant at baseline demonstrated a "favorable" response (eradication) at the time point evaluated.
Time frame: At time of last IV dose of study drug (up to post-randomization day 14)
Percentage of Participants With an Elevated Aspartate Aminotransferase (AST) or Alanine Aminotransferase (ALT) Laboratory Value That Was Greater Than or Equal to 5 Times the Upper Limit of Normal (ULN)
All randomized participants who received ≥1 dose of study treatment had AST and ALT levels measured up to 14 days following completion of all study medication. Participants who had 2 confirmed elevations of either AST or ALT that were 5 times ULN or greater were recorded.
Time frame: Up to 14 days following completion of all study therapy (up to 28 days)
Percentage of Participants With Elevated AST or ALT Laboratory Values ≥ 3 Times the ULN, as Well as Elevated Total Bilirubin ≥ 2 Times the ULN, and Alkaline Phosphatase Values That Were < 2 Times the ULN
All randomized participants who received ≥1 dose of study treatment had AST, ALT, total bilirubin, and Alkaline Phosphatase (ALP) levels measured up to 14 days following completion of all study medication. Participants who had elevations of AST or ALT that were ≥3 times ULN, total bilirubin measurements that were ≥2 times ULN and, at the same time, an ALP measurement of \< 2X ULN were recorded.
Time frame: Up to 14 days following completion of all study therapy (up to 28 days)
Percentage of Participants With at Least 1 Adverse Event (AE)
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product/protocol-specified procedure, whether or not considered related to the medicinal product/protocol-specified procedure. Any worsening of a preexisting condition temporally associated with the use of the product was also an AE.
Time frame: Up to 14 days following completion of all study therapy (up to 28 days)
Percentage of Participants With Any Serious Adverse Event (SAE)
A SAE was an AE that resulted in death, was life threatening, resulted in persistent or significant disability/incapacity, resulted in or prolonged an existing inpatient hospitalization, was a congenital anomaly/birth defect, was a cancer, was associated with an overdose, was another important medical event.
Time frame: Up to 14 days following completion of all study therapy (up to 28 days)
Percentage of Participants With Any Drug-related AE
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product/protocol-specified procedure, whether or not considered related to the medicinal product/protocol-specified procedure. Any worsening of a preexisting condition temporally associated with the use of the product was also an AE. A drug-related (DR) AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product that the investigator determined to be possibly, probably, or definitely related to the treatment.
Time frame: Up to 14 days following completion of all study therapy (up to 28 days)
Percentage of Participants With a Drug-related SAE
A serious, drug-related (DR) AE was an AE that resulted in death, was life threatening, resulted in persistent or significant disability/incapacity, resulted in or prolonged an existing inpatient hospitalization, was a congenital anomaly/birth defect, was a cancer, was associated with an overdose, was another important medical event. The SAE was determined to be possibly, probably, or definitely related to the treatment by the investigator.
Time frame: Up to 42 days following completion of all study therapy (up to 56 days)
Percentage of Participants Who Discontinued IV Study Therapy Due to an AE
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product/protocol-specified procedure, whether or not considered related to the medicinal product/protocol-specified procedure. Any worsening of a pre-existing condition temporally associated with the use of the product was also an AE.
Time frame: Up to 14 days
Percentage of Participants Who Discontinued IV Study Therapy Due to a Drug-related AE
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product/protocol-specified procedure, whether or not considered related to the medicinal product/protocol-specified procedure. Any worsening of a preexisting condition temporally associated with the use of the product was also an AE. A drug-related AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product that the investigator determined to be possibly, probably, or definitely related to the treatment.
Time frame: Up to 14 days
Percentage of Participants With Specific AEs With Incidence of >= 4 Participants in One Treatment Group
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product/protocol-specified procedure, whether or not considered related to the medicinal product/protocol-specified procedure. Any worsening of a preexisting condition temporally associated with the use of the product was also an AE. Analysis includes specific adverse events with an incidence of ≥4 participants in one treatment group or system organ class.
Time frame: Up to 14 days following completion of all study therapy (up to 28 days)
Percentage of Participants With a Favorable Microbiological Response at Completion of IV Study Therapy Who Had Imipenem-resistant, Gram-negative cUTI Infections.
Microbiological response was assessed based on results of bacterial cultures obtained at completion of IV study medication relative to cultures obtained at baseline. A favorable microbiological response was defined as eradication of all pathogens identified at baseline. Microbiological response was assessed separately for each participant and pathogen identified in the Microbiologically Evaluable (ME) population that included participants with a urine culture confirmed to be positive for imipenem-resistant gram-negative or anaerobic infections at baseline. The overall microbiological response was determined as "favorable" if all pathogens isolated from a participant at baseline demonstrated a "favorable" response (eradication) at the time point evaluated.
Time frame: At time of last IV dose of study drug (up to post-randomization day 14)
Percentage of Participants With a Favorable Microbiological Response at Early Follow-up
Microbiological response was assessed based on results of bacterial cultures obtained up to 9 days following completion of all study medication (IV and oral) relative to cultures obtained at baseline. A favorable microbiological response was defined as eradication of all pathogens identified at baseline. Microbiological response was assessed separately for each participant and pathogen identified in the ME population that included participants with a urine culture confirmed to be positive for at least 1 gram-negative and/or anaerobic pathogen(s) commonly isolated in UTI. The overall microbiological response was determined as "favorable" if all pathogens isolated from a participant at baseline demonstrated a "favorable" response (eradication) at the time point evaluated.
Time frame: Up to 9 days following completion of all study IV and oral therapy (up to Day 23)
Percentage of Participants With a Favorable Clinical Response at Completion of IV Study Therapy
Clinical response was assessed as favorable (cured or improved) or unfavorable (failure) relative to baseline. Response determination was based on physical findings including fever (or history of fever), chills or rigors (accompanied by fever), flank pain, costovertebral angle tenderness, dysuria, urinary urgency, urinary frequency, suprapubic or pelvic pain, nausea, or vomiting. Clinical response was assessed in the ME population that included participants with a urine culture confirmed to be positive for at least 1 gram-negative and/or anaerobic pathogen(s) commonly isolated in UTI.
Time frame: At time of last IV dose of study drug (up to postrandomization day 14)
Percentage of Participants With a Favorable Clinical Response at Early Follow-up
Clinical response was assessed as favorable (cured or improved) or unfavorable (failure) relative to baseline. Response determination was based on physical findings including fever (or history of fever), chills or rigors (accompanied by fever), flank pain, costovertebral angle tenderness, dysuria, urinary urgency, urinary frequency, suprapubic or pelvic pain, nausea, or vomiting. Clinical response was assessed in the ME population that included participants with a urine culture confirmed to be positive for at least 1 gram-negative and/or anaerobic pathogen(s) commonly isolated in UTI.
Time frame: Up to 9 days following completion of all study IV and oral therapy (up to Day 23)
Percentage of Participants With a Favorable Clinical Response at Late Follow-up
Clinical response was assessed as favorable (cured or improved) or unfavorable (failure) relative to baseline. Response determination was based on physical findings including fever (or history of fever), chills or rigors (accompanied by fever), flank pain, costovertebral angle tenderness, dysuria, urinary urgency, urinary frequency, suprapubic or pelvic pain, nausea, or vomiting. Clinical response was assessed in the ME population that included participants with a urine culture confirmed to be positive for at least 1 gram-negative and/or anaerobic pathogen(s) commonly isolated in UTI.
Time frame: Up to 42 days following completion of all study IV and oral therapy (up to Day 56)
Percentage of Participants With a Favorable Microbiological Response at Late Follow-up
Microbiological response was assessed based on results of bacterial cultures obtained up to 42 days following completion of all study medication (IV and oral) relative to cultures obtained at baseline. A favorable microbiological response was defined as eradication of all pathogens identified at baseline. Microbiological response was assessed separately for each participant and pathogen identified in the ME population that included participants with a urine culture confirmed to be positive for at least 1 gram-negative and/or anaerobic pathogen(s) commonly isolated in UTI. The overall microbiological response was determined as "favorable" if all pathogens isolated from a participant at baseline demonstrated a "favorable" response (eradication) at the time point evaluated.
Time frame: Up to 42 days following completion of all study IV and oral therapy (up to Day 56)
Participants were enrolled with complicated urinary tract infection (cUTI) or acute pyelonephritis judged by the investigator to be serious (requiring hospitalization and intravenous (IV) antibiotic therapy); pyuria; and 1 positive urine culture within 48 hours of enrollment.
| Milestone | Relebactam 250 mg With Imipenem/Cilastatin | Relebactam 125 mg With Imipenem/Cilastatin | Relebactam Placebo With Imipenem/Cilastatin |
|---|---|---|---|
| Started | 101 | 101 | 100 |
| Treated | 99 | 99 | 100 |
| Completed | 92 | 91 | 94 |
| Not completed | 9 | 10 | 6 |
| Withdrew: Withdrawal by subject | 2 | 5 | 1 |
| Withdrew: Physician decision | 1 | 1 | 0 |
| Withdrew: Adverse event | 1 | 0 | 0 |
| Withdrew: Insufficient supply of drug at site | 1 | 0 | 0 |
| Withdrew: Protocol violation | 2 | 0 | 0 |
| Withdrew: Lost to follow-up | 1 | 4 | 4 |
| Withdrew: Death | 1 | 0 | 0 |
| Withdrew: In a conflict zone | 0 | 0 | 1 |
Microbiological response (MR) was assessed based on results of bacterial cultures obtained at completion of IV study medication relative to cultures obtained at baseline. A favorable microbiological response was defined as eradication of all pathogens identified at baseline. Microbiological response was assessed separately for each participant and pathogen identified in the Microbiologically Evaluable (ME) population that included participants with a urine culture confirmed to be positive for at least 1 gram-negative and/or anaerobic pathogen(s) commonly isolated in UTI. The overall microbiological response was determined as "favorable" if all pathogens isolated from a participant at baseline demonstrated a "favorable" response (eradication) at the time point evaluated.
| Percentage of Participants | Relebactam 250 mg With Imipenem/Cilastatin | Relebactam 125 mg With Imipenem/Cilastatin | Relebactam Placebo With Imipenem/Cilastatin |
|---|---|---|---|
| Percentage of Participants With a Favorable Microbiological Response at Completion of IV Study Therapy | 95.5 (87.5 to 99.1) | 98.6 (92.4 to 100.0) | 98.7 (92.8 to 100.0) |
All randomized participants who received ≥1 dose of study treatment had AST and ALT levels measured up to 14 days following completion of all study medication. Participants who had 2 confirmed elevations of either AST or ALT that were 5 times ULN or greater were recorded.
| Percentage of participants | Relebactam 250 mg With Imipenem/Cilastatin | Relebactam 125 mg With Imipenem/Cilastatin | Relebactam Placebo With Imipenem/Cilastatin |
|---|---|---|---|
| Percentage of Participants With an Elevated Aspartate Aminotransferase (AST) or Alanine Aminotransferase (ALT) Laboratory Value That Was Greater Than or Equal to 5 Times the Upper Limit of Normal (ULN) | 1.0 | 1.0 | 0 |
All randomized participants who received ≥1 dose of study treatment had AST, ALT, total bilirubin, and Alkaline Phosphatase (ALP) levels measured up to 14 days following completion of all study medication. Participants who had elevations of AST or ALT that were ≥3 times ULN, total bilirubin measurements that were ≥2 times ULN and, at the same time, an ALP measurement of \< 2X ULN were recorded.
| Percentage of participants | Relebactam 250 mg With Imipenem/Cilastatin | Relebactam 125 mg With Imipenem/Cilastatin | Relebactam Placebo With Imipenem/Cilastatin |
|---|---|---|---|
| Percentage of Participants With Elevated AST or ALT Laboratory Values ≥ 3 Times the ULN, as Well as Elevated Total Bilirubin ≥ 2 Times the ULN, and Alkaline Phosphatase Values That Were < 2 Times the ULN | 0 | 0 | 0 |
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product/protocol-specified procedure, whether or not considered related to the medicinal product/protocol-specified procedure. Any worsening of a preexisting condition temporally associated with the use of the product was also an AE.
| Percentage of participants | Relebactam 250 mg With Imipenem/Cilastatin | Relebactam 125 mg With Imipenem/Cilastatin | Relebactam Placebo With Imipenem/Cilastatin |
|---|---|---|---|
| Percentage of Participants With at Least 1 Adverse Event (AE) | 28.3 | 29.3 | 30.0 |
A SAE was an AE that resulted in death, was life threatening, resulted in persistent or significant disability/incapacity, resulted in or prolonged an existing inpatient hospitalization, was a congenital anomaly/birth defect, was a cancer, was associated with an overdose, was another important medical event.
| Percentage of participants | Relebactam 250 mg With Imipenem/Cilastatin | Relebactam 125 mg With Imipenem/Cilastatin | Relebactam Placebo With Imipenem/Cilastatin |
|---|---|---|---|
| Percentage of Participants With Any Serious Adverse Event (SAE) | 3.0 | 1.0 | 3.0 |
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product/protocol-specified procedure, whether or not considered related to the medicinal product/protocol-specified procedure. Any worsening of a preexisting condition temporally associated with the use of the product was also an AE. A drug-related (DR) AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product that the investigator determined to be possibly, probably, or definitely related to the treatment.
| Percentage of participants | Relebactam 250 mg With Imipenem/Cilastatin | Relebactam 125 mg With Imipenem/Cilastatin | Relebactam Placebo With Imipenem/Cilastatin |
|---|---|---|---|
| Percentage of Participants With Any Drug-related AE | 10.1 | 9.1 | 9.0 |
A serious, drug-related (DR) AE was an AE that resulted in death, was life threatening, resulted in persistent or significant disability/incapacity, resulted in or prolonged an existing inpatient hospitalization, was a congenital anomaly/birth defect, was a cancer, was associated with an overdose, was another important medical event. The SAE was determined to be possibly, probably, or definitely related to the treatment by the investigator.
| Percentage of participants | Relebactam 250 mg With Imipenem/Cilastatin | Relebactam 125 mg With Imipenem/Cilastatin | Relebactam Placebo With Imipenem/Cilastatin |
|---|---|---|---|
| Percentage of Participants With a Drug-related SAE | 1.0 | 0 | 1.0 |
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product/protocol-specified procedure, whether or not considered related to the medicinal product/protocol-specified procedure. Any worsening of a pre-existing condition temporally associated with the use of the product was also an AE.
| Percentage of participants | Relebactam 250 mg With Imipenem/Cilastatin | Relebactam 125 mg With Imipenem/Cilastatin | Relebactam Placebo With Imipenem/Cilastatin |
|---|---|---|---|
| Percentage of Participants Who Discontinued IV Study Therapy Due to an AE | 3.0 | 1.0 | 2.0 |
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product/protocol-specified procedure, whether or not considered related to the medicinal product/protocol-specified procedure. Any worsening of a preexisting condition temporally associated with the use of the product was also an AE. A drug-related AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product that the investigator determined to be possibly, probably, or definitely related to the treatment.
| Percentage of participants | Relebactam 250 mg With Imipenem/Cilastatin | Relebactam 125 mg With Imipenem/Cilastatin | Relebactam Placebo With Imipenem/Cilastatin |
|---|---|---|---|
| Percentage of Participants Who Discontinued IV Study Therapy Due to a Drug-related AE | 2.0 | 1.0 | 1.0 |
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product/protocol-specified procedure, whether or not considered related to the medicinal product/protocol-specified procedure. Any worsening of a preexisting condition temporally associated with the use of the product was also an AE. Analysis includes specific adverse events with an incidence of ≥4 participants in one treatment group or system organ class.
| Percentage of participants | Relebactam 250 mg With Imipenem/Cilastatin | Relebactam 125 mg With Imipenem/Cilastatin | Relebactam Placebo With Imipenem/Cilastatin |
|---|---|---|---|
| Diarrhoea | 5.1 | 2.0 | 4.0 |
| Nausea | 4.0 | 6.1 | 4.0 |
| Bacteriuria | 1.0 | 2.0 | 4.0 |
| White blood cells urine positive | 1.0 | 1.0 | 4.0 |
| Headache | 7.1 | 3.0 | 4.0 |
Microbiological response was assessed based on results of bacterial cultures obtained at completion of IV study medication relative to cultures obtained at baseline. A favorable microbiological response was defined as eradication of all pathogens identified at baseline. Microbiological response was assessed separately for each participant and pathogen identified in the Microbiologically Evaluable (ME) population that included participants with a urine culture confirmed to be positive for imipenem-resistant gram-negative or anaerobic infections at baseline. The overall microbiological response was determined as "favorable" if all pathogens isolated from a participant at baseline demonstrated a "favorable" response (eradication) at the time point evaluated.
| Percentage of participants | Relebactam 250 mg With Imipenem/Cilastatin | Relebactam 125 mg With Imipenem/Cilastatin | Relebactam Placebo With Imipenem/Cilastatin |
|---|---|---|---|
| Percentage of Participants With a Favorable Microbiological Response at Completion of IV Study Therapy Who Had Imipenem-resistant, Gram-negative cUTI Infections. | 100.0 (69.2 to 100.0) | 100.0 (59.0 to 100.0) | 100.0 (54.1 to 100.0) |
Microbiological response was assessed based on results of bacterial cultures obtained up to 9 days following completion of all study medication (IV and oral) relative to cultures obtained at baseline. A favorable microbiological response was defined as eradication of all pathogens identified at baseline. Microbiological response was assessed separately for each participant and pathogen identified in the ME population that included participants with a urine culture confirmed to be positive for at least 1 gram-negative and/or anaerobic pathogen(s) commonly isolated in UTI. The overall microbiological response was determined as "favorable" if all pathogens isolated from a participant at baseline demonstrated a "favorable" response (eradication) at the time point evaluated.
| Percentage of participants | Relebactam 250 mg With Imipenem/Cilastatin | Relebactam 125 mg With Imipenem/Cilastatin | Relebactam Placebo With Imipenem/Cilastatin |
|---|---|---|---|
| Percentage of Participants With a Favorable Microbiological Response at Early Follow-up | 61.5 (48.6 to 73.3) | 68.1 (56.0 to 78.6) | 70.4 (58.4 to 80.7) |
Clinical response was assessed as favorable (cured or improved) or unfavorable (failure) relative to baseline. Response determination was based on physical findings including fever (or history of fever), chills or rigors (accompanied by fever), flank pain, costovertebral angle tenderness, dysuria, urinary urgency, urinary frequency, suprapubic or pelvic pain, nausea, or vomiting. Clinical response was assessed in the ME population that included participants with a urine culture confirmed to be positive for at least 1 gram-negative and/or anaerobic pathogen(s) commonly isolated in UTI.
| Percentage of participants | Relebactam 250 mg With Imipenem/Cilastatin | Relebactam 125 mg With Imipenem/Cilastatin | Relebactam Placebo With Imipenem/Cilastatin |
|---|---|---|---|
| Percentage of Participants With a Favorable Clinical Response at Completion of IV Study Therapy | 97.1 (89.9 to 99.6) | 98.7 (93.1 to 100.0) | 98.8 (93.2 to 100.0) |
Clinical response was assessed as favorable (cured or improved) or unfavorable (failure) relative to baseline. Response determination was based on physical findings including fever (or history of fever), chills or rigors (accompanied by fever), flank pain, costovertebral angle tenderness, dysuria, urinary urgency, urinary frequency, suprapubic or pelvic pain, nausea, or vomiting. Clinical response was assessed in the ME population that included participants with a urine culture confirmed to be positive for at least 1 gram-negative and/or anaerobic pathogen(s) commonly isolated in UTI.
| Percentage of Participants | Relebactam 250 mg With Imipenem/Cilastatin | Relebactam 125 mg With Imipenem/Cilastatin | Relebactam Placebo With Imipenem/Cilastatin |
|---|---|---|---|
| Percentage of Participants With a Favorable Clinical Response at Early Follow-up | 89.1 (78.8 to 95.5) | 91.8 (83.0 to 96.9) | 93.4 (85.3 to 97.8) |
Clinical response was assessed as favorable (cured or improved) or unfavorable (failure) relative to baseline. Response determination was based on physical findings including fever (or history of fever), chills or rigors (accompanied by fever), flank pain, costovertebral angle tenderness, dysuria, urinary urgency, urinary frequency, suprapubic or pelvic pain, nausea, or vomiting. Clinical response was assessed in the ME population that included participants with a urine culture confirmed to be positive for at least 1 gram-negative and/or anaerobic pathogen(s) commonly isolated in UTI.
| Percentage of participants | Relebactam 250 mg With Imipenem/Cilastatin | Relebactam 125 mg With Imipenem/Cilastatin | Relebactam Placebo With Imipenem/Cilastatin |
|---|---|---|---|
| Percentage of Participants With a Favorable Clinical Response at Late Follow-up | 88.7 (78.1 to 95.3) | 87.3 (77.3 to 94.0) | 88.2 (78.7 to 94.4) |
Microbiological response was assessed based on results of bacterial cultures obtained up to 42 days following completion of all study medication (IV and oral) relative to cultures obtained at baseline. A favorable microbiological response was defined as eradication of all pathogens identified at baseline. Microbiological response was assessed separately for each participant and pathogen identified in the ME population that included participants with a urine culture confirmed to be positive for at least 1 gram-negative and/or anaerobic pathogen(s) commonly isolated in UTI. The overall microbiological response was determined as "favorable" if all pathogens isolated from a participant at baseline demonstrated a "favorable" response (eradication) at the time point evaluated.
| Percentage of participants | Relebactam 250 mg With Imipenem/Cilastatin | Relebactam 125 mg With Imipenem/Cilastatin | Relebactam Placebo With Imipenem/Cilastatin |
|---|---|---|---|
| Percentage of Participants With a Favorable Microbiological Response at Late Follow-up | 68.3 (55.3 to 79.4) | 65.2 (52.8 to 76.3) | 62.5 (50.3 to 73.6) |
Collected over Up to 42 days following completion of all study therapy for drug-related serious adverse events (up to 56 days); and up to 14 days following completion of all study therapy for all-cause serious and non-serious adverse events (up to 28 days).. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Relebactam 250 mg With Imipenem/Cilastatin | 2/99 (2%) | 5/99 (5.1%) | 11/99 (11.1%) |
| Relebactam 125 mg With Imipenem/Cilastatin | 0/99 (0%) | 2/99 (2%) | 9/99 (9.1%) |
| Relebactam Placebo With Imipenem/Cilastatin | 0/100 (0%) | 3/100 (3%) | 7/100 (7%) |
| Event | Relebactam 250 mg With Imipenem/Cilastatin | Relebactam 125 mg With Imipenem/Cilastatin | Relebactam Placebo With Imipenem/Cilastatin |
|---|---|---|---|
| Cardiac arrestCardiac disorders | 1/99 | 0/99 | 0/100 |
| DiarrhoeaGastrointestinal disorders | 1/99 | 0/99 | 1/100 |
| Duodenal ulcerGastrointestinal disorders | 1/99 | 0/99 | 0/100 |
| Duodenal ulcer perforationGastrointestinal disorders | 1/99 | 0/99 | 0/100 |
| PeritonitisInfections and infestations | 1/99 | 0/99 | 0/100 |
| Pyelonephritis acuteInfections and infestations | 1/99 | 0/99 | 0/100 |
| UrosepsisInfections and infestations | 0/99 | 1/99 | 0/100 |
| Postoperative wound complicationInjury, poisoning and procedural complications | 0/99 | 1/99 | 0/100 |
| Renal cancerNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 1/99 | 0/99 | 0/100 |
| Renal neoplasmNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 1/99 | 0/99 | 0/100 |
| Event | Relebactam 250 mg With Imipenem/Cilastatin | Relebactam 125 mg With Imipenem/Cilastatin | Relebactam Placebo With Imipenem/Cilastatin |
|---|---|---|---|
| HeadacheNervous system disorders | 7/99 | 3/99 | 4/100 |
| NauseaGastrointestinal disorders | 4/99 | 6/99 | 4/100 |
| Age, Continuous(Years) | Relebactam 250 mg With Imipenem/Cilastatin | Relebactam 125 mg With Imipenem/Cilastatin | Relebactam Placebo With Imipenem/Cilastatin | Total |
|---|---|---|---|---|
| Mean | 57.9 ± 17.3 | 55.9 ± 17.5 | 55.7 ± 19.2 | 56.5 ± 18.0 |
| Sex: Female, Male(Participants) | Relebactam 250 mg With Imipenem/Cilastatin | Relebactam 125 mg With Imipenem/Cilastatin | Relebactam Placebo With Imipenem/Cilastatin | Total |
|---|---|---|---|---|
| Female | 51 | 60 | 42 | 153 |
| Male | 50 | 41 | 58 | 149 |
No study locations are listed for this record.
Plan to share: Yes — http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
Data sharing details ↗ · engagezone.msd.com
Ran from May 2012 to primary completion in Jul 2015, 38 months.
Results were first posted in May 2019, 3 years 9 months after primary completion.
Of 30 phase 2 interventional studies under Urinary Tract Infections, half reached primary completion within 29 months of starting (the median), counting those still running; a quarter within 16 and three quarters within 38. This study's 38 months is above that.
How these figures are worked out, and which studies are left out of them.
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Studies of the drug tested here: Relebactam