Community-Acquired Bacterial Pneumonia MedDRA version: 19.0 Level: LLT Classification code 10010120 Term: Community acquired pneumonia System Organ Class: 100000004862
Conditions
Interventions
Product Name: Delafloxacin
Product Code: RX-3341-83
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: Delafloxacin meglumine
CAS Number: 352458-37-8
Current Sponsor code: RX-3
Sponsors
Melinta Therapeutics, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male and female subjects 18 years of age or older. • Patients from a nursing home setting may be enrolled if they are normally ambulatory and are not on enteral feeding 2. Evidence of acute onset of CABP. Subjects must have at least 2 of the following clinical signs and symptoms (new or worsening): • Cough • Production of purulent sputum consistent with a bacterial infection • Difficulty breathing (dyspnea) • Chest pain due to pneumonia and Subjects must also have at least 2 of the following findings: • Fever (oral temperature > 38°C or equivalent) within 24 hours prior to randomization • Hypothermia (oral temperature 100 beats per minute) • Tachypnea (elevated respiratory rate >18 breaths per minute) and Subjects must also have at least 1 of the following findings: • Hypoxemia (oxygen saturation 10,000/mm3 or 15% immature neutrophils (bands), regardless of total peripheral WBC count or leukopenia with WBC < 4500/mm3 3. Presence of lobar, multilobar, or patchy parenchymal infiltrate(s) consistent with acute bacterial pneumonia on a pulmonary imaging study (e.g., chest radiograph [CXR] [posteroanterior and lateral preferred; single view acceptable if conclusive] or computed tomography [CT] of thorax) as per local standard of care within 48 hours before the first dose of study drug. 4. PORT risk class of II, III, or IV or V PSI score greater than 50). Subjects may be initially screened based on meeting CURB-65 score of 2 to 4. PORT risk class II will be limited to 25% of randomized subjects. 5. In the opinion of the investigator, the subject must be a suitable candidate for possible IV to oral switch antibiotic therapy and must also be able to swallow large tablets/capsules intact without crushing. 6. Females of childbearing potential (including females less than 2 years post-menopausal) must have a negative pregnancy test prior to enrollment. Sexually active women and men with partners of childbearing potential must agree to use an acceptable form of contraception, as determined by the investigator (e.g., abstinence, oral contraceptives, double barrier methods, hormonal injectable, transdermal, or implanted contraceptives, tubal ligation, or vasectomy) during participation in the study and through the Follow-up Visit (Day 28). Female partners of male subjects should also use an additional reliable method of contraception, such as spermicide with male or female condoms, cervical sponge, intrauterine device, cervical cap or diaphragm, or oral, implantable, transdermal, or injectable contraceptives during study and through the Follow-up Visit (Day 28). 7. In the opinion of the investigator, the subject must be able and willing to comply with protocol requirements. 8. A written, voluntarily signed informed consent must be obtained from the subject or where allowed by local regulations, legally authorized representative, in accordance with local regulations, before the initiation of any study-related procedures. The subject or legally authorized representative must be able to read and/or understand the informed consent form as required by the legal jurisdiction and the institutional review board/in
Exclusion criteria
Exclusion criteria: 1. Medical history of significant hypersensitivity or allergic reaction to antibiotics of the quinolone or oxazolidinone class or study drug excipients according to the judgment of the investigator. 2. Women who are pregnant or lactating. 3. Any infection expected to require other systemic antibacterial agents in addition to study drug. 4. Receipt of systemic antibiotic therapy in the 7 days before enrollment unless one of the following is documented: • The subject received at least 48 hours of antibiotic therapy for CABP and the clinic notes or pulmonary imaging document treatment failure and/or isolation of a resistant pathogen while on pre-study therapy. • The subject received 1 dose of a single, potentially effective, short-acting antimicrobial drug or a short-acting antimicrobial drug regimen for treatment of the CABP under study within 24 hours of enrollment. (Note: 1 dose of a regimen is defined as the standard therapy for CABP at the study site.) Subjects who received prior antimicrobial drug under this criterion will be limited to no more than 25% of total randomized subjects. 5. Respiratory infection confirmed or suspected to be secondary to hospital-acquired or ventilator-associated pneumonia or that requires treatment in an intensive care setting at the time of informed consent. 6. Intubated at the time of informed consent or clinical presentation with pneumonia that would require invasive mechanical ventilation. 7. Current or suspected diagnosis of: • Viral pneumonia, fungal pneumonia, including Pneumocystis jiroveci pneumonia • Aspiration pneumonia • Other noninfectious causes of pulmonary infiltrates (e.g., pulmonary embolism, hypersensitivity pneumonia, congestive heart failure) • Primary or metastatic lung cancer • Cystic fibrosis • Active or suspected tuberculosis • Empyema (not including sterile parapneumonic effusions) 8. Known anatomical or pathological bronchial obstruction or a history of bronchiectasis or documented Global initiative for chronic Obstructive Lung Disease (GOLD) Stage 4 chronic obstructive pulmonary disease or a history of post obstructive pneumonia. 9. Severely compromised immune systems, e.g.: • Known absolute neutropenia (absolute neutrophil count 20 mg prednisone per day or equivalent) prior to enrollment 10. Known history of Child-Pugh Class B or C liver disease and/or presence or possible signs of significant hepatic disease or alanine aminotransferase (ALT) > 3× the upper limit of normal (ULN). 11. Severe renal disease or creatinine clearance (CrCl) = 29 mL/min using Cockcroft-Gault formula or need for hemodialysis or peritoneal dialysis. 12. Uncorrected hypokalemia at time of enrollment or known uncorrected hypomagnesemia. 13. Ongoing treatment for seizures or untreated history of seizures. 14. History of peripheral neuropathy. 15. History of tendon damage/disorders due to quinolone therapy. 16. Known history of myasthenia gravis. 17. History of post-antibiotic colitis within the last 3 months. 18. Ventricular arrhythmia, and /or ongoing proarrhythmic conditions such as clinically significant bradycardia, acute myocardial ischemia. 19. History of prolonged QT syndrome or mean QTcF (QT interval cor
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to assess the noninferiority of clinical efficacy of intravenous (IV) to oral delafloxacin in adult subjects with community-acquired bacterial pneumonia (CABP) based on Early Clinical Response (ECR) defined as improvement at 96 hours (± 24 hours) after the first dose of study drug compared to IV to oral moxifloxacin in the Intent-to-Treat (ITT) population.;Secondary Objective: • To assess the clinical efficacy of IV to oral delafloxacin in adult subjects with CABP based on Clinical Outcome at the Test of Cure (TOC) visit, 5 to 10 days after the last dose of study drug, compared to IV to oral comparator study drug arm in the CE and ITT populations. • To assess the noninferiority of clinical efficacy of IV to oral delafloxacin in adult subjects with CABP based on ECR compared to IV to oral moxifloxacin in the microbiologic ITT (MITT) population. • To assess the microbiologic response to delafloxacin in respiratory pathogens. • To assess the safety and tolerability of IV to oral delafloxacin in adult subjects with CABP. • To assess the all-cause mortality in adult subjects with CABP on Day 28. • To assess delafloxacin pharmacokinetics (PK) in adult subjects with CABP.;Primary end point(s): The primary efficacy endpoint is the ECR defined as improvement at 96 hours (± 24 hours) after first dose of study drug in at least 2 of the following symptoms: chest pain, frequency or severity of cough, amount and quality of productive sputum and difficulty breathing in the ITT population.;Timepoint(s) of evaluation of this end point: Day 4 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary efficacy endpoints are: • ECR with the addition of improvement in vital signs and no worsening of the 4 symptoms required as Response in the ITT populations. • Clinical Outcome at TOC (Clinically Evaluable [CE] and ITT population) • Clinical outcome at the end of treatment (EOT) • ECR in MITT population • Microbiologic response (ME and MITT) • All-cause mortality (ITT) ;Timepoint(s) of evaluation of this end point: Clinical Outcome at the Test of Cure (TOC) visit, 5 to 10 days after the last dose of study drug All-cause mortality (ITT)- Day 28 96 h ± 24 h for Early Clinical Response | — |
Countries
Argentina, Brazil, Bulgaria, Colombia, Georgia, Germany, Greece, Hungary, Latvia, Poland, Romania, Russian Federation, Serbia, Slovenia, South Africa, Spain, Ukraine, United States
Contacts
Public ContactJerri Swerdlow
Melinta Therapeutics, Inc.
Outcome results
None listed