Addex Pharmaceuticals has announced that the company has decided to end prematurely the migraine prevention study 206.
Routine safety monitoring of blinded data in study 206 has revealed an incidence of abnormalities of liver function tests that is higher than expected in this population. The abnormalities are apparent from day 28 of dosing but the incidence and severity appear to increase progressively with increasing duration of participation in the study. Despite the fact that the treatment allocation remains blinded, Addex is of the opinion that the risk to benefit profile of the drug observed in the study is not sufficiently favourable to justify continuation of the trial and is terminating the study in the best interests of patient safety. The full benefit risk profile of ADX10059 in this indication will be evaluated once the study has been unblinded and all efficacy and safety data have been analyzed.
"No liver function abnormalities have been seen in any of the previously reported clinical trials, several of which explored higher doses, including the recently reported study ADX10059-204, a 2-week study of monotherapy in 103 GERD patients. Study 205 a 4-week study of ADX10059 as an add-on therapy to PPIs in GERD patients, is due to un-blind around the end of the year. The data from that study will also help in the determination of the overall safety profile of the drug," said Charlotte Keywood, chief medical officer.
"This is an unfortunate and unexpected development," said Vincent Mutel, chief executive officer. "We are working to rapidly understand the relationship of the liver function abnormalities to the treatment and the implications for development of ADX10059 in migraine prevention and other indications."
Study ADX10059-206 is a double-blind, placebo-controlled, dose range finding, multi-centre European phase-IIb trial in 240 patients who suffer from three or more migraine attacks per month. Following a one-month baseline period, patients take study medication for three months. The primary endpoint compares migraine frequency and severity in the last month of treatment with the baseline. The data are being un-blinded and will be analyzed and any indications of efficacy will be reported in early January.
Study ADX10059-205 is a double-blind, placebo-controlled, multi-centre US and European phase-IIb trial in 280 GERD patients who are partial responders to proton pump inhibitors (PPIs). In Study 205 ADX10059 is being used as an add-on therapy to the patients' existing PPI treatment. There was a baseline symptom evaluation period followed by four weeks of administration of twice-daily ADX10059 (50mg, 100mg or 150mg). The primary endpoint is patient reported symptom control compared to baseline. Data are expected to be communicated in early January.
Study ADX10059-204 was a double-blind, placebo-controlled, multi-centre European phase-IIb trial in 103 GERD patients known to respond well to PPIs. There was a two-week baseline symptom evaluation period followed by two weeks of administration of ADX10059 120 mg twice daily. ADX10059 achieved the co-primary endpoints of patient reported symptom control compared to baseline and the effects of ADX10059 on lower esophageal sphincter (LES) function as well as multiple secondary endpoints. There were no serious adverse events in the study and safety monitoring parameters were within normal limits. Mild or moderate adverse events included dizziness, vertigo and sleep disturbance.
ADX10059 is a metabotropic glutamate receptor 5 (mGluR5) negative allosteric modulator (NAM). Glutamate overstimulation is thought to contribute via different mechanisms to pathology in both migraine and GERD.
Addex Pharmaceuticals discovers and develops allosteric modulators for human health. Allosteric modulators are a different kind of orally available small molecule therapeutic agent, which we believe will offer a competitive advantage over classical drugs.