- Study highlights results from the first DURATION-NEO trial evaluating investigational formulation of exenatide once-weekly suspension for autoinjection
- Reductions in fasting plasma glucose and weight were similar between treatment groups
- Patients treated with exenatide once-weekly suspension for autoinjection reported greater total treatment satisfaction, with similar gastrointestinal tolerability and adverse events compared to Byetta
AstraZeneca today announced 28-week results from DURATION-NEO-1, a Phase III study comparing an investigational formulation of exenatide once-weekly suspension for autoinjection to twice-daily exenatide (Byetta®) injection in adult patients with type 2 diabetes who had inadequate glycaemic control. The study met its primary endpoint of non-inferiority, demonstrating that exenatide once-weekly suspension for autoinjection provided greater mean reductions in HbA1c (blood glucose levels) compared to Byetta at 28 weeks (-1.4% vs. -1.0%, respectively; p-value = 0.007).1,2 The results were presented today at the 50th Annual Meeting of the European Association for the Study of Diabetes (EASD) in Vienna, Austria.
“In this study, the formulation of once-weekly exenatide suspension for autoinjection demonstrated superior reductions in HbA1c as well as similar reductions in weight and other glycaemic measures compared to Byetta,” said Carol H. Wysham, M.D., Department of Endocrinology, Rockwood Clinic, Spokane, Washington, and lead study investigator. “The results provide evidence of the tolerability and efficacy of this investigational formulation of once-weekly exenatide suspension delivered through a single-use autoinjector.”
Among secondary endpoints, the study demonstrated that a similar number of patients in the exenatide autoinjection group and Byetta group reached a HbA1c target of < 7% at 28 weeks (49% vs. 43%, respectively; p-value = 0.22)1,2; however, more patients in the exenatide autoinjection group achieved further HbA1c reductions to ≤ 6.5% (36% vs. 26% of patients treated with Byetta; p-value = 0.05).2 Patients in the exenatide autoinjection group and Byetta group had similar reductions in mean body weight (-1.5 kg vs. -1.9 kg, respectively; p-value = 0.4)1,2 as well as reductions in fasting plasma glucose levels (-1.8 mmol/L vs. -1.3 mmol/L, respectively; p-value = 0.17), at 28 weeks.2 Patients in both the exenatide autoinjection group and Byetta group also experienced improvements in post-prandial glucose (two-hour glucose excursions of 1.7 mmol/L vs. 3.9 mmol/L, respectively) at 16 weeks.2
The proportion of patients experiencing treatment-emergent adverse events was similar in the exenatide autoinjection group compared to the Byetta group (70.7% vs. 74%, respectively).2 Gastrointestinal adverse events including nausea, vomiting and diarrhoea were also similar in the exenatide autoinjection group compared to the Byetta group (9.6% vs. 21.2%; 3.5% vs. 6.2%; and 5.2% vs. 11.6%, respectively),2 while patients in the exenatide autoinjection group experienced more injection site nodules compared to the Byetta group (12.7% vs. 0.7%, respectively).1,2 There were no major hypoglycaemic events in either treatment group. Minor hypoglycaemia occurred primarily in patients with concomitant sulphonylurea use.1,2 The percentage of patients with serious adverse events and with adverse events leading to withdrawal from the study was low in both treatment groups (2.6% and 2.2% for the exenatide autoinjection group, vs. 4.8% for both measures in the Byetta group, respectively).1,2
Patients in the exenatide autoinjection group also reported significantly greater total treatment satisfaction compared to patients treated with Byetta, indicated by higher average increases in patients’ scores of treatment convenience and flexibility of treatment on the Diabetes Treatment Satisfaction Questionnaire.2
“AstraZeneca is committed to better understanding the diverse needs of diabetes patients, including the need for enhanced delivery methods,” said Elisabeth Björk, Head of Cardiovascular & Metabolism, Global Medicines Development, AstraZeneca. “The results from DURATION-NEO-1 support our continued commitment to diabetes patients through developing this new formulation of exenatide once-weekly suspension for autoinjection and investigating a new delivery device.”
Study Design
The DURATION-NEO-1 study was a 28-week, randomised, open-label trial conducted across 59 centres.1 In the study, 377 patients with type 2 diabetes who were not achieving adequate HbA1c control using diet and exercise or other oral anti-diabetic medications (metformin, sulphonylurea or pioglitazone) were randomised to receive 2 mg of exenatide once-weekly suspension for autoinjection or Byetta 10 mg.1
The primary endpoint was change in HbA1c from baseline to week 28.1,4 Secondary endpoints included change from baseline in fasting plasma glucose and body weight at week 28, change from baseline in two-hour postprandial glucose at week 16, and the proportion of patients achieving HbA1c of < 7% and ≤ 6.5% at week 28.4 Non-inferiority was concluded upon the data meeting the upper limit of a two-sided 95% confidence interval, defined as less than 0.4%. Superiority was defined as the upper limit being less than zero. In addition, the upper limit from the same 95% confidence interval was compared to 0.3% as a key secondary analysis for the primary endpoint. Non-inferiority was evaluated first, and superiority and the key secondary analysis for the primary endpoint were evaluated only after non-inferiority was achieved.3
About Diabetes
Diabetes is estimated to affect more than 382 million people worldwide. The prevalence of diabetes is projected to reach more than 592 million people worldwide by 2035.5 Type 2 diabetes accounts for approximately 90-95 percent of all cases of diagnosed diabetes.6 Type 2 diabetes is a chronic disease7 characterised by pathophysiologic defects leading to elevated glucose levels.8 Significant unmet needs still exist, as many patients remain inadequately controlled on their current glucose-lowering regimen.9
References
1 Wysham CH, Rosenstock J, Malloy J, et al. DURATION-NEO-1: Greater HbA1c reductions with exenatide suspension once-weekly by autoinjector pen vs exenatide twice-daily in inadequately controlled type 2 diabetes. European Associated for the Study of Diabetes (EASD) Abstract. Accessed 29 July 2014.
2 DURATION-NEO-1: Greater HbA1c reductions with exenatide suspension once weekly by autoinjector pen vs exenatide twice-daily in inadequately controlled type 2 diabetes. EASD draft presentation. Accessed 29 July 2014.
3 DURATION-NEO-1 Study Protocol. Accessed 14 August 2014.
4 Clinicaltrials.gov. Efficacy and Safety of Exenatide Once Weekly Suspension in Subjects With Type 2 Diabetes (DURATION-NEO-1). Available at: http://clinicaltrials.gov/show/NCT01652716. Accessed 29 July 2014.
5 International Diabetes Federation. IDF Diabetes Atlas, 6th edn., 2013. Available at: http://www.idf.org/diabetesatlas. Accessed 1 May 2014.
6 Centers for Disease Control and Prevention. National Diabetes Factsheet 2011. Available at: http://www.cdc.gov/diabetes/pubs/pdf/ndfs_2011.pdf. Accessed 1 May 2014.
7 World Health Organization. Media Centre – Diabetes. 2011. Available at: http://www.who.int/mediacentre/factsheets/fs312/en/. Accessed 1 May 2014.
8 Kahn SE. The relative contributions of insulin resistance and beta-cell dysfunction to the pathophysiology of type 2 diabetes. Diabetologia. 2003;46:3-19.
9 Cheung B, Lond, Edin et al. Diabetes Prevalence and Therapeutic Target Achievement in the United States, 1999-2006. American Journal of Medicine. 2009;122:443-453.
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