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

NCT01293669 | Completed Phase 2

• 1 other identifier: TC-6987-23-CRD-002
• Study Type: interventional
• Target: 440
• Locations: 1 country
• Sites: 18

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.

Conditions

Type 2 Diabetes Mellitus

Keywords

Type 2 Diabetes; Type 2 Diabetes Mellitus

Outcome Measures

Primary Outcomes (1)

• Changes in fasting plasma glucose (FPG)

  The primary efficacy endpoint will be FPG values obtained at Week 4 compared to Day 1 (baseline). This change from baseline will be analyzed using MMRM techniques with an alpha of 0.10 (one-sided), to examine differences between the TC-6987 and placebo treatment cohorts. This change from baseline will be analyzed using the primary efficacy endpoints for the mITT analysis set. The efficacy analyses based on the Per Protocol (PP) analysis set will be considered secondary.

  Day 1 and Week 4

Secondary Outcomes (4)

• Change in FPG from Day 1 (Baseline) at each time point

  Day 1, Week 1 and Week 4

• Change in FPG and insulin from Day 1 (Baseline) at each time point

  Day 1, Week 1 and Week 4

• Change in AUC FPG from Day 1 (Baseline) and at Week 4

  Day 1 and Week 4

• Change in AUC insulin from Day 1 (Baseline) at Week 4

  Day 1 and Week 4

Study Arms (2)

TC-6987

EXPERIMENTAL

Drug: TC-6987

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

TC-6987 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.

TC-6987

Placebo DRUG

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

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Targacept Inc.: lead

Study Sites (18)

Clopton Clinic

Jonesboro, Arkansas, 72401, United States

Location

NCA Medical Center

Mountain Home, Arkansas, 72653, United States

Location

Associated Pharmaceutical Research Center

Buena Park, California, 90620, United States

Location

Cedar Crosse Research Center

Chicago, Illinois, 60607, United States

Location

Medex Healthcare Research, Inc

St Louis, Missouri, 63117, United States

Location

Om Medical

Henderson, Nevada, 89052, United States

Location

MEDEX Healthcare Research, Inc

New York, New York, 10004, United States

Location

PMG Research of WS

Winston-Salem, North Carolina, 27103, United States

Location

Rapid Medical Research, Inc.

Cleveland, Ohio, 44122, United States

Location

Providence Health Partners - Center for Research

Dayton, Ohio, 45439, United States

Location

Omega Medical Research

Warwick, Rhode Island, 02888, United States

Location

Ellipsis Research

Columbia, South Carolina, 29201, United States

Location

PMG Research of Charleston

Mt. Pleasant, South Carolina, 29464, United States

Location

New Phase Research and Development

Knoxville, Tennessee, 37923, United States

Location

Mercury Clinical Research

Houston, Texas, 77093, United States

Location

Quality Research, Inc.

San Antonio, Texas, 78209, United States

Location

Highland Clinical Research

Salt Lake City, Utah, 84124, United States

Location

Strelitz Diabetes Center, Eastern Virginia Medical School

Norfolk, Virginia, 23510, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Aaron Vinik, MD

  Strelitz Diabetes Center, Eastern Virginia Medical School

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 9, 2011
• First Posted: February 10, 2011
• Study Start: January 1, 2011
• Primary Completion: January 1, 2012
• Study Completion: January 1, 2012
• Last Updated: September 13, 2013

Record last verified: 2012-07

Locations

US (18)