Phase 1b/2a randomised, double-blind, placebo-controlled trial (GOAL-HF1) evaluating the safety, tolerability, and pharmacokinetics of AC01 — an oral calcium-sensitising inotrope and ghrelin receptor agonist — in adults aged 18–80 with HFrEF (EF ≤40%) across 14 sites in Europe, over 7 days (phase 1b, ascending doses 0.1–3.0 mg BID) and 28 days (phase 2a, 1.0 mg or 3.0 mg BID vs placebo).
No AC01-related serious adverse events occurred in 41 patients receiving AC01; mild-to-moderate treatment-emergent adverse events occurred in 80% of AC01 patients vs 71% of placebo patients. The most common events were hypotension, non-sustained ventricular tachycardia, dyspnoea, hyperglycaemia, dizziness/vertigo, and headache. No symptomatic hypotension, tachyarrhythmia, myocardial ischaemia, conduction abnormalities, or deaths were observed, and there were no apparent effects on high-sensitivity troponin I or NT-proBNP.
- Small sample size (n=58 total; only 26 in phase 2a) limits power to detect efficacy or rare safety signals. - Predominantly male cohort (91%) limits generalisability to women. - Short treatment duration (maximum 28 days) precludes assessment of long-term safety or clinical outcomes.
AC01 appeared safe and well tolerated in this early-phase HFrEF study, with no major harms identified at doses up to 3.0 mg BID over 28 days. Clinicians should note this is an exploratory study only; larger trials are needed before AC01 can be considered for clinical use.
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