Clinical trial NCT01293669: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Type 2 Diabetes Mellitus
Keywords: Type 2 Diabetes
Type 2 Diabetes Mellitus
Lead sponsor: Targacept Inc.
Sponsor class: INDUSTRY
First posted: 2011-02-10
Enrollment: 440
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Changes in fasting plasma glucose (FPG)
timeFrame: Day 1 and Week 4
Secondary outcomes:
measure: Change in FPG from Day 1 (Baseline) at each time point
timeFrame: Day 1, Week 1 and Week 4
measure: Change in FPG and insulin from Day 1 (Baseline) at each time point
timeFrame: Day 1, Week 1 and Week 4
measure: Change in AUC FPG from Day 1 (Baseline) and at Week 4
timeFrame: Day 1 and Week 4
measure: Change in AUC insulin from Day 1 (Baseline) at Week 4
timeFrame: Day 1 and Week 4
Other outcomes:
Locations:
city: Jonesboro
country: United States
facility: Clopton Clinic
state: Arkansas
city: Mountain Home
country: United States
facility: NCA Medical Center
state: Arkansas
city: Buena Park
country: United States
facility: Associated Pharmaceutical Research Center
state: California
city: Chicago
country: United States
facility: Cedar Crosse Research Center
state: Illinois
city: St. Louis
country: United States
facility: Medex Healthcare Research, Inc
state: Missouri
city: Henderson
country: United States
facility: Om Medical
state: Nevada
city: New York
country: United States
facility: MEDEX Healthcare Research, Inc
state: New York
city: Winston-Salem
country: United States
facility: PMG Research of WS
state: North Carolina
city: Cleveland
country: United States
facility: Rapid Medical Research, Inc.
state: Ohio
city: Dayton
country: United States
facility: Providence Health Partners - Center for Research
state: Ohio
city: Warwick
country: United States
facility: Omega Medical Research
state: Rhode Island
city: Columbia
country: United States
facility: Ellipsis Research
state: South Carolina
city: Mt. Pleasant
country: United States
facility: PMG Research of Charleston
state: South Carolina
city: Knoxville
country: United States
facility: New Phase Research and Development
state: Tennessee
city: Houston
country: United States
facility: Mercury Clinical Research
state: Texas
city: San Antonio
country: United States
facility: Quality Research, Inc.
state: Texas
city: Salt Lake City
country: United States
facility: Highland Clinical Research
state: Utah
city: Norfolk
country: United States
facility: Strelitz Diabetes Center, Eastern Virginia Medical School
state: Virginia
Study officials:
affiliation: Strelitz Diabetes Center, Eastern Virginia Medical School
name: Aaron Vinik, MD
role: PRINCIPAL_INVESTIGATOR
References: