An Efficacy and Safety Study of Lanabecestat (LY3314814) in Early Alzheimer's Disease
Summary
The purpose of this study is to assess the efficacy and safety of lanabecestat compared with placebo administered for 104 weeks in the treatment of early Alzheimer´s disease. The study will test the hypothesis that lanabecestat is a disease-modifying treatment for participants with early Alzheimer´s disease, defined as the continuum of participants with mild cognitive impairment (MCI) due to Alzheimer´s disease and participants diagnosed with mild dementia of the Alzheimer´s type, as measured by change from baseline on the 13-item Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog13) score at week 104 in each of the 2 lanabecestat treatment groups compared with placebo.
Timeline
- Start
- 2014-09-30
- Primary completion
- 2018-10-04
- Completion
- 2018-10-04
Outcome
Missed primary endpoint
Stopped: “An independent assessment concluded the trial was not likely to meet the primary endpoint upon completion and therefore, trial stopped for futility”
registry analysis (superiority test); Placebo vs Lanabecestat 20 mg; p = 0.232; LS Mean Difference (Final Values) -0.93 (95% CI -2.447 to 0.594); Mixed Models Analysis NCT02245737 ↗
registry analysis (superiority test); Placebo vs Lanabecestat 50 mg; p = 0.599; LS Mean Difference (Final Values) 0.41 (95% CI -1.124 to 1.947); Mixed Models Analysis NCT02245737 ↗
release “the AMARANTH trial, in early Alzheimer's disease, and the DAYBREAK-ALZ trial, in mild Alzheimer's disease dementia, were not likely to meet their primary endpoints” lilly.com ↗
Publications
- Chandler JM, Lansdall CJ, Ye W, McDougall F, Belger M, Toth B, Mi X, Sink KM, Atkins AS. The Alzheimer's Disease Cooperative Study - Activities of Daily Living dependence score: revision and validation of an algorithm evaluating patient dependence across the spectrum of AD severity. J Prev Alzheimers Dis. 2025 Sep;12(8):100261. doi: 10.1016/j.tjpad.2025.100261. Epub 2025 Jul 1.
- Wessels AM, Lines C, Stern RA, Kost J, Voss T, Mozley LH, Furtek C, Mukai Y, Aisen PS, Cummings JL, Tariot PN, Vellas B, Dupre N, Randolph C, Michelson D, Andersen SW, Shering C, Sims JR, Egan MF. Cognitive outcomes in trials of two BACE inhibitors in Alzheimer's disease. Alzheimers Dement. 2020 Nov;16(11):1483-1492. doi: 10.1002/alz.12164. Epub 2020 Oct 13.
- Wessels AM, Tariot PN, Zimmer JA, Selzler KJ, Bragg SM, Andersen SW, Landry J, Krull JH, Downing AM, Willis BA, Shcherbinin S, Mullen J, Barker P, Schumi J, Shering C, Matthews BR, Stern RA, Vellas B, Cohen S, MacSweeney E, Boada M, Sims JR. Efficacy and Safety of Lanabecestat for Treatment of Early and Mild Alzheimer Disease: The AMARANTH and DAYBREAK-ALZ Randomized Clinical Trials. JAMA Neurol. 2020 Feb 1;77(2):199-209. doi: 10.1001/jamaneurol.2019.3988.
- Cebers G, Alexander RC, Haeberlein SB, Han D, Goldwater R, Ereshefsky L, Olsson T, Ye N, Rosen L, Russell M, Maltby J, Eketjall S, Kugler AR. AZD3293: Pharmacokinetic and Pharmacodynamic Effects in Healthy Subjects and Patients with Alzheimer's Disease. J Alzheimers Dis. 2017;55(3):1039-1053. doi: 10.3233/JAD-160701.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Lanabecestat | Small molecule | 20 mg | Oral |
| Subject | Lanabecestat | Small molecule | 50 mg | Oral |