The SimpliciT1 Study: A Randomized, Double-Blind, Placebo-Controlled Phase 1b/2 Adaptive Study of TTP399, a Hepatoselective Glucokinase Activator, for Adjunctive Treatment of Type 1 Diabetes

OBJECTIVE Despite advances in exogenous insulin therapy, many patients with type 1 diabetes do not achieve acceptable glycemic control and remain at risk for ketosis insulin-induced hypoglycemia. We conducted a randomized controlled trial to determine whether TTP399, novel hepatoselective glucokinase activator, improved people without increasing hypoglycemia or ketosis. RESEARCH DESIGN AND METHODS SimpliciT1 was phase 1b/2 adaptive study. Phase 2 activities were two parts. Part randomly assigned 20 participants using continuous glucose monitors subcutaneous infusion (CSII). 85 receiving multiple daily injections of CSII. In both parts 2, 800 mg TTP399 matched placebo (fully blinded) treated 12 weeks. The primary end point change HbA1c from baseline week 12. RESULTS difference between −0.7% (95% CI −1.3, −0.07) part −0.21% −0.39, −0.04) 2. greater decrease the frequency severe symptomatic decreased by 40% relative plasma β-hydroxybutyrate urinary ketones lower during treatment than placebo. CONCLUSIONS lowers reduces should be further evaluated as an adjunctive therapy diabetes.