1886. Cardiac Safety of Omadacycline in the IV/oral Phase 3 Acute Bacterial Skin and Skin Structure Infection (ABSSSI) and in the IV/oral Phase 3 Community-acquired Bacterial Pneumonia (CABP) Studies
Session: Poster Abstract Session: Clinical Study with New Antibiotics and Antifungals
Saturday, October 7, 2017
Room: Poster Hall CD
Posters
  • ID Week Cardiac Poster_Final_02OCT2017.pdf (403.2 kB)
  • Background: Omadacycline (OMC) is a novel aminomethylcycline antibiotic. In Phase 1 studies asymptomatic increases in heart rate (HR) were observed following OMC dosing in healthy volunteers. In vitro studies showed OMC inhibits binding of acetylcholine to the M2-subtype of the muscarinic receptor, resulting in a nonadrenergic, vagolytic effect. In a thorough QT study, OMC had no clinically meaningful effect on the QTc interval or any other ECG parameters. Phase 3 studies of OMC as an oral (PO) and intravenous (IV) monotherapy for ABSSSI and CABP were recently completed.

    Methods: In the ABSSSI and CABP studies OMC was dosed 100 mg IV q12h × 2 doses then 100 mg IV q24h. After ≥ 3 days IV therapy subjects could switch to 300 mg PO q24h for a total treatment duration of 7-14 days. The comparator for ABSSSI was linezolid (LZD) 600 mg IV/PO q12h and for CABP moxifloxacin (MOX) 400 mg IV/PO q24h. HR and blood pressure (BP) were measured at screening, before and after the first 3 doses and at all visits through Post Therapy Evaluation. A 12-lead ECG was performed at screening, before and after doses 1 and 3, on Day 7 and at the end of treatment. Adverse events (AEs) were monitored through a Final Follow-up visit 30-37 days after first dose.

    Results: The safety populations included 323 OMC and 322 LZD subjects in ABSSSI and 382 OMC and 388 MOX subjects in CABP. In the ABSSSI study the incidence of cardiac treatment-emergent AEs (TEAEs) was 4 (1.2%) and 3 (0.9%) and of tachycardia TEAEs specifically was 1 (0.3%) and 0 in OMC and LZD subjects, respectively. In the CABP study the incidence of cardiac TEAEs was 15 (3.9%) and 20 (5.2%) and tachycardia was 4 (1.0%) and 3 (0.8%) in OMC and MOX subjects, respectively. In both studies HR tended to decline over time in OMC and comparator groups. At any given post-Baseline time point, the mean HR in OMC subjects was slightly higher than comparator subjects (difference of < 6 bpm from LZD in ABSSSI, < 3 bpm from MOX in CABP), with no clinically significant difference in outlying values. No clinically meaningful changes in BP or ECG parameters were noted in either study.

    Conclusion: OMC inhibition of acetylcholine binding to the M2-subtype of the muscarinic receptor was not associated with clinically meaningful effects on HR, BP, ECG or cardiac safety in ABSSSI or CABP subjects.

    Borje Darpo, MD, PhD1, Evan Tzanis, BA2, Lynne Garrity-Ryan, PhD3, Amy Manley, BS2, Paul McGovern, MD2 and Evan Loh, MD3, (1)Karolinska institute, Stockholm, Sweden, (2)Paratek Pharmaceuticals, Inc., King of Prussia, PA, (3)Paratek Pharmaceuticals, King of Prussia, PA

    Disclosures:

    B. Darpo, iCardiac Technologies: Shareholder , Stock Options

    E. Tzanis, Paratek Pharmaceuticals: Employee and Shareholder , Salary

    L. Garrity-Ryan, Paratek Pharmaceuticals: Employee and Shareholder , Salary

    A. Manley, Paratek Pharmaceuticals: Employee and Shareholder , Salary

    P. McGovern, Paratek Pharmaceuticals: Employee and Shareholder , Salary

    E. Loh, Paratek Pharmaceuticals: Board Member , Employee and Shareholder , Salary

    Findings in the abstracts are embargoed until 12:01 a.m. PDT, Wednesday Oct. 4th with the exception of research findings presented at the IDWeek press conferences.