Date: 2015-03-02
Type of information: Completion of the trial
phase: 1
Announcement: completion of the trial
Company: Durect Corporation (USA - CA)
Product: DUR-928
Action
mechanism: DUR-928 is an endogenous, small-molecule, new chemical entity (NCE), which may have broad applicability in metabolic diseases such as nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH), and in acute organ injuries such as acute kidney injury (AKI). The biological activity of DUR-928 has been demonstrated in 6 different animal disease models involving three animal species. Three of these models represented acute toxic or ischemic organ injury (kidney and liver) and three represented chronic disorders of hepatic lipid accumulation and dysfunction (NAFLD/NASH).
Disease: NASH (non-alcoholic steatohepatitis)
Therapeutic area: Hepatic diseases - Liver diseases - Metabolic diseases
Country:
Trial
details: The Phase 1 trial of DUR-928 was a single-site, randomized, double-blinded, placebo-controlled, single-ascending-dose study that evaluated the safety, tolerability and pharmacokinetics of DUR-928 when orally administered. The 30-subject study evaluated DUR-928 in five cohorts of healthy volunteers receiving DUR-928 at escalating doses that resulted in peak plasma concentrations at least 100-fold higher than endogenous levels.
Latest
news: * On March 2, 2015, Durect Corporation announced its Epigenomic Regulator Program, and the successful completion of a Phase 1 clinical trial with the program\'s lead product candidate DUR-928. Durect\'s Epigenomic Regulator Program involves a collaborative effort now in its fourth year between Durect and the Department of Internal Medicine at Virginia Commonwealth University (VCU), the VCU Medical Center, and the McGuire VA Medical Center. The discoveries from this program are the result of more than 20 years of lipid research by Shunlin Ren, MD, PhD, Associate Professor of Internal Medicine at the VCU Medical Center and a recipient of multiple NIH grants for metabolic disease research. Durect holds the exclusive worldwide right to develop and commercialize DUR-928 and related molecules discovered in the program. During the course of this program, a number of compounds have been identified that may have therapeutic utility for various diseases and syndromes for orphan indications as well as for broader patient populations. The lead compound from this program DUR-928 is an endogenous, orally bioavailable small molecule that modulates the activity of various nuclear receptors that play an important regulatory role in lipid homeostasis, inflammation and cell survival. A systems biology study involving over 23,000 genes showed that DUR-928 modulates the activity of more than 240 genes, including ACC, FAS, HMGR, Cyp7A1, LXR, PPARγ, NFκB/IκB, TNFα, IL-1α, IL-6, COX-2, PCSK9, and others. The Phase 1 trial of DUR-928 was a single-site, randomized, double-blinded, placebo-controlled, single-ascending-dose study that evaluated the safety, tolerability and pharmacokinetics of DUR-928 when orally administered. The 30-subject study evaluated DUR-928 in five cohorts of healthy volunteers receiving DUR-928 at escalating doses that resulted in peak plasma concentrations at least 100-fold higher than endogenous levels. DUR-928 was well-tolerated at all dose levels, with no treatment-related adverse events reported and no subjects withdrawing from the study. Durect anticipates commencing a Phase 1 multiple-ascending-dose, oral administration trial in healthy subjects in mid-2015, as well as a Phase 1 single-dose, injectable administration trial in healthy subjects in the second half of 2015 as precursor to a multiple-ascending-dose Phase 1 trial. Assuming no undue safety results from these trials, Durect would then be positioned to commence one or more Phase 2 patient trials in 2016. Durect is currently evaluating potential indications for DUR-928 in order to prioritize the development program. Long term opportunities fall into four broad categories: (a) orphan acute indications, (b) broader acute indications, (c) orphan chronic indications, and (d) broader chronic indications. Durect\'s initial Phase 2 studies will be designed to show an efficacy signal in patients suffering from one orphan acute condition such as acute kidney injury and one broad chronic indication such as NAFLD/NASH. Durect plans to provide more detail on the Phase 2 studies later this year.
