Addex Successfully Completes ADX48621 Phase I Program

30-Jan-2009 - Switzerland

Addex Pharmaceuticals announced the successful completion of two phase I studies of a newly developed modified release formulation of ADX48621. The studies showed that ADX48621, a metabotropic glutamate receptor 5 (mGluR5) negative allosteric modulator (NAM) in development for Parkinson's disease levodopa induced dyskinesia (PD-LID), is safe and well-tolerated in healthy volunteers, including those over 50 years old.

Study ADX48621-102 consisted of two parts. Part One was a randomized, two-way crossover comparison in 12 healthy subjects of the pharmacokinetics, safety and tolerability of the original active pharmaceutical ingredient (API) in capsule with the modified release capsule. Part Two was a double-blind, placebo-controlled, multiple ascending, repeat dose study in 24 healthy subjects using three different doses of the modified release formulation. The study showed that the new formulation achieved satisfactory pharmacokinetics, safety and tolerability with single and repeat dose administration across the dose range planned to be used for the Phase IIa proof of concept study in PD-LID, which is expected to start later this year.

Study ADX48621-103 was a two-period crossover study that evaluated the safety, tolerability and pharmacokinetics of ADX48621 following single oral dosing in older healthy subjects (aged over 50 years) both fasting and following a high fat meal. ADX48621 was well tolerated by this group of older subjects and gave satisfactory drug exposure both in the fasted and fed states.

mGluR5 inhibition has achieved clinical proof of concept in humans with PD-LID and separately in a primate model of PD-LID in studies with another company's mGluR5 inhibitor. Inhibition of mGluR5 has therapeutic potential in multiple indications because mGluR5 is involved in a variety of functions in the central and peripheral nervous systems.

In addition to PD-LID, mGluR5 inhibitors have achieved clinical proof of concept in separate studies in patients with gastroesophageal reflux disease (GERD), migraine and generalized anxiety disorder (GAD). Inhibition of mGluR5 also has potential in Fragile X syndrome. Our lead product, the mGluR5 inhibitor ADX10059, has been shown to have a superior effect to placebo in acute treatment of GERD and migraine headache in Phase IIa testing.

https://www.bionity.com/en/news/94767/addex-successfully-completes-adx48621-phase-i-program.html