ADL-2-1294 (Adolor)

Adolor is developing various local and topical formulations of the antidiarrheal compound loperamide (ADL-2-1294), which acts as an opiate receptor agonist in the peripheral nervous system, for the potential treatment of pruritus and pain associated with burns, wounds, eye diseases and inflammation. Both the topical formulation and ophthalmic formulation are in phase II clinical trials. TOPICAL FORMULATION: A topical formulation is being developed for pain associated with cutaneous inflammatory lesions and other indications associated with inflammatory pain. Phase I trials were completed in spring 1997. The trials assessed the safety, tolerance, pharmacokinetics, and topical sensitivity of ADL-2-1294 in 35 burn patient volunteers. Following positive results, Adolor began two dose-ranging phase II trials in patients with minor burns, abrasions and sunburn in the first half of 1997. In July 1997, Adolor was to initiate the preclinical development of ADL-2-1294 for the potential treatment of hyperalgesia associated with surgical wounds. OPHTHALMIC FORMULATION: By July 1999, phase II clinical trials of ADL-2-1294 for the potential treatment of inflammatory corneal pain were underway. In June 1998, the FDA accepted an IND for ADL-2-1294 for the treatment of inflammatory pain associated with corneal abrasions, surgical and laser keratectomies and keratoconjunctivitis. By this time, a phase I study had been initiated to assess safety and efficacy parameters. By July 1997, an ophthalmic formulation was in preclinical development for the treatment of corneal hyperalgesia. In preclinical studies with the compound, efficacy was demonstrated in animal models of inflammatory pain. OTHER FORMULATIONS: By 1999, Adolor was also investigating mucosal, post-surgical and intra-articular indications for the compound. By 1996, Adolor had plans to carry out clinical development alone, up to and including phase II trials. Then, the company were to seek a corporate partner, probably from Japan, and hold on to US and European rights. Beyond phase III trials, Adolor had expected to sell the compound to a major US or European company. In 1997, Adolor licensed ADL-2-1294 to the South Korean OTC topically-administered epidermal analgesic. In July 1999, Adolor licensed worldwide (excluding Korea) prescription and OTC development and commercial rights to topical dermal ADL-2-1294, for use in the treatment of inflammatory pain, itching and other undisclosed indications, to SmithKline Beecham. The company was issued US-05849761 and US-05849762 in January 1999 covering the use of antidiarrheal opioid compounds for the treatment of inflammatory pain and the treatment of pruritus.