Add Glucokinase Activator to Target A1c (AGATA)

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

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.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: Placebo; Drug: TTP399 400 mg; Drug: TTP399 800 mg; Drug: Sitagliptin 100 mg

• Study Type: Interventional
• Enrollment (Actual): 190
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Mesa, Arizona, United States, 85213
    • Tuscon, Arizona, United States, 85741
  • California
    • Canoga Park, California, United States, 91303
    • Huntington Park, California, United States, 90255
    • Los Angeles, California, United States, 90056
    • West Hills, California, United States, 91307
  • Colorado
    • Centennial, Colorado, United States, 80112
    • Littleton, Colorado, United States, 80127
  • Connecticut
    • Waterbury, Connecticut, United States, 06708
  • Florida
    • West Palm Beach, Florida, United States, 33409
  • Illinois
    • Gurnee, Illinois, United States, 60031
  • Indiana
    • Evansville, Indiana, United States, 47725
  • Minnesota
    • Rochester, Minnesota, United States, 55905
  • North Carolina
    • Greensboro, North Carolina, United States, 27408
  • South Carolina
    • Moncks Corner, South Carolina, United States, 29461
  • Texas
    • San Antonio, Texas, United States, 78229
    • San Antonio, Texas, United States, 78209
    • Schertz, Texas, United States, 78154
  • Virginia
    • Norfolk, Virginia, United States, 23507
  • Washington
    • Richland, Washington, United States, 99352

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo once daily	Drug: Placebo; once daily
Experimental: TTP399 400 mg; TTP399 once daily	Drug: TTP399 400 mg; once daily
Experimental: TTP399 800 mg; TTP399 once daily	Drug: TTP399 800 mg; once daily
Active Comparator: Sitagliptin 100 mg; Sitagliptin once daily	Drug: Sitagliptin 100 mg; once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in HbA1c (Glycosylated haemoglobin)	Day 1 to Day 168

Secondary Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: vTv Therapeutics
• Investigators: Study Chair: Carmen Valcarce, Ph.D., vTv Therapeutics

Study record dates

Study Major Dates

• Study Start: March 1, 2015
• Primary Completion (Actual): July 1, 2016
• Study Completion (Actual): September 1, 2016

Study Registration Dates

• First Submitted: March 27, 2015
• First Submitted That Met QC Criteria: March 27, 2015
• First Posted (Estimate): April 1, 2015

Study Record Updates

• Last Update Posted (Actual): February 10, 2017
• Last Update Submitted That Met QC Criteria: February 9, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Incretins; Dipeptidyl-Peptidase IV Inhibitors; Sitagliptin Phosphate
• Other Study ID Numbers: TTP399-202