This excerpt taken from the ADLR 10-Q filed Oct 28, 2008.
We maintain a portfolio of product candidates to treat opioid bowel dysfunction (OBD), a condition that often results from chronic use of opioid analgesics to treat persistent pain conditions. These OBD product candidates include alvimopan, alvimopan/opioid analgesic combinations and ADL7445. In September 2008, we announced that Glaxo returned to us all worldwide rights to alvimopan in chronic OBD. We currently are exploring partnering opportunities for the further development of our OBD product candidates, including alvimopan for OBD.
Alvimopan for OBD
Prior to its return of the alvimopan OBD rights to us, Glaxo conducted several clinical studies of alvimopan for the treatment of OBD in patients taking opioid analgesics for persistent pain conditions. In September 2006, Glaxo and we announced top-line results from two Phase 3 registration studies, Study 012 and Study 013, of alvimopan for the treatment of
OBD in patients with chronic non-cancer pain. Study 012 enrolled 518 patients who experienced symptoms of OBD. This study achieved statistical significance for the primary endpoint, the proportion of patients who had a weekly average of three or more spontaneous bowel movements (SBMs) and an increase from baseline of one or more SBMs a week over the 12-week treatment period in patients treated with alvimopan 0.5 mg twice daily. Study 013 enrolled 485 patients and had the same primary endpoint as Study 012. The Study 013 results were not statistically significant.
In April 2007, Glaxo and we announced the results of Study 014, a Phase 3 long-term safety study of alvimopan in patients taking opioids for chronic non-cancer pain and experiencing OBD. Results from Study 014 showed numerically more myocardial infarctions and other cardiovascular serious adverse events reported by patients treated with alvimopan compared to placebo. The results of Study 014 also showed an increase in the incidence of benign neoplasms, malignant neoplasms, skin cancers and unspecified neoplasms, including polyps, and the incidence of fractures reported in patients receiving alvimopan, compared to placebo. At that time, Glaxo and we put the OBD development program on hold and withdrew the protocol for an additional Phase 3 safety and efficacy study in patients with OBD (Study 015). In addition, Glaxo stopped Study 101684, an extension of Study 008 in a cancer pain population, and we stopped Study 228, a study of our combination product candidate described below. In June 2007, the FDA placed the alvimopan Investigational New Drug Applications (INDs) on clinical hold pending submission and analysis of additional information and notification by the FDA that clinical studies with alvimopan may resume.
In July 2008, the clinical hold was lifted by the FDA and, in September 2008, Glaxo returned to us the worldwide rights to alvimopan in the chronic OBD indication. Also in September 2008, we filed with the FDA a Special Protocol Assessment (SPA) for a Phase 3 safety and efficacy trial of alvimopan in OBD. We have not yet received a response from the FDA on our SPA.
We have been developing product candidates that combine alvimopan and an opioid analgesic. This combination is intended to produce the pain relief of an opioid while reducing constipating side effects. During the second quarter of 2006, we commenced Study 228, a Phase 2 dose-ranging study in which alvimopan was co-administered with hydrocodone/APAP. Based on the data from Study 014, we suspended enrollment in Study 228 in rotator cuff surgery patients and later discontinued the study. We also filed an IND for a co-formulated hydrocodone/APAP and alvimopan product candidate and have completed a Phase 1 pharmacokinetic study that showed comparable drug levels in the co-formulated product and co-administered products. We do not have any active clinical studies for our combination product candidates.
ADL7445 is a proprietary small molecule, peripherally-acting mu-opioid receptor antagonist intended to block the adverse effects of opioid analgesics on the GI tract without affecting analgesia. ADL7445 has demonstrated safety and efficacy in preclinical models.