Table 3.
Summary table of phase II and III clinical trials of plazomicin.
| Trial |
Phase |
Indication |
Primary outcome |
Results No. patients (%) |
|
|---|---|---|---|---|---|
| P2-01 | II | cUTI | Microbiological eradication at TOC | PLZ | LVX |
| MITT population: | 31 (60.8) | 17 (58.6) | |||
| Difference: | 2.2% (95% CI: –22.9 to 27.2%) | ||||
| ME population: | 31 (88.6) | 17 (81.0) | |||
| Difference: | 7.6% (95% CI: –16.0 to 31.3%) | ||||
| EPIC | III | cUTI | Composite cureb | PLZ | MEM |
| Treatment day 5: | 168 (88.0) | 180 (91.4) | |||
| Difference: | –3.4% (95% CI: –10.0 to 3.1%) | ||||
| TOC visit: | 156 (81.7) | 138 (70.1) | |||
| Difference: | 11.6% (95% CI: 2.7 to 20.3%) | ||||
| CARE | III | CRE infectiona | Composite day 28 all-cause mortality and disease related complications | PLZc | CSTc |
| MMITT population: | 4 (24) | 10 (50) | |||
| Difference: | –26% (95% CI: –55 to 6%) | ||||
Dosages for trial drugs were: plazomicin 15 mg/kg intravenously (IV) once daily with therapeutic drug monitoring for maintenance dosing, levofloxacin 750 mg IV once daily, meropenem 1 g IV q 8 h, and colistin 5 mg/kg IV loading dose with 5 mg/kg per day IV divided into 8–12 h dosing intervals maintenance dosing.
P2-01: [ClinicalTrials.gov identifier: NCT01096849], Connolly et al.,43 EPIC44, CARE.45
Included blood stream infection, hospital-acquired pneumonia, and ventilator-associated pneumonia.
Composite cure defined as both clinical cure and microbiological cure. Clinical cure was defined as reduced symptom severity at day 5/end of the infusion, complete symptom resolution at the TOC visit, or return to patient baseline prior to urinary tract infection. Microbiological eradication was defined as reduction in causative pathogen to <104 CFU/mL.
Given in combination with either meropenem 2 g IV q 8h (3 h extended-interval infusion) or tigecycline 100–200 mg IV loading dose with 50–100 mg IV q 12 h maintenance dosing.
CFU, colony-forming units; CI, confidence interval; CRE, carbapenem-resistant Enterobacteriaceae; CST, colistin; cUTI, complicated urinary tract infection; LVX, levofloxacin; ME, microbiologically evaluable; MEM, meropenem; MITT, modified-intent-to-treat; MMITT, microbiologic MITT; PLZ, plazomicin; TOC, test-of-cure.