Clinical trial NCT02405260: Add Glucokinase Activator to Target A1c
Official title: A Multi-Center, Adaptive Phase 2, Randomized, Double-Blind, Placebo- and Active-Controlled (Sitagliptin), Parallel Group Study to Evaluate the Safety and Efficacy of TTP399 Following 6 Months Administration in Subjects With Type 2 Diabetes Mellitus on A Stable Dose of Metformin
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Diabetes Mellitus, Type 2
Lead sponsor: vTv Therapeutics
Sponsor class: INDUSTRY
First posted: 2015-04-01
Enrollment: 190
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This trial is a multi-center, adaptive, randomized, double-blind, placebo- and active- controlled, parallel group, Phase 2 study in subjects with T2DM to evaluate the effect of TTP399 on HbA1c following administration for 6 months.


Eligibility criteria: Inclusion Criteria:

* A historical diagnosis of Type 2 Diabetes in accordance with the American Diabetes Association (ADA) guidelines, with diagnosis at least 6 months prior to Screening.
* On a stable (for the last 3 months prior to screening) regimen of metformin monotherapy equivalent of at least 1000 mg once daily.
* Males, females of childbearing potential (must have a negative pregnancy test and be willing to comply with protocol contraception), and females of non-childbearing potential.
* Age 18 to 75 years, inclusive, at the time of screening.
* HbA1c ≥7.0% and ≤9.5%.
* Generally stable health without active infection or history of major surgery or significant injuries within the last year.

Exclusion Criteria:

* Diagnosis of Type 1 diabetes mellitus, maturity-onset diabetes of the young, insulin-requiring Type 2 Diabetes, other unusual or rare forms of diabetes mellitus, or history of diabetic ketoacidosis.
* Clinically significant abnormal lab values including eGFR \<50ml/min/1.73m2, ALT, bilirubin or AST \>1.5 X ULN, hypokalemia or other clinically significant electrolyte abnormality.
* History of myocardial infarction, unstable angina, coronary revascularization, stroke, or transient ischemic attack within 2 years of screening.
* Presence of symptomatic congestive heart failure.
* History of cardiac arrhythmias requiring treatment or prophylaxis with drugs or devices during the last 2 years or any history of atrial fibrillation or flutter beyond a single short-term episode (e.g., lasting 1-2 days).
* History or presence of a 2nd degree or greater atrioventricular block in the absence of a pacemaker.
* A 12-lead ECG, from screening or baseline demonstrating QTcF interval \>450 msec for males or \>47 msec for females.
* A family or personal history of long QT syndrome.
* History of pancreatitis.
* Persistent, uncontrolled hypertension.
* Presence of chronic active hepatitis (hepatitis B, hepatitis C, nonalcoholic steatohepatitis \[NASH\]) and/or known liver cirrhosis.
* Participation in any formal weight loss program, or fluctuation of \> 5% in body weight, or having received medications approved for weight loss within 3 months prior to screening.
* A positive pre-study drug screen.
* Participation in a clinical trial and receipt of an investigational product within 30 days.
* Have a history of drug abuse within 2 years of screening or a positive pre-screen drug screen.
* Have a history of hypoglycemic episode requiring glucose, glucagon, or orange juice administered by someone other than the patient within 6 months prior to screening.
* A history of excessive alcohol consumption within the last 2 years prior to screening
* Mental or legal incapacitation.
* Blood donation of approximately 1 pint (500 mL) within 8 weeks.
* History of MEN-2 or family history of medullary thyroid cancer.
* History of cancer, other than non-melanoma skin cancer, that required therapy in the 5 years prior study start.

Primary outcomes:
measure: Change in HbA1c (Glycosylated haemoglobin)
timeFrame: Day 1 to Day 168
Secondary outcomes:
measure: HbA1c < 7% at 6 months
timeFrame: Day 1 to Day 168
measure: HbA1c < 6.5% at 6 months
timeFrame: Day 1 to Day 168
measure: Plasma Glucose Levels
timeFrame: Day 1 to Day 168
measure: Lipid Levels
timeFrame: Day 1 to Day 168
measure: Insulin Levels
timeFrame: Day 1 to Day 168
measure: Lactate Levels
timeFrame: Day 1 to Day 168
measure: C-peptide Levels
timeFrame: Day 1 to Day 168
measure: Glucagon Levels
timeFrame: Day 1 to Day 168
measure: Glucagon-like Peptide-1 Levels
timeFrame: Day 1 to Day 168
measure: Change in Body Weight
timeFrame: Day 1 to Day 168
measure: Adverse Events
timeFrame: Day 1 to Day 182
measure: Blood Pressure
timeFrame: Day 1 to Day 182
measure: Electrocardiogram Parameters
timeFrame: Day 1 to Day 182
measure: Hematology
timeFrame: Day 1 to Day 182
measure: Blood Chemistry
timeFrame: Day 1 to Day 182
measure: Urinalysis
timeFrame: Day 1 to Day 182
measure: Pulse
timeFrame: Day 1 to Day 182
Other outcomes:
Locations:
city: Mesa
country: United States
state: Arizona
city: Tuscon
country: United States
state: Arizona
city: Canoga Park
country: United States
state: California
city: Huntington Park
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: West Hills
country: United States
state: California
city: Centennial
country: United States
state: Colorado
city: Littleton
country: United States
state: Colorado
city: Waterbury
country: United States
state: Connecticut
city: West Palm Beach
country: United States
state: Florida
city: Gurnee
country: United States
state: Illinois
city: Evansville
country: United States
state: Indiana
city: Rochester
country: United States
state: Minnesota
city: Greensboro
country: United States
state: North Carolina
city: Moncks Corner
country: United States
state: South Carolina
city: San Antonio
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Schertz
country: United States
state: Texas
city: Norfolk
country: United States
state: Virginia
city: Richland
country: United States
state: Washington
Study officials:
affiliation: vTv Therapeutics
name: Carmen Valcarce, Ph.D.
role: STUDY_CHAIR
References: