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

Targacept

Status and phase

Completed

Phase 2

Conditions

Type 2 Diabetes Mellitus

Treatments

Drug: Placebo

Drug: TC-6987

Study type

Interventional

Funder types

Industry

Identifiers

NCT01293669

TC-6987-23-CRD-002

Details and patient eligibility

About

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.

Full description

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.

Enrollment

440 patients

Sex

All

Ages

18 to 65 years old

Volunteers

Accepts Healthy Volunteers

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