CombinatoRx Says Arthritis Trial Misses Primary Endpoint

CombinatoRx has announced preliminary results of a Phase II clinical trial studying CRx-139 (a synergistic combination of 3 mg of prednisolone and the antidepressant paroxetine) and 3 mg of prednisolone alone in patients with rheumatoid arthritis (RA).

This trial was a multicenter, blinded, randomized study evaluating the effectiveness of two doses of CRx-139 (containing 10 or 20 mg of paroxetine with prednisolone) and 3 mg of prednisolone in subjects with active RA who were on stable disease modifying anti-rheumatic drug therapies. The primary endpoint was an American College of Rheumatology (ACR) score of 20 at day 70. Other endpoints of the trial included ACR 50 and ACR 70 scores.

One purpose of the trial was to determine the effect of 3 mg of prednisolone alone in RA and to contrast this effect with the activity previously reported with CRx-102, a synergistic combination of very low dose prednisolone and dipyridamole. The results with 3 mg prednisolone confirm that the anti-inflammatory benefits previously observed in three Phase IIa clinical trials with CRx-102 are due to the synergistic activity of CRx-102's components, as opposed to an effect derived from the prednisolone component alone. Another purpose of the trial was to evaluate the activity of CRx-139 compared with prednisolone alone. CRx-139 did not show statistical significance on the primary endpoint of the trial, but it did show statistical significance on multiple other endpoints, requiring further analysis.

Comparison of treatment outcomes for CRx-102 versus low-dose prednisolone alone shows that CRx-102 is superior to the 3mg of prednisolone alone. Importantly, subjects in the past and present studies had the same demographics and similar baseline disease status, allowing for comparison of study results.

In this trial, CRx-139 was generally well tolerated and there were no drug-related serious adverse events reported for subjects treated with CRx-139. The most common adverse events observed with CRx-139 that occurred with a frequency of greater than 5 percent were headache and nausea, which are known side effects of paroxetine, one of the two components of CRx-139.