Dose-finding results in an adaptive, seamless, randomized trial of once-weekly dulaglutide combined with metformin in type 2 diabetes patients (AWARD-5)

Diabetes, Obesity and Metabolism

Volumn 16, Issue 8, 2014, Pages 748-756

  Skrivanek, Z ^a   Gaydos, B L ^a   Chien, J Y ^a   Geiger, M J ^b   Heathman, M A ^a   Berry, S ^c   Anderson, J H ^d   Forst, T ^e   Milicevic, Z ^a   Berry, D ^c  

^a ELI LILLY AND COMPANY   (United States)

^b REGENERON PHARMACEUTICALS INC   (United States)

^c BERRY CONSULTANTS   (United States)

^d Diabetes and Cardiometabolic Medicine   (United States)

^e Profil   (Germany)

Author keywords

AWARD 5; Bayesian adaptive; Dose finding; Dulaglutide dose; GLP 1; GLP 1 receptor agonist; Metformin; Type 2 diabetes

Indexed keywords

ALPHA AMYLASE PANCREAS ISOENZYME; DULAGLUTIDE; GLUCOSE; HEMOGLOBIN A1C; INSULIN; METFORMIN; PLACEBO; SITAGLIPTIN; ANTIDIABETIC AGENT; ANTIOBESITY AGENT; GLUCAGON LIKE PEPTIDE; GLUCAGON RECEPTOR; GLUCAGON-LIKE PEPTIDE-1 RECEPTOR; HYBRID PROTEIN; IMMUNOGLOBULIN FC FRAGMENT;

ADULT; AGED; ARTICLE; BODY MASS; BODY WEIGHT; CONTROLLED STUDY; DIABETIC PATIENT; DIARRHEA; DIASTOLIC BLOOD PRESSURE; DISEASE DURATION; DOSE CALCULATION; DOUBLE BLIND PROCEDURE; DRUG EFFICACY; DRUG SAFETY; DRUG WITHDRAWAL; FEMALE; GASTROENTERITIS; GLUCOSE BLOOD LEVEL; HUMAN; INSULIN BLOOD LEVEL; INSULIN SENSITIVITY; MAJOR CLINICAL STUDY; MALE; NAUSEA AND VOMITING; NON INSULIN DEPENDENT DIABETES MELLITUS; OPTIMAL DRUG DOSE; PHASE 3 CLINICAL TRIAL; PNEUMONIA; PULSE RATE; RANDOMIZED CONTROLLED TRIAL; SIDE EFFECT; SYSTOLIC BLOOD PRESSURE; THYROID MEDULLARY CARCINOMA; TREATMENT DURATION; URINARY TRACT INFECTION; ADOLESCENT; ADVERSE EFFECTS; AGONISTS; ANALOGS AND DERIVATIVES; BLOOD; CLINICAL TRIAL; COMPLICATION; DIABETES MELLITUS, TYPE 2; DIABETIC DIET; DOSE RESPONSE; DRUG COMBINATION; EXERCISE; HYPERGLYCEMIA; LOW CALORY DIET; MIDDLE AGED; MULTIMODALITY CANCER THERAPY; OVERWEIGHT; SUBCUTANEOUS DRUG ADMINISTRATION; YOUNG ADULT;

ADOLESCENT; ADULT; AGED; ANTI-OBESITY AGENTS; COMBINED MODALITY THERAPY; DIABETES MELLITUS, TYPE 2; DIABETIC DIET; DIET, REDUCING; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG THERAPY, COMBINATION; EXERCISE; FEMALE; GLUCAGON-LIKE PEPTIDES; HUMANS; HYPERGLYCEMIA; HYPOGLYCEMIC AGENTS; IMMUNOGLOBULIN FC FRAGMENTS; INJECTIONS, SUBCUTANEOUS; MALE; METFORMIN; MIDDLE AGED; OVERWEIGHT; RECEPTORS, GLUCAGON; RECOMBINANT FUSION PROTEINS; YOUNG ADULT;

EID: 84904308261     PISSN: 14628902     EISSN: 14631326     Source Type: Journal    
DOI: 10.1111/dom.12305     Document Type: Article

References (29)

1. Barrington P, Chien JY, Showalter HD et al. A 5-week study of the pharmacokinetics and pharmacodynamics of LY2189265, a novel, long-acting glucagon-like peptide-1 analogue, in patients with type 2 diabetes. Diabetes Obes Metab 2011; 13: 426-433.
2. Barrington P, Chien JY, Tibaldi F, Showalter HD, Schneck K, Ellis B. LY2189265, a long-acting glucagon-like peptide-1 analogue, showed a dose-dependent effect on insulin secretion in healthy subjects. Diabetes Obes Metab 2011; 13: 434-438.
3. Glaesner W, Vick AM, Millican R et al. Engineering and characterization of the long-acting glucagon-like peptide-1 analogue LY2189265, an Fc fusion protein. Diabetes Metab Res Rev 2010; 26: 287-296.
4. Umpierrez G, Povedano ST, Manghi FP, Shurzinske L, Pechtner V. Efficacy and safety of dulaglutide monotherapy vs metformin in type 2 diabetes in a randomized controlled trial (AWARD-3). Diabetes Care 2014; in press.
5. Nauck M, Weinstock R, Umpierrez G et al. Efficacy and safety of dulaglutide vs. sitagliptin after 52 weeks in type 2 diabetes (AWARD-5). Diabetes 2013; 62(Suppl 1): A17.
6. Weinstock R, Umpierrez G, Guerci B et al. Safety and efficacy of dulaglutide vs. sitagliptin after 104 weeks in type 2 diabetes (AWARD-5). Diabetes 2013; 62(Suppl 1): A258.
7. WMA. World Medical Association declaration of Helsinki. Recommendations guiding physicians in biomedical research involving human subjects. JAMA 1997; 277: 925-926.
8. Geiger MJ, Skrivanek Z, Gaydos B, Chien J, Berry S, Berry D. An adaptive, dose-finding, seamless phase 2/3 study of a long-acting glucagon-like Peptide-1 analog (dulaglutide): trial design and baseline characteristics. J Diabetes Sci Technol 2012; 6: 1319-1327.
9. Skrivanek Z, Berry S, Berry D et al. Application of adaptive design methodology in development of a long-acting glucagon-like Peptide-1 analog (dulaglutide): statistical design and simulations. J Diabetes Sci Technol 2012; 6: 1305-1318.
10. Spencer K, Colvin K, Braunecker B et al. Operational challenges and solutions with implementation of an adaptive seamless phase 2/3 study. J Diabetes Sci Technol 2012; 6: 1296-1304.
11. Skrivanek Z, Chien J, Gaydos B, Heathman M, Geiger MJ, Milicevic Z. Dose-finding results in an adaptive trial of dulaglutide combined with metformin in type 2 diabetes (AWARD-5). Diabetes 2013; 62(Suppl 1): A269.
12. Grunberger G, Chang A, Garcia Soria G, Botros FT, Bsharat R, Milicevic Z. Monotherapy with the once-weekly GLP-1 analogue dulaglutide for 12 weeks in patients with Type 2 diabetes: dose-dependent effects on glycaemic control in a randomized, double-blind, placebo-controlled study. Diabet Med 2012; 29: 1260-1267.
13. Umpierrez G, Manghi F, Perez M, Tofé PS, Shurzinske L, Pechtner V. Efficacy and safety of dulaglutide vs. metformin in type 2 diabetes (AWARD-3). Diabetes 2013; 62(Suppl 1): A17.
14. Wysham C, Blevins T, Arakaki R et al. Efficacy and safety of dulaglutide versus placebo and exenatide in type 2 diabetes (AWARD-1). Diabetes 2013; 62(Suppl 1): A16.
15. Umpierrez G, Blevins T, Rosenstock J, Cheng C, Anderson JH, Bastyr E. The effects of LY2189265, a long-acting glucagon-like peptide-1 analog, in a randomized, placebo-controlled, double-blind study of overweight/obese patients with type 2 diabetes: the EGO study. Diabetes Obes Metab 2011; 13: 418-425.
16. Ferdinand K, Calhoun D, Lonn E et al. Long-term effects of dulaglutide, a novel GLP-1 agonist, on ambulatory blood pressure and heart rate in patients with type 2 diabetes. J Clin Hypertens 2012; 14: 488.
17. Pratley RE, Nauck M, Bailey T et al. Liraglutide versus sitagliptin for patients with type 2 diabetes who did not have adequate glycaemic control with metformin: a 26-week, randomised, parallel-group, open-label trial. Lancet 2010; 375: 1447-1456.
18. Bergenstal RM, Wysham C, Macconell L et al. Efficacy and safety of exenatide once weekly versus sitagliptin or pioglitazone as an adjunct to metformin for treatment of type 2 diabetes (DURATION-2): a randomised trial. Lancet 2010; 376: 431-439.
19. Blevins T, Pullman J, Malloy J et al. DURATION-5: exenatide once weekly resulted in greater improvements in glycemic control compared with exenatide twice daily in patients with type 2 diabetes. J Clin Endocrinol Metab 2011; 96: 1301-1310.
20. Buse JB, Nauck M, Forst T et al. Exenatide once weekly versus liraglutide once daily in patients with type 2 diabetes (DURATION-6): a randomised, open-label study. Lancet 2013; 381: 117-124.
21. Diamant M, Van Gaal L, Stranks S et al. Once weekly exenatide compared with insulin glargine titrated to target in patients with type 2 diabetes (DURATION-3): an open-label randomised trial. Lancet 2010; 375: 2234-2243.
22. Meier JJ. GLP-1 receptor agonists for individualized treatment of type 2 diabetes mellitus. Nat Rev Endocrinol 2012; 8: 728-742.
23. Malloy J, Gurney K, Shan K, Yan P, Chen S. Increased variability and abnormalities in pancreatic enzyme concentrations in otherwise asymptomatic subjects with type 2 diabetes. Diabetes Metab Syndr Obes 2012; 5: 419-424.
24. Steinberg WDJ, Wadden T, Jensen C, Svendsen C, Rosenstock J (eds). Longitudinal Monitoring of Lipase and Amylase in Adults With Type 2 Diabetes and Obesity: Evidence From Two Phase 3 Randomized Clinical TrialsWith the Once-Daily GLP-1 Analog Liraglutide. Miami, FL: American Gastroenterological Association; 2013, 2012.
25. Lando HM, Alattar M, Dua AP. Elevated amylase and lipase levels in patients using glucagonlike peptide-1 receptor agonists or dipeptidyl-peptidase-4 inhibitors in the outpatient setting. Endocr Pract 2012; 18: 472-477.
26. Berry D. Bayesian clinical trials. Nat Rev Drug Discov 2006; 5: 27-36.
27. Berry S, Carlin B, Lee J, Mueller P. Bayesian Adaptive Methods for Clinical Trials, Vol. 38. New York: Chapman & Hall/CRC Biostatistics Series, 2010.
28. Moretto TJ, Milton DR, Ridge TD et al. Efficacy and tolerability of exenatide monotherapy over 24 weeks in antidiabetic drug-naive patients with type 2 diabetes: a randomized, double-blind, placebo-controlled, parallel-group study. Clin Ther 2008; 30: 1448-1460.
29. Vilsboll T, Brock B, Perrild H et al. Liraglutide, a once-daily human GLP-1 analogue, improves pancreatic B-cell function and arginine-stimulated insulin secretion during hyperglycaemia in patients with Type 2 diabetes mellitus. Diabet Med 2008; 25: 152-156.