Effect of Omadacycline on Cardiac Parameters in ABSSSI and CABP

This article is part of Infectious Disease Advisor’s in-depth coverage of IDWeek 2017™, which took place in San Diego, CA. Our staff will be reporting on the latest treatment advancements and research initiatives for skin infections. Check back regularly for highlights from IDWeek 2017.

There are no clinically significant differences on cardiac parameters in patients with acute bacterial skin and skin structure infection (ABSSSI) or community-acquired bacterial pneumonia (CABP) treated with omadacycline (OMC), linezolid (LZD), or moxifloxacin (MOX), according to 2 phase 3 studies presented at IDWeek 2017, held October 4-8, in San Diego, California.

“In vitro studies showed OMC inhibits binding of acetylcholine to the M2-subtype of the muscarinic receptor, resulting in a nonadrenergic, vagolytic effect,” noted the investigators. “In a thorough QT study, OMC had no clinically meaningful effect on the QTc interval or any other electrocardiography (ECG) parameters.”

Investigators presented results of the phase 3 OPTIC and OASIS-1 studies, which featured people with CABP and ABSSSI, respectively. Specifically, researchers evaluated the effect of various treatment strategies for these conditions on heart rate, blood pressure, ECG parameters, and treatment-emergent adverse events (TEAEs). Participants in each study were provided intravenous (IV) OMC (100 mg every 12 hours times 2 doses, then 100 mg every 24 hours) followed by oral OMC (300 mg every 24 hours; treatment duration 7-14 days) after ≥3 days (ABSSSI: n=323 and CABP: n=382). In the ABSSSI study, LZD was the comparator medication (n=322), with a dosing of 600 mg IV/oral every 12 hours vs MOX (n=388) for the CABP study, with a dosing of 400 mg IV/oral every 24 hours.

In the ABSSSI study, a total of 4 TEAEs occurred among patients receiving OMC vs 3 TEAEs in the LZD group. Conversely, cardiac TEAEs occurred at an incidence rate of 15 (3.9%) and 20 (5.2%) among patients receiving OMC and MOX, respectively, in the CABP study.

Heart rate declined in both the ABSSSI and CABP studies, with no significant difference among medications. The average heart rate among study participants receiving OMC was higher than in those receiving LZD and MOX (difference of <6 bpm from LZD in ABSSSI and <3 bpm from MOX in CABP). Despite this difference, the investigators could not establish significance. Additionally, researchers observed no statistically significant changes in ECG or blood pressure values in either study group.

“OMC was not associated with clinically relevant changes in cardiac safety, heart rate, blood pressure, or ECG values in OPTIC or OASIS-1,” concluded the investigators.

Disclosures: The OPTIC and OASIS-1 studies were funded by Paratek Pharmaceuticals, Inc. Borje Darpo, MD, PhD, is a shareholder of stock options of iCardiac Technologies. The remaining authors are employees of Paratek Pharmaceuticals, Inc.

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Reference

Darpo B, Tzanis E, Garrity-Ryan L, Manley A, McGovern P, Loh E. 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. Presented at: IDWeek 2017; October 4-8, 2017; San Diego, CA. Poster 1886.