Date: 2016-02-23
Type of information: Results
phase: 3
Announcement: results
Company: Novo Nordisk (Denmark)
Product: Tresiba® (insulin degludec)
Action
mechanism: ultra-long-acting insulin analog.
Disease: type 1 and type 2 diabetes
Therapeutic area: Metabolic diseases
Country: Poland, Puerto Rico, USA
Trial
details: SWITCH 1 (NCT02034513) and SWITCH 2 ( NCT02030600) are two 2x32-weeks randomised, double-blind, cross-over, treat-to-target trials that were initiated in January 2014 with purpose of comparing the safety and efficacy of Tresiba® and insulin glargine. The overall purpose of the trials is to document the hypoglycaemia profile in type 1 diabetes and type 2 diabetes respectively, compared to insulin glargine. In SWITCH 1, 501 people with type 1 diabetes were randomised to crossover treatment with Tresiba® and insulin glargine in combination with insulin aspart. In SWITCH 2, 721 people with type 2 diabetes were randomised to crossover treatment with Tresiba® and insulin glargine in combination with oral antidiabetics.
Latest
news: * On February 23, 2016, Novo Nordisk announced the headline results from SWITCH 1, the second of two 2x32-weeks randomised, double-blind, cross-over, treat-to-target trials, comparing the safety and efficacy of Tresiba® (insulin degludec) and Lantus® (insulin glargine U100). The overall purpose of the trial was to compare the hypoglycaemia occurrence in people with type 1 diabetes treated with Tresiba® or insulin glargine. * On January 29, 2016, Novo Nordisk announced the headline results from SWITCH 2, the first of two 2x32-weeks randomised, double-blind, cross-over, treat-to-target trials, comparing the safety and efficacy of Tresiba® (insulin degludec) and insulin glargine. The overall purpose of the trial was to compare the hypoglycaemia occurrence in people with type 2 diabetes treated with Tresiba® or insulin glargine.
In the trial, 501 people with type 1 diabetes were randomised to cross-over treatment with Tresiba® and insulin glargine U100 in combination with insulin aspart. The timing of the daily injections of both Tresiba® and insulin glargine was randomised equally to take place either in the morning or evening. The primary end-point of the trial was the number of treatment emergent severe or blood glucose confirmed symptomatic hypoglycaemia episodes during the maintenance period (ie after 16 weeks of treatment) in each treatment period.
From a mean baseline of 7.6%, the trial showed non-inferiority in HbA1c reduction for Tresiba® compared to insulin glargine, thus fulfilling the requirements for objectively comparing hypoglycaemia rates between the two treatments. Likewise, the end-of-trial insulin doses were similar at the end of treatment in the two treatment periods.
The trial met the primary end-point by demonstrating non-inferiority in the rate of severe or blood glucose confirmed symptomatic hypoglycemia of Tresiba® compared to insulin glargine. The observed rate was 2,201 events per 100 patient years exposed to Tresiba® and 2,463 events per 100 patient years exposed to insulin glargine during the maintenance period, corresponding to a statistically significant reduction of 11%.
Similarly, non-inferiority was demonstrated for the rate of severe or blood glucose confirmed symptomatic nocturnal hypoglycaemia in the maintenance period. The observed rate of severe or blood glucose confirmed symptomatic nocturnal hypoglycaemia was 277 events per 100 patient years exposed to Tresiba® and 429 events per 100 patient years exposed to insulin glargine, corresponding to a statistically significant 36% reduction with Tresiba® compared to insulin glargine.
Finally, superiority was demonstrated for the confirmatory secondary endpoint of proportions of subjects experiencing severe hypoglycaemia during the maintenance period. The proportion of patients experiencing severe hypoglycaemia was 10% for Tresiba® and 17% for insulin glargine, corresponding to a statistically significant reduction with Tresiba® compared to insulin glargine. The rates of severe hypoglycaemia were 69 and 92 events per 100 patient years exposed, respectively, corresponding to a statistically significant 35% reduction.
All of the above analyses showed similar results for the total treatment period.
In the trial, Tresiba® appeared to have a safe and well-tolerated profile. Adverse events were comparable between the two treatment arms. The most common adverse events were nasopharyngitis, upper respiratory tract infections and hypoglycaemia.
Novo Nordisk expects to initiate filing of the data from the SWITCH trials with regulatory authorities in Q3 2016 with the aim of updating the label for Tresiba®.
In the trial, 721 people with type 2 diabetes were randomised to cross-over treatment with Tresiba® and insulin glargine in combination with metformin. The timing of the daily injections of both Tresiba® and insulin glargine was randomised equally to take place either in the morning or evening. The primary end-point of the trial was the number of treatment emergent severe or blood glucose confirmed symptomatic hypoglycaemia episodes during the maintenance period (ie after 16 weeks of treatment) in each treatment period.
From a mean baseline of 7.6%, the trial showed non-inferiority in HbA1c reduction of Tresiba® compared to insulin glargine, thus fulfilling the requirements for objectively comparing hypoglycaemia rates between the two treatments. Likewise, the end-of-trial insulin doses were similar at the end of treatment in the two treatment periods.
The observed rate of severe or blood glucose confirmed symptomatic hypoglycemia was 186 events per 100 patient years exposed to Tresiba® and 265 events per 100 patient years exposed to insulin glargine during the maintenance period. This reduction was statistically significant, and the trial thus met its primary endpoint by demonstrating a reduction of 30% when people were treated with Tresiba® compared to insulin glargine.
The observed rate of severe or blood glucose symptomatic nocturnal confirmed hypoglycaemia in the maintenance period was 55 events per 100 patient years exposed to Tresiba® and 94 events per 100 patient years exposed to insulin glargine, corresponding to a 42% reduction with Tresiba® compared to insulin glargine and showing statistical significance on this confirmatory secondary end-point.
The confirmatory secondary endpoint of proportions of subjects experiencing severe hypoglycaemia during the maintenance period did not reach statistical significance. However, the supportive end-point, rate of severe hypoglycaemia, showed a 46% reduction with Tresiba® in the maintenance period and a statistical significant reduction of 51% with Tresiba® in the full treatment period.
In the trial, Tresiba® appeared to have a safe and well-tolerated profile. Adverse events were comparable between the two treatment arms. The most common adverse events were nasopharyngitis and upper respiratory tract infections.
Novo Nordisk expects to announce headline results of SWITCH 1 later in the first quarter of 2016.
