glycemic control, safety and tolerability of tc-6987 monotherapy in type 2 diabetes mellitus

Conditions: Type 2 Diabetes Mellitus

Summary: tc-6987 is a selective nicotinic α-7 receptor ligand (open channel stabilizer) that has demonstrated potent anti-inflammatory/antioxidant properties in animal models. following the oral administration of a 1mg/kg dose of tc-6987 to diabetic mice (db/db mouse) for 7 weeks, numerous metabolic improvements were observed. specifically, plasma glucose and triglyceride concentrations declined by approximately 30%; hb1ac was reduced by nearly 50%; and tnf-α declined more than 60% relative to control db/db mice therefore, it appears that tc-6987 could prove beneficial in reducing elevated glucose concentrations in diabetic patients as well as in ameliorating organ damage associated with inflammation, oxidative stress and hyperglycemia.

this is a phase ii, multicenter, randomized, double-blind, parallel group, placebo-controlled study to assess the efficacy, safety, tolerability, and pharmacokinetic parameters of tc-6987 in subjects with type 2 diabetes mellitus (t2dm). the study is organized into three phases: (a) screening phase consisting of a 1-week screening (week -5)and a 4-week washout (week -4 to day 1); (b) 4-week, double-blind treatment (day 1 to week 4) during which subjects are randomized to either tc-6987 (20 mg on day 1 and 10 mg from day 2 to week 4) or placebo; and (c) 2-week follow-up (week 6). unscheduled visits will be allowed between visits from washout through follow-up to evaluate a subject's glycemic status or other safety issues, as required. subjects will fast overnight for a minimum of 10 hrs and refrain from drinking alcohol 24 hrs prior to each visit.

Eligibility criteria:
inclusion criteria: * males or postmenopausal/surgically sterile females * being treated for t2dm with oral antidiabetic agents (excluding glitazones) * bmi limit ≤ 38 * subjects at least 80% compliant on reporting daily smbg values during washout * at the end of washout the subject's fasting smbg is higher than it was at the start of washout and the fasting smbg ≤ 280.g treated for t2dm with oral antidiabetic agents (excluding glitazones) exclusion criteria: * type 1 diabetes mellitus * severe complications of t2dm (especially diabetic retinopathy imminently requiring treatment for preserving or restoring vision, diabetic neuropathy with symptomatic orthostatic hypotension, urinary retention, gastric stasis, or pedal ulcers) * current treatment with insulin or a glitazone * use of moderate to strong cytochrome p450 3a4 (cyp3a4) inhibitors * fsh level of \< 35 iu/l and a lh level \< 25 iu/l except for confirmed surgically sterile women with functioning ovaries * significant cardiovascular diseases (including arrhythmia) or congestive heart failure, or severe ischemic disease within the last 3 months prior to screening, or evidence of stroke, myocardial infarction, unstable angina, coronary bypass and/or percutaneous transluminal coronary angioplasty * history of significant other major or unstable neurological, metabolic, hepatic, renal, hematological, pulmonary, cv, gi, or urological disorder; or diagnosis of major depressive disorder; if stable medical disorder, any medical treatment must be stable for last 2 months prior to screening * history of diabetic ketoacidosis * patients who have an increased red blood cell (rbc) turn-over or thalassemia or anemia * known hiv or history of viral hepatitis type b or c * systemic infection with tb * current or previous use of oral or injectable corticosteroids 3 months prior to screening. * subject has persistent, uncontrolled severe hypertension as indicated by a systolic blood pressure \> 180 mmhg or a diastolic blood pressure of \> 110 mmhg, with or without treatment * subject has had a malignancy in the last 5 years, except for successfully treated basal or squamous cell carcinoma of the skin or of the cervix * subject is receiving chemotherapy * tobacco user within 4 months prior to screening * smoking cessation therapy within 4 months prior to screening and/or planned during the study * use of prohibited concomitant medications including psychoactive agents * history within 6 months prior to screening of alcohol abuse or illicit drug abuse * was administered study medication in another clinical trial in the past 3 months prior to screening

Keywords: type 2 diabetes type 2 diabetes mellitus