A double‐blind, placebo‐controlled, enriched population study of tacrine in patients with Alzheimer's disease

Abstract

The efficacy of tacrine in the treatment of patients with probable Alzheimer's disease (AD) was evaluated in a double-blind, placebo-controlled, enriched population multicenter study in France. A total of 280 patients entered the dose titration phase of the study. The assessment of potential benefit of tacrine ("best dose") was based on demonstrating improvement on the Alzheimer's Disease Assessment Scale (ADAS) total score versus a blinded placebo. One hundred and thirty of 242 (54%) patients achieved a "best dose" and were eligible for the double-blind, parallel group (pivotal) phase. Primary efficacy measures were ADAS-Cognitive and Clinical Global Impression of Change; secondary efficacy measures of cognition and activities of daily living were also included. Results indicated that tacrine-treated patients showed improved functioning based on the ADAS-Cognitive in comparison to placebo-treated patients. Transaminase elevations above the upper limit of normal occurred in 32% of patients, were more frequent in women than in men, demonstrated a delayed onset, and returned to normal limits for all patients following discontinuation of treatment The results from this study are supportive of the efficacy of tacrine in the treatment of AD as demonstrated in a study of similar design conducted in the US and studies using different designs.

Tacrine Treatment of Alzheimer’s Disease: Many Expectations,Few Certainties

“…No differences before and after treatment with THA were present in patients with reference to MMSE and ADL scores, showing that this drug produces no clinically relevant improvement. Similar results have been achieved in the remaining studies examined [16][17][18].…”

“…In the studies analyzed, regression of cognitive, behavioral and memory symptoms, and of evolution of the disease, was only observed in a few patients per study, implying that improvement induced by THA was occasional rather than statistically signifi-Malaguarnera/Pistone/Vinci/Motta/ di Fazio/Rampello cant (table 1). Our meta-analysis showed the limits and benefits of this statistical method of evaluation [17]. We compared the best performed trials aimed to assess the real efficacy of THA in AD and we obtained mathematical results in favor of this drug (OR 61 and large 95% CI).…”

Experimental and clinical methods in the development of anti‐Alzheimer drugs

“…The consequence has been the identification of clinical subgroups and specific risk factors and even a revision of the concept of the disease itself [ 1291. Empirically, one pharmacological approach to these subgroups is to use "enriched" protocols [42] to detect "responders" in an open trial prior to the doubleblind period. Today, the question is to decide whether such a priori categorizations or stratifications should be used in all clinical trials.…”

North of England evidence based guidelines development project: guideline for the primary care management of dementia

“…Similar in efficacy to tacrine, velnacrine also leads to substantial hepatotoxicity and seems, on current evidence, to have no advantage over tacrine. [98][99][100][101][102][103][104][105][106][107][108][109][110][111] Donepezil hydrochloride Donepezil has shown a moderate effect on cognitive function in short term treatment trials of patients with mild to moderate Alzheimer's disease (I). These changes in cognitive function have not been accompanied by measured changes in quality of life, and evidence of the effects on activities of daily living is inadequate (I).…”