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Table 3 Ongoing phase 3 trials on nonanti-amyloid therapy in AD in 2019

From: Clinical trials of new drugs for Alzheimer disease

Agent

Mechanism of action

Target type and therapeutic purpose

NCT number

Status

AC-1204

Induction of ketosis

Metabolic; symptomatic cognitive enhancer

NCT01741194

Completed

AGB101 (levetiracetam)

SV2A modulator

Amyloid-related and neuroprotective; disease-modifying therapy

NCT03486938

Recruiting

Aripiprazole

Partial agonist at dopamine D2 and 5-HT 1A receptors

Neurotransmitter based; symptomatic cognitive enhancer

NCT02168920

Terminated

AVP-786

Sigma-1 receptor agonist, NMDA receptor antagonist

Neurotransmitter based; BPSD (agitation)

NCT03393520

Recruiting

   

NCT02446132

Recruiting

   

NCT02442765

Completed

   

NCT02442778

Completed

AXS-05

Sigma-1 receptor agonist; NMDA receptor antagonist and dopamine-norepinephrine reuptake inhibitor

Neurotransmitter based; BPSD (agitation)

NCT03226522

Recruiting

Azeliragon

Microglial activation inhibitor, antagonist of the receptor for advanced glycation end products

Amyloid-related and antineuroinflammatory; disease modifying therapy

NCT02916056

Terminated

   

NCT02080364

Terminated

   

NCT03980730

Recruiting

OPC-34712 (brexpiprazole)

A partial agonist at serotonin 5-hydroxytryptamine1A and dopamine D2 receptors and an antagonist at serotonin 5-hydroxytryptamine2A

Neurotransmitter based; BPSD (agitation)

NCT01922258

Completed

   

NCT01862640

Completed

   

NCT03620981

Recruiting

   

NCT03548584

Recruiting

   

NCT03594123

Recruiting

   

NCT03724942

Recruiting

Coconut oil

Reduction in ADP-ribosylation factor

1 protein expression

Anti-amyloid, antineuroinflammatory, anti-oxidative, and neuroprotective; symptomatic cognitive enhancer

NCT01883648

Terminated

COR388

Bacterial protease inhibitor

Antineuroinflammatory; disease-modifying therapy

NCT03823404

Recruiting

Escitalopram

Serotonin reuptake inhibition

Neurotransmitter based; BPSD (agitation)

NCT03108846

Recruiting

Gabapentin Enacarbil

Glutamate receptor-independent mechanisms

Neurotransmitter based and neuroprotective; symptomatic cognitive enhancer

NCT03082755

Recruiting

Ginkgo biloba

Antioxidant and anti-amyloid aggregation

Antioxidant and anti-amyloid; symptomatic cognitive enhancer

NCT03090516

Recruiting

Guanfacine

Alpha-2A-adrenoceptor agonist, a potent 5-HT2B receptor agonist

Neurotransmitter based; symptomatic cognitive enhancer

NCT03116126

Recruiting

Icosapent ethyl (IPE)

Omega-3 fatty acids protect neurons from disease

Neuroprotective; disease-modifying therapy

NCT02719327

Recruiting

Idalopirdine

5-HT6 receptor antagonist

Neurotransmitter based; symptomatic cognitive enhancer

NCT02006641

Completed

   

NCT01955161

Completed

   

NCT02006654

Completed

   

NCT02079246

Completed

RVT-101 (intepirdine)

5-HT6 receptor antagonist

Neurotransmitter based; symptomatic cognitive enhancer

NCT02586909

Terminated

   

NCT02585934

Completed

Insulin (Humulin® R U-100)

Metabolic

Metabolic; symptomatic cognitive enhancer

NCT01767909

Completed

ITI-007 (lumateperone)

A potent 5-HT2A antagonist

Neurotransmitter based; symptomatic cognitive enhancer

NCT02817906

Terminated

Losartan, amlodipine, aerobic exercise training, and others

Angiotensin II receptor blocker, calcium channel blocker, cholesterol agent

Antineuroinflammatory and metabolic; symptomatic cognitive enhancer

NCT02913664

Recruiting

Masitinib

Selective tyrosine kinase inhibitor

Antineuroinflammatory; disease modifying therapy

NCT01872598

Active, not recruiting

Methylphenidate

Dopamine reuptake inhibitor

Neurotransmitter based; BPSD (apathy)

NCT03811847

Recruiting

   

NCT02346201

Recruiting

Mirtazapine

Alpha-1 antagonist

Neurotransmitter based; BPSD (agitation)

NCT03031184

Recruiting

MK-4305 (suvorexant)

Orexin antagonist

BPSD (sleep)

NCT02750306

Completed

EVP-6124

Selective α7 nicotinic acetylcholine receptor partial agonist

Cholinergic system; symptomatic cognitive enhancer

NCT02004392

Terminated

   

NCT01969136

Terminated

   

NCT01969123

Terminated

Nabilone

Agonists at cannabinoid receptors 1 and 2 (CB1/2)

Neurotransmitter based; BPSD (agitation)

NCT02351882

Completed

Nilvadipine

Dihydropyridine calcium channel blocker

Amyloid-related, neuroprotective, and antineuroinflammatory; disease-modifying therapy

NCT02017340

Completed

AVP-923 (nuedexta)

Uncompetitive NMDA glutamate receptor antagonist, a sigma-1 receptor agonist, and a serotonin and norepinephrine reuptake inhibitor

Neurotransmitter based and neuroprotective; symptomatic cognitive enhancer

NCT01832350

Unknown

Pioglitazone

Peroxisome proliferator-activated receptor gamma (PPAR-γ) agonists

Antineuroinflammatory and neuroprotective; symptomatic cognitive enhancers

NCT02284906

Terminated

   

NCT01931566

Terminated

Troriluzole

Glutamate modulator

Neuroprotective; disease modifying therapy

NCT03605667

Recruiting

TRx0237 (LMTX)

Tau stabilizers and aggregation inhibitors

Anti-tau; disease-modifying therapy

NCT01689233

Completed

   

NCT02245568

Terminated

   

NCT03446001

Recruiting

Vitamin D3 (cholecalciferol)

Agonist of vitamin D receptor and other membrane-based receptors such as MARRS

Metabolic; symptomatic cognitive enhancer

NCT01409694

Completed

Zolpidem Zoplicone

Allosteric modulator of GABA-A receptors

Neurotransmitter based; BPSD (sleep)

NCT03075241

Recruiting

  1. BPSD = behavioral psychological symptoms of dementia; NMDA = N-methyl-D-aspartate