Addex Starts Phase I ADX10059 Interaction Study
Geneva, Switzerland, 4 June 2008 – Addex Pharmaceuticals (SWX:ADXN) announced that it has started Study 105, a Phase I clinical trial evaluating the interaction of a new formulation of ADX10059 with proton pump inhibitors and food. A formulation of ADX10059 was selected at the end of May, upon completion of part one of Study 104, a separate ongoing Phase I trial.
In 2007 ADX10059, a metabotropic glutamate receptor 5 (mGluR5) negative allosteric modulator (NAM), achieved clinical proof of concept demonstrating clinically and statistically significant effects in separate Phase IIa trials for gastroesophageal reflux disease (GERD) and migraine. In preparation for Phase IIb testing, starting later this year, Addex developed a more commercial formulation of ADX10059.
The objective for the new formulations is to reduce the rapid absorption and onset of action of ADX10059 while optimizing the exposure profile compared to the original form, the active pharmaceutical ingredient (API) in capsules, which was used in Phase IIa testing. In preclinical studies new formulations of ADX10059 reduced the rapid absorption and improved the exposure profile compared to API filled capsules.
Charlotte Keywood, chief medical officer, said: “In part one of Study 104 both of the new formulations of ADX10059 were well differentiated from the original API filled capsules. We have selected the best new formulation for further study. In addition to studying the interactions of ADX10059 with proton pump inhibitors and food in Study 105, our goal in part two of Study 104 is to show that we are able to achieve the optimized exposure profile in humans.”
Study 105 is a Phase I three-way crossover study of a single-dose of ADX10059, to study potential interactions with proton-pump inhibitors and food. The primary objectives are pharmacokinetics, tolerability and safety. The study in 15 healthy volunteers is scheduled to report data in September 2008.
Study 104 is a two part trial in 36 healthy subjects, the first of which has been completed. Part one was a single-dose, three-way crossover trial in 12 subjects where the pharmacokinetics, safety and tolerability of two new formulations of ADX10059 were compared to the API filled capsule.
Part two of Study 104 is a multiple ascending-dose study of the pharmacokinetics, safety and tolerability of three different doses of the new formulation in 24 additional healthy subjects. Also, to support the selection of the optimal dose range for the Phase IIb studies, the pharmacodynamic efficacy of each dose will be assessed using a human model of GERD, which involves measuring reflux episodes with pH impedance monitoring following a high fat, large volume meal. Data from Study 104 are also scheduled to be reported in September 2008.
Phase IIb trials of ADX10059 are scheduled to start in the fourth quarter of 2008 in GERD and migraine prevention, two blockbuster indications.
Addex Pharmaceuticals Ltd (www.addexpharma.com) discovers and develops allosteric modulators, an emerging class of small molecule therapeutic agents. Allosteric modulation may offer more sophisticated ways to normalize biological signaling compared to classical orthosteric agonist or antagonist drugs. Allosteric, literally translated from its Greek roots, means “other site”. Thus, allosteric modulators bind receptors at sites that are distinct from the binding sites of classical small molecule orthosteric agonist and antagonist drugs.
The most advanced drug candidate, ADX10059, a negative allosteric modulator (NAM) of metabotropic glutamate receptor 5 (mGluR5), recently demonstrated clinically and statistically significant efficacy in separate Phase IIa clinical trials in gastroesophageal reflux disease (GERD) patients and migraine headache patients.
The Addex allosteric modulation discovery and development platform has been additionally validated through collaborations with Merck & Co., Inc. and Johnson & Johnson.
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