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.
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
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