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

Primary Purpose

Type 2 Diabetes Mellitus

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
TC-6987
Placebo
Sponsored by
Targacept Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Type 2 Diabetes Mellitus focused on measuring Type 2 Diabetes, Type 2 Diabetes Mellitus

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesAccepts 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

Sites / Locations

  • Clopton Clinic
  • NCA Medical Center
  • Associated Pharmaceutical Research Center
  • Cedar Crosse Research Center
  • Medex Healthcare Research, Inc
  • Om Medical
  • MEDEX Healthcare Research, Inc
  • PMG Research of WS
  • Rapid Medical Research, Inc.
  • Providence Health Partners - Center for Research
  • Omega Medical Research
  • Ellipsis Research
  • PMG Research of Charleston
  • New Phase Research and Development
  • Mercury Clinical Research
  • Quality Research, Inc.
  • Highland Clinical Research
  • Strelitz Diabetes Center, Eastern Virginia Medical School

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

TC-6987

Placebo

Arm Description

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Change in FPG from Day 1 (Baseline) at each time point
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
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
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
Change in AUC insulin from Day 1 (Baseline) compared to week 4

Full Information

First Posted
February 9, 2011
Last Updated
September 3, 2013
Sponsor
Targacept Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT01293669
Brief Title
Glycemic Control, Safety and Tolerability of TC-6987 Monotherapy in Type 2 Diabetes Mellitus
Official Title
Phase II Study of Glycemic Control, Safety, Tolerability and Pharmacokinetic Parameters of TC-6987 Monotherapy in Subjects With Type 2 Diabetes Mellitus
Study Type
Interventional

2. Study Status

Record Verification Date
July 2012
Overall Recruitment Status
Completed
Study Start Date
January 2011 (undefined)
Primary Completion Date
January 2012 (Actual)
Study Completion Date
January 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Targacept Inc.

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 2 Diabetes Mellitus
Keywords
Type 2 Diabetes, Type 2 Diabetes Mellitus

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
440 (Actual)

8. Arms, Groups, and Interventions

Arm Title
TC-6987
Arm Type
Experimental
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
TC-6987
Intervention Description
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
Intervention Name(s)
Placebo
Intervention Description
Matching placebo: Mode of administration: p.o. (microcrystalline cellulose in capsule) given once daily.
Primary Outcome Measure Information:
Title
Changes in fasting plasma glucose (FPG)
Description
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.
Time Frame
Day 1 and Week 4
Secondary Outcome Measure Information:
Title
Change in FPG from Day 1 (Baseline) at each time point
Description
Change in FPG from Day 1 (Baseline) compared to weeks 1 and 4
Time Frame
Day 1, Week 1 and Week 4
Title
Change in FPG and insulin from Day 1 (Baseline) at each time point
Description
Change in FPG and insulin from Day 1 (Baseline) compared to weeks 1 and 4
Time Frame
Day 1, Week 1 and Week 4
Title
Change in AUC FPG from Day 1 (Baseline) and at Week 4
Description
Change in AUC FPG from Day 1 (Baseline) compared to weeks 1 and 4
Time Frame
Day 1 and Week 4
Title
Change in AUC insulin from Day 1 (Baseline) at Week 4
Description
Change in AUC insulin from Day 1 (Baseline) compared to week 4
Time Frame
Day 1 and Week 4

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Aaron Vinik, MD
Organizational Affiliation
Strelitz Diabetes Center, Eastern Virginia Medical School
Official's Role
Principal Investigator
Facility Information:
Facility Name
Clopton Clinic
City
Jonesboro
State/Province
Arkansas
ZIP/Postal Code
72401
Country
United States
Facility Name
NCA Medical Center
City
Mountain Home
State/Province
Arkansas
ZIP/Postal Code
72653
Country
United States
Facility Name
Associated Pharmaceutical Research Center
City
Buena Park
State/Province
California
ZIP/Postal Code
90620
Country
United States
Facility Name
Cedar Crosse Research Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60607
Country
United States
Facility Name
Medex Healthcare Research, Inc
City
St. Louis
State/Province
Missouri
ZIP/Postal Code
63117
Country
United States
Facility Name
Om Medical
City
Henderson
State/Province
Nevada
ZIP/Postal Code
89052
Country
United States
Facility Name
MEDEX Healthcare Research, Inc
City
New York
State/Province
New York
ZIP/Postal Code
10004
Country
United States
Facility Name
PMG Research of WS
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27103
Country
United States
Facility Name
Rapid Medical Research, Inc.
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44122
Country
United States
Facility Name
Providence Health Partners - Center for Research
City
Dayton
State/Province
Ohio
ZIP/Postal Code
45439
Country
United States
Facility Name
Omega Medical Research
City
Warwick
State/Province
Rhode Island
ZIP/Postal Code
02888
Country
United States
Facility Name
Ellipsis Research
City
Columbia
State/Province
South Carolina
ZIP/Postal Code
29201
Country
United States
Facility Name
PMG Research of Charleston
City
Mt. Pleasant
State/Province
South Carolina
ZIP/Postal Code
29464
Country
United States
Facility Name
New Phase Research and Development
City
Knoxville
State/Province
Tennessee
ZIP/Postal Code
37923
Country
United States
Facility Name
Mercury Clinical Research
City
Houston
State/Province
Texas
ZIP/Postal Code
77093
Country
United States
Facility Name
Quality Research, Inc.
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78209
Country
United States
Facility Name
Highland Clinical Research
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84124
Country
United States
Facility Name
Strelitz Diabetes Center, Eastern Virginia Medical School
City
Norfolk
State/Province
Virginia
ZIP/Postal Code
23510
Country
United States

12. IPD Sharing Statement

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

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