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

Purpose

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.

Condition	Intervention	Phase
Type 2 Diabetes Mellitus	Drug: TC-6987 Drug: Placebo	Phase 2


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	Phase II Study of Glycemic Control, Safety, Tolerability and Pharmacokinetic Parameters of TC-6987 Monotherapy in Subjects With Type 2 Diabetes Mellitus

Resource links provided by NLM:

MedlinePlus related topics: Diabetes Type 2

U.S. FDA Resources

Further study details as provided by Targacept Inc.:

Primary Outcome Measures:

Changes in fasting plasma glucose (FPG) [ Time Frame: Day 1 and Week 4 ] [ Designated as safety issue: No ]
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.

Secondary Outcome Measures:

Change in FPG from Day 1 (Baseline) at each time point [ Time Frame: Day 1, Week 1 and Week 4 ] [ Designated as safety issue: No ]
Change in FPG from Day 1 (Baseline) compared to weeks 1 and 4
Change in FPG and insulin from Day 1 (Baseline) at each time point [ Time Frame: Day 1, Week 1 and Week 4 ] [ Designated as safety issue: No ]
Change in FPG and insulin from Day 1 (Baseline) compared to weeks 1 and 4
Change in AUC FPG from Day 1 (Baseline) and at Week 4 [ Time Frame: Day 1 and Week 4 ] [ Designated as safety issue: No ]
Change in AUC FPG from Day 1 (Baseline) compared to weeks 1 and 4
Change in AUC insulin from Day 1 (Baseline) at Week 4 [ Time Frame: Day 1 and Week 4 ] [ Designated as safety issue: No ]
Change in AUC insulin from Day 1 (Baseline) compared to week 4


Enrollment:	440
Study Start Date:	January 2011
Study Completion Date:	January 2012
Primary Completion Date:	January 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: TC-6987	Drug: 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.
Placebo Comparator: Placebo	Drug: Placebo Matching placebo: Mode of administration: p.o. (microcrystalline cellulose in capsule) given once daily.

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.

Eligibility


Ages Eligible for Study:	18 Years to 65 Years (Adult)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

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

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01293669

Locations


United States, Arkansas
Clopton Clinic
Jonesboro, Arkansas, United States, 72401
NCA Medical Center
Mountain Home, Arkansas, United States, 72653
United States, California
Associated Pharmaceutical Research Center
Buena Park, California, United States, 90620
United States, Illinois
Cedar Crosse Research Center
Chicago, Illinois, United States, 60607
United States, Missouri
Medex Healthcare Research, Inc
St. Louis, Missouri, United States, 63117
United States, Nevada
Om Medical
Henderson, Nevada, United States, 89052
United States, New York
MEDEX Healthcare Research, Inc
New York, New York, United States, 10004
United States, North Carolina
PMG Research of WS
Winston-Salem, North Carolina, United States, 27103
United States, Ohio
Rapid Medical Research, Inc.
Cleveland, Ohio, United States, 44122
Providence Health Partners - Center for Research
Dayton, Ohio, United States, 45439
United States, Rhode Island
Omega Medical Research
Warwick, Rhode Island, United States, 02888
United States, South Carolina
Ellipsis Research
Columbia, South Carolina, United States, 29201
PMG Research of Charleston
Mt. Pleasant, South Carolina, United States, 29464
United States, Tennessee
New Phase Research and Development
Knoxville, Tennessee, United States, 37923
United States, Texas
Mercury Clinical Research
Houston, Texas, United States, 77093
Quality Research, Inc.
San Antonio, Texas, United States, 78209
United States, Utah
Highland Clinical Research
Salt Lake City, Utah, United States, 84124
United States, Virginia
Strelitz Diabetes Center, Eastern Virginia Medical School
Norfolk, Virginia, United States, 23510

Sponsors and Collaborators

Targacept Inc.

Investigators


Principal Investigator:	Aaron Vinik, MD	Strelitz Diabetes Center, Eastern Virginia Medical School

More Information


Responsible Party:	Targacept Inc.
ClinicalTrials.gov Identifier:	NCT01293669 History of Changes
Other Study ID Numbers:	TC-6987-23-CRD-002
Study First Received:	February 9, 2011
Last Updated:	September 3, 2013
Health Authority:	United States: Food and Drug Administration

Keywords provided by Targacept Inc.:


Type 2 Diabetes Type 2 Diabetes Mellitus

Additional relevant MeSH terms:


Diabetes Mellitus Diabetes Mellitus, Type 2 Glucose Metabolism Disorders Metabolic Diseases Endocrine System Diseases

ClinicalTrials.gov processed this record on September 23, 2016