In this small trial, administration of lanadelumab to patients with hereditary angioedema with C1 inhibitor deficiency reduced cleavage of high-molecular-weight kininogen and attacks of angioedema. (Funded by Dyax; ClinicalTrials.gov number, NCT02093923 .).

Data indicate that monophosphoryl lipid A, in a dose 10,000 times that of endotoxin, used in experimental pyrogenicity trials, is well tolerated in human volunteers. Pretreatment of normal human volunteers with monophosphoryl lipid A attenuated the systemic response to bacterial endotoxin. These data support further clinical testing of monophosphoryl lipid A for the prevention or amelioration of the severe sequelae of sepsis.

OBJECTIVE -The objectives of this exploratory study were to assess the postprandial glucose-lowering effects and evaluate the safety and tolerability of single, escalating doses of an oral insulin product, hexyl-insulin monoconjugate 2 (HIM2), in patients with type 2 diabetes. Subcutaneous insulin and oral placebo were also administered for comparison.RESEARCH DESIGN AND METHODS -Eighteen patients with type 2 diabetes were enrolled in this randomized, single-blind, placebo-controlled, three-way crossover, doseescalation study. A single dose of each of the following study drugs was administered to each patient on 3 separate days: oral HIM2 (at one of three dose levels: 0.375, 0.5, or 1.0 mg/kg), subcutaneous regular insulin (8 units Humulin R), and oral placebo. At 30 min after dosing, patients ingested a standardized test meal (16 oz/720 calories of Boost Plus). Serial blood samples were collected for determination of plasma glucose and insulin concentrations during the 4-h postdose period. ⅐ dl -1 , respectively). For pooled data from the 0.5-and 1.0-mg/kg dose groups, the HIM2/ subcutaneous insulin ratios for the 2-h postprandial glucose concentration (0.97, 95% CI 0.90 -1.06), maximum postprandial glucose concentration (0.99, 95% CI 0.93-1.06), and glucose AUC 0 -240 (0.98, 95% CI 0.9 -1.06) were within 10% of unity, implying glucodynamic equivalence. Although HIM2 (0.5 and 1.0 mg/kg) and subcutaneous insulin (8 units) provided comparable control of postprandial plasma glucose concentrations, HIM2 resulted in peripheral insulin concentrations that were lower than subcutaneous insulin (mean insulin AUC 0 -240 of 193.1 vs. 233.6 and 230.8 vs. 270.3 U ⅐ h -1 ⅐ ml -1 , respectively). RESULTSCONCLUSIONS -Single, oral doses of HIM2 were safe and well tolerated. HIM2 (0.5 and 1.0 mg/kg) was more effective than placebo and as effective as subcutaneous regular insulin (8 units) at controlling postprandial glycemia with respect to the following parameters: 2-h postprandial glucose concentration, maximum glucose concentration, and glucose AUC 0 -240 . This occurred even though peripheral insulin concentrations were lower following the administration of HIM2 (0.5 and 1.0 mg/kg) than subcutaneous insulin. Thus, HIM2 therapy may control postprandial glycemia without causing peripheral hyperinsulinemia in patients with type 2 diabetes. Diabetes Care 26:421-426, 2003I nadequate control of hyperglycemia in patients with type 2 diabetes is associated with severe microvascular and macrovascular complications (1-4). Clinical studies demonstrated that tight control of fasting and postprandial glycemia in patients with type 2 diabetes resulted in dramatic reductions in the incidence and rate of progression of microvascular complications (5,6).To adequately control postprandial glycemia, several daily injections of insulin are necessary. However, insulin therapy via subcutaneous or other parenteral routes is known to result in peripheral hyperinsulinemia. In addition to the risk of hypoglycemia, some studies have suggested that per...