add glucokinase activator to target a1c

Conditions: Diabetes Mellitus, Type 2

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 \ 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.