Rivastigmine: A placebo-controlled trial of BID and TID regimens in patients with Alzheimer’s disease

Abstract

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

Methods: This was a 26-week international, randomized, 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 (PDS), ADAS- cogA, Mini-Mental State Examination (MMSE) and Global Deterioration Scale (GDS).

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 TID and BID rivastigmine- treated groups were -0.2 (SD 7.3) and 1.2 (SD 7.2) vs 2.8 (SD 7.2) for placebo (p<0.05). Differences between rivastigmine TID and placebo on the CIBIC-Plus categorical responder analysis were significant (31% vs 19%, p<0.05; ITT). No significant differences were seen between BID and placebo on this outcome measure. Adverse events were predominantly gastrointestinal, occurring mainly during dose titration. Withdrawal due to adverse events accounted for 17% of BID, 11% of TID, and 9% of placebo patients.

Conclusions: Rivastigmine dosed both in a BID and TID regimen significantly benefits 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.