"By comparing two available Alzheimer's disease medications, physicians now have clinical evidence that will help them prescribe the most appropriate treatment for their patients," said study investigator Roy Jones, MD, Research Institute for the Care of the Elderly, St Martin's Hospital, Bath, United Kingdom. "This three month study is encouraging news for mild to moderate Alzheimer's disease patients currently on ARICEPT®, as well as those who have yet to initiate treatment." The 12-week, multinational (United Kingdom, Finland, Norway and Germany), head-to-head, randomized open-label study was designed primarily to evaluate the safety and tolerability of ARICEPT® (n= 64) and Reminyl® (n= 56) in 120 patients with possible or probable mild to moderate Alzheimer's disease. The study also investigated the effects of both treatments on cognition and ADLs, such as meal preparation and finance and correspondence. Trained raters who were blinded to study medication and trial results administered testing, using the modified ADAS-cog and the MMSE to measure cognition. ADLs were assessed with the DAD scale, a 40-item scale developed to assess both instrumental and basic ADLs across the full spectrum of AD.
Key study findings include:
- More patients were able to tolerate and remain on the maximum daily dose of ARICEPT® (10 mg once daily) than the maximum daily dose of Reminyl® (12 mg twice daily) (92 percent vs. 71 percent) until study end or final patient visit. Almost one-quarter of Reminyl®-treated patients titrated down from the maximum dose to a lower maintenance dose due to tolerability.
- Significantly greater improvements in cognition were observed for ARICEPT® compared with Reminyl®. At Week 12 and endpoint (Week 12 LOCF), ARICEPT®-treated patients showed at least a two-point advantage over patients receiving Reminyl® on the 13-item modified ADAS-cog scale (p-value < 0.05). Modified ADAS-cog assesses elements of cognition including the ability to recognize and recall words, comprehend spoken language, and name fingers and objects. The modified version used in this trial added two additional items: delayed recall and concentration/distractibility.
- At endpoint, ARICEPT®-treated patients achieved significant improvements over patients receiving Reminyl®, as measured using the MMSE (p-value < 0.05).
- Patients receiving ARICEPT® had significantly greater improvements in ADLs than those receiving Reminyl®, according to the DAD total score (p-value <0.05 at both Week 12 and endpoint). DAD assesses instrumental and basic ADLs such as preparing meals, handling finances and correspondence and eating.
- More gastrointestinal adverse events were observed in Reminyl®-treated patients than the ARICEPT® treatment group. More patients taking Reminyl® reported nausea and diarrhea than those taking ARICEPT®(23.2 percent vs. 15.6 percent and 14.3 percent vs. 9.4 percent, respectively). Almost 13 percent of patients on Reminyl® reported vomiting as compared to zero patients on ARICEPT®.
During a 12-week period, patients with an average age of 73.8 years were treated with ARICEPT®, while patients with an average age of 75.1 were treated with Reminyl®. Patients were treated according to the recommended dosing on the approved product labeling and dosing adjustments were allowed to reflect real world clinical practice.
"This study shows that more than 92 percent of patients were able to tolerate and remain on the maximum effective dose of ARICEPT® treatment until their final visit," said David Geldmacher, MD, clinical director, University Memory & Aging Center, University Hospitals of Cleveland, and associate professor, Case Western Reserve University, Cleveland, Ohio. "For patients and their caregivers, these results, along with a simple dosing regimen, will likely mean better ability to tolerate the medication, fewer phone calls and less frequent office visits for managing problematic side effects."
In this study, the most frequent treatment-emergent adverse events for ARICEPT® versus Reminyl® included: nausea (15.6 percent vs. 23.2 percent); vomiting (0 percent vs. 12.5 percent); anorexia (4.7 percent vs. 8.9 percent); diarrhea (9.4 percent vs. 14.3 percent); headache (6.3 percent vs. 5.4 percent); dizziness (1.6 percent vs. 5.4 percent); and urinary tract infection (3.1 percent vs. 7.1 percent).++
In a previous, comparative, open-label study between ARICEPT® and Exelon® (rivastigmine tartrate), another cholinesterase inhibitor, results showed that almost twice as many patients were able to remain at the maximum effective daily dose of ARICEPT® than Exelon® at the final study visit (87.5 percent vs 47.3 percent, respectively). Furthermore, ARICEPT® was better tolerated than Exelon® in patients with mild to moderate Alzheimer's disease. These data were first presented at the 13th European College of Neuropsychopharmacology Congress (ECNP) in September 2000.
Information About ARICEPTâ (donepezil HCl tablets) Treatment
While there is no cure for Alzheimer's disease, medical treatments are available to manage symptoms of the disease. Once-a-day prescription ARICEPT®, indicated for mild to moderate Alzheimer's disease, can improve cognition and maintain patient function. In a progressively degenerative disease such as Alzheimer's, improvement, stabilization or a less-than-expected decline over time is considered a positive response to treatment. These types of responses have been observed in patients treated with ARICEPT® in clinical trials. Individual responses to treatment may vary.
ARICEPT® is well tolerated but may not be for everyone. Some people may experience nausea, diarrhea, insomnia, vomiting, muscle cramps, fatigue, or loss of appetite. In studies, these side effects were usually mild and temporary. Some people taking ARICEPT® may experience fainting. People at risk for ulcers should tell their doctors because their condition may get worse. ARICEPT® is available by prescription in more than 50 countries. In November 1994, Eisai Co., Ltd. and Pfizer Inc announced the formation of a strategic alliance for the promotion of ARICEPT® and development of new treatments for Alzheimer's disease and other cognitive disorders. First launched in the United States in February 1997, ARICEPT® has been well-received in the Alzheimer's disease community with more than 717 million days of patient use worldwide, and more than 1.7 million people in the United States have received a prescription for ARICEPT®. Eisai Co., Ltd., and Pfizer Inc are committed to a collaboration dedicated to advances in Alzheimer's therapy. These studies were funded by Eisai and Pfizer Inc.
Full prescribing information is available upon request from Melissa Furrie of Porter Novelli or Susan Yarin of Pfizer Inc (see contact information above).
ARICEPT® is a registered trademark of Eisai Co., Ltd. Reminyl® is a registered trademark of Janssen. Exelon® is a registered trademark of Novartis AG.
News Source: Eisai Ltd. (European Office) and Pfizer Inc.