1374. Integrated Safety Summary of Omadacycline: A Novel Aminomethylcycline Antibiotic
Session: Poster Abstract Session: Novel Agents
Friday, October 5, 2018
Room: S Poster Hall
Posters
  • IDWeek Poster 1374.pdf (181.6 kB)
  • Background:

    Omadacycline (OMC) is a novel aminomethylcycline with activity against Gram-positive, many Gram-negative, anaerobic, and atypical pathogens. It is in clinical development as once-daily oral (PO) and intravenous (IV) monotherapy for acute bacterial skin and skin structure infections (ABSSSI) and community-acquired bacterial pneumonia (CABP). Cumulative safety results from phase 3 clinical trials are reported.

    Methods:

    This pooled safety analysis is based on 2150 subjects: OASIS-1 (N=645), OASIS-2 (N=735) in ABSSSI; OPTIC (N=770) in CABP. Comparators were linezolid (LZD) 600 mg IV then PO in ABSSSI (n=689); moxifloxacin (MOX) 400 mg IV then PO in CABP (n=388). Safety parameters included treatment-emergent adverse events (TEAEs), laboratory evaluations, vital signs, and electrocardiogram (ECG) findings.

    Results:

    1073 subjects received OMC: 705 received OMC IV then PO (ABSSSI, n=323; CABP, n=382); 368 received OMC PO only for ABSSSI. Overall, 60.6% were male and 91.6% white; mean age ranges were 44.7–45.1 and 60.9–62.1 years in ABSSSI and CABP studies, respectively. TEAEs were observed in 47.5% (OMC), 41.2% (LZD), and 48.5% (MOX) of subjects, with gastrointestinal events the most common TEAEs. Serious TEAEs were low (3.6% OMC, 1.9% LZD, 6.7% MOX). Nausea (14.9% OMC, 8.7% LZD, 5.4% MOX) and vomiting (8.3% OMC, 3.9% LZD, 1.5% MOX) were the most frequently reported TEAEs. Diarrhea was observed in 2.4% OMC, 2.9% LZD, and 8.0% MOX subjects, with no cases of Clostridium difficile in OMC-treated subjects. Most TEAEs were mild to moderate and did not result in study drug discontinuation (3.1% OMC, 1.5% LZD, 7.0% MOX); 4 OMC, 1 LZD, and 0 MOX subjects discontinued for nausea and vomiting. Frequency of hepatic TEAEs was similar for OMC, LZD, and MOX: 4.3% OMC, 4.1% LZD, and 4.5% MOX subjects had post-baseline ALT >3x upper limit of normal. Vital signs and ECGs had comparable clinically notable values post-baseline in each treatment group. Known tetracycline class adverse events such as fungal infections were similar in all groups.

    Conclusion:

    Pooled analyses demonstrate a favorable OMC safety profile, consistent with its tetracycline heritage. OMC was generally well-tolerated in subjects with ABSSSI and CABP, with infrequent treatment discontinuations. 

     

    Steven Opal, MD1, Thomas M. File Jr., MD2,3, Tom Van Der Poll, MD, PhD4,5, Paul McGovern, MD6, Evan Tzanis, BA6 and Surya Chitra, PhD, MBA6, (1)Warren Alpert Medical School, Brown University, Providence, RI, (2)Northeast Ohio Medical University, Rootstown, OH, (3)Summa Health, Akron, OH, (4)Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands, (5)Division of Infectious Diseases, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands, (6)Paratek Pharmaceuticals, Inc., King of Prussia, PA

    Disclosures:

    S. Opal, None

    T. M. File Jr., BioMerieux: Consultant , Consulting fee . Curetis: Consultant , Consulting fee . Melinta Therapeutics: Consultant , Consulting fee . Merck: Consultant , Consulting fee . Motif Bio: Consultant , Consulting fee . Nabriva Therapeutics: Consultant and Investigator , Consulting fee and Research grant . Paratek Pharmaceuticals: Consultant , Consulting fee . Pfizer: Consultant , Consulting fee .

    T. Van Der Poll, Paratek Pharmaceuticals: Consultant , Consulting fee .

    P. McGovern, Paratek Pharmaceuticals: Employee , Salary .

    E. Tzanis, Paratek Pharmaceuticals: Employee , Salary .

    S. Chitra, None

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