PMID- 22138370
OWN - NLM
STAT- MEDLINE
DCOM- 20130206
LR  - 20211021
IS  - 1552-5279 (Electronic)
IS  - 1552-5260 (Linking)
VI  - 8
IP  - 5
DP  - 2012 Sep
TI  - Safety profile of Alzheimer's disease populations in Alzheimer's Disease 
      Neuroimaging Initiative and other 18-month studies.
PG  - 407-16
LID - 10.1016/j.jalz.2011.05.2413 [doi]
AB  - BACKGROUND: Demonstration of a disease-modifying effect of a therapeutic agent on 
      Alzheimer's disease (AD) requires a trial lasting for at least 18 months. An 
      understanding of expected rates of adverse events (AEs), overall 
      discontinuations, and discontinuations due to AEs, serious AEs, and deaths would 
      be useful in planning such trials. METHODS: We examined safety information for 
      patients taking placebo from five published 18-month AD trials and for patients 
      from the Alzheimer's Disease Neuroimaging Initiative study. RESULTS: AEs reported 
      consistently across multiple studies were dyspnea (occurring in 5.3%-5.8% of 
      patients), headache (4.0%-5.5%), constipation (4.3%-4.7%), nausea (2.0%-5.8%), 
      joint swelling (3.6%-3.7%), vomiting (3.6%-3.7%), and anxiety (3.2%-3.6%). Larger 
      multinational studies, as compared with smaller studies with fewer sites and 
      geographies, demonstrated greater overall discontinuations (24.6%-33.0% vs 
      8.2%-21.0%) and greater discontinuations due to AEs (9.5%-11.6% vs 2.7%-3.2%). 
      Rates of death (1.8%-2.4%) and SAEs (19.9%-21.2%) were consistent across 18 month 
      published studies and in ADNI; fall was the most common SAE (2.6%-4.0%) where 
      SAEs were reported. CONCLUSIONS: In general, comparable types of AEs, frequency 
      of deaths, and serious AEs were seen for patients taking placebo in five 
      randomized, controlled 18-month AD trials and in Alzheimer's Disease Neuroimaging 
      Initiative, whereas rates of discontinuations were more variable. Evaluation 
      across studies was complicated by inconsistent methods of reporting safety 
      information. Evaluation of large databases of placebo patients from therapeutic 
      AD trials is needed to further enhance the understanding of expected safety 
      outcomes in clinical trials of AD patients.
CI  - Copyright (c) 2012 The Alzheimer's Association. Published by Elsevier Inc. All 
      rights reserved.
FAU - Henley, David B
AU  - Henley DB
AD  - Lilly Research Laboratories, Indianapolis, IN, USA. henleyda@lilly.com
FAU - Sundell, Karen L
AU  - Sundell KL
FAU - Sethuraman, Gopalan
AU  - Sethuraman G
FAU - Siemers, Eric R
AU  - Siemers ER
CN  - Alzheimer's Disease Neuroimaging Initiative
LA  - eng
GR  - P30 AG010129/AG/NIA NIH HHS/United States
GR  - K01 AG030514/AG/NIA NIH HHS/United States
GR  - U01AG024904/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20111203
PL  - United States
TA  - Alzheimers Dement
JT  - Alzheimer's & dementia : the journal of the Alzheimer's Association
JID - 101231978
RN  - 0 (Antipsychotic Agents)
RN  - 0 (Placebos)
SB  - IM
MH  - Aged
MH  - Aged, 80 and over
MH  - Alzheimer Disease/*diagnosis/*drug therapy
MH  - Antipsychotic Agents/*adverse effects
MH  - Clinical Trials as Topic
MH  - Databases, Factual/statistics & numerical data
MH  - Female
MH  - Humans
MH  - Longitudinal Studies
MH  - Male
MH  - Middle Aged
MH  - *Neuroimaging
MH  - Placebos/adverse effects
MH  - Retrospective Studies
MH  - Time Factors
EDAT- 2011/12/06 06:00
MHDA- 2013/02/07 06:00
CRDT- 2011/12/06 06:00
PHST- 2011/01/05 00:00 [received]
PHST- 2011/05/06 00:00 [revised]
PHST- 2011/05/19 00:00 [accepted]
PHST- 2011/12/06 06:00 [entrez]
PHST- 2011/12/06 06:00 [pubmed]
PHST- 2013/02/07 06:00 [medline]
AID - S1552-5260(11)02595-7 [pii]
AID - 10.1016/j.jalz.2011.05.2413 [doi]
PST - ppublish
SO  - Alzheimers Dement. 2012 Sep;8(5):407-16. doi: 10.1016/j.jalz.2011.05.2413. Epub 
      2011 Dec 3.