Seaport Therapeutics has dosed the first subject in the Phase I trial of the Glyphed oral prodrug of agomelatine, GlyphAgo (SPT-320 or Glyph Agomelatine), being developed to treat generalised anxiety disorder (GAD).
The study aims to assess the tolerability, pharmacokinetics, and safety profile of the drug in healthy adult volunteers.
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It will feature several stages, including single-and multiple-ascending dose phases, alongside a food-effect crossover section.
The trial will use both placebo-controlled and open-label designs to compare GlyphAgo with agomelatine.
The company stated that agomelatine has previously demonstrated a significant advantage over a placebo in four independent, third-party, placebo-controlled trials for GAD, offering better tolerability and efficacy than existing standard of care medications.
Despite this, more than 90% of unaltered agomelatine is lost to first-pass liver metabolism, limiting its utility due to the dose-dependent elevation of liver enzymes and the need for ongoing liver function monitoring.
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By GlobalDataGlyphAgo has been designed using the Glyph platform to bypass first-pass liver metabolism, potentially lowering the required dose, reducing liver exposure, and possibly eliminating the need for liver enzyme monitoring.
Seaport Therapeutics clinical development president and chief medical officer Antony Loebel said: “Our Phase I proof-of-concept study could be highly derisking for the GlyphAgo programme, as agomelatine’s efficacy in GAD is already well established.
“The key question is whether we can achieve effective exposure at a lower dose, which would demonstrate GlyphAgo’s ability to avoid agomelatine’s dose-dependent liver issues.”
Preclinical proof-of-concept trials have indicated that GlyphAgo can enhance lymphatic absorption, achieving higher systemic exposure to agomelatine than when the drug is administered alone.
GlyphAgo’s oral dosing has been shown to transport more than 50% of agomelatine through the mesenteric lymphatics, compared to less than 1% for agomelatine’s oral dose alone.
Agomelatine is approved for treating GAD in Australia and for major depressive disorder in both Australia and the European Union.
Seaport has previously reported that its investigational allopregnanolone prodrug, SPT-300, was well tolerated in a Phase I trial.
