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Radiprodil fails in diabetic neuropathy

Forest Laboratories reported that its new drug for neuropathic pain, radiprodil, had failed to achieve its objectives in stage 2 clinical trials. The medicine was developed in partnership with Hungarian drug maker Gedeon Richter, Ltd. It had been hoped that it would be useful for patients with peripheral neuropathy resulting from diabetes.

The drug did not produce significant reductions in patient-reported pain scores for all the dosages tested. Forest says that it and Gedeon Richter will review the findings before making a decision about the further development of radiprodil.

The results reported from a Phase II placebo and positive comparator-controlled, parallel-arm, double-blind, dose-response clinical trial of the novel drug of Ferst, the NR2B-selective NMDA (N-methyl D-aspartate) receptor antagonist, radiprodil (RGH-896), for the treatment of neuropathic pain associated with diabetic peripheral neuropathy (DPNP). Treatment with radiprodil did not show statistically significant or clinically meaningful reductions in mean daily pain scores, the primary endpoint, compared to placebo for any of the dosages studied.

This was the design Forrest labs followed:

1: Experimental	Drug: RGH-896 45 mg TID, capsules, 14 weeks.
2: Experimental	Drug: RGH-896 30 mg TID, capsules, 14 weeks.
3: Experimental	Drug: RGH-896 15 mg TID, capsules, 14 weeks.
4: Active Comparator	Drug: pregabalin 100 mg, TID, capsules, 14 weeks.
5: Placebo Comparator	Drug: placebo TID, capsules, 14 weeks.

And these were the protocol endpoints:

Primary Outcome Measures:

Change in mean daily pain rating [ Time Frame: Baseline to Week 14 ]

Secondary Outcome Measures:

50% reduction in pain [ Time Frame: Baseline to Week 14 ]

Radiprodil is an orally active and selective NMDA NR2B antagonist; based on preclinical pharmacology it was a potential therapeutic agent in treatment of neuropathic pain and possibly other chronic pain conditions. It blocks pain signaling without interacting with other NMDA receptor subtypes thus potentially improving therapeutic index and side effect profile.

No published literature on this ligand to date.

This is again a drawback for the family of NMDA antagonists, a class of compounds looking for diseases since the 80s of last century.

Jan M. Keppel Hesselink, MD, PhD, juli 2010