Effectiveness and safety of velnacrine for the treatment of Alzheimer's disease. A double-blind, placebo-controlled study. Mentane Study Group

Clinical Trial

. 1995 Sep 11;155(16):1766-72.

Affiliations

PMID: 7654110

Clinical Trial

P G Antuono. Arch Intern Med. 1995.

Abstract

Background: Alzheimer's disease is characterized by cognitive and behavioral disturbances that are mediated in part by cholinergic brain deficits.

Objective: To evaluate the long-term effectiveness and safety of an investigational cholinesterase inhibitor, that is, velnacrine maleate, in treating patients with clinically probable Alzheimer's disease (according to the criteria of the National Institute of Neurological Disorders and Stroke [Washington, DC]-Alzheimer Disease and Related Disorders Association [Chicago, Ill]).

Methods: This was a double-blind, placebo-controlled study. After a single-blind washout period, patients were randomized to receive placebo (n = 152), velnacrine maleate, 150 mg/d (n = 149), or velnacrine maleate, 225 mg/d (n = 148) for 24 weeks. Primary end points were cognitive behavior and memory components of the Alzheimer's Disease Assessment Scale and the Clinical Global Impression of Change scale. Secondary end points were caregiver-rated scales.

Results: The scores for the cognitive behavior and memory components of the Alzheimer's Disease Assessment Scale deteriorated in the placebo-treated group (P < .05) but not in the velnacrine-treated groups. Between-group comparisons favored velnacrine maleate, 225 mg over 150 mg (P < .05). Findings were similar for the Clinical Global Impression of Change scale and three of the four caregiver-rated scales. Treatment-related adverse clinical events occurred in 36%, 28%, and 30% of patients in the groups that received placebo, velnacrine maleate (150 mg), and velnacrine maleate (225 mg), respectively. The most common adverse clinical event was diarrhea, which rarely interrupted therapy. Treatment was stopped because of reversible abnormal liver function test results (five or more times the upper limits of normal) in 3%, 30%, and 24% of the patients who received placebo, velnacrine maleate (150 mg), and velnacrine maleate (225 mg), respectively.

Conclusions: Velnacrine produces modest but significant benefits in patients with Alzheimer's disease. Velnacrine maleate (225 mg) is more effective than 150 mg of velnacrine. Both dosages have acceptable safety profiles.

PubMed Disclaimer

Cited by

Cholinesterase inhibitors for behavioral disturbance in dementia.
Daly EJ, Falk WE, Brown P. Daly EJ, et al. Curr Psychiatry Rep. 2001 Jun;3(3):251-8. doi: 10.1007/s11920-001-0061-7. Curr Psychiatry Rep. 2001. PMID: 11353590 Review.
Rivastigmine. A review of its use in Alzheimer's disease.
Spencer CM, Noble S. Spencer CM, et al. Drugs Aging. 1998 Nov;13(5):391-411. doi: 10.2165/00002512-199813050-00005. Drugs Aging. 1998. PMID: 9829166 Review.
A risk-benefit assessment of tacrine in the treatment of Alzheimer's disease.
Samuels SC, Davis KL. Samuels SC, et al. Drug Saf. 1997 Jan;16(1):66-77. doi: 10.2165/00002018-199716010-00005. Drug Saf. 1997. PMID: 9010644 Review.
Velnacrine for the treatment of Alzheimer's disease: a double-blind, placebo-controlled trial. The Mentane Study Group.
Zemlan FP. Zemlan FP. J Neural Transm (Vienna). 1996;103(8-9):1105-16. doi: 10.1007/BF01291795. J Neural Transm (Vienna). 1996. PMID: 9013398 Clinical Trial.
Mechanisms of drug-induced diarrhoea in the elderly.
Ratnaike RN, Jones TE. Ratnaike RN, et al. Drugs Aging. 1998 Sep;13(3):245-53. doi: 10.2165/00002512-199813030-00007. Drugs Aging. 1998. PMID: 9789728 Review.

Effectiveness and safety of velnacrine for the treatment of Alzheimer's disease. A double-blind, placebo-controlled study. Mentane Study Group - PubMed (original) (raw)