Adolor Corporation announced positive, statistically significant top line results from its two phase II 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, MD, Department of Anaesthesiology, director, Clinical Research, Huntington Memorial Hospital in Pasadena, California, and lead investigator for the phase II programme. “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 favourable tolerability profile.”

“Our phase II programme 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 III programme. There has been significant interest in ADL5945 and we look forward to sharing these data and initiating pivotal studies as expeditiously as possible.”

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 per cent response rate for the active arm and a 26 per cent 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.

In Study 243, statistical significance (p= 0.01) also was achieved for the primary endpoint. The average change from baseline in SBM frequency over the 4-week treatment period was 1.4 SBMs for the placebo group and 2.6 SBMs for the 0.25 mg ADL5945 treatment group.

Although the proportion of responders was higher in the 0.25 mg treatment group (42.5% vs. 29.3% in placebo), statistical significance was not achieved.

Other exploratory endpoints evaluating changes in bowel function trended in favor of ADL5945 as compared to placebo.

ADL5945 was well tolerated in both studies. The overall number of patients reporting at least one treatment-emergent adverse event was comparable across both studies (ADL5945: 29%; placebo: 26%). There was no evidence of drug-related central opioid withdrawal or reversal of analgesia in any of the ADL5945 treatment groups across both studies.

ADL5945 is a potent, peripherally-acting mu opioid receptor antagonist intended to block the adverse effects of opioid analgesics on the GI tract without compromising centrally-mediated analgesia. Peripheral mu opioid receptors in the GI tract regulate functions such as motility, secretion and absorption. Stimulation of these GI mu opioid receptors by morphine, or other opioid analgesics, disrupts normal gut motility.

Over 250 million opioid prescriptions are written annually in the United States. For those patients treated with prescription opioids for long-term pain management, many will develop constipation, as well as other associated gastrointestinal complications. Currently, there are no FDA-approved therapies to treat opioid-induced constipation in patients with chronic non-cancer pain.

Adolor Corporation is a biopharmaceutical company specializing in the discovery, development and commercialization of novel prescription pain and pain management products.