Growth hormone-releasing activity of hexarelin in humans - a dose-response study

Phase 1 study conducted in London in collaboration with the Deghenghi group (Europharm), responsible for the original development of hexarelin (Hex) — synthetic hexapeptide His-D-2-Me-Trp-Ala-Trp-D-Phe-Lys-NH₂ that became one of the first GHRPs clinically characterized in humans. The objective was to establish the dose-response curve and pharmacokinetics in healthy volunteers.

The design was double-blind, placebo-controlled and rising-dose. Twelve healthy male adult volunteers received single intravenous boluses of hexarelin at doses of 0.5, 1 and 2 µg/kg, plus placebo, in separate sessions. The primary outcome was the plasma GH time curve; secondary outcomes included cortisol, prolactin, ACTH, IGF-1, glycemia, LH, FSH, TSH and tolerability.

The GH increase was dose-dependent, peaking at ~30 minutes and returning to baseline by 240 minutes, with functional half-life of ~55 minutes. Mean Cmax was 3.9, 26.9, 52.3 and 55.0 ng/mL for placebo, 0.5, 1 and 2 µg/kg, respectively — demonstrating response saturation from 1 µg/kg upward. Estimated ED50 was ~0.5 µg/kg. Importantly, IGF-1 did not change acutely, and glycemia, LH, FSH and TSH remained unchanged. There was mild elevation of prolactin, cortisol and ACTH — a characteristic profile that distinguishes hexarelin from more selective secretagogues like ipamorelin.

This work is a classic reference for hexarelin pharmacology, frequently cited to ground clinical and diagnostic protocols. It established hexarelin as a potent and fast-acting GH secretagogue, but also documented the characteristic side effect — elevation of adrenal and lactotropic axes — that led to its clinical disuse in favor of cleaner analogs.