A phase2, randomized, double-blind, double-dummy study of IV sulopenem with switch to oral sulopenem etzadroxil compared to ceftriaxone with switch to amoxicillinclavulanate in subjects with community-acquired pneumonia requiring hospitalization

Abstract number: P1225

Soma K., Silvia A.M., Hazra A., Puttagunta S., Durham K., Kirby D.

Objectives: Assess efficacy of 7–10 days (d) treatment for 3 regimens: single dose IV sulopenem (S) 600 mg with switch to oral sulopenem etzadroxil (SE) 1,000 mg BID (S-SIV); 2 d minimum IV S 600 mg BID with switch to SE 1,000 mg BID (S-MIV); and 2 d minimum IV ceftriaxone 2 gm QD with switch to amoxicillin/clavulanate suspension (800 mg/10 mL) BID (COMP).

Methods: Adult subjects were enrolled if presenting in Pneumonia Severity Index (PSI) risk class III-IV and with 3 symptoms/signs of pneumonia. IV treatment could continue >2 days if needed and oral switch was allowed after: a minimum 2 d on IV treatment (active or placebo); improved cough and dyspnoea; afebrile or improved fever; improved WBC. The primary endpoint was the proportion of clinically evaluable (CE) subjects cured at the test of cure (TOC) visit, 7–14 days after end of treatment. Safety was assessed in the intent to treat group.

Results: Although a greater number of subjects was initially planned, 33 subjects were enrolled: 10, 11, and 12, respectively, for S-SIV, S-MIV, and COMP. Baseline demographic characteristics were similar. Ten, 8, and 8 subjects, respectively, met CE criteria. PSI risk class in the CE population for S-SIV, S-MIV, and COMP was III for 9, 5, and 6 subjects, and IV for 1, 3, and 2 subjects, respectively. Twenty-three subjects completed and 10 discontinued, with median treatment duration of 8.5, 10.0, and 8.0 d for S-SIV, S-MIV, and COMP, respectively. Subjects not assessed due to early discontinuation were considered failures. Results of the primary efficacy analysis are presented in the table. Cure rates for the CE population at TOC were 90%, 88%, and 63%, for S-SIV, S-MIV, and COMP, respectively.

Adverse drug reactions (ARs) occurred in 4/10 (40%), 3/11 (27%), and 4/12 (25%) subjects for S-SIV, S-MIV, and COMP, respectively, with gastrointestinal (GI) ARs reported in 2 (20%), 2 (18%), and 3 (25%) subjects, respectively. Four subjects (1 S-SIV, 3 COMP) discontinued for adverse events (AEs), one of which was an AR (COMP). Four subjects (2 S-MIV, 2 COMP) reported serious AEs, one of which was an AR (COMP). No deaths were reported.

Conclusions: These efficacy results were not statistically significant due to the small numbers enrolled; however, both S/SE regimens appeared to be comparable to COMP. ARs were comparable in all groups, including GI ARs. S/SE regimens should be investigated further for subjects with moderate to severe community acquired pneumonia.

Clinical response at TOC, CE population