Table 3.
Ongoing phase 3 trials on nonanti-amyloid therapy in AD in 2019
| 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 |
BPSD = behavioral psychological symptoms of dementia; NMDA = N-methyl-D-aspartate