Tarenflurbil Trial Encouraging For Mild Alzheimer's Disease Patients

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Main Category: Alzheimer's / Dementia
Also Included In: Seniors / Aging;  Clinical Trials / Drug Trials;  Neurology / Neuroscience
Article Date: 30 Apr 2008 - 17:00 PDT

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An article published in The Lancet Neurology recommends a phase III study for the drug tarenflurbil, a medication given to patients with mild Alzheimer's disease (AD). The phase II study found that patients who took 800 mg of tarenflurbil twice daily had better functional ability results than patients taking placebo.

One neuropathological indicator and a possible explanation for neuronal damage in patients with AD is the brain's deposition of the protein amyloid-β (Aβ). Researchers think that a molecule called 42-amino-acid peptide Aβ42 starts the damage process, and the drug tarenflurbil reduces production of Aβ42. Tarenflurbil is a type of drug called a selective Aβ lowering agent (SALA), and it has been shown to prevent learning and memory defects in mice.

The randomized phased II trial, conducted by Professor Gordon Wilcock (Nuffield Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK) and colleagues, consisted of 210 AD patients who lived in the community and were diagnosed as having mild to moderate AD (their scores on the mini-mental state examination (MMSE) were from 15 to 19 for mild and from 20 to 26 for moderate). Random assignment was designed so that 69 patients received 400 mg tarenflurbil twice per day, 70 patients received 800 mg tarenflurbil twice per day, and 71 patients received placebo. The researchers determined how effective each treatment was by analyzing three standard scores: 1) AD assessment cognitive subscale (ADAS-cog), 2) the Alzheimer's Disease Cooperative Study activities of daily living scale (ADCS-ADL), and 3) the clinical dementia rating sum of boxes (CDR-sb /global function). Patients received their assigned intervention for the first 12 months, and during the second 12 months, some patients who had received tarenflurbil maintained their dosage, while some patients taking placebo were randomly reassigned to receive either 400 mg or 800 mg of tarenflurbil.

Wilcock and colleagues found that ADAS-cog and ADCS-ADL scores for patients with mild AD and moderate AD were different and decided to separately analyze the two groups. Mild AD patients who took 800mg of tarenflurbil had a 46% slower rate of decline in the activities of daily living scale compared to patients who took placebo. Measurements from the CDR-sb indicated that tarenflurbil resulted in a 36% slower pace of decline in global function. Tarenflurbil, however, had no significant effect on ADAS-cog or ADCS-ADL for patients with moderate AD, and for these patients the drug led to more advanced global function decline as measured by CDR-sb. Commonly noted adverse side effects in all three groups included diarrhea, nausea, and dizziness. Mild AD patients who took 800 mg tarenflurbil group for the 24 month period responded with lower rates of decline for all three main outcomes compared to patients who took placebo for the first 12 months and switched to either tarenflurbil group for the second 12 months.

"800 mg tarenflurbil twice per day was well tolerated for up to 24 months of treatment, with evidence of a dose-related effect on measures of daily activities and global function in patients with mild AD...these findings justify phase III studies of tarenflurbil at the 800mg twice daily dose in patients with mild AD," conclude the researchers.

Dr Paul Aisen (University of California, San Diego, CA, USA) responds to the research in accompanying Comment by writing: "Are these results sufficient to support continuation of a large phase III development programme? Thankfully, the sponsor's view was affirmative. With the need so enormous, and the potential effect of the benefit suggested (although not proven) by these phase II results, the effort is indeed justified despite the substantial uncertainty. In a few months, we will learn whether tarenflurbil will be the first anti-amyloid intervention to be efficacious in a pivotal trial."

Efficacy and safety of tarenflurbil in mild to moderate Alzheimer's disease: a randomised phase II trial
Gordon K Wilcock, Sandra E Black, Suzanne B Hendrix, Kenton H Zavitz, Edward A Swabb, Mark A Laughlin, on behalf of the Tarenflurbil Phase II Study investigators
The Lancet Neurology (June 2008)
DOI:10.1016/S1474-4422(08)70090-5
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Written by: Peter M Crosta
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