NCT03006679

Withdrawn

Phase 3

A Phase IIIb, Multicenter, Double-Blind, Randomized, Comparative Study to Evaluate the Efficacy, Safety, and Tolerability of Meropenem-Vaborbactam Versus Piperacillin/Tazobactam in the Treatment of Hospital-Acquired Bacterial Pneumonia and Ventilator-Associated Bacterial Pneumonia in Hospitalized Adults (TANGO III)

Melinta Therapeutics, Inc.0 sitesAugust 2018

ConditionsHospital-Acquired Bacterial Pneumonia Ventilator-Associated Bacterial Pneumonia Hospital-Acquired Pneumonia Ventilator-Associated Pneumonia

InterventionsMeropenem-Vaborbactam Piperacillin/Tazobactam

DrugsMeropenem-Vaborbactam Piperacillin/Tazobactam

Overview

Phase: Phase 3
Intervention: Meropenem-Vaborbactam
Conditions: Hospital-Acquired Bacterial Pneumonia
Sponsor: Melinta Therapeutics, Inc.
Primary Endpoint: Percentage of Participants who Achieve a Clinical Outcome of Cure at the Test of Cure (TOC) Visit in the ITT and Clinically Evaluable (CE) Populations
Status: Withdrawn
Last Updated: 7 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Similar Trials

Overview

Brief Summary

The purpose of this study is to determine the efficacy, safety, tolerability, and pharmacokinetics (PK) of meropenem-vaborbactam compared to piperacillin/tazobactam for 7 to 14 days in the treatment of hospitalized adults who meet clinical, radiographic, and microbiological criteria for hospital-acquired bacterial pneumonia (HABP) or ventilator-associated bacterial pneumonia (VABP).

Registry

clinicaltrials.gov

Start Date

August 2018

End Date

December 2020

Last Updated

7 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Melinta Therapeutics, Inc.

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Willingness to comply with all study procedures and provide a signed written informed consent prior to any study-specific procedures; however, if unable to do so, the participant's legally authorized representative may provide written consent as approved by institutional-specific guidelines. Participants who are unconscious or considered by the investigator to be clinically unable to consent at Screening and who are entered into the study by the consent of a legally authorized representative, should provide their own written informed consent for continuing to participate in the study as soon as possible on recovery, as applicable in accordance with local regulations.
•Hospitalized male or female participants, ≥18 years of age.
•Females must be surgically sterile or at least 2 years postmenopausal, or if of childbearing potential, have a negative screening urine pregnancy test and be willing to practice sexual abstinence or use an accepted form of contraception with her partner (for example, barrier or hormonal methods) during treatment and for at least 28 days after the last dose of study drug.
•Expectation, in the opinion of the Investigator, that the participant's infection will require treatment with IV antibiotics for a minimum of 7 days.
•Have a confirmed diagnosis of HABP or VABP requiring antibiotic therapy by meeting all clinical, microbiological, and radiographic criteria as defined in the following:
•For HABP participants:
•To meet the study definition of HABP, participants must meet all of the following clinical, microbiological, and radiographic criteria:
•A chest radiograph (chest X-ray \[CXR\], magnetic resonance imaging \[MRI\] or computed tomography \[CT\]) reveals the presence of new or progressive pulmonary infiltrate(s) consistent with bacterial pneumonia within 48 hours prior to randomization.
•Onset of symptoms at least 48 hours after hospitalization or within 7 days after discharge from an inpatient acute or chronic care facility (for example, long-term care, rehabilitation center, hospital, or skilled nursing home).
•Have at least one of the following:

Exclusion Criteria

•Participants who meet any of the following exclusion criteria will not be enrolled in the study:
•History of any severe hypersensitivity to any beta-lactam antibiotic (for example, cephalosporins, penicillins, or carbapenems).
•History of any severe allergic reaction that would preclude the use of either all aminoglycosides or adjunctive gram-positive antimicrobials (that is, allergy to both glycopeptides and oxazolidinones).
•Requirement or anticipated need for additional systemic antibiotic (other than study drug) or antifungal, including prophylactic antimicrobials and antifungals.
•Requirement or anticipated need for more than 14 days of systemic antimicrobial therapy to treat HABP or VABP.
•Known deep-tissue infection (including undrained abscess, meningitis, endocarditis, or osteomyelitis) within 7 days prior to randomization.
•Participant has received more than 24 hours of any potentially effective systemic antibacterial therapy for the current episode of HABP or VABP within 72 hours before randomization. Exceptions:
•Evidence of clinical failure of the current episode of HABP or VABP (for example, worsening signs and symptoms) following at least 48 hours of prior systemic antimicrobial therapy (participants with evidence of clinical failure of piperacillin/tazobactam are not eligible for inclusion), or
•The clinical symptoms and signs of the current episode of HABP or VABP started at least 48 hours after the prior antibacterial therapy was initiated.
•Pulmonary disease that precludes evaluation of a therapeutic response (including, but not limited to, lung cancer, active tuberculosis, cystic fibrosis, granulomatous disease, fungal pulmonary infection, pulmonary embolism, lung abscess, pleural empyema, or post obstructive pneumonia).

Arms & Interventions

Meropenem-Vaborbactam HABP

Participants with a clinical diagnosis of HABP will be treated with meropenem 2 grams (g) and vaborbactam 2 g in 250 milliliters (mL) infused intravenously for 3 hours every 8 hours for 7 days to a maximum of 14 days.

Intervention: Meropenem-Vaborbactam

Piperacillin/Tazobactam HABP

Participants with a clinical diagnosis of HABP will be treated with piperacillin 4 g and tazobactam 0.5 g in 100 mL infused intravenously for 30 minutes every 6 hours for 7 days to a maximum of 14 days.

Intervention: Piperacillin/Tazobactam

Meropenem-Vaborbactam VABP

Participants with a clinical diagnosis of VABP will be treated with meropenem 2 g and vaborbactam 2 g in 250 mL infused intravenously for 3 hours every 8 hours for 7 days to a maximum of 14 days.

Intervention: Meropenem-Vaborbactam

Piperacillin/Tazobactam VABP

Participants with a clinical diagnosis of VABP will be treated with piperacillin 4 g and tazobactam 0.5 g in 100 mL infused intravenously for 30 minutes every 6 hours for 7 days to a maximum of 14 days.

Intervention: Piperacillin/Tazobactam

Outcomes

Primary Outcomes

Percentage of Participants who Achieve a Clinical Outcome of Cure at the Test of Cure (TOC) Visit in the ITT and Clinically Evaluable (CE) Populations

Time Frame: 12-23 days (TOC visit) after first dose of study drug

Rate of Participants with All-Cause Mortality at Day 28 in the Intent-to-Treat (ITT) Population

Time Frame: Day 28

Secondary Outcomes

Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) of Meropenem(Days 1 and 3)
Pharmacokinetics: Maximum Plasma Concentration (Cmax) of Meropenem(Days 1 and 3)
Percentage of Participants with Clinical Outcome of Cure per Pathogen at EOT, TOC, and LFU Visits in the mMITT and ME Populations(1 day (EOT visit), 12-23 days (TOC visit), and 19-30 days (LFU visit) after first dose of study drug)
Pharmacokinetics: Maximum Plasma Concentration (Cmax) of Vaborbactam(Days 1 and 3)
Rate of Participants with All-Cause Mortality at Day 28 in the mMITT, CE, and ME Populations(Day 28)
Percentage of Participants who Survive and Did Not Have a "Major Nonfatal Event" (Treatment-Emergent Events of Acute Respiratory Distress Syndrome, Septic Shock, or Pleural Empyema) up to Day 28 in the ITT and CE Populations(Up to Day 28)
Rate of Participants with All-Cause Mortality at Day 14 in the ITT, microbiological Modified ITT (mMITT), CE, and Microbiologically Evaluable (ME) Populations(Day 14)
Pharmacokinetics: Time to Maximum Plasma Concentration (Tmax) of Meropenem(Days 1 and 3)
Percentage of Participants with Clinical Outcome of Cure at EOT, TOC, and Last Follow Up (LFU) Visits in the ITT, CE, and ME Populations(1 day (EOT visit), 12-23 days (TOC visit), and 19-30 days (LFU visit) after first dose of study drug)
Percentage of Participants with Microbiological Eradication Per-Participant and Per-Pathogen Microbiological Response at EOT and TOC visits in the mMITT and ME Populations(1 day (EOT visit) and 12-23 days (TOC visit) after first dose of study drug)
Pharmacokinetics: Time to Maximum Plasma Concentration (Tmax) of Vaborbactam(Days 1 and 3)
Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) of Vaborbactam(Days 1 and 3)