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

Type 2 Diabetes Mellitus Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01293669
• Other study ID #: TC-6987-23-CRD-002
• Status: Completed
• Phase: Phase 2
• First received: February 9, 2011
• Last updated: September 3, 2013
• Start date: January 2011
• Est. completion date: January 2012

Study information

• Verified date: July 2012
• Source: Targacept Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 440
• Est. completion date: January 2012
• Est. primary completion date: January 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus

Intervention

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

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Targacept Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Change in FPG from Day 1 (Baseline) at each time point	Change in FPG from Day 1 (Baseline) compared to weeks 1 and 4	Day 1, Week 1 and Week 4	No
Secondary	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	Day 1, Week 1 and Week 4	No
Secondary	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	Day 1 and Week 4	No
Secondary	Change in AUC insulin from Day 1 (Baseline) at Week 4	Change in AUC insulin from Day 1 (Baseline) compared to week 4	Day 1 and Week 4	No