LONDON—An investigational drug did not effectively treat symptoms of
mild to moderate Alzheimer’s disease in
phase III trials, according to results presented at the 2017 Alzheimer’s Association
Investigators evaluated the efficacy and
safety of idalopirdine, a selective 5-HT6 receptor antagonist, as adjunctive therapy in
patients taking acetylcholinesterase inhibitors. Researchers conducted three 24-week,
double-blind, placebo-controlled trials that
included more than 2,500 patients. Patients received 10,
30, or 60 mg/day of idalopirdine or placebo.
The drug had a good safety and tolerability profile,
but did not effectively alleviate clinical symptoms, said
Alireza Atri, MD, PhD, Ray Dolby Endowed Chair in
Brain Health Research at California Pacific Medical Center
in San Francisco and Lecturer in Neurology at Harvard
Medical School in Boston.
Serotonin 5-HT6 receptor antagonists nevertheless
may prove effective in other trials with different compounds and doses, he said. “We have to wait for the
other clinical trials to see whether they are positive,”
Dr. Atri said.
In a phase II study in patients with moderate Alzheimer’s disease (defined as a Mini-Mental State Examination [MMSE] score from 12 to 19), idalopirdine (90
mg/day [ 30 mg tid]) added to stable donepezil treatment significantly improved
cognitive performance, compared with
The phase III trials included patients
age 50 or older with mild to moderate
The phase III trials had similar designs.
STARSHINE enrolled patients taking donepezil
who received placebo, idalopirdine ( 30 mg/day),
or idalopirdine (60 mg/day). STARBEAM enrolled
patients taking donepezil who received placebo,
idalopirdine ( 10 mg/day), or idalopirdine ( 30 mg/
day). STARBRIGHT enrolled patients taking any
acetylcholinesterase inhibitor who received placebo
or idalopirdine (60 mg/day).
About 4,000 patients were screened, and 2,525
patients were randomized across the three studies.
Patients had a mean age of 74, baseline ADAS-cog
score of 26, and baseline MMSE score of 17. Patients on average had been diagnosed with Alzheimer’s disease for 2. 2 years and had been on cholinesterase therapy for 1. 7 years. About 55% to 60%
of patients were APOE positive, and 62% to 65%
None of the doses of idalopirdine met the prespecified efficacy criteria. An analysis suggested some
indication of potential efficacy for the 60-mg/day
Investigational Alzheimer’s Disease
Drug Is Not Effective in Phase III Trials
Patients received idalopirdine, a 5-HT6 receptor antagonist, or placebo in addition to a
cholinesterase inhibitor for 24 weeks.
Alireza Atri, MD, PhD
Serotonin 5-HT6 receptor antagonists
nevertheless may prove effective
in trials with different compounds