title: Efficacy and safety of oral solithromycin versus oral moxifloxacin for treatment of community-acquired bacterial pneumonia: a global, double-blind, multicentre, randomised, active-controlled, non-inferiority trial (SOLITAIRE-ORAL).
abstract: BACKGROUND
  Community-acquired bacterial pneumonia (CABP) is a leading cause of morbidity and mortality, and treatment recommendations, each with specific limitations, vary globally. We aimed to compare the efficacy and safety of solithromycin, a novel macrolide, with moxifloxacin for treatment of CABP.
  
  
  METHODS
  We did this global, double-blind, double-dummy, randomised, active-controlled, non-inferiority trial at 114 centres in North America, Latin America, Europe, and South Africa. Patients (aged ≥18 years) with clinically and radiographically confirmed pneumonia of Pneumonia Outcomes Research Team (PORT) risk class II, III, or IV were randomly assigned (1:1), via an internet-based central block randomisation procedure (block size of four), to receive either oral solithromycin (800 mg on day 1, 400 mg on days 2-5, placebo on days 6-7) or oral moxifloxacin (400 mg on days 1-7). Randomisation was stratified by geographical region, PORT risk class (II vs III or IV), and medical history of asthma or chronic obstructive pulmonary disease. The study sponsor, investigators, staff, and patients were masked to group allocation. The primary outcome was early clinical response, defined as an improvement in at least two of four symptoms (cough, chest pain, sputum production, dyspnoea) with no worsening in any symptom at 72 h after the first dose of study drug, with a 10% non-inferiority margin. The primary analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT-01756339.
  
  
  RESULTS
  Between Jan 3, 2013, and Sept 24, 2014, we randomly assigned 860 patients to receive solithromycin (n=426) or moxifloxacin (n=434). Patients were followed up to days 28-35 after first dose. Solithromycin was non-inferior to moxifloxacin in achievement of early clinical response: 333 (78·2%) patients had an early clinical response in the solithromycin group versus 338 (77·9%) patients in the moxifloxacin group (difference 0·29, 95% CI -5·5 to 6·1). Both drugs had a similar safety profile. 43 (10%) of 155 treatment-emergent adverse events in the solithromycin group and 54 (13%) of 154 such events in the moxifloxacin group were deemed to be related to study drug. The most common adverse events, mostly of mild severity, were gastrointestinal disorders, including diarrhoea (18 [4%] patients in the solithromycin group vs 28 [6%] patients in the moxifloxacin group), nausea (15 [4%] vs 17 [4%] patients) and vomiting (ten [2%] patients in each group); and nervous system disorders, including headache (19 [4%] vs 11 [3%] patients) and dizziness (nine [2%] vs seven [2%] patients).
  
  
  CONCLUSIONS
  Oral solithromycin was non-inferior to oral moxifloxacin for treatment of patients with CABP, showing the potential to restore macrolide monotherapy for this indication.
  
  
  BACKGROUND
  Cempra.
authors: A&L Clinical Research, Miami, FL, USA.
authors: Carlos M
authors: CM
authors: Barrera
authors: Instituto Medico Platense, La Plata, Argentina.
authors: Analia
authors: A
authors: Mykietiuk
authors: Specialized Hospital for Active Treatment of Pneumo-Phthisiatric Diseases, Ruse, Bulgaria.
authors: Hristo
authors: H
authors: Metev
authors: Dr Victor Babes Clinical Hospital for Infectious Diseases and Pneumophthisiology, Craiova, Romania.
authors: Mimi Floarea
authors: MF
authors: Nitu
authors: Delta County Medical Center, Houston, TX, USA.
authors: Najumuddin
authors: N
authors: Karimjee
authors: Centro Medico, Buenos Aires, Argentina.
authors: Pablo Alexis
authors: PA
authors: Doreski
authors: World Wide Clinical Trials, Benoni, South Africa.
authors: Ismail
authors: I
authors: Mitha
authors: St Pantelimon Emergency Clinical Hospital, Bucharest, Romania.
authors: Cristina Mihaela
authors: CM
authors: Tanaseanu
authors: Hospital Vernaza, Guayaquil, Ecuador.
authors: Joseph McDermott
authors: JM
authors: Molina
authors: Medsantrud City Clinical Hospital #23, Moscow, Russia.
authors: Yuri
authors: Y
authors: Antonovsky
authors: Park Medical Center, Witbank, South Africa.
authors: Dirkie Johanna
authors: DJ
authors: Van Rensburg
authors: Department of Emergency Medicine and School of Public Health, University of Alberta, Edmonton, AB, Canada.
authors: Brian H
authors: BH
authors: Rowe
authors: JM Research, Houston, TX, USA.
authors: Jose
authors: J
authors: Flores-Figueroa
authors: Good Doctor Specialist Outpatient Clinics, Cracow, Poland.
authors: Barbara
authors: B
authors: Rewerska
authors: Cempra Pharmaceuticals, Chapel Hill, NC, USA.
authors: Kay
authors: K
authors: Clark
authors: Cempra Pharmaceuticals, Chapel Hill, NC, USA.
authors: Kara
authors: K
authors: Keedy
authors: Cempra Pharmaceuticals, Chapel Hill, NC, USA.
authors: Amanda
authors: A
authors: Sheets
authors: Cempra Pharmaceuticals, Chapel Hill, NC, USA.
authors: Drusilla
authors: D
authors: Scott
authors: Cempra Pharmaceuticals, Chapel Hill, NC, USA.
authors: Gary
authors: G
authors: Horwith
authors: Das Consulting, San Francisco, CA, USA.
authors: Anita F
authors: AF
authors: Das
authors: Cempra Pharmaceuticals, Chapel Hill, NC, USA.
authors: Brian
authors: B
authors: Jamieson
authors: Cempra Pharmaceuticals, Chapel Hill, NC, USA.
authors: Prabhavathi
authors: P
authors: Fernandes
authors: Cempra Pharmaceuticals, Chapel Hill, NC, USA. Electronic address: doldach@cempra.com.
authors: David
authors: D
authors: Oldach
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000627:therapeutic use*; D017714:Community-Acquired Infections / Q000188:drug therapy*; D004311:Double-Blind Method; D005060:Europe; D005260:Female; D024841:Fluoroquinolones / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007843:Latin America; D018942:Macrolides / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D000077266:Moxifloxacin; D009656:North America; D018410:Pneumonia, Bacterial / Q000188:drug therapy*; D013019:South Africa; D014230:Triazoles / Q000009:adverse effects / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D018942:Macrolides; D014230:Triazoles; C547755:solithromycin; D000077266:Moxifloxacin