Replies to post #23808 on RespireRx Pharmaceuticals Inc (RSPI)

[bladerunner1717]

Neuro,

Can you comment on this? (posted by masterlongevity on Dew's I hub board):



Post # of 73757

[P06.074] Disease Modifying Effect of Dimebon in Alzheimer's Disease: Results from a 12-Month Study of Dimebon and a 6-Month Open-Label Period Analyzed Using a Staggered Start Approach and a Natural-History Staggered Start (NHSS) Approach

Suzanne Hendrix, Bryan Selby, Lynn Seely, Jeffrey Cummings, Salt Lake City, UT, San Francisco, CA, Los Angeles, CA

OBJECTIVE: To estimate the proportion of the 12-month Dimebon effect in Alzheimer's disease (AD) patients due to disease modification using a staggered-start analysis of the open-label data (12 to 18 months), and a NHSS approach. BACKGROUND: Dimebon is an investigational drug under evaluation as a novel treatment for neurodegenerative disease (AD and Huntington's disease). Dimebon enhances mitochondrial function and increases cell viability and neurite outgrowth. Dimebon showed benefit on all five outcome measures in a 12-month placebo-controlled AD study assessing cognition and memory, function, and behavior (Doody, 2008). DESIGN/METHODS: The 12 to 18 month data were analyzed as a staggered start study design (Leber, 1997) in order to estimate the disease modifying component of the drug effect, ignoring dropouts during the first phase. A NHSS approach was used to separate disease-modifying and symptomatic effects by using patients' differing baseline severities to reflect a staggered initiation of drug using data up to 12 months. RESULTS: In the open-label extension, patients originally treated with placebo showed treatment benefit from Dimebon, but did not catch-up with patients originally treated with Dimebon who maintained a 3.0 point advantage on the ADAS-cog, which was 50% of the 6.0 point difference seen at 12 months. This staggered start estimate underestimates the disease modification effect due to dropout bias. A NHSS estimate was obtained which is less subject to dropout bias and gives a larger disease modifying estimate than the staggered start approach. CONCLUSIONS/RELEVANCE: The majority of Dimebon's treatment effect in patients with AD is due to disease modification based upon estimates from the NHSS approach, which has less dropout bias than a staggered start estimate. This suggests that Dimebon has an early and sustained disease-modifying effect resulting in an improved clinical course for patients with AD. Supported by: Medivation, Inc.
Category - Aging and Dementia - Clinical

Wednesday, April 29, 2009 4:00 PM

Poster Session VI: Aging and Dementia: Clinical II (4:00 PM-7:00 PM)



Bladerunner