Hollis-Eden Commences Phase II Clinical Trial with TRIOLEX™ in Type-2 Diabetes Patients
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Hollis-Eden Pharmaceuticals, Inc. has announced that it has commenced a Phase II clinical trial with its oral drug candidate TRIOLEX™ (HE3286) in type 2 diabetes patients, and that it is expanding the number of clinical sites to accelerate enrollment.
The Phase II, double-blinded placebo controlled 12-week dosing trial will enroll approximately 90 patients who are stable on metformin treatment only, the current first-line therapy for type 2 diabetes, with a hemoglobin A1c (HbA1c) level in excess of 7.5 percent.
The primary endpoints for the trial will be safety and a reduction in HbA1c. Hollis-Eden plans to release preliminary interim data from this trial in the fourth quarter of 2008, and to completely enroll by the end of the year.
TRIOLEX may represent a first-in-class insulin sensitizer that Hollis-Eden believes acts by modulating inflammatory pathways. Recently announced interim data from the Company’s on-going Phase I/II clinical trial with TRIOLEX demonstrate that the compound is safe and well tolerated to date, and that it significantly improved insulin sensitivity and lowered fasting blood glucose, insulin and triglyceride levels in obese insulin resistant subjects treated orally with the compound for 28 days when compared to placebo-treated subjects.
As would be expected in a population of insulin resistant subjects, blood levels of the chemokine monocyte chemoattractant protein (MCP-1) were elevated at baseline, before initiating treatment. MCP-1 plays a central role in the evolution of insulin resistance because it causes increased migration of macrophages into adipose tissue (and other tissues), leading to low-grade chronic inflammation and gradual loss of insulin sensitivity.
Subjects treated with TRIOLEX at the highest dose showed a significant drop in MCP-1 in blood and IL-6 production by peripheral blood mononuclear cells, compared to placebo-treated subjects. This finding is consistent with what the Company believes is the anti-inflammatory mechanism of action of TRIOLEX.
Leading academic researchers have linked inflammation and type-2 diabetes, reporting that the chronic stimulation of the inflammatory kinases JNK and IKK can impair insulin signaling by inhibiting the biological function of insulin receptor substrate-1 (IRS-1), a protein that acts as a major mediator of insulin action in target cells.
The involvement of inflammation through this pathway in causing insulin resistance and type 2 diabetes is well described in the scientific literature. In addition, activation of NF-kappaB due to inflammatory mediators or oxidative stress leads to a feed forward cycle of increased production of inflammatory cytokines such as MCP-1, TNF-alpha, IL-6 and IL-1beta.
