GSK2374697, a Novel Albumin-Binding Domain Antibody (AlbudAb), Extends Systemic Exposure of Exendin-4: First Study in Humans - PK/PD and Safety

Clinical Pharmacology and Therapeutics

Volumn 96, Issue 6, 2014, Pages 704-712

  O'Connor Semmes, R L ^a   Lin, J ^a   Hodge, R J ^a   Andrews, S ^a   Chism, J ^a   Choudhury, A ^a   Nunez, D J ^a  

^a GLAXOSMITHKLINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALBUMIN ANTIBODY; EXENDIN 4; GLUCAGON LIKE PEPTIDE 1 RECEPTOR AGONIST; GLUCOSE; GSK 2374697; HUMAN SERUM ALBUMIN; INSULIN; UNCLASSIFIED DRUG; ANTIBODY; ANTIDIABETIC AGENT; GLUCAGON RECEPTOR; GLUCAGON-LIKE PEPTIDE-1 RECEPTOR; GLUCOSE BLOOD LEVEL; GSK2374697; HYBRID PROTEIN; PARACETAMOL; PEPTIDE; PROTEIN BINDING; SERUM ALBUMIN; VENOM;

ADULT; AREA UNDER THE CURVE; ARTICLE; BINDING AFFINITY; CONSTIPATION; CONTROLLED STUDY; DECREASED APPETITE; DIARRHEA; DIZZINESS; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG DOSE ESCALATION; DRUG DOSE TITRATION; DRUG ELIMINATION; DRUG HALF LIFE; DRUG POTENCY; DRUG PROTEIN BINDING; DRUG SAFETY; DRUG TOLERABILITY; DRUG WITHDRAWAL; FEMALE; FLU LIKE SYNDROME; GLUCOSE BLOOD LEVEL; HEADACHE; HUMAN; HUMAN EXPERIMENT; INJECTION SITE REACTION; INSULIN BLOOD LEVEL; MALE; NAUSEA; NORMAL HUMAN; POSTPRANDIAL STATE; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; SIDE EFFECT; SINGLE DRUG DOSE; STOMACH EMPTYING; VOLUME OF DISTRIBUTION; VOMITING; AGED; AGONISTS; ANALYSIS; CHEMICALLY INDUCED; DRUG EFFECTS; METABOLISM; MIDDLE AGED;

ACETAMINOPHEN; ADULT; AGED; ANTIBODIES; BLOOD GLUCOSE; FEMALE; GASTRIC EMPTYING; HUMANS; HYPOGLYCEMIC AGENTS; MALE; MIDDLE AGED; NAUSEA; PEPTIDES; PROTEIN BINDING; RECEPTORS, GLUCAGON; RECOMBINANT FUSION PROTEINS; SERUM ALBUMIN; VENOMS;

EID: 84925552579     PISSN: 00099236     EISSN: 15326535     Source Type: Journal    
DOI: 10.1038/clpt.2014.187     Document Type: Article

References (28)

1. Holt, L.J. et al. Anti-serum albumin domain antibodies for extending the halflives of short lived drugs. Protein Eng. Des. Sel. 21, 283-288 (2008
2. Herring, C. & Schon, O. AlbudabTM technology platform-versatile albumin binding domains for the development of therapeutics with tunable half-lives. In Therapeutic Proteins: Strategies To Modulate Their Plasma Half-Lives Ch. 13 (ed. Kontermann, R.) (Wiley-VCH, Weinheim, Germany, 2012
3. Walker, A. et al. Anti-serum albumin domain antibodies in the development of highly potent, efficacious and long-acting interferon. Protein Eng. Des. Sel. 23, 271-278 (2010
4. Bao, W. et al. Novel fusion of GLP-1 with a domain antibody to serum albumin prolongs protection against myocardial ischemia/reperfusion injury in the rat. Cardiovasc. Diabetol. 12, 148 (2013
5. Nauck, M.A., Kleine, N., Orskov, C., Holst, J.J., Willms, B. & Creutzfeldt, W. Normalization of fasting hyperglycaemia by exogenous glucagon-like peptide 1 (7-36 amide) in type 2 (non-insulin-dependent) diabetic patients. Diabetologia 36, 741-744 (1993
6. Parkes, D.G., Pittner, R., Jodka, C., Smith, P. & Young, A. Insulinotropic actions of exendin-4 and glucagon-like peptide-1 in vivo and in vitro. Metab. Clin. Exp. 50, 583-589 (2001
7. Nauck, M.A. et al. Effects of subcutaneous glucagon-like peptide 1 (GLP-1 [7-36 amide]) in patients with NIDDM. Diabetologia 39, 1546-1553 (1996
8. Brubaker, P.L. Minireview: Update on incretin biology: Focus on glucagon-like peptide-1. Endocrinology 151, 1984-1989 (2010
9. Drucker, D.J. Biological actions and therapeutic potential of the glucagon-like peptides. Gastroenterology 122, 531-544 (2002
10. Astrup, A. et al.; NN8022-1807 Investigators. Safety, tolerability and sustained weight loss over 2 years with the once-daily human GLP-1 analog, liraglutide. Int. J. Obes. (Lond). 36, 843-854 (2012
11. Vilsbøll, T., Agersø, H., Krarup, T. & Holst, J.J. Similar elimination rates of glucagon-like peptide-1 in obese type 2 diabetic patients and healthy subjects. J. Clin. Endocrinol. Metab. 88, 220-224 (2003
12. Davidson, M.B., Bate, G. & Kirkpatrick, P. Exenatide. Nat. Rev. Drug Discov. 4, 713-714 (2005
13. DeYoung, M.B., MacConell, L., Sarin, V., Trautmann, M. & Herbert, P. Encapsulation of exenatide in poly-(D,L-lactide-co-glycolide) microspheres produced an investigational long-acting once-weekly formulation for type 2 diabetes. Diabetes Technol. Ther. 13, 1145-1154 (2011
14. Buse, J.B. et al. Exenatide once weekly versus liraglutide once daily in patients with type 2 diabetes (DURATION-6): A randomised, open-label study. Lancet 381, 117-124 (2013
15. Bush, M.A. et al. Safety, tolerability, pharmacodynamics and pharmacokinetics of albiglutide, a long-acting glucagon-like peptide-1 mimetic, in healthy subjects. Diabetes. Obes. Metab. 11, 498-505 (2009
16. Peters, T. Jr. Metabolism: Albumin in the body. In All About Albumin: Biochemistry, Genetics, and Medical Application (ed. Peters, T. Jr.) 188-249 (Academic, San Diego, CA, 1996
17. Sleep, D., Cameron, J. & Evans, L.R. Albumin as a versatile platform for drug half-life extension. Biochim. Biophys. Acta 1830, 5526-5534 (2013
18. Paulik, M. et al. Long-acting PYY and GLP-1 agonism in combination synergistically normalizes weight, glucose, metabolic and metabolomic parameters in diet induced obese mice. Diabetes 61, A497 (2012
19. Bois, F.Y., Tozer, T.N., Hauck, W.W., Chen, M.L., Patnaik, R. & Williams, R.L. Bioequivalence: Performance of several measures of extent of absorption. Pharm. Res. 11, 715-722 (1994
20. Holland, M.C. et al. Autoantibodies to variable heavy (VH) chain Ig sequences in humans impact the safety and clinical pharmacology of a VH domain antibody antagonist of TNF-a receptor 1. J. Clin. Immunol. 33, 1192-1203 (2013
21. Porchet, H.C., Benowitz, N.L. & Sheiner, L.B. Pharmacodynamic model of tolerance: Application to nicotine. J. Pharmacol. Exp. Ther. 244, 231-236 (1988
22. Barrington, P. 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. 13, 426-433 (2011
23. Blase, E., Taylor, K., Gao, H.Y., Wintle, M. & Fineman, M. Pharmacokinetics of an oral drug (acetaminophen) administered at various times in relation to subcutaneous injection of exenatide (exendin-4) in healthy subjects. J. Clin. Pharmacol. 45, 570-577 (2005
24. Darpo, B. et al. Albiglutide Does Not Prolong QTc Interval in Healthy Subjects: A Thorough ECG Study. Diabetes Ther. 5, 141-153 (2014
25. Drucker, D.J. et al.; DURATION-1 Study Group. Exenatide once weekly versus twice daily for the treatment of type 2 diabetes: A randomised, open-label, non-inferiority study. Lancet 372, 1240-1250 (2008
26. Loghin, C., De La Pena, A., Cui, X., & Chien, J. Gastric emptying effects of dulaglutide in patients with type 2 diabetes mellitus. American Association of Clinical Endocrinologists 23rd Annual Scientific and Clinical Congress , Las Vegas, NV, 14-16 May 2014. Abstract 243.
27. Nauck, M.A., Kemmeries, G., Holst, J.J. & Meier, J.J. Rapid tachyphylaxis of the glucagon-like peptide 1-induced deceleration of gastric emptying in humans. Diabetes 60, 1561-1565 (2011
28. Ouellet, D., Sutherland, S., Wang, T., Griffini, P. & Murthy, V. First-time-in-human study with GSK1018921, a selective GlyT1 inhibitor: Relationship between exposure and dizziness. Clin. Pharmacol. Ther. 90, 597-604 (2011).