Affiliations: [a] Cerecin, Inc, Denver, CO, USA and Singapore | [b] Department of Brain Health, School of Integrated Health Sciences, University of Nevada, Las Vegas (UNLV), Las Vegas, NV, USA
| [c] Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, NV, USA
| [d] Department of Neurology, Indiana University School of Medicine, Indianapolis, IN, USA
Correspondence:
[*]
Correspondence to: Samuel T. Henderson, PhD, Cerecin Inc., 44 Cook Street, Suite 100-71, Denver, CO 80206,
USA. Tel.: +1 303 999 3702; E-mail: [email protected].
Abstract: Background:Alzheimer’s disease (AD) is characterized by amyloid-β plaques, neurofibrillary tangles, and regional cerebral glucose hypometabolism. Providing an alternative metabolic substrate, such as ketone bodies, may be a viable therapeutic option. Objective:The objective was to determine the efficacy and safety of the AC-1204 formulation of caprylic triglyceride administered daily for 26 weeks in APOE4 non-carrier participants with mild-to-moderate AD. Methods:In a double-blind, placebo-controlled, randomized study (AC-12-010, NOURISH AD, NCT 01741194), 413 patients with mild-to-moderate probable AD were stratified by APOE genotype and randomized (1 : 1) to receive either placebo or AC-1204 for 26 weeks. The primary outcome was the change from baseline to week 26 on the 11-item Alzheimer’s Disease Assessment Scale - Cognitive subscale (ADAS-Cog11) among APOE4 non-carriers. The key secondary outcome was the change from baseline to week 26 in the Alzheimer’s Disease Cooperative Study – Clinician’s Global Impression of Change scale. Results:Administration of AC-1204 was safe and well-tolerated. Mean changes from baseline in the primary outcome at 26 weeks in ADAS-Cog11 for placebo (n = 138) was 0.0 and for AC-1204 (n = 137) was 0.6 (LS differences of mean – 0.761, p = 0.2458) and secondary outcome measures failed to detect any drug effects. Conclusion:The AC-1204 formulation of caprylic triglyceride failed to improve cognition or functional ability in subjects with mild-to-moderate AD. The lack of efficacy observed in this study may have several contributing factors including a lower ketone body formation from AC-1204 than expected and a lack of decline in the patients receiving placebo.
