PAPERS

Rivastigmine: a placebo controlled trial of twice daily and three times daily regimens in patients with Alzheimer’s disease

Howard H Feldman¹, Roger Lane² and on behalf of the Study 304 Group

¹ Division of Neurology, University of British Columbia, Clinic for Alzheimer’s Disease and Related Disorders, Vancouver, British Columbia, Canada
² Novartis Pharmaceuticals Corporation, New Jersey, USA

Correspondence to:
Dr Howard H Feldman, S192-2211 Westbrook Mall, Division of Neurology, Department of Medicine, University of British Columbia Hospital, Vancouver, British Columbia, Canada V6T 2B5; hfeldman{at}interchange.ubc.ca

Objective: To evaluate the efficacy and safety of rapidly titrated rivastigmine administered twice (BID) or three times (TID) daily in patients with mild to moderate Alzheimer’s disease (AD).

Methods: This was a 26 week international, randomised, double blind, placebo controlled study in which 678 patients with probable AD received placebo or rivastigmine 2–12 mg/day BID or TID. Primary outcome measures included the cognitive subscale of the AD Assessment Scale (ADAS-cog) and categorical analysis of the Clinician Interview Based Impression of Change incorporating caregiver information (CIBIC-Plus). Secondary outcomes were the CIBIC-Plus change from baseline, Progressive Deterioration Scale, ADAS-cogA, Mini-Mental State Examination and Global Deterioration Scale.

Results: At week 26, mean rivastigmine dose was 9.6 (2.76) mg/day in the TID group and 8.9 (2.93) mg/day in the BID group. Mean ADAS-cog changes from baseline in the TID and BID rivastigmine treated groups were –0.2 (SD 7.3) and 1.2 (SD 7.2) versus 2.8 (SD 7.2) for the placebo group (p<0.05). Differences between rivastigmine TID and placebo on the CIBIC-Plus categorical responder analysis were significant (31% vs 19%; p<0.05, intention to treat). No significant differences were seen between BID and placebo for this outcome measure. Adverse events were predominantly gastrointestinal, occurring mainly during dose titration. Withdrawal because of adverse events accounted for 17% of BID, 11% of TID and 9% of placebo patients.

Conclusions: Rivastigmine administered as a BID or TID regimen significantly benefited cognitive, function and global performances in AD patients. The TID regimen showed a tendency for superior tolerability and permitted titration to higher doses, an outcome that is significant as the efficacy of rivastigmine is dose related.

Abbreviations: ACh, acetylcholine; AChE, acetylcholinesterase; AD, Alzheimer’s Disease; ADAS-cog, cognitive subscale of the Alzheimer’s Disease Assessment Scale; AE, adverse event; BID, twice daily; BuChE, butyrylcholinesterase; ChE-Is, cholinesterase inhibitors; CIBIC-Plus, Clinician Interview Based Impression of Change incorporating caregiver information; GDS, Global Deterioration Scale; ITT, intention to treat; LOCF, last observation carried forward; MMSE, Mini-Mental State Examination; OC, observed cases; PDS, Progressive Deterioration Scale; RCT, randomised controlled trial; TID, three times daily

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?