Although administration of rotigotine did not significantly affect global cognition in patients with Alzheimer disease, improvement was found in cognitive functions associated with activities of daily living, according to a study published in JAMA Network Open.
Researchers conducted a phase 2 randomized clinical trial (ClinicalTrials.gov identification NCT03250741) of patients aged 50 to 85 years with probable, mild, or moderate Alzheimer disease who were treated with an acetylcholinesterase inhibitor for at least 6 months and who underwent a lumbar puncture for cerebrospinal fluid biomarkers. Participants underwent medical and neurological evaluations including magnetic resonance imaging or computed tomography.
The trial consisted of a 24-week treatment period with 1 week of dose escalation via rotigotine transdermal patch (2 mg/d) and 23 weeks of dose maintenance (4 mg/d). After recruitment and baseline assessments, patients were randomly assigned in a 1:1 ratio to receive either rotigotine or matching placebo in addition to their stable drug regimen.
The primary endpoint was the change at 24 weeks from baseline on the Alzheimer Disease Assessment Scale-Cognitive Subscale (ADAS-Cog-11). The scale has a score range of 0 to 70 points where higher scores indicate worse performance. The secondary key endpoint was the change at 24 weeks from baseline on the Activities of Daily Living (ADCS-ADL), the Frontal Assessment Battery, and the Neuropsychiatric Inventory. Prefrontal cortex activity was evaluated through transcranial magnetic stimulation combined with electroencephalography.
A total of 94 patients (mean age, 73.9±5.6 years; 62% women) underwent randomization. Of the 94 patients, 83% completed the full treatment period (n=78). The mean baseline ADAS-Cog-11 total score was 19.8 for the rotigotine group and 18.7 for the placebo group (n=47 for both groups). The ADAS-Cog-11 total score showed no significant differences at baseline vs week 24 in cognitive performance in the rotigotine group compared with placebo; the estimated mean change in ADAS-Cog-11 score was 2.92 (95% CI, 2.51-3.33) for the rotigotine group and 2.66 (95% CI, 2.31-3.01) for the placebo group.
When analyzing secondary outcomes, the researchers found significant differences between the rotigotine group and the placebo group for Frontal Assessment Battery and ADCS-ADL scores, but not for Neuropsychiatric Inventory scores. The estimated mean change in Frontal Assessment Battery score was 0.48 for the rotigotine group (95% CI, 0.31-0.65) and -0.66 for the placebo group (95% CI -0.80 to -0.52), suggesting that frontal lobe functions improved for patients in the rotigotine group. Estimated mean change in ADCS-ADL score was -3.32 for the rotigotine group (95% CI, -4.02 to -2.62) and -7.24 for the placebo group (95% CI, -7.84 to -6.64), demonstrating an advantage with rotigotine treatment compared with placebo.
Adverse effects were more common with rotigotine than with placebo. A total of 16 patients dropped out of the study, 11 of whom were assigned to rotigotine treatment and 5 to placebo, due to adverse effects associated with the trial.
“In this trial, a daily dose of rotigotine showed no benefit with respect to the primary clinical outcome as measured by change in the ADAS-Cog-11 score from baseline to week 24 as compared with placebo,” concluded the study authors. “Nevertheless, our results showed that rotigotine at a relatively low dosage was safe and well tolerated in patients with mild to moderate Alzheimer disease.”
Koch G, Motta C, Bonni S, et al. Effect of rotigotine vs placebo on cognitive functions among patients with mild to moderate Alzheimer disease: a randomized clinical trial. JAMA Netw Open. 2020;3(7):e2010327.