title: Randomized, double-blind, multicenter phase 2 study comparing the efficacy and safety of oral solithromycin (CEM-101) to those of oral levofloxacin in the treatment of patients with community-acquired bacterial pneumonia.
abstract: Solithromycin, a new macrolide, and the first fluoroketolide in clinical development, with activity against macrolide-resistant bacteria, was tested in 132 patients with moderate to moderately severe community-acquired bacterial pneumonia (CABP) in a multicenter, double-blind, randomized phase 2 study. Patients were enrolled and randomized (1:1) to either 800 mg solithromycin orally (PO) on day 1, followed by 400 mg PO daily on days 2 to 5, or 750 mg levofloxacin PO daily on days 1 to 5. Efficacy outcome rates of clinical success at the test-of-cure visit 4 to 11 days after the last dose of study drug were comparable in the intent-to-treat (ITT) (84.6% for solithromycin versus 86.6% for levofloxacin) and microbiological-intent-to-treat (micro-ITT) (77.8% for solithromycin versus 71.4% for levofloxacin) populations. Early response success rates at day 3, defined as improvement in at least two cardinal symptoms of pneumonia, were also comparable (72.3% for solithromycin versus 71.6% for levofloxacin). More patients treated with levofloxacin than with solithromycin experienced treatment-emergent adverse events (TEAEs) during the study (45.6% versus 29.7%). The majority of TEAEs were mild or moderate gastrointestinal symptoms and included nausea (1.6% for solithromycin; 10.3% for levofloxacin), diarrhea (7.8% for solithromycin; 5.9% for levofloxacin), and vomiting (0% for solithromycin; 4.4% for levofloxacin). Six patients, all of whom received levofloxacin, discontinued the study drug due to an adverse event. Solithromycin demonstrated comparable efficacy and favorable safety relative to levofloxacin. These findings support a phase 3 study of solithromycin for the treatment of CABP. (This study has been registered at ClinicalTrials.gov under registration no. NCT01168713.).
authors.affiliation: Cempra Inc, Chapel Hill, North Carolina, USA.
authors.forename: David
authors.initials: D
authors.lastname: Oldach
authors.forename: Kay
authors.initials: K
authors.lastname: Clark
authors.forename: Jennifer
authors.initials: J
authors.lastname: Schranz
authors.forename: Anita
authors.initials: A
authors.lastname: Das
authors.forename: J Carl
authors.initials: JC
authors.lastname: Craft
authors.forename: Drusilla
authors.initials: D
authors.lastname: Scott
authors.forename: Brian D
authors.initials: BD
authors.lastname: Jamieson
authors.forename: Prabhavathi
authors.initials: P
authors.lastname: Fernandes
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017714:Community-Acquired Infections / Q000188:drug therapy* / Q000382:microbiology; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D064704:Levofloxacin; D018942:Macrolides / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D015242:Ofloxacin / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D018410:Pneumonia, Bacterial / Q000188:drug therapy* / Q000382:microbiology; D016896:Treatment Outcome; D014230:Triazoles / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D018942:Macrolides; D014230:Triazoles; D064704:Levofloxacin; C547755:solithromycin; D015242:Ofloxacin