Abstract Body (Do not enter title and authors here): INTRODUCTION Nicorandil, a dual mechanism anti-anginal used in Europe, Asia, and Australia for >20 years acts as NO donor and K⁺ATP channel opener, providing balanced pre- and afterload vasodilation. Antianginal efficacy matches beta and calcium channel blockers, and long-acting nitrates but without tolerance build-up. Immediate release nicorandil (IR NIC) taken 2-3 times daily with 80% dose release in 45 min, requires high patient adherence. While EU labeling and trials highlight no proarrhythmogenicity lack of recent data remains along with prior reports of potential impact of IR NIC on EKG patterns. Once-daily extended-release nicorandil (ER-NIC) AUX-001 is being developed to improve compliance, symptom control, and QoL for chronic stable angina patients.
ONJECTIVE Examine ER NIC impact on EKG patterns before and after 2 sequential 24h single-dose exposures during fed and fasting status.
METHODS 12-lead EKG was recorded in 16 adult healthy volunteers at baseline. Peak systemic exposure of ER NIC was predicted at 6h post dose. Consequently, postdose EKG was scheduled at 6h after AUX-001 administration, with 24h monitoring. Variables included PR, ST, QT, and TP interval and P, QRS and T wave duration. QT interval was corrected using Bazett’s and Fridericia’s formula.
RESULTS 12-lead EKGs were available on 16 fasting and 15 fed patients. None discontinued due to safety or tolerability. 13 EKGs at baseline on day 1, and 14 on day 8 showed non-clinically relevant abnormalities. No clinically relevant abnormalities were found at baseline or 6h postdose. Mean HR was 58±5.8 and 59±6.2 at baseline and 68±8.2 and 67±6.7 at 6h for fasting and fed. Mean QTc (Bazett) was 395±19 ms pre- and 400±18 ms 6h postdose under fasting and 395±14 and 399±16 ms under fed status. Mean PR interval was 170±22 ms pre- and 160±21 ms 6h post-dose fasting and 169±17 and 158±18 under fed status. CONCLUSION Single dose AUX-001 caused near no QTc changes in healthy volunteers compared to baseline. 6h postdose PR intervals physiologically adjusted to changing HR, and stayed within normal range. Similar to IR NIC, AUX-001 had no discernable effect on EKG patterns during fasting or fed conditions. Findings highlight no relevant AUX-001 effect on electrophysiological safety providing additional safety information supporting development of ER NIC. Findings also confirm previous healthy volunteer trials with IR NIC highlighting no tendency promoting arrhythmia in normal, non-ischemic myocardium.