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Adaptive, dose-finding phase 2 trial evaluating the safety and efficacy of ABT-089 in mild to moderate Alzheimer disease
Lenz RA, Pritchett YL, Berry SM, Llano DA, Han S, Berry DA, Sadowsky CH, Abi-Saab WM et al.. Alzheimer disease and associated disorders, 2015-07-01
Topic: Amyloid, tau and blood-test diagnosis
ABT-089, an α4β2 neuronal nicotinic receptor partial agonist, was evaluated for efficacy and safety in mild to moderate Alzheimer disease patients receiving stable doses of acetylcholinesterase inhibitors. This phase 2 double-blind, placebo-controlled, proof-of-concept, and dose-finding study adaptively randomized patients to receive ABT-089 (5, 10, 15, 20, 30, or 35 mg once daily) or placebo for 12 weeks. The primary efficacy endpoint was the Alzheimer's Disease Assessment Scale, cognition subscale (ADAS-Cog) total score. A Bayesian response-adaptive randomization algorithm dynamically assigned allocation probabilities based on interim ADAS-Cog total scores. A normal dynamic linear model for dose-response relationships and a longitudinal model for predicting final ADAS-cog score were employed in the algorithm. Stopping criteria for futility or success were defined. The futility stopping criterion was met, terminating the study with 337 patients randomized. No dose-response relationship was observed and no dose demonstrated statistically significant improvement over placebo on ADAS-Cog or any secondary endpoint. ABT-089 was well tolerated at all dose levels. When administered as adjunctive therapy to acetylcholinesterase inhibitors, ABT-089 was not efficacious in mild to moderate Alzheimer disease. The adaptive study design enabled the examination of a broad dose range, enabled rapid determination of futility, and reduced patient exposure to nonefficacious doses of the investigational compound.
Key findings
- No dose-response relationship was observed and no dose demonstrated statistically significant improvement over placebo on ADAS-Cog or any secondary endpoint.
Why it matters
The drug ABT-089 showed no dose-response relationship and no statistically significant improvement over placebo on cognition or any other endpoint in mild to moderate Alzheimer's disease. This phase 2 trial found the drug was not efficacious as an add-on to acetylcholinesterase inhibitors.
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Study details
- Study designlongitudinal study
- Participants337
- Evidence strengthHigh
How this study scored 59/100
Published in a peer-reviewed journal, and it is a randomised controlled trial. Scored zero for effect reported because the record does not state it. We have no data on senior author's track record, so that was left out: it earned 57 of the 96 points we could judge it on, which is 59 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Alzheimer disease and associated disorders) |
| Journal's citation record | 1 / 4 | Alzheimer Disease & Associated Disorders: journal h-index 131 (OpenAlex, 2026-10-29) |
| Study design | 11 / 12 | A randomised controlled trial (from PubMed type “Randomized Controlled Trial”) |
| Strength of evidence | 5 / 5 | Rated “high” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2015 — within 20 year(s) of the newest study here |
| Sample size | 2 / 4 | 337 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 2 / 2 | Randomised and blinded or placebo-controlled (as stated in the record) |
| Times cited | 3 / 7 | Cited 28 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 2.2 citations a year over 13 year(s) since 2015 |
| Impact for its field and year | 2 / 6 | Cited 2.4× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 3 other studies in this library |
| Still being cited | 1 / 4 | Cited 6 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | 2 / 3 | The University of Texas MD Anderson Cancer Center: institution h-index 1,800 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 9 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 25973909) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 57 / 96 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 57 of the 96 points we could judge it on is 59 out of 100. |
| Total | 59 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
May need a subscription Unpaywall, Europe PMC and OpenAlex found no free copy of the full text (checked 10 Oct 2026), so the publisher may charge for it. The PubMed abstract is free.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Lenz, R. A., Pritchett, Y. L., Berry, S. M., Llano, D. A., Han, S., Berry, D. A., et al. (2015). Adaptive, dose-finding phase 2 trial evaluating the safety and efficacy of ABT-089 in mild to moderate Alzheimer disease. Alzheimer disease and associated disorders. https://doi.org/10.1097/wad.0000000000000093
Vancouver
Lenz RA, Pritchett YL, Berry SM, Llano DA, Han S, Berry DA, et al. Adaptive, dose-finding phase 2 trial evaluating the safety and efficacy of ABT-089 in mild to moderate Alzheimer disease. Alzheimer disease and associated disorders. 2015. doi:10.1097/wad.0000000000000093. PMID: 25973909.
BibTeX
@article{lenz2015-25973909,
author = {Lenz, R. A. and Pritchett, Y. L. and Berry, S. M. and Llano, D. A. and Han, S. and Berry, D. A. and Sadowsky, C. H. and Abi-Saab, W. M. and others},
title = {{Adaptive, dose-finding phase 2 trial evaluating the safety and efficacy of ABT-089 in mild to moderate Alzheimer disease}},
journal = {Alzheimer disease and associated disorders},
year = {2015},
doi = {10.1097/wad.0000000000000093},
pmid = {25973909},
url = {https://doi.org/10.1097/wad.0000000000000093}
}
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