Acoltremon

{{Short description|Chemical compound}} {{Use dmy dates|date=May 2025}} {{cs1 config|name-list-style=vanc|display-authors=6}} {{Infobox drug | image = Acoltremon.svg | image_class = skin-invert-image | width = | alt = | caption = Molecular structure of acoltremon | image2 = Acoltremon 3D.png | image_class2 = bg-transparent | alt2 = | caption2 = 3D representation of an acoltremon molecule | pronounce = | tradename = Tryptyr | Drugs.com = {{drugs.com|monograph|acoltremon}} | MedlinePlus = a625071 | DailyMedID = Acoltremon | pregnancy_AU = | pregnancy_AU_comment = | pregnancy_category = | routes_of_administration = Eye drop | class = | ATC_prefix = None | ATC_suffix = | ATC_supplemental =  | legal_AU =  | legal_AU_comment = | legal_BR =  | legal_BR_comment = | legal_CA =  | legal_CA_comment = | legal_DE =  | legal_DE_comment = | legal_NZ =  | legal_NZ_comment = | legal_UK =  | legal_UK_comment = | legal_US = Rx-only | legal_US_comment = <ref name="Tryptyr FDA label">{{cite web | title=Tryptyr- acoltremon solution | website=DailyMed | date=12 June 2025 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=2b7715a1-035c-4002-b582-5238efee5d58 | access-date=6 July 2025}}</ref> | legal_EU = | legal_EU_comment = | legal_UN =  | legal_UN_comment = | legal_status =

| IUPAC_name = (1R,2S,5R)-N-(4-methoxyphenyl)-5-methyl-2-propan-2-ylcyclohexane-1-carboxamide | C = 18 | H = 27 | N = 1 | O = 2 | SMILES = C[C@@H]1CC[C@H]([C@@H](C1)C(=O)NC2=CC=C(C=C2)OC)C(C)C | StdInChI = 1S/C18H27NO2/c1-12(2)16-10-5-13(3)11-17(16)18(20)19-14-6-8-15(21-4)9-7-14/h6-9,12-13,16-17H,5,10-11H2,1-4H3,(H,19,20)/t13-,16+,17-/m1/s1 | StdInChIKey = HNSGVPAAXJJOPQ-XOKHGSTOSA-N | density = | density_notes = | melting_point = | melting_high = | melting_notes = | boiling_point = | boiling_notes = | solubility = | sol_units = | specific_rotation = }}

'''Acoltremon''' sold under the brand name '''Tryptyr''', is a medication used for the treatment of dry eye syndrome.<ref name="Tryptyr FDA label" /> Acoltremon is a transient receptor potential melastatin 8 (TRPM8) thermoreceptor agonist.<ref name="Tryptyr FDA label" /> It is used as an eye drop.<ref name="Tryptyr FDA label" />

The most common treatment-emergent adverse event experienced during the clinical studies was instillation site pain (burning or stinging) events.<ref name="Tryptyr FDA snapshot">{{cite web | title=Drug Trials Snapshot: Tryptyr | website=U.S. Food and Drug Administration | date=28 May 2025 | url=https://www.fda.gov/drugs/drug-approvals-and-databases/drug-trials-snapshot-tryptyr | access-date=24 August 2025}} {{PD-notice}}</ref>

Acoltremon was approved for medical use in the United States in May 2025.<ref name="Tryptyr FDA snapshot" />

== Medical uses == Acoltremon is indicated for the treatment of the signs and symptoms of dry eye disease.<ref name="Tryptyr FDA label" /><ref name="Tryptyr FDA snapshot" />

== Pharmacology == Acoltremon acts as a potent and selective activator (opener) of the TRPM8 calcium channel, which is responsible for the sensation of coldness produced by menthol.<ref name="Ma_2008">{{cite journal | vauthors = Ma S, Gisselmann G, Vogt-Eisele AK, Doerner JF, Hatt H | title = Menthol derivative WS-12 selectively activates transient receptor potential melastatin-8 (TRPM8) ion channels | journal = Pakistan Journal of Pharmaceutical Sciences | volume = 21 | issue = 4 | pages = 370–378 | date = October 2008 | pmid = 18930858 }}</ref> It is slightly less potent as a TRPM8 activator compared to icilin, but is a much more selective TRPM8 ligand when compared to menthol.<ref name="Frank_2009">{{cite journal | vauthors = Kühn FJ, Kühn C, Lückhoff A | title = Inhibition of TRPM8 by icilin distinct from desensitization induced by menthol and menthol derivatives | journal = The Journal of Biological Chemistry | volume = 284 | issue = 7 | pages = 4102–4111 | date = February 2009 | pmid = 19095656 | doi = 10.1074/jbc.M806651200 | doi-access = free }}</ref>

== History == The US Food and Drug Administration (FDA) approved acoltremon based on evidence from two clinical trials (COMET-2 and COMET-3) of 931 participants with dry eye disease.<ref name="Tryptyr FDA snapshot" /> The trials were conducted at 46 sites in the United States.<ref name="Tryptyr FDA snapshot" /> Two additional studies: COMET-1 and COMET-4 were included in the evaluation of safety benefit of acoltremon.<ref name="Tryptyr FDA snapshot" /> The number of participants representing efficacy findings may differ from the number of participants representing safety findings due to different pools of study participants analyzed for efficacy and safety.<ref name="Tryptyr FDA snapshot" /> Both COMET-2 and COMET-3 are phase III, multi-center, vehicle-controlled, double-masked, randomized studies whose primary endpoint was proportion of participants with ≥10 mm increase from baseline in unanesthetized Schirmer Score on day 14.<ref name="Tryptyr FDA snapshot" /> COMET-1 was a phase IIb multi-center, vehicle-controlled, double-masked, randomized study conducted at 15 sites in the United States which randomized 369 participants with a history of dry eye disease.<ref name="Tryptyr FDA snapshot" /> COMET-4 was a multi-center, vehicle-controlled, double-masked, randomized study conducted at approximately 10 sites in the United States which enrolled 275 participants with a history of dry eye disease.<ref name="Tryptyr FDA snapshot" /> Study COMET-2 and COMET-3 have a similar design.<ref name="Tryptyr FDA snapshot" /> Each study is a multi-center, randomized, double-masked, vehicle-controlled phase III study.<ref name="Tryptyr FDA snapshot" /> The primary objective of these studies was to evaluate the safety and efficacy of acoltremon compared to vehicle.<ref name="Tryptyr FDA snapshot" /> Participants 30 years and older with a history of artificial tear use for dry eye disease were qualified based on signs and symptoms of dry eye disease at screening, and were requalified at baseline (day 1) following a 14-day vehicle run-in.<ref name="Tryptyr FDA snapshot" /> COMET 2 enrolled 465 participants at 23 study sites, whereas COMET-3 enrolled 466 participants at 23 sites.<ref name="Tryptyr FDA snapshot" />

== Society and culture == === Legal status === Acoltremon was approved for medical use in the United States in May 2025.<ref>{{cite press release | title=Alcon Announces FDA Approval of Tryptyr (acoltremon ophthalmic solution) 0.003% for the Treatment of the Signs and Symptoms of Dry Eye Disease | publisher=Alcon | via=Business Wire | date=28 May 2025 | url=https://www.businesswire.com/news/home/20250526316115/en/Alcon-Announces-FDA-Approval-of-TRYPTYR-acoltremon-ophthalmic-solution-0.003-for-the-Treatment-of-the-Signs-and-Symptoms-of-Dry-Eye-Disease | access-date=29 May 2025 | archive-date=29 May 2025 | archive-url=https://web.archive.org/web/20250529233003/https://www.businesswire.com/news/home/20250526316115/en/Alcon-Announces-FDA-Approval-of-TRYPTYR-acoltremon-ophthalmic-solution-0.003-for-the-Treatment-of-the-Signs-and-Symptoms-of-Dry-Eye-Disease | url-status=live }}</ref>

=== Names === Acoltremon is the international nonproprietary name.<ref>{{cite journal | year = 2023 | title = International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 89 | journal = WHO Drug Information | volume = 37 | issue = 1 | hdl = 10665/366661 | hdl-access = free}}</ref>

Acoltremon is sold under the brand name Tryptyr.<ref name="Tryptyr FDA snapshot" />

== References == {{Reflist}}

== External links == * {{ClinicalTrialsGov|NCT05285644|Study Evaluating the Safety and Efficacy of AR-15512 (COMET-2)}} * {{ClinicalTrialsGov|NCT05360966|Study Evaluating the Safety and Efficacy of AR-15512 (COMET-3)}}

Category:Ophthalmology drugs Category:Ion channel openers Category:Amides Category:Cooling flavors

Acoltremon

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