Add Glucokinase Activator to Target A1c

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 190

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
TTP399 800 mg	TTP399 800 mg	TTP399 once daily
Sitagliptin 100 mg	Sitagliptin 100 mg	Sitagliptin once daily
TTP399 400 mg	TTP399 400 mg	TTP399 once daily
Placebo	Placebo	Placebo once daily

Primary Outcome Measures

Name	Time	Method
Change in HbA1c (Glycosylated haemoglobin)	Day 1 to Day 168

Secondary Outcome Measures

Name	Time	Method
HbA1c < 7% at 6 months	Day 1 to Day 168
HbA1c < 6.5% at 6 months	Day 1 to Day 168
Plasma Glucose Levels	Day 1 to Day 168
Lipid Levels	Day 1 to Day 168
Insulin Levels	Day 1 to Day 168
Lactate Levels	Day 1 to Day 168
C-peptide Levels	Day 1 to Day 168
Glucagon Levels	Day 1 to Day 168
Glucagon-like Peptide-1 Levels	Day 1 to Day 168
Change in Body Weight	Day 1 to Day 168
Adverse Events	Day 1 to Day 182
Blood Pressure	Day 1 to Day 182
Electrocardiogram Parameters	Day 1 to Day 182
Hematology	Day 1 to Day 182
Blood Chemistry	Day 1 to Day 182
Urinalysis	Day 1 to Day 182
Pulse	Day 1 to Day 182