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

NCT ID: NCT01293669

Last Updated: 2013-09-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 440 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-01-31
• Study Completion Date: 2012-01-31

Brief 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.

Detailed 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.

Conditions

Type 2 Diabetes Mellitus

Keywords

Type 2 Diabetes; Type 2 Diabetes Mellitus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

TC-6987

Group Type: EXPERIMENTAL

TC-6987

Intervention Type: DRUG

TC-6987-23 (TC-6987 HCl) as experimental treatment: 20 mg loading dose (2 capsules) on Day 1 and 10 mg (1 capsule) on Days 2 to 28 (dose expressed as free base). Each dose will be given once daily.

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Matching placebo: Mode of administration: p.o. (microcrystalline cellulose in capsule) given once daily.

Interventions

TC-6987

TC-6987-23 (TC-6987 HCl) as experimental treatment: 20 mg loading dose (2 capsules) on Day 1 and 10 mg (1 capsule) on Days 2 to 28 (dose expressed as free base). Each dose will be given once daily.

Intervention Type: DRUG

Placebo

Matching placebo: Mode of administration: p.o. (microcrystalline cellulose in capsule) given once daily.

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Targacept Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Aaron Vinik, MD

Role: PRINCIPAL_INVESTIGATOR

Strelitz Diabetes Center, Eastern Virginia Medical School

Locations

Clopton Clinic

Jonesboro, Arkansas, United States

NCA Medical Center

Mountain Home, Arkansas, United States

Associated Pharmaceutical Research Center

Buena Park, California, United States

Cedar Crosse Research Center

Chicago, Illinois, United States

Medex Healthcare Research, Inc

St Louis, Missouri, United States

Om Medical

Henderson, Nevada, United States

MEDEX Healthcare Research, Inc

New York, New York, United States

PMG Research of WS

Winston-Salem, North Carolina, United States

Rapid Medical Research, Inc.

Cleveland, Ohio, United States

Providence Health Partners - Center for Research

Dayton, Ohio, United States

Omega Medical Research

Warwick, Rhode Island, United States

Ellipsis Research

Columbia, South Carolina, United States

PMG Research of Charleston

Mt. Pleasant, South Carolina, United States

New Phase Research and Development

Knoxville, Tennessee, United States

Mercury Clinical Research

Houston, Texas, United States

Quality Research, Inc.

San Antonio, Texas, United States

Highland Clinical Research

Salt Lake City, Utah, United States

Strelitz Diabetes Center, Eastern Virginia Medical School

Norfolk, Virginia, United States

Countries

United States

Other Identifiers

TC-6987-23-CRD-002

Identifier Type: -

Identifier Source: org_study_id