ABT-126 monotherapy in mild-to-moderate Alzheimer's dementia: Randomized double-blind, placebo and active controlled adaptive trial and open-label extension

Alzheimer's Research and Therapy

Volumn 8, Issue 1, 2016, Pages

  Gault, Laura M ^a   Lenz, Robert A ^a,b   Ritchie, Craig W ^c   Meier, Andreas ^d   Othman, Ahmed A ^a,e   Tang, Qi ^a   Berry, Scott ^f   Pritchett, Yili ^a,g   Robieson, Weining Z ^a  

^a ABBVIE INC   (United States)

^b AMGEN INC   (United States)

^c UNIVERSITY OF EDINBURGH   (United Kingdom)

^d PFIZER INC   (United States)

^e CAIRO UNIVERSITY   (Egypt)

^f BERRY CONSULTANTS   (United States)

^g MEDIMMUNE   (United States)

Author keywords

ABT 126; Adaptive design; Alzheimer's dementia drug therapy; Alzheimer's disease; Assessment of cognitive disorders dementia; Nicotinic agonists; Randomized controlled trial

Indexed keywords

4 [(5 PHENYL 1,3,4 THIADIAZOL 2 YL)OXY] 1 AZONIATRICYCLO[3.3.1.1 3,7]DECANE 3,4 DICARBOXY 3 HYDROXYBUTANOATE; DONEPEZIL; PLACEBO; ABT-126; CHOLINERGIC RECEPTOR STIMULATING AGENT; CHOLINESTERASE INHIBITOR; INDAN DERIVATIVE; PIPERIDINE DERIVATIVE; QUINUCLIDINE DERIVATIVE; THIADIAZOLE DERIVATIVE;

AGED; ALZHEIMER DISEASE; ALZHEIMER DISEASE ASSESSMENT SCALE; ARTICLE; CONSTIPATION; CONTROLLED STUDY; DEPRESSION; DIARRHEA; DISEASE SEVERITY; DOUBLE BLIND PROCEDURE; DRUG BLOOD LEVEL; DRUG EFFICACY; DRUG SAFETY; DRUG WITHDRAWAL; FEMALE; HEADACHE; HUMAN; MAJOR CLINICAL STUDY; MALE; MONOTHERAPY; NAUSEA; OPEN STUDY; PATIENT COMPLIANCE; PHASE 2 CLINICAL TRIAL; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; SIDE EFFECT; TREATMENT OUTCOME; URINARY TRACT INFECTION; ANALYSIS OF VARIANCE; COGNITION DISORDERS; COMPLICATION; DOSE RESPONSE; MENTAL HEALTH; MIDDLE AGED; VERY ELDERLY;

AGED; AGED, 80 AND OVER; ALZHEIMER DISEASE; ANALYSIS OF VARIANCE; CHOLINERGIC AGONISTS; CHOLINESTERASE INHIBITORS; COGNITION DISORDERS; DOSE-RESPONSE RELATIONSHIP, DRUG; DOUBLE-BLIND METHOD; FEMALE; HUMANS; INDANS; MALE; MENTAL STATUS SCHEDULE; MIDDLE AGED; PIPERIDINES; QUINUCLIDINES; THIADIAZOLES; TREATMENT OUTCOME;

EID: 84992205977     PISSN: None     EISSN: 17589193     Source Type: Journal    
DOI: 10.1186/s13195-016-0210-1     Document Type: Article

References (34)

1. Hebert LE, Weuve J, Scherr PA, Evans DA. Alzheimer disease in the United States (2010-2050) estimated using the 2010 census. Neurology. 2013;80(19):1778-83. doi: 10.1212/WNL.0b013e31828726f5.
2. Yakel JL. Cholinergic receptors: functional role of nicotinic ACh receptors in brain circuits and disease. Pflugers Arch. 2013;465(4):441-50. doi: 10.1007/s00424-012-1200-1.
3. Lendvai B, Kassai F, Szajli A, Nemethy Z. alpha7 nicotinic acetylcholine receptors and their role in cognition. Brain Res Bull. 2013;93:86-96. doi: 10.1016/j.brainresbull.2012.11.003.
4. Colovic MB, Krstic DZ, Lazarevic-Pasti TD, Bondzic AM, Vasic VM. Acetylcholinesterase inhibitors: pharmacology and toxicology. Curr Neuropharmacol. 2013;11(3):315-35. doi: 10.2174/1570159x11311030006.
5. Ritchie CW, Zhinchin G. Low dose, high dose, or no dose: better prescribing of cholinesterase inhibitors for Alzheimer's disease. Int Psychogeriatr. 2013;25(4):511-5. doi: 10.1017/s1041610212002414.
6. Deardorff WJ, Shobassy A, Grossberg GT. Safety and clinical effects of EVP-6124 in subjects with Alzheimer's disease currently or previously receiving an acetylcholinesterase inhibitor medication. Expert Rev Neurother. 2015;15(1):7-17. doi: 10.1586/14737175.2015.995639.
7. Memory Pharmaceuticals. Press release: Memory Pharmaceuticals announces positive Phase 2a results for MEM 3454 in Alzheimer's Disease. 2 Nov 2007. http://www.drugs.com/clinical-trials/memory-pharmaceuticals-announces-positive-phase-2a-results-mem-3454-alzheimer-s-2538.html. Accessed 11 Nov 2015.
8. Masterman D, Awipi T, Ashford E, Nave S, Yoo K, B Vellas et al. A nicotinic-alpha-7 partial agonist as adjunctive therapy to stable donepezil. J Nutr Health Aging. 2012;16(9):838.
9. FORUM Pharmaceuticals. Press release: FORUM Pharmaceuticals Inc. Updates Encenicline Phase 3 Clinical Trial Programs in Alzheimer's Disease and Cognitive Impairment in Schizophrenia. http://www.alzforum.org/news/research-news/rare-severe-side-effects-sideline-some-phase-3-encenicline-trials. Accessed 30 Sept 2016.
10. Gopalakrishnan M, Bitner R, Anderson D, Drescher K, Kohlhaas K, Grønlien J, et al. Preclinical characterization of a selective α7 neuronal nicotinic acetylcholine receptor agonist ABT-126: a novel therapeutic agent for the treatment of cognitive impairment in Alzheimer's disease and schizophrenia. Alzheimers Dement. 2013;9(4 Suppl):817-18. doi: http://dx.doi.org/10.1016/j.jalz.2013.05.1755.
11. Gault L, Ritchie C, Robieson W, Pritchett Y, Othman A, Lenz R. A phase 2 randomized, controlled trial of the 7 agonist ABT-126 in mild-to-moderate Alzheimer's dementia. Alzheimers Dement TRCI. 2015;1(1):81-90.
12. Mohs RC, Knopman D, Petersen RC, Ferris SH, Ernesto C, Grundman M, et al. Development of cognitive instruments for use in clinical trials of antidementia drugs: additions to the Alzheimer's Disease Assessment Scale that broaden its scope. The Alzheimer's Disease Cooperative Study. Alzheimer Dis Assoc Disord. 1997;11 Suppl 2:S13-21.
13. Rosen WG, Mohs RC, Davis KL. A new rating scale for Alzheimer's disease. Am J Psychiatry. 1984;141(11):1356-64.
14. Folstein MF, Folstein SE, McHugh PR. "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975;12(3):189-98.
15. Alexopoulos GS, Abrams RC, Young RC, Shamoian CA. Cornell Scale for Depression in Dementia. Biol Psychiatry. 1988;23(3):271-84.
16. Hachinski VC, Iliff LD, Zilhka E, Du Boulay GH, McAllister VL, Marshall J, et al. Cerebral blood flow in dementia. Arch Neurol. 1975;32(9):632-7.
17. Boothby H, Mann A, Barker A. Factors determining interrater agreement with rating global change in dementia: the CIBIC-plus. Int J Geriatric Psychiatry. 1995;10:1037-45.
18. Cummings JL. The Neuropsychiatric Inventory: assessing psychopathology in dementia patients. Neurology. 1997;48(5 Suppl 6):S10-6.
19. Cummings JL, Mega M, Gray K, Rosenberg-Thompson S, Carusi DA, Gornbein J. The Neuropsychiatric Inventory: comprehensive assessment of psychopathology in dementia. Neurology. 1994;44(12):2308-14.
20. Galasko D, Bennett D, Sano M, Ernesto C, Thomas R, Grundman M, et al. An inventory to assess activities of daily living for clinical trials in Alzheimer's disease. The Alzheimer's Disease Cooperative Study. Alzheimer Dis Assoc Disord. 1997;11 Suppl 2:S33-9.
21. Wechsler D. Wechsler Memory Scale - third edition. Administration and scoring manual. New York: The Psychological Corporation; 1997.
22. Smith SC, Lamping DL, Banerjee S, Harwood RH, Foley B, Smith P, et al. Development of a new measure of health-related quality of life for people with dementia: DEMQOL. Psychol Med. 2007;37(5):737-46. doi: 10.1017/s0033291706009469.
23. Reilly MC, Relkin NR, Zbrozek AS. Development and testing of a new outcome measure of relationship between patients with Alzheimer's disease and their partners. Am J Alzheimers Dis Other Demen. 2006;21(4):249-57.
24. Wimo A, Winblad B. Resource utilization in dementia: RUD-Lite. Brain Aging. 2003;3(1):48-59.
25. Group EQ. EuroQol - a new facility for the measurement of health-related quality of life. Health Policy. 1990;16(3):199-208.
26. Posner K, Brown GK, Stanley B, Brent DA, Yershova KV, Oquendo MA, et al. The Columbia-Suicide Severity Rating Scale: initial validity and internal consistency findings from three multisite studies with adolescents and adults. Am J Psychiatry. 2011;168(12):1266-77. doi: 10.1176/appi.ajp.2011.10111704.
27. Birks J, Harvey RJ. Donepezil for dementia due to Alzheimer's disease. Cochrane Database Syst Rev. 2006;1:CD001190. doi: 10.1002/14651858.CD001190.pub2.
28. Boess FG, de Vry J, Erb C, Flessner T, Hendrix M, Luithle J, et al. Pharmacological and behavioral profile of N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-6-chinolincarboxamide (EVP-5141), a novel alpha7 nicotinic acetylcholine receptor agonist/serotonin 5-HT3 receptor antagonist. Psychopharmacology (Berl). 2013;227(1):1-17. doi: 10.1007/s00213-012-2933-4.
29. Rezvani AH, Kholdebarin E, Brucato FH, Callahan PM, Lowe DA, Levin ED. Effect of R3487/MEM3454, a novel nicotinic alpha7 receptor partial agonist and 5-HT3 antagonist on sustained attention in rats. Prog Neuropsychopharmacol Biol Psychiatry. 2009;33(2):269-75. doi: 10.1016/j.pnpbp.2008.11.018.
30. Beach TG, Monsell SE, Phillips LE, Kukull W. Accuracy of the clinical diagnosis of Alzheimer disease at National Institute on Aging Alzheimer Disease Centers, 2005-2010. J Neuropathol Exp Neurol. 2012;71(4):266-73. doi: 10.1097/NEN.0b013e31824b211b.
31. Ossenkoppele R, Jansen WJ, Rabinovici GD, Knol DL, van der Flier WM, van Berckel BN, et al. Prevalence of amyloid PET positivity in dementia syndromes: a meta-analysis. JAMA. 2015;313(19):1939-49. doi: 10.1001/jama.2015.4669.
32. Doody RS, Thomas RG, Farlow M, Iwatsubo T, Vellas B, Joffe S, et al. Phase 3 trials of solanezumab for mild-to-moderate Alzheimer's disease. N Engl J Med. 2014;370(4):311-21. doi: 10.1056/NEJMoa1312889.
33. Salloway S, Sperling R, Fox NC, Blennow K, Klunk W, Raskind M, et al. Two phase 3 trials of bapineuzumab in mild-to-moderate Alzheimer's disease. N Engl J Med. 2014;370(4):322-33. doi: 10.1056/NEJMoa1304839.
34. Florian H, Meier A, Gauthier S, Lipschitz S, Lin Y, Tang Q, et al. Efficacy and safety of ABT-126 in subjects with mild-to-moderate Alzheimer's disease on stable doses of acetylcholinesterase inhibitors: a randomized, double-blind, placebo-controlled study. J Alzheimers Dis. 2016;51(4):1237-47. doi: 10.3233/JAD-150978.