Metrifonate improves the cognitive deficits of patients with Alzheimer's disease relative to placebo treatment and to baseline performance

Martin Farlow, P. A. Cyrus

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Abstract

Objective: To evaluate the relative efficacy of two doses of metrifonate, a long-acting acetylcholinesterase (ACHE) inhibitor, in improving the cognitive performance of patients with mild to moderate Alzheimer's disease. Design: A retrospective analysis of data pooled from four prospective, randomized, placebo-controlled trials of metrifonate. Study A had a 12-week, double-blind treatment period; Studies B, C, and D involved a 26-week, double-blind treatment period. Setting: 120 ambulatory clinics, including contract research organizations, public health facilities, and universities in the United States, Canada, England, and France. Participants: Patients with Alzheimer's disease who had Mini-Mental State Examination scores of 10 to 26 and weighed between 43 kg and 98 kg. Intervention: Once- daily placebo or a metrifonate maintenance dose of either 30 mg-60 mg, or 60 mg or 80 mg based on weight. Measurements: The Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog). Results: As evaluated by the ADAS-Cog, 60 mg or 80 mg of metrifonate significantly improved cognitive performance, both when compared with placebo (Δ = 3.81, P = .0001) and when compared with the patients' baseline (ie, pretreatment) performance (Δ= 2.21, P = .0001). The difference shown by those taking 60 mg or 80 mg of metrifonate versus those taking placebo was statistically superior to that shown by those taking 30 mg to 60 mg of metrifonate (P = .0068), confirming a dose-response effect. The 60-mg or 80-mg dose of metrifonate demonstrated efficacy by week 12 of treatment and maintained effectiveness through week 26. Metrifonate was safe and well-tolerated: 85% of patients receiving 60 mg or 80 mg of metrifonate completed double-blind treatment; only 6% discontinued as a result of adverse events. Conclusion: Metrifonate safely improves the cognitive performance of patients with mild to moderate Alzheimer's disease, not only relative to placebo, but also relative to baseline levels-the first such finding reported for an AChE inhibitor. Furthermore, metrifonate at a dose of 60 mg or 80 mg daily provides superior efficacy when compared with a dose of 30 mg to 60 mg daily for the treatment of the cognitive deficits of patients with Alzheimer's disease.

Original languageEnglish
Pages (from-to)328-333
Number of pages6
JournalAnnals of Long-Term Care
Volume7
Issue number9
StatePublished - 1999

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Trichlorfon
Alzheimer Disease
Placebos
Therapeutics
Public Facilities
Health Facilities
Cholinesterase Inhibitors
Contracts
England
France
Canada

ASJC Scopus subject areas

  • Geriatrics and Gerontology

Cite this

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title = "Metrifonate improves the cognitive deficits of patients with Alzheimer's disease relative to placebo treatment and to baseline performance",
abstract = "Objective: To evaluate the relative efficacy of two doses of metrifonate, a long-acting acetylcholinesterase (ACHE) inhibitor, in improving the cognitive performance of patients with mild to moderate Alzheimer's disease. Design: A retrospective analysis of data pooled from four prospective, randomized, placebo-controlled trials of metrifonate. Study A had a 12-week, double-blind treatment period; Studies B, C, and D involved a 26-week, double-blind treatment period. Setting: 120 ambulatory clinics, including contract research organizations, public health facilities, and universities in the United States, Canada, England, and France. Participants: Patients with Alzheimer's disease who had Mini-Mental State Examination scores of 10 to 26 and weighed between 43 kg and 98 kg. Intervention: Once- daily placebo or a metrifonate maintenance dose of either 30 mg-60 mg, or 60 mg or 80 mg based on weight. Measurements: The Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog). Results: As evaluated by the ADAS-Cog, 60 mg or 80 mg of metrifonate significantly improved cognitive performance, both when compared with placebo (Δ = 3.81, P = .0001) and when compared with the patients' baseline (ie, pretreatment) performance (Δ= 2.21, P = .0001). The difference shown by those taking 60 mg or 80 mg of metrifonate versus those taking placebo was statistically superior to that shown by those taking 30 mg to 60 mg of metrifonate (P = .0068), confirming a dose-response effect. The 60-mg or 80-mg dose of metrifonate demonstrated efficacy by week 12 of treatment and maintained effectiveness through week 26. Metrifonate was safe and well-tolerated: 85{\%} of patients receiving 60 mg or 80 mg of metrifonate completed double-blind treatment; only 6{\%} discontinued as a result of adverse events. Conclusion: Metrifonate safely improves the cognitive performance of patients with mild to moderate Alzheimer's disease, not only relative to placebo, but also relative to baseline levels-the first such finding reported for an AChE inhibitor. Furthermore, metrifonate at a dose of 60 mg or 80 mg daily provides superior efficacy when compared with a dose of 30 mg to 60 mg daily for the treatment of the cognitive deficits of patients with Alzheimer's disease.",
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T1 - Metrifonate improves the cognitive deficits of patients with Alzheimer's disease relative to placebo treatment and to baseline performance

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AU - Cyrus, P. A.

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N2 - Objective: To evaluate the relative efficacy of two doses of metrifonate, a long-acting acetylcholinesterase (ACHE) inhibitor, in improving the cognitive performance of patients with mild to moderate Alzheimer's disease. Design: A retrospective analysis of data pooled from four prospective, randomized, placebo-controlled trials of metrifonate. Study A had a 12-week, double-blind treatment period; Studies B, C, and D involved a 26-week, double-blind treatment period. Setting: 120 ambulatory clinics, including contract research organizations, public health facilities, and universities in the United States, Canada, England, and France. Participants: Patients with Alzheimer's disease who had Mini-Mental State Examination scores of 10 to 26 and weighed between 43 kg and 98 kg. Intervention: Once- daily placebo or a metrifonate maintenance dose of either 30 mg-60 mg, or 60 mg or 80 mg based on weight. Measurements: The Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog). Results: As evaluated by the ADAS-Cog, 60 mg or 80 mg of metrifonate significantly improved cognitive performance, both when compared with placebo (Δ = 3.81, P = .0001) and when compared with the patients' baseline (ie, pretreatment) performance (Δ= 2.21, P = .0001). The difference shown by those taking 60 mg or 80 mg of metrifonate versus those taking placebo was statistically superior to that shown by those taking 30 mg to 60 mg of metrifonate (P = .0068), confirming a dose-response effect. The 60-mg or 80-mg dose of metrifonate demonstrated efficacy by week 12 of treatment and maintained effectiveness through week 26. Metrifonate was safe and well-tolerated: 85% of patients receiving 60 mg or 80 mg of metrifonate completed double-blind treatment; only 6% discontinued as a result of adverse events. Conclusion: Metrifonate safely improves the cognitive performance of patients with mild to moderate Alzheimer's disease, not only relative to placebo, but also relative to baseline levels-the first such finding reported for an AChE inhibitor. Furthermore, metrifonate at a dose of 60 mg or 80 mg daily provides superior efficacy when compared with a dose of 30 mg to 60 mg daily for the treatment of the cognitive deficits of patients with Alzheimer's disease.

AB - Objective: To evaluate the relative efficacy of two doses of metrifonate, a long-acting acetylcholinesterase (ACHE) inhibitor, in improving the cognitive performance of patients with mild to moderate Alzheimer's disease. Design: A retrospective analysis of data pooled from four prospective, randomized, placebo-controlled trials of metrifonate. Study A had a 12-week, double-blind treatment period; Studies B, C, and D involved a 26-week, double-blind treatment period. Setting: 120 ambulatory clinics, including contract research organizations, public health facilities, and universities in the United States, Canada, England, and France. Participants: Patients with Alzheimer's disease who had Mini-Mental State Examination scores of 10 to 26 and weighed between 43 kg and 98 kg. Intervention: Once- daily placebo or a metrifonate maintenance dose of either 30 mg-60 mg, or 60 mg or 80 mg based on weight. Measurements: The Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog). Results: As evaluated by the ADAS-Cog, 60 mg or 80 mg of metrifonate significantly improved cognitive performance, both when compared with placebo (Δ = 3.81, P = .0001) and when compared with the patients' baseline (ie, pretreatment) performance (Δ= 2.21, P = .0001). The difference shown by those taking 60 mg or 80 mg of metrifonate versus those taking placebo was statistically superior to that shown by those taking 30 mg to 60 mg of metrifonate (P = .0068), confirming a dose-response effect. The 60-mg or 80-mg dose of metrifonate demonstrated efficacy by week 12 of treatment and maintained effectiveness through week 26. Metrifonate was safe and well-tolerated: 85% of patients receiving 60 mg or 80 mg of metrifonate completed double-blind treatment; only 6% discontinued as a result of adverse events. Conclusion: Metrifonate safely improves the cognitive performance of patients with mild to moderate Alzheimer's disease, not only relative to placebo, but also relative to baseline levels-the first such finding reported for an AChE inhibitor. Furthermore, metrifonate at a dose of 60 mg or 80 mg daily provides superior efficacy when compared with a dose of 30 mg to 60 mg daily for the treatment of the cognitive deficits of patients with Alzheimer's disease.

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