Date: 2013-10-10
Type of information: Initiation of preclinical development
phase: 3
Announcement: initiation of the study
Company: Lundbeck (Denmark)
Product: Lu AE58054 (idalopirdine)
Action
mechanism: 5-HT6-receptor antagonist. Lu AE58054 is a novel, selective 5HT6 receptor antagonist with a different mechanism of action than currently available Alzheimer’s medications based on the amyloid and tau hypotheses.
Disease: Alzheimer’s disease
Therapeutic area: Neurodegenerative diseases
Country: Canada, USA, Europe
Trial
details: * The phase III program includes four currently planned trials with Lu AE58054. Several doses ranging from 10-60 mg will be used in combination with donepezil in order to explore the effect of the compound in mild-to-moderate Alzheimer’s disease as adjunctive therapy to acetylcholinesterase inhibitors. The key endpoints are Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog), Activities of Daily Living (ADL), and the Clinical Global Impression of Change Scale (CGIC). The program will enroll approximately 3,000 patients worldwide. The first trial will enroll 930 patients in the U.S., Canada and 15 other countries mainly in Europe and is expected to last up to three years.
* The phase II study was conducted in 278 patients suffering from moderate Alzheimer’s disease, and Lu AE58054 was administered as add-on to donepezil, a commonly used acetylcholinesterase inhibitor for a period of 24 weeks. In the study, Lu AE58054 as adjunctive treatment to donepezil was compared with placebo plus donepezil. Lu AE58054 (plus donepezil) demonstrated significant improvements in cognitive function in Alzheimer’s disease compared to placebo (plus donepezil), as assessed by ADAS-cog. Lu AE58054 was considered overall to be well tolerated at the selected dose. The study has been initiated in December 2009 and was conducted in Australia, Canada, Czech Republic, Germany, Italy, Poland, Spain. (NCT01019421)
Latest
news: * On October 10, 2013, Lundbeck and Otsuka Pharmaceutical have announced the continuation of the development program of Lu AE58054 for the treatment of Alzheimer’s disease, initiating the first out of four currently planned phase III clinical trials with Lu AE58054. Several doses ranging from 10-60 mg will be used in combination with donepezil in order to explore the effect of the compound in mild-to-moderate Alzheimer’s disease as adjunctive therapy to acetylcholinesterase inhibitors (AChEls).The program will enroll approximately 3,000 patients worldwide. The first trial will enroll 930 patients in the U.S., Canada and 15 other countries mainly in Europe and is expected to last up to three years.
Data from the phase II clinical study were presented at the Alzheimer’s Association International Conference (AAIC) in July 2013. This study showed that adjunctive therapy with Lu AE58054 (plus 10 mg/day donepezil) at the selected dose resulted in statistically significant improvement in cognitive performance, as measured by the ADAS-cog (Alzheimer's Disease Assessment Scale-cognitive sub-scale) over a 24 week treatment period versus placebo (plus 10mg/day donepezil). Secondary endpoints, including measures of global status and activities of daily living, also showed positive trends with the addition of Lu AE58054 compared with patients who only received donepezil, however the differences were not statistical significant.
* On July 16, 2013, Lundbeck and Otsuka Pharmaceutical have announced the presentation of the first clinical data on the investigational drug Lu AE58054 in Alzheimer’s disease at the Alzheimer’s Association International Conference 2013 (AAIC 2013) in Boston. The phase II clinical study demonstrated that treatment with Lu AE58054 as add-on to donepezil for six months improved cognitive performance in patients with moderate Alzheimer’s disease. Lundbeck and Otsuka will initiate a phase III clinical program in about 3,000 patients during the second half of 2013. Last March, the partners have concluded a license and development agreement for LU AE58054.
* On May 29, 2012, Lundbeck has announced that Lu AE58054 has met its primary endpoint in a fixed dose, randomized, placebo-controlled clinical study in 278 patients suffering from Alzheimer’s disease. Augmentation therapy with Lu AE58054 (plus 10mg/day donepezil) at the selected dose resulted in statistically significant improvement in cognition, as measured by the ADAS-cog (Alzheimer\'s Disease Assessment Scale-cognitive sub-scale) over a 24 week treatment period versus placebo (plus10mg/day donepezil). Secondary endpoints, including measures of global status and activities of daily living also showed positive trends with the addition of Lu AE58054, compared with patients who only received donepezil. Treatment with Lu AE58054 in this study was well tolerated. Lundbeck is now evaluating the future development strategy of Lu AE58054 with the intention to initiate a major pivotal clinical programme potentially including development and commercial partnerships.
