CombinatoRx, Inc (CAMBRIDGE, Massachusetts), pioneering the new field of synergistic combination pharmaceuticals, announced disappointing preliminary results of its multicenter, randomized, blinded, placebo-controlled, clinical trial of CRx-150, a synergistic cytokine modulator combining the antidepressant amoxapine and the cardiovascular drug dipyridamole, in patients with rheumatoid arthritis (RA). The phase II trial compared CRx-150 plus a disease-modifying antirheumatic drug (DMARD) with placebo plus DMARD (control) in 64 subjects with established RA and moderate disease activity.

At day 42 in the preliminary analysis, CRx-150 demonstrated statistically significant effects on DAS28 composite measure of disease activity and pain, activity on ACR20, but no effect on C-reactive protein, the primary endpoint in the trial. The CRx-150 group scored -0.51 on the DAS28, significantly better than the -0.05 in the control group (P = .05). For CRx-150-treated subjects, median baseline pain, as measured on a visual analogue scale (VAS), went from 63 mm to 37 mm at day 42, a median change of -11.5 mm, whereas placebo went from 64.5 mm to 59.5 mm at day 42, a median change of -2 mm (P = .04).

CombinatoRx has decided to terminate further development of CRx-150 in favor of its leading RA product candidate CRx-102, an oral synergistic drug candidate containing dipyridamole and an unconventionally low dose of prednisolone 3 mg. CRx-102 works through a novel mechanism of action in which dipyridamole selectively amplifies prednisolone's anti-inflammatory and immunomodulatory activities without replicating its side effects. CRx-102 is being advanced into two phase IIb studies. One randomized, double-blind, placebo-controlled, 98-day study with a 1-year safety extension will involve approximately 600 RA subjects at approximately 100 sites in the US, Canada, Europe, and South America. The other phase IIb study will involve approximately 250 subjects with osteoarthritis of the knee and will be conducted at approximately 35 sites in the US and Canada.

—A. Techman