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Chest Infections |

Results from a Phase 3 trial in Moderate to Moderately Severe Community Acquired Bacterial Pneumonia (CABP) Treated As Outpatients With a New Oral Macrolide, Solithromycin

David Oldach, MD; Carlos Barrera, MD; Brian Rowe, MD; Floarea Mimi Nitu; Analia Mykietiuk, MD; Hristo Metev, MD; Jessica Laabs, PA-C; Ismail Mitha, MD; Cristina Mihaela Tanaseanu, MD; Joseph McDermott Molina, MD; Yuri Antonovsky, MD; Dirkie Johanna Van Rensburg, MD; Jose Flores, MD; Barbara Sokolowska, MD; Alexis Doreski; Anita Das, PhD; Kay Clark, RN; Brian Jamieson, MD; Amanda Sheets, PhD; Kara Keedy, PhD; Prabhavathi Fernandes, PhD
Author and Funding Information

Cempra, Inc., Chapel Hill, NC


Chest. 2015;148(4_MeetingAbstracts):78A. doi:10.1378/chest.2277759
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Abstract

SESSION TITLE: Chest Infections

SESSION TYPE: Original Investigation Slide

PRESENTED ON: Sunday, October 25, 2015 at 01:30 PM - 03:00 PM

PURPOSE: Macrolides are sometimes used in monotherapy but more often with a cephalosporin for CABP. Pneumococcal macrolide resistance is now at >40% (US). We report the results of an outpatient Phase 3 study with oral solithromycin (soli) a 4th generation macrolide that had sufficient potency to be tested in monotherapy in comparison to moxifloxacin (moxi) in CABP.

METHODS: Patients with CABP, PORT Risk II-IV (NCT#01756339) were double-blind randomized (1:1) to oral soli (5 days) or oral moxi (7 days). Evaluations were performed on Day 4 for early clinical response (ECR), Day 7, Day 12-17 short term follow up (SFU) visit, and Day 28. ECR was defined as improvement in at least 2 of 4 cardinal symptoms (cough, chest pain, dyspnea, sputum production) without worsening in any. Investigators assessed success at SFU. Primary objectives were demonstration of non-inferiority (10% NI margin) in ECR (intent-to-treat (ITT) population) and in success at SFU (ITT and clinically evaluable (CE) populations).

RESULTS: 860 patients from 16 countries were randomized (ITT population), 90% met key protocol criteria (CE population). 50.7% of soli patients had PORT III/IV disease (11.3% PORT IV), vs. 48.6% of moxi patients (8.8% PORT IV). Soli was non-inferior to moxi in the ITT population in ECR (78.2% vs. 77.9%) and SFU success (84.5% vs. 86.6%) and in the CE-SFU population (88.1% vs. 91.3%). ECR success was higher among soli patients ≧ age 75 (83.9% vs 69.8%, n=125). Soli had safety comparable to moxi in occurrence of adverse events (AEs) (36.6% vs 35.6%), study-drug related AEs (10.1% vs 12.5%), Serious AEs (6.6% vs 6.3%; none attributed to study drug) and deaths (1.4% vs 1.4%). Grade 4 ALTs (>8xULN) were observed in 5 moxi patients and 2 soli patients (without symptoms or bilirubin elevation). Two episodes of C. difficile diarrhea were diagnosed in moxi recipients. 15 patients had S. pneumoniae (Spn) bacteremia; treatment was successful in the majority, with equal success rates (soli vs moxi). Among all Spn patients, treatment was successful at SFU in 85.3 % (soli) and 87.3 % (moxi) of patients. 100% success at SFU was observed in all soli patients with macrolide-resistant Spn at SFU.

CONCLUSIONS: Oral soli was non-inferior to moxi for treatment of CABP. Safety outcomes were comparable, although moxi was associated with more Grade 4 ALT elevation and C. difficile diarrhea.

CLINICAL IMPLICATIONS: Solithromycin, a potent new macrolide, has potential for use as monotherapy in moderate to moderately severe CABP, even on the outpatient basis.

DISCLOSURE: David Oldach: Employee: Employee of Cempra, which is developing solithromycin Carlos Barrera: Other: As part of IRB and ethics committee approved trial sponsored by Cempra, Inc., institution received compensation for execution of trial protocol Brian Rowe: Other: As part of IRB and ethics committee approved trial sponsored by Cempra, Inc., institution received compensation for execution of trial protocol Floarea Mimi Nitu: Other: As part of IRB and ethics committee approved trial sponsored by Cempra, Inc., institution received compensation for execution of trial protocol Analia Mykietiuk: Other: As part of IRB and ethics committee approved trial sponsored by Cempra, Inc., institution received compensation for execution of trial protocol Hristo Metev: Other: As part of IRB and ethics committee approved trial sponsored by Cempra, Inc., institution received compensation for execution of trial protocol Jessica Laabs: Other: As part of IRB and ethics committee approved trial sponsored by Cempra, Inc., institution received compensation for execution of trial protocol Ismail Mitha: Other: As part of IRB and ethics committee approved trial sponsored by Cempra, Inc., institution received compensation for execution of trial protocol Cristina Mihaela Tanaseanu: Other: As part of IRB and ethics committee approved trial sponsored by Cempra, Inc., institution received compensation for execution of trial protocol Joseph McDermott Molina: Other: As part of IRB and ethics committee approved trial sponsored by Cempra, Inc., institution received compensation for execution of trial protocol Yuri Antonovsky: Other: As part of IRB and ethics committee approved trial sponsored by Cempra, Inc., institution received compensation for execution of trial protocol Dirkie Johanna Van Rensburg: Other: As part of IRB and ethics committee approved trial sponsored by Cempra, Inc., institution received compensation for execution of trial protocol Jose Flores: Other: As part of IRB and ethics committee approved trial sponsored by Cempra, Inc., institution received compensation for execution of trial protocol Barbara Sokolowska: Other: As part of IRB and ethics committee approved trial sponsored by Cempra, Inc., institution received compensation for execution of trial protocol Alexis Doreski: Other: As part of IRB and ethics committee approved trial sponsored by Cempra, Inc., institution received compensation for execution of trial protocol Anita Das: Consultant fee, speaker bureau, advisory committee, etc.: Statistical consultant to Cempra, which is developing solithormycin Kay Clark: Employee: Employee of Cempra, which is developing solithromycin Brian Jamieson: Employee: Employee of Cempra, which is developing solithromycin Amanda Sheets: Employee: Employee of Cempra, which is developing solithromycin Kara Keedy: Employee: Employee of Cempra, which is developing solithromycin Prabhavathi Fernandes: Employee: CEO of Cempra, Inc., which is developing solithromycin

Solithromycin is an antibiotic in clinical development for the treatment of community-acquired bacterial pneumonia.


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