Article Text

PDF
Rivastigmine: a placebo controlled trial of twice daily and three times daily regimens in patients with Alzheimer’s disease
  1. Howard H Feldman1,
  2. Roger Lane2
  1. 1
    Division of Neurology, University of British Columbia, Clinic for Alzheimer’s Disease and Related Disorders, Vancouver, British Columbia, Canada
  2. 2
    Novartis Pharmaceuticals Corporation, New Jersey, USA
  1. 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

Abstract

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.

Statistics from Altmetric.com

Footnotes

  • This study was supported by funding from Novartis Pharma AG, Basle, Switzerland.

  • Competing interests: HF has received honoraria for consulting, advisory boards and for participation in CME programs sponsored by Novartis. He has also received grant-in-aid funding for research from Novartis. RL is an employee of Novartis. The study was commissioned by Novartis Pharma AG in Switzerland.

  • 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

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.