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

September 3, 2013 updated by: Targacept Inc.

Phase II Study of Glycemic Control, Safety, Tolerability and Pharmacokinetic Parameters of TC-6987 Monotherapy in Subjects With Type 2 Diabetes Mellitus

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
440

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 65 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
PLACEBO_COMPARATOR: Placebo
Drug: Placebo
Matching placebo: Mode of administration: p.o. (microcrystalline cellulose in capsule) given once daily.
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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Changes in fasting plasma glucose (FPG)
Time Frame: Day 1 and Week 4
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change in FPG from Day 1 (Baseline) at each time point
Time Frame: Day 1, Week 1 and Week 4
Change in FPG from Day 1 (Baseline) compared to weeks 1 and 4
Day 1, Week 1 and Week 4
Change in FPG and insulin from Day 1 (Baseline) at each time point
Time Frame: Day 1, Week 1 and Week 4
Change in FPG and insulin from Day 1 (Baseline) compared to weeks 1 and 4
Day 1, Week 1 and Week 4
Change in AUC FPG from Day 1 (Baseline) and at Week 4
Time Frame: Day 1 and Week 4
Change in AUC FPG from Day 1 (Baseline) compared to weeks 1 and 4
Day 1 and Week 4
Change in AUC insulin from Day 1 (Baseline) at Week 4
Time Frame: Day 1 and Week 4
Change in AUC insulin from Day 1 (Baseline) compared to week 4
Day 1 and Week 4

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Targacept Inc.

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Aaron Vinik, MD, Strelitz Diabetes Center, Eastern Virginia Medical School

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 1, 2011

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 1, 2012

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 1, 2012

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 9, 2011

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 9, 2011

First Posted (ESTIMATE)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 10, 2011

Study Record Updates

Last Update Posted (ESTIMATE)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 13, 2013

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 3, 2013

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • TC-6987-23-CRD-002

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings