• Margot Roozekrans, Rutger van der Schrier, Pieter Okkerse, Justin Hay, James F McLeod, and Albert Dahan.
• From the Department of Anesthesiology, Leiden University Medical Center, Leiden, The Netherlands (A.D., M.R., R.v.d.S.); Centre for Human Drug Research, Leiden, The Netherlands (P.O., J.H.); and Galleon Pharmaceuticals Corp., Horsham, Pennsylvania (J.F.M.).
• Anesthesiology. 2014 Sep 1; 121 (3): 459-68.

BackgroundOpioid-induced respiratory depression is potentially lethal. GAL021 is a calcium-activated potassium (BKCa) channel blocker that causes reversal of opioid-induced respiratory depression in animals due to a stimulatory effect on ventilation at the carotid bodies. To assess in humans whether GAL021 stimulates breathing in established opioid-induced respiratory depression and to evaluate its safety, a proof-of-concept double-blind randomized controlled crossover study on isohypercapnic ventilation (study 1) and subsequent double-blind exploratory study on poikilocapnic ventilation and nonrespiratory end points (study 2) was performed.MethodsIn study 1, intravenous low- and high-dose GAL021 and placebo were administrated on top of low- and high-dose alfentanil-induced respiratory depression in 12 healthy male volunteers on two separate occasions. In study 2, the effect of GAL021/placebo on poikilocapnic ventilation, analgesia, and sedation were explored in eight male volunteers. Data are mean difference between GAL021 and placebo (95% CI).ResultsStudy 1: Under isohypercapnic conditions, a separation between GAL021 and placebo on minute ventilation was observed by 6.1 (3.6 to 8.6) l/min (P < 0.01) and 3.6 (1.5 to 5.7) l/min (P < 0.01) at low-dose alfentanil plus high-dose GAL021 and high-dose-alfentanil plus high-dose GAL021, respectively. Study 2: Similar observations were made on poikilocapnic ventilation and arterial pCO2. GAL021 had no effect on alfentanil-induced sedation, antinociception and no safety issues or hemodynamic effects became apparent.ConclusionGAL021 produces respiratory stimulatory effects during opioid-induced respiratory depression with containment of opioid-analgesia and without any further increase of sedation. Further studies are needed to confirm these preliminary data.

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