No abstract

These results do not support a benefit of TC-5619 for negative or cognitive symptoms in schizophrenia.

Adult patients with cancer who were taking oxycodone CR were readily converted to oxymorphone ER and required half the milligram dose to stabilize their pain. Within 72 h, most patients achieved a stable dose that provided adequate relief with similar opioid adverse events.

Despite advances in exogenous insulin therapy, many patients with type 1 diabetes do not achieve acceptable glycemic control and remain at risk for ketosis and insulininduced hypoglycemia. We conducted a randomized controlled trial to determine whether TTP399, a novel hepatoselective glucokinase activator, improved glycemic control in people with type 1 diabetes without increasing hypoglycemia or ketosis. RESEARCH DESIGN AND METHODS SimpliciT1 was a phase 1b/2 adaptive study. Phase 2 activities were conducted in two parts. Part 1 randomly assigned 20 participants using continuous glucose monitors and continuous subcutaneous insulin infusion (CSII). Part 2 randomly assigned 85 participants receiving multiple daily injections of insulin or CSII. In both parts 1 and 2, participants were randomly assigned to 800 mg TTP399 or matched placebo (fully blinded) and treated for 12 weeks. The primary end point was change in HbA 1c from baseline to week 12. RESULTS The difference in change in HbA 1c from baseline to week 12 between TTP399 and placebo was 20.7% (95% CI 21.3, 20.07) in part 1 and 20.21% (95% CI 20.39, 20.04) in part 2. Despite a greater decrease in HbA 1c with TTP399, the frequency of severe or symptomatic hypoglycemia decreased by 40% relative to placebo in part 2. In both parts 1 and 2, plasma b-hydroxybutyrate and urinary ketones were lower during treatment with TTP399 than placebo. CONCLUSIONS TTP399 lowers HbA 1c and reduces hypoglycemia without increasing the risk of ketosis and should be further evaluated as an adjunctive therapy for the treatment of type 1 diabetes.

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