SAN FRANCISCO – The investigative liver-selective glucokinase activator TTP399 lowered glucose and did not increase lipids in subjects with type 2 diabetes, results from a randomized study demonstrated.
"The compound was extremely well tolerated," Carmen Valcarce, Ph.D., said at the annual scientific sessions of the American Diabetes Association.
Results were presented from a phase Ib/IIa double-blind, 6-week, multiple-dose trial studying TTP399 in 120 type 2 diabetes patients on stable doses of metformin. Three doses were tested: 400 mg twice daily, 800 mg once daily, and 800 mg twice daily, plus a placebo group. The major objective was to assess the safety and tolerability of TTP399 and to evaluate its pharmacodynamics and pharmacokinetics.
The mean age of study participants was 57 years, their mean body mass index was 31.4 kg/m2, their mean HbA1c was 8.2%, and their mean duration of diabetes was about 7 years.
Dr. Valcarce, TransTech Pharma’s senior vice president and scientific liaison, reported that the most frequent adverse event was headache, followed by dizziness and diarrhea. There was only one case of symptomatic hypoglycemia, which occurred in the placebo group. There were no increases in fasting triglycerides, cholesterol, lactate, insulin, or C-peptide.
The researchers observed decreases in the mean daily glucose profile in all treatment groups. In well-controlled subjects (defined as those with a baseline hemoglobin A1c of 7.5% or lower), 85% of those in the 800-mg twice-daily arm and 40% of those receiving any dose of TTP399 achieved normalization. None of the placebo-treated subjects reached an HbA1c of 6.5% or less.
"The clinical results to date are completely consistent with preclinical data and with the mechanism of action of liver-selective glucokinase activators," Dr. Valcarce said.
The study was funded and conducted by Forest Laboratories under a license agreement with TransTech Pharma, which is now continuing the development of TTP399 and will soon begin a 6-month phase IIb study. Dr. Valcarce is an employee of TransTech.
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