Safety, tolerability, and pharmacokinetics of oral FM888 in healthy Chinese adults: a Phase I, randomized,...

Targeting adenylate cyclase 1 (AC1) offers a novel, non-opioid strategy for pain treatment. The active moiety of FM888 had been evaluated previously in an older tablet formulation. Phase I study assessed the safety, tolerability, pharmacokinetics, and metabolite profile of a new capsule formulation in healthy Chinese volunteers, with single doses escalated to 1200 mg and multiple doses to 600 mg Q12h-three times the previous maximum-to support Phase II dose selection.

In this single-center, randomized, double-blind, placebo-controlled trial, 86 healthy Chinese adults received single (100-1200 mg; n = 50) or multiple ascending doses (200-600 mg Q12h for 7 days; n = 36). Safety, tolerability, pharmacokinetics, and metabolite profiling were assessed.

FM888 was well tolerated across all doses. The maximum tolerated dose was 1200 mg (single) and 600 mg Q12h (multiple). All adverse events were mild, with no serious events, discontinuations, or dose‑limiting toxicities. Pharmacokinetics were dose‑proportional over 100-1200 mg. Mean terminal half‑life was 12.66-36.49 h, steady state was reached by Day 5 with minimal accumulation (R_{ac, AUC}: 1.34-1.68), and renal excretion of unchanged drug was low (<1.52%). Six major metabolites were identified, formed mainly via hydroxylation, oxidation, and N‑dealkylation.

FM888 demonstrated a favorable safety profile and predictable pharmacokinetics in healthy subjects. These results support the continued clinical development of FM888 and progression to Phase II trials for chronic pain.