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TACRINE/LECITHIN FOR ALZHEIMER’s "CANNOT BE RECOMMENDED"

Executive Summary

TACRINE/LECITHIN FOR ALZHEIMER's "CANNOT BE RECOMMENDED" as an effective treatment, a study in the current issue of the British Medical Journal concludes. The randomized, double-blind, placebo-controlled crossover study of the combination was conducted by G. Chatellier and L. Lacombiez of Hopital de la Pitie-Salpetriere in Paris. "We conclude that combined oral treatment with tacrine and lecithin does not improve the cognitive or behavioral symptoms of patients with Alzheimer's disease. As tacrine also carries a high risk of...hepatitis, its use cannot be recommended," the study says. The investigators also stated that "we failed to find the strikingly beneficial effect of tacrine and lecithin reported by Summers et al., in patients with Alzheimer's disease, though we used a comparable methodology." In a letter to the editor of the New England Journal of Medicine, which appeared in the Nov. 13, 1986 edition of the journal, William Summers, MD, reported the results of a study he had conducted with THA and lecithin in Alzheimer's patients that suggested dramatic improvements in the patients. FDA later criticized the study for deviating from the regulations governing the clinical testing of investigational drugs ("The Pink Sheet" March 7, 1988, T&G-2). The French researchers cited several reasons why their results differed from Summers' study. One reason for the differing conclusion, the investigators suggested, was "all our patients met the criteria for Alzheimer's disease, whereas six of the 23 patients initially studied by Summers et al. were subsequently found not to have Alzheimer's disease." In addition, the researchers noted that the dosages were different: Summers gave up to 200 mg daily of THA, while the French group provided a maximum of 125 mg. The French investigators selected 67 outpatients for the study based on seven inclusion criteria. Initially, the maximum tolerated dose of tacrine was determined for each patient. The patients received a mean dose of 114 mg tacrine, or placebo, daily as well as 1,200 mg lecithin daily for one four-week treatment period and one four-week control period without a washout period at crossover. Each patient underwent a battery of tests by the physician and a patient's relative. The study determined that "no appreciable changes were observed during the study in the groups given tacrine or placebo first as regards the scores in the cognitive and behavioral tests." The physician and the patient's relatives provided subjective impressions of overall efficacy. "As scored by the physician, efficacy was greater with tacrine than with placebo," the researchers noted. However, the patients' relatives determined that there was "no significant improvement" with tacrine versus placebo. Fifty-two patients agreed to enter a four-month follow-up study in which patients received either tacrine or placebo. Three patients were withdrawn from the tacrine group. "Overall evaluations showed the same difference between the tacrine and placebo treatment groups as regards efficacy." * In response to the French study, Warner-Lambert, which has marketing rights to the compound, asserted that the French investigation was "compromised in its design, term and sample size." The article states "that it had only 75% power to detect a three-point change in patient condition," Warner-Lambert said. "That represents a change in Alzheimer's condition normally seen over a full year, an unreasonably high standard to achieve in just four weeks." The company also maintained that "no attempt" was made by the investigators "to develop a select study population." Warner-Lambert said the study "would have no effect" on the company's plans to submit an NDA in the U.S. for THA (Cognex) early this summer or marketing applications in Europe "this spring." Warner-Lambert and the National Institute on Aging are conducting a Phase III, placebo-controlled, crossover study of Cognex' effects on 300 Alzheimer's patients in 16 centers. The company emphasized that only patients responding to the drug are enrolled in their study. Last summer, an interim analysis of the trial found that "continuation of the study is warranted" despite an increase in liver enzymes seen in 30% of the 100 patients tested. The company is also studying a THA/lecithin combination in treating Alzheimer's.
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