Piromelatine for Alzheimer's Disease

Not currently recruiting at 37 trial locations

Overseen By Stephen Thein, Dr.

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Neurim Pharmaceuticals Ltd.

Must be taking: Acetylcholinesterase inhibitors, Memantine

Must not be taking: Benzodiazepines, Sedative hypnotics, Melatonin

Disqualifiers: Schizophrenia, Bipolar, Cardiovascular, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 26 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness and safety of piromelatine, a medication, in individuals with mild Alzheimer's disease. Researchers aim to determine if piromelatine improves cognitive function compared to a placebo. Participants will take a pill daily before bed, with changes in memory and thinking skills tracked over 26 weeks. Ideal candidates have experienced memory decline due to Alzheimer's for at least a year and do not carry a specific gene variant related to the disease. As a Phase 2 trial, this study measures how well piromelatine works in an initial, smaller group, offering participants a chance to contribute to important research.

Will I have to stop taking my current medications?

The trial does not require you to stop taking your current medications if they are for non-excluded conditions and you have been on a stable dose for at least 4 weeks before screening. However, you cannot use melatonin or certain sedative medications before and during the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that piromelatine has been tested for safety in people with mild Alzheimer's disease. In one study, participants took up to 50 mg daily for six months without major safety concerns, indicating that the treatment is generally well-tolerated. Another study found no safety issues with piromelatine. These findings suggest that piromelatine is safe for humans at the doses tested.

This trial uses a 20 mg dose, and previous research provides a good understanding of its safety. Participants in earlier studies did not experience significant unwanted side effects. This offers some confidence in the treatment's safety for those considering joining the trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Piromelatine is unique because it combines multiple mechanisms of action, targeting both melatonin and serotonin receptors, which are thought to play a role in improving sleep and potentially cognitive functions in Alzheimer's patients. Unlike traditional treatments for Alzheimer's, which often focus on managing symptoms through cholinesterase inhibitors or NMDA receptor antagonists, piromelatine's dual-receptor approach may offer benefits in both sleep regulation and neuroprotection. Researchers are excited about its potential to not only enhance sleep quality but also slow cognitive decline, offering a more comprehensive approach to managing Alzheimer's disease.

What evidence suggests that piromelatine might be an effective treatment for Alzheimer's disease?

Research has shown that piromelatine may help with symptoms of mild Alzheimer's disease. In earlier studies, participants taking piromelatine demonstrated better memory and thinking skills compared to those taking a placebo, which contains no active medicine. In this trial, participants will receive either piromelatine or a placebo. Researchers used the Alzheimer's Disease Assessment Scale to evaluate memory and thinking abilities. The studies suggest that piromelatine might be more effective for individuals without a certain genetic trait that could influence treatment efficacy. These early results are promising and indicate potential for this treatment in supporting brain health. ^{1 2 3 4 6}

Who Is on the Research Team?

Lon Schneider, MD

Principal Investigator

Keck School of Medicine of USC, Los Angeles, CA

Are You a Good Fit for This Trial?

This trial is for adults aged 60-85 with mild dementia due to Alzheimer's, living at home or in assisted living, who can attend all visits and have a reliable study partner. They must be stable on current AD medications if used, not carriers of specific genetic polymorphisms, able to spend time in daylight daily, and agree to contraception if applicable. Exclusions include severe other diseases or conditions that could interfere with the study.

Inclusion Criteria

My mental abilities have been getting worse over the last year.

I have been diagnosed with mild dementia.

I am a woman who has not had a period in at least 2 years or I am surgically sterile.

Exclusion Criteria

You must be willing to limit alcohol intake, avoid caffeine overconsumption, and maintain a regular lifestyle during the study. You must also not have a history of suicidal behavior or present a serious risk of suicide.

I chose not to have genetic testing for specific DNA changes and APOE4.

My dementia is not caused by Alzheimer's disease.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either piromelatine 20 mg or placebo for 26 weeks

26 weeks

Regular visits as per study protocol

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension

Placebo-treated participants will receive piromelatine, and piromelatine-treated participants will continue treatment for an additional 12 months

52 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Piromelatine 20 mg
• Placebo

Trial Overview The trial tests Piromelatine 20 mg against a placebo in participants with mild Alzheimer's-related dementia. It aims to see how well Piromelatine works compared to a placebo by measuring cognitive function after 26 weeks using the AD Assessment Scale cognitive subscale (ADAS-cog14). Participants are randomly assigned either the drug or placebo.

How Is the Trial Designed?

Group I: Piromelatine 20 mg Experimental Treatment 1 Intervention

Piromelatine 20 mg tablets once daily taken before going to bed, preferably between 2100h and 2300h, and after food consumption.

Group II: Placebo Placebo Group 1 Intervention

Matched placebo tablets, with identical features to the piromelatine tablets, will be used as control treatment

Who Is Running the Clinical Trial?

Neurim Pharmaceuticals Ltd.

Lead Sponsor

Trials

17

Recruited

2,300+

Syneos Health

Collaborator

Trials

181

Recruited

69,600+

Published Research Related to This Trial

In a 24-week study involving 470 patients with mild to moderate Alzheimer's disease, memantine (20mg/day) demonstrated significant improvements in cognitive function compared to placebo, particularly at weeks 12 and 18.

Memantine was well tolerated, with side effects similar to those experienced by patients taking placebo, indicating a favorable safety profile for this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Memantine treatment in patients with mild to moderate Alzheimer's disease: results of a randomised, double-blind, placebo-controlled 6-month study. Bakchine, S., Loft, H.[2019]

In a 24-week study involving 470 patients with mild to moderate Alzheimer's disease, memantine (20 mg/day) demonstrated significant improvements in cognitive function compared to placebo, particularly at weeks 12 and 18.

Memantine was well tolerated, with side effects similar to those experienced by patients on placebo, indicating a favorable safety profile for its use in treating Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Memantine treatment in patients with mild to moderate Alzheimer's disease: results of a randomised, double-blind, placebo-controlled 6-month study. Bakchine, S., Loft, H.[2022]

In a multicenter trial involving 92 patients with Alzheimer's disease, idebenone treatment over 90 days showed effectiveness in improving memory, attention, and orientation, while also slowing disease progression.

The treatment was generally well-tolerated, with mild side effects such as insomnia and nausea, which did not require specific medical interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Idebenone, a new drug in the treatment of cognitive impairment in patients with dementia of the Alzheimer type. Bergamasco, B., Scarzella, L., La Commare, P.[2022]

In a study involving 1,920 patients with mild to moderate Alzheimer's disease, donepezil was found to be well tolerated, with a completion rate of 79% and a favorable safety profile at doses of 5 mg and 10 mg.

While 11% of patients on donepezil withdrew due to adverse events compared to 7% on placebo, the most common side effects were manageable and included nausea and dizziness, with no significant impact on laboratory tests or liver function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Donepezil: tolerability and safety in Alzheimer's disease. Pratt, RD., Perdomo, CA., Surick, IW., et al.[2022]

In a 1-year study involving 33 patients with early Alzheimer's disease, high doses of piracetam (8 g/day) did not show overall improvement in cognitive functions compared to placebo, but it may help slow cognitive decline.

The study found some significant differences in memory recall tasks, suggesting that while piracetam may not improve cognition, it could potentially slow the progression of memory deterioration in Alzheimer's patients, and it was well-tolerated by participants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term and high-dose piracetam treatment of Alzheimer's disease. Croisile, B., Trillet, M., Fondarai, J., et al.[2019]

In a 132-week study involving 579 patients with mild to moderate Alzheimer's disease, donepezil demonstrated long-term efficacy, with cognitive improvements observed after 6 weeks of treatment and slight improvements in dementia ratings over the first 12 weeks.

Donepezil was generally well tolerated, although 85% of patients experienced at least one adverse event, with common side effects including diarrhea, nausea, and infections, indicating that while effective, monitoring for side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of donepezil over 3 years: an open-label, multicentre study in patients with Alzheimer's disease. Burns, A., Gauthier, S., Perdomo, C.[2018]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05267535

Piromelatine 20 mg in Participants With Mild Dementia Due ... This study of piromelatine 20 mg versus placebo in participants with mild dementia due to Alzheimer's disease is conducted as a confirmatory, ...

2. alzdiscovery.org alzdiscovery.org/uploads/cognitive_vitality_media/Piromelatine-Cognitive-Vitality-For-Researchers.pdf

Piromelatine A phase 2 clinical trial testing the safety and efficacy of piromelatine in mild Alzheimer's disease patients was scheduled to be completed in November 2019 ( ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35542997/

A Polymorphism Cluster at the 2q12 locus May Predict ... Conclusions: The 2q12 (2:107,510,000-107,540,000) 5-6 SNPs cluster may predict efficacy of piromelatine for mild AD. These findings warrant further ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT02615002?term=Neu-P11&viewType=Table&rank=5

Safety and Efficacy of Piromelatine in Mild Alzheimer's ... This study is a Phase 2, randomized, placebo-controlled, dose-ranging study of piromelatine (5, 20, and 50 mg daily for 6 months) versus placebo to ...

5. ctv.veeva.com ctv.veeva.com/study/safety-and-efficacy-of-piromelatine-in-mild-alzheimers-disease-patients-recognition

Safety and Efficacy of Piromelatine in Mild Alzheimer's ... This study is a Phase 2, randomized, placebo-controlled, dose-ranging study of piromelatine (5, 20, and 50 mg daily for 6 months) versus ...

6. withpower.com withpower.com/trial/phase-2-and-3-alzheimers-disease-ad-4-2022-358c0

Piromelatine for Alzheimer's Disease · Info for Participants In a study with people having mild Alzheimer's disease, Piromelatine was given in doses up to 50 mg daily for 6 months, and there were no safety concerns ...