1347. Omadacycline for Acute Bacterial Skin and Skin Structure Infections: Integrated Analysis of Randomized Clinical Trials
Authors: Abrahamian Fredrick M , Sakoulas George , Tzanis Evan , Manley Amy , Steenbergen Judith N , Das Anita , Eckburg Paul , McGovern Paul 
Published: November 2018

Abstract

Background
Skin infections are a significant medical burden for affected individuals and the healthcare system. The purpose of this investigation was to integrate the findings of two randomized studies of omadacycline (OMC) in ABSSSI.

Methods
OMC in Acute Skin and Skin Structure Infections Study (OASIS)-1 initiated patients on intravenous (IV) OMC or linezolid (LZD) with a possible transition to oral formulation after at least 3 days of IV therapy. OASIS-2 investigated oral-only OMC. Treatment duration in both studies was 7–14 days. Early clinical response (ECR) in the mITT population, the primary endpoint in both studies, was defined as a ≥20% reduction in lesion size at 48–72 hours after treatment initiation. The secondary endpoint was investigator assessment of clinical response (IACR) at post-therapy evaluation (PTE) in the mITT and CE populations, 7–14 days after treatment initiation.

Results
A total of 691 patients receiving OMC and 689 patients receiving LZD were included. The mean age of patients was 45 years, 64% were male, and 83% enrolled at US sites. Infection types: wound infections (46.8%), cellulitis/erysipelas (30.5%), major abscess (22.7%). Median lesion size was 316 cm2 and 304 cm2 in OMC and LZD patients, respectively. S. aureus was detected in 74.6% of patients, of which 43.4% had MRSA. 71% were mono-microbial Gram-positive infections, 15% were poly-microbial Gram-positive infections. OMC showed similar efficacy to LZD for the primary and secondary endpoints, as well as for mono-microbial and poly-microbial infections (figure). Clinical responses were similar across different infection types, lesion sizes, and baseline pathogens. Treatment-emergent adverse events (TEAEs), most mild or moderate, were reported by 51% and 41% of patients receiving OMC or LZD, respectively. Nausea and vomiting were more frequent for OMC patients in the OASIS-2 oral-only study while receiving the loading dose on Day 1 and 2. Serious AEs were reported by 2.3% and 1.9%, respectively. TEAEs leading to study drug discontinuation were reported by 1.7% and 1.5%, respectively.

Conclusion
The integrated analysis of OASIS trials showed that oral and IV omadacycline was effective in the treatment of ABSSSI and was safe and generally well-tolerated by patients.

Disclosures
F. M. Abrahamian, Allergan: Speaker’s Bureau, Speaker honorarium. Melinta: Speaker’s Bureau, Speaker honorarium. Merck: Speaker’s Bureau, Speaker honorarium. Nabriva: Scientific Advisor, Consulting fee. Paratek: Scientific Advisor, Consulting fee. G. Sakoulas, Allergan: Consultant and Speaker, Consulting fee and Speaker honorarium. Sunovion Pharmaceuticals: Speaker, Speaker honorarium. The Medicines Company: Speaker, Speaker honorarium. Paratek Pharmaceuticals: Consultant, Consulting fee. Cidara Therapeutics: Scientific Advisor, Consulting fee. Arsanis Pharmaceuticals: Scientific Advisor, Consulting fee. E. Tzanis, Paratek Pharmaceuticals: Employee, Salary. A. Manley, Paratek Pharmaceuticals: Employee and Shareholder, Salary. J. N. Steenbergen, Paratek Pharmaceuticals: Employee and Shareholder, Salary. A. Das, Achaogen: Consultant, Consulting fee. Cempra: Consultant, Consulting fee. Contrafect: Consultant, Consulting fee. Nabriva: Consultant, Consulting fee. Paratek: Consultant, Consulting fee. Tetraphase: Consultant, Consulting fee. Theravance: Consultant, Consulting fee. Wockhardt: Consultant, Consulting fee. P. Eckburg, Paratek: Consultant, Consulting fee. P. McGovern, Paratek Pharmaceuticals: Employee, Salary.