Neurim Launches Phase 2 Trial to Test Sleep Therapy Piromelatine In Alzheimer’s Patients

Israel’s Neurim Pharmaceuticals is now recruiting up to 500 U.S. patients with mild Alzheimer’s disease for a Phase 2 trial to study the safety and efficacy of its experimental drug, piromelatine.

Alzheimer’s is caused by the accumulation of faulty proteins that lead to the formation of beta-amyloid plaques, which greatly interfere with proper neuronal activity and eventually kill neurons. Among other symptoms, Alzheimer’s patients may experience poor sleep, which may be related to the accumulation of these plaques.

Results of previous preclinical studies suggest that piromelatine — originally studied as a sleep drug — may also improve cognitive function and slow Alzheimer’s progress by promoting better sleep. Piromelatine works in the brain by activating the MT1 and MT2 protein receptors — causing sleep and neuroprotective effects — and the 5-HT1A/D receptors, which are involved in antidepressant and anti-anxiety mechanisms.

“This study is the result of recent developments in Alzheimer’s disease research that recognizes the role of deep sleep in clearing excessive beta-amyloid from the brain,” Amnon Katz, Neurim’s vice-president for clinical trials, said in a news release. The company, based in Tel Aviv, cites a “growing body of evidence linking compromised sleep with these plaques and with cognitive decline.”

In the ReCOGNITION trial (NCT02615002), patients will randomly receive different piromelatine oral doses (5, 20, and 50 mg daily for six months) for 26 weeks to determine an effective dose based on efficacy (cognitive performance), safety and tolerability, compared to placebo.

The study’s primary outcome is the change in a battery of computerized neuropsychological tests from baseline to week 26. Secondary outcomes include measures of daily living activities and cognitive assessment.

To enroll, patients must be 60 to 85 years old and have already been diagnosed with mild dementia associated with Alzheimer’s. In addition, they must have been treated with stable doses of acetylcholinesterase inhibitors (including Aricept, Exelon and Razadyne) and must have a caregiver who stays under the same roof at least three nights a week and is willing to attend all study visits.

Patients will also be seen by a doctor and receive all study-related care and medications at no cost. The trial will be carried out at about 75 sites across the United States. More information on this trial can be found here.