title: Randomized, double-blind, phase II, multicenter study evaluating the safety/tolerability and efficacy of JNJ-Q2, a novel fluoroquinolone, compared with linezolid for treatment of acute bacterial skin and skin structure infection.
abstract: JNJ-Q2 is a fluoroquinolone with broad coverage including methicillin-resistant Staphylococcus aureus (MRSA). A double-blind, multicenter, phase II noninferiority study treated 161 patients for 7 to 14 days, testing the efficacy of JNJ-Q2 (250 mg, twice a day [BID]) versus linezolid (600 mg, BID) in patients with acute bacterial skin and skin structure infections (ABSSSI). The prespecified criterion for noninferiority was 15%. Primary intent-to-treat analysis was unable to declare noninferiority, as the risk difference lower bound of the 95% confidence interval between treatments was 19% at 36 to 84 h postrandomization for the composite end point of lesion assessment and temperature. Prespecified clinical cure rates 2 to 14 days after completion of therapy were similar (83.1% for JNJ-Q2 versus 82.1% for linezolid). Post hoc analyses revealed that JNJ-Q2 was statistically noninferior to linezolid (61.4% versus 57.7%, respectively; P = 0.024) based on the 2010 FDA guidance, which defines treatment success as lack of lesion spread and afebrile status within 48 to 72 h postrandomization. Despite evidence of systemic disease, <5% of patients presented with fever, suggesting fever is not a compelling surrogate measure of systemic disease resolution for this indication. Nausea and vomiting were the most common adverse events. Of the patients, 86% (104/121) had S. aureus isolated from the infection site; 63% of these were MRSA. The results suggest JNJ-Q2 shows promise as an effective treatment for ABSSSI, demonstrating (i) efficacy for early clinical response (i.e., lack of spread of lesions and absence of fever at 48 to 72 h), and (ii) cure rates for ABSSSI pathogens (especially MRSA) consistent with the historical literature.
authors.affiliation: Furiex Pharmaceuticals Inc, 3900 Paramount Parkway, Suite 150, Morrisville, North Carolina 27560, USA. Paul.Covington@furiex.com
authors.forename: Paul
authors.initials: P
authors.lastname: Covington
authors.forename: J Michael
authors.initials: JM
authors.lastname: Davenport
authors.forename: David
authors.initials: D
authors.lastname: Andrae
authors.forename: William
authors.initials: W
authors.lastname: O'Riordan
authors.forename: Lisa
authors.initials: L
authors.lastname: Liverman
authors.forename: Gail
authors.initials: G
authors.lastname: McIntyre
authors.forename: June
authors.initials: J
authors.lastname: Almenoff
mesh_terms: D000081:Acetamides / Q000009:adverse effects / Q000627:therapeutic use; D000293:Adolescent; D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000627:therapeutic use; D004311:Double-Blind Method; D005260:Female; D024841:Fluoroquinolones / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D000069349:Linezolid; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus / Q000302:isolation & purification; D008875:Middle Aged; D023303:Oxazolidinones / Q000009:adverse effects / Q000627:therapeutic use; D017192:Skin Diseases, Bacterial / Q000188:drug therapy* / Q000382:microbiology; D018461:Soft Tissue Infections / Q000188:drug therapy* / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects / Q000302:isolation & purification; D016896:Treatment Outcome; D014481:United States; D055815:Young Adult
chemical_list: C550935:7-(3-(2-amino-1-fluoroethylidene)-1-piperidinyl)-1-cyclopropyl-6-fluoro-1,4-dihydro-8-methoxy-4-oxo-3-quinolinecarboxylic acid; D000081:Acetamides; D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D023303:Oxazolidinones; D000069349:Linezolid