Glycemic Control, Safety and Tolerability of TC-6987 Monotherapy in Type 2 Diabetes Mellitus

• Status: Completed
• Trial end date: 2012-01-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Targacept Inc.

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