Adolor Corporation (NasdaqGM:ADLR) today announced positive, statistically significant top line results from its two Phase 2 studies of ADL5945 in chronic non-cancer pain patients with opioid-induced constipation (OIC). ADL5945, a peripherally-acting mu opioid receptor antagonist, is an investigational drug being evaluated for the treatment of OIC as well as other associated gastrointestinal (GI) complications. Both randomized, double-blind, placebo-controlled studies were identical in design; Study 242 evaluated 0.25 mg and 0.10 mg of ADL5945 administered twice daily (BID) and Study 243 evaluated 0.25 mg of ADL5945 administered once daily (QD).
“Opioid analgesics have become a cornerstone of multimodal therapy for the management of patients who suffer with chronic non-cancer pain,” said Neil Singla, M.D., Department of Anesthesiology, Director, Clinical Research, Huntington Memorial Hospital in Pasadena, California, and lead investigator for the Phase 2 program. “Unfortunately, OIC presents a very serious burden to most patients treated on long-term opioid therapy, and currently there are no adequate therapies to address this common and debilitating condition. The results of these studies of ADL5945 are very encouraging – demonstrating both clinically meaningful effects and a favorable tolerability profile.”
“Our Phase 2 program achieved all of our objectives and validates our view that ADL5945 is a potentially important drug for patients suffering from OIC and related GI symptoms,” said Michael R. Dougherty, Adolor’s President and CEO. “Adolor has extensive experience in this therapeutic area that we will continue to leverage as we now focus on the Phase 3 program. There has been significant interest in ADL5945 and we look forward to sharing these data and initiating pivotal studies as expeditiously as possible.”
Study ResultsTwice-daily Dosing (Study 242) Statistical significance ( p = 0.0003) was achieved for the primary endpoint in the 0.25 mg BID dose group. The primary endpoint of both studies was the change from baseline in the weekly average number of spontaneous bowel movements (SBMs). Response to treatment was dose dependent in Study 242, with an average change from baseline in SBM frequency over the 4-week treatment period of 1.4 SBMs for the placebo group, and 2.0 and 3.4 SBMs for the 0.10 mg and 0.25 mg doses of ADL5945, respectively. Statistical significance was not achieved for the 0.10 mg dose. Statistical significance ( p = 0.005) also was achieved in the 0.25 mg BID dose group for a key secondary endpoint, a responders analysis, with a 56% response rate for the active arm and a 26% response rate for the placebo arm of the study. This translates into a clinically relevant number needed to treat (NNT) of 3.3. For this analysis, responders were defined as those patients who achieved an average weekly frequency of at least three SBMs and an increase of at least one SBM above baseline. Other exploratory endpoints (patients’ global impression of change, BM comfort and satisfaction scores) demonstrated greater improvement as compared to baseline in the ADL5945 0.25 mg treatment group as compared to placebo.