Date: 2015-03-25
Type of information: Results
phase: 3
Announcement: results
Company: Novo Nordisk (Denmark)
Product: FIAsp (faster-acting formulation of insulin aspart NovoRapid®) (NN1218)
Action
mechanism: insulin analog. Faster-acting insulin aspart is a mealtime insulin for control of postprandial glucose excursions in type 1 and type 2 diabetes as well as in pump treatment. Faster-acting insulin aspart is insulin aspart (NovoRapid®) in a new formulation in which two new excipients have been added to ensure early and fast absorption.
Disease: type 1 and type 2 diabetes
Therapeutic area: Metabolic diseases
Country: Belgium, Canada, Croatia, Czech Republic, Finland, Germany, Hungary, India, Israel, Poland, Puerto Rico, Russian Federation, Serbia Slovakia, UK, USA
Trial
details: The onset® programme is a phase 3 clinical programme with faster-acting insulin aspart that consists of four trials encompassing more than 2,000 people with type 1 and type 2 diabetes mellitus. onset® 1 is conducted in Europe and the United States of America (USA). The aim of the trial is to investigate efficacy and safety of FIAsp (faster-acting insulin aspart) compared to insulin aspart, both in combination with insulin detemir in adults with type 1 diabetes. This trial consists of two periods: a 26 week treatment period followed by a 26 week additional treatment period. (NCT01831765) onset® 2 is conducted in Asia, Europe and North America. The aim of the trial is to compare FIAsp (faster-acting insulin aspart) to insulin aspart, both in combination with insulin glargine and metformin in adults with type 2 diabetes.(NCT01819129) The onset® 3 trial (236 people randomised) - an 18-week randomised, open-label, basal-bolus vs basal trial confirming superiority (in terms of HbA1c) of mealtime faster-acting insulin aspart in a full basal-bolus regimen versus basal insulin therapy, both in combination with metformin. The results were reported in January 2015. The onset® 4 trial (37 people randomised) - a six-week randomised, double-blind, parallel-group trial confirming pump compatibility and safety of faster-acting insulin aspart and NovoRapid® in type 1 diabetes. The results were reported in August 2014.
Latest
news: * On March 25, 2015, Novo Nordisk announced headline results from the final phase 3a trials for faster-acting insulin aspart, onset® 1 and onset®2. The trials investigated the efficacy and safety of faster-acting insulin aspart compared with NovoRapid® (insulin aspart) in a basal-bolus regimen in people with type 1 and type 2 diabetes, respectively. Both trials achieved their primary objectives by demonstrating that treatment with faster-acting insulin aspart is non-inferior to NovoRapid® with regard to lowering of HbA1c. For people with type 1 diabetes, the HbA1c lowering achieved with faster-acting insulin aspart was statistically significantly larger than that achieved with NovoRapid® when the insulins were given at mealtime. In addition, treatment with faster-acting insulin aspart was associated with less increase of postprandial glucose than NovoRapid® during meal tests in both trials. In both trials, the previously reported safety and tolerability profiles of faster-acting insulin aspart and NovoRapid® were confirmed, and there were no apparent differences between the two treatment groups with respect to adverse events and other safety parameters.Novo Nordisk expects to file faster-acting insulin aspart for regulatory review in the US and EU around the turn of the year. In onset® 1, a total of 1,290 people with type 1 diabetes had their basal insulin therapy optimised during an eight-week run-in period. After the run-in period, 1,143 people with type 1 diabetes, who had successfully optimised their basal insulin therapy following conversion to Levemir®, were randomised in a double-blinded fashion to addition of either faster-acting insulin aspart or NovoRapid® at mealtimes for 52 weeks, or to open-label treatment with faster-acting insulin aspart post-meal for a period of 26 weeks. After 26 weeks, the mean baseline HbA1c of 7.6% was reduced by 0.32%, 0.17% and 0.13% for people treated with mealtime faster-acting insulin aspart, mealtime NovoRapid® and post-meal faster-acting insulin aspart, respectively. This confirmed the trial's primary objective of non-inferiority in HbA1c improvement for mealtime faster-acting insulin aspart compared to NovoRapid®. The HbA1c improvement with mealtime faster-acting insulin aspart was statistically significantly greater than with NovoRapid® and the improvement with post-meal faster-acting insulin aspart was non-inferior compared with NovoRapid® at mealtime. In the trial, people treated with faster-acting insulin aspart achieved statistically significantly larger improvements in both 1- and 2-hour postprandial glucose (PPG) increments during a meal test compared with people treated with NovoRapid®. The largest difference in PPG increment was achieved at 1 hour and was more than 1 mmol/l.The overall rate of severe or blood glucose confirmed hypoglycaemia was similar for faster-acting insulin aspart and NovoRapid®. A higher rate of hypoglycaemia was observed for mealtime faster-acting insulin aspart within the first hour after start of a meal. In onset® 2, a total of 881 people with type 2 diabetes inadequately controlled on a combination of basal insulin and oral antidiabetic drugs had their basal therapy optimised during an eight-week run-in period. The 689 people who had reached the prespecified HbA1c target of 7.0-9.5% in the run-in period were randomised to addition of either faster-acting insulin aspart or NovoRapid® as mealtime insulin for a period of 26 weeks. After 26 weeks, the mean HbA1c had improved from around 7.9% to around 6.6% for both people treated with faster-acting insulin aspart and people treated with NovoRapid®. This confirmed the primary objective of non-inferiority in HbA1c. In the trial, people treated with faster-acting insulin aspart achieved a statistically significantly larger improvement of around 0.6 mmol/l in 1-hour PPG increment during a meal test compared with people treated with NovoRapid®. The improvement in 2-hour PPG increment was numerically larger for people treated with faster-acting insulin aspart compared with NovoRapid® but the difference was not statistically significant. The overall rate of severe or blood glucose confirmed hypoglycaemia was similar for faster-acting insulin aspart and NovoRapid®. A higher rate of hypoglycaemia was observed for faster-acting insulin aspart within the first two hours after start of a meal. * On December 19, 2012, Novo Nordisk has announced the decision to initiate phase 3 development for FIAsp, a faster-acting formulation of insulin aspart (NovoRapid®). The phase 1 proof–of-concept trials for FIAsp have now been completed. Pharmacokinetic and pharmacodynamic properties of insulin aspart in a number of different formulations have been analysed in people with type 1 and type 2 diabetes, in order to identify the formulation with the most attractive profile with regard to speed of onset of appearance, as well as stability. The new formulation of insulin aspart selected for phase 3 development has a faster onset of appearance than NovoRapid® (NovoLog® in the US) and thereby mimics the endogenous insulin secretory response in a non-diabetic individual more closely. This potentially enables more flexible insulin administration in connection with meals, as well as improved post-prandial glucose control. In the proof of concept trials, no apparent differences between NovoRapid® and the new formulations of insulin aspart were observed with respect to adverse events and standard safety parameters.
Novo Nordisk expects to initiate the phase 3 programme, onset®, expected to include around 3,000 people with type 1 or type 2 diabetes, towards the end of 2013.
