AR-15512 / Alcon - LARVOL DELTA

Tear production with the novel TRPM8 agonist acoltremon: a phase 1 methodology study (ARVO 2025) - "Acoltremon (previously AR-15512) is a potent and highly selective TRPM8 agonist in development as a treatment option for dry eye disease (DED)...The most common adverse event in the study was mild instillation site burning/stinging, reported by 20% of subjects receiving acoltremon. These findings are consistent with the mechanism of acoltremon as an activator of the TRPM8 receptor, and suggest that future clinical studies with acoltremon are best performed in a real-world setting in the absence of topical anesthetic."

P1 data • Dry Eye Disease • Ophthalmology • TRPM8

A Study to Investigate the Effect of 0.003% AR-15512 on Subjects With Dry Eye Disease (clinicaltrials.gov) - P3 | N=79 | Completed | Sponsor: Alcon Research | Active, not recruiting ➔ Completed

Trial completion • Dry Eye Disease • Ophthalmology

A Study to Evaluate 0.003% AR-15512 Safety and Drop Attributes (clinicaltrials.gov) - P3 | N=55 | Completed | Sponsor: Alcon Research | Recruiting ➔ Completed

Trial completion • Dry Eye Disease • Ophthalmology

A Study Designed to Evaluate Tear Production (clinicaltrials.gov) - P3 | N=81 | Completed | Sponsor: Alcon Research | Recruiting ➔ Completed

Trial completion • Dry Eye Disease • Ophthalmology

A Study to Investigate the Effect of 0.003% AR-15512 on Subjects With Dry Eye Disease (clinicaltrials.gov) - P3 | N=79 | Active, not recruiting | Sponsor: Alcon Research | Recruiting ➔ Active, not recruiting

Enrollment closed • Dry Eye Disease • Ophthalmology

A Study to Evaluate 0.003% AR-15512 Safety and Drop Attributes (clinicaltrials.gov) - P3 | N=55 | Recruiting | Sponsor: Alcon Research | Not yet recruiting ➔ Recruiting

Enrollment open • Dry Eye Disease • Ophthalmology

A Study to Evaluate 0.003% AR-15512 Safety and Drop Attributes (clinicaltrials.gov) - P3 | N=55 | Not yet recruiting | Sponsor: Alcon Research

New P3 trial • Dry Eye Disease • Ophthalmology

A Study Designed to Evaluate Tear Production (clinicaltrials.gov) - P3 | N=80 | Recruiting | Sponsor: Alcon Research | Not yet recruiting ➔ Recruiting

Enrollment open • Dry Eye Disease • Ophthalmology

A Study to Investigate the Effect of 0.003% AR-15512 on Subjects With Dry Eye Disease (clinicaltrials.gov) - P3 | N=70 | Recruiting | Sponsor: Alcon Research | Not yet recruiting ➔ Recruiting

Enrollment open • Dry Eye Disease • Ophthalmology

AR-15512: A Novel TRPM8 Agonist for the Treatment of the Signs and Symptoms of Dry Eye: Phase 3 Pivotal Study Results (AAO 2024) - "Persistent production of basal tears led to DED symptom improvement, demonstrated by reduced SANDE scores in favor of 512. Data support 512 as a potential new option to rapidly and effectively treat signs and symptoms of DED."

P3 data • Dry Eye Disease • Ophthalmology • TRPM8

Ar-15512, A Novel Trpm8 Agonist For The Treatment Of The Signs And Symptoms Of Dry Eye Disease: Topline Efficacy And Safety Data From Phase 3 Pivotal Clinical Studies (Comet-2 And Comet-3) (ESCRS 2024) - No abstract available

Clinical • P3 data • P3 data: top line • Dry Eye Disease • Ophthalmology • TRPM8

A Study Designed to Evaluate Tear Production (clinicaltrials.gov) - P3 | N=80 | Not yet recruiting | Sponsor: Alcon Research

New P3 trial • Dry Eye Disease • Ophthalmology

A Study to Investigate the Effect of 0.003% AR-15512 on Subjects With Dry Eye Disease (clinicaltrials.gov) - P3 | N=70 | Not yet recruiting | Sponsor: Alcon Research

New P3 trial • Dry Eye Disease • Ophthalmology

COMET-1: A Phase 2b Study Evaluating the Safety and Efficacy of AR-15512 Ophthalmic Solution for the Treatment of Dry Eye Disease (clinicaltrials.gov) - P2 | N=369 | Completed | Sponsor: Aerie Pharmaceuticals | Phase classification: P2b ➔ P2

Phase classification • Dry Eye Disease • Ophthalmology

COMET-4: A Long-Term Safety Study Evaluating the Safety and Systemic Exposure of AR-15512 (clinicaltrials.gov) - P3 | N=275 | Completed | Sponsor: Aerie Pharmaceuticals | Active, not recruiting ➔ Completed

Trial completion • Dry Eye Disease • Ophthalmology

Study Evaluating the Safety and Efficacy of AR-15512 (COMET-3) (clinicaltrials.gov) - P3 | N=467 | Completed | Sponsor: Aerie Pharmaceuticals | Active, not recruiting ➔ Completed

Trial completion • Dry Eye Disease • Ophthalmology

COMET-2: Study Evaluating the Safety and Efficacy of AR-15512 (clinicaltrials.gov) - P3 | N=465 | Completed | Sponsor: Aerie Pharmaceuticals | Active, not recruiting ➔ Completed

Trial completion • Dry Eye Disease • Ophthalmology

Study Evaluating the Safety and Efficacy of AR-15512 (COMET-3) (clinicaltrials.gov) - P3 | N=467 | Active, not recruiting | Sponsor: Aerie Pharmaceuticals | Recruiting ➔ Active, not recruiting

Enrollment closed • Dry Eye Disease • Ophthalmology

COMET-2: Study Evaluating the Safety and Efficacy of AR-15512 (clinicaltrials.gov) - P3 | N=465 | Active, not recruiting | Sponsor: Aerie Pharmaceuticals | Recruiting ➔ Active, not recruiting

Enrollment closed • Dry Eye Disease • Ophthalmology

TRPM8 Agonists: A New Approach to Dry Eye Disease Treatment (ARVO 2023) - "Purpose AR-15512, (1 R ,2 S ,5 R )-N-(4-methoxyphenyl)- p -menthane carboxamide), a small molecule in Phase 3 clinical trials for treating Dry Eye disease, is a potent and long-lasting transient receptor potential melastatin 8 (TRPM8) ligand agonist...A potential new treatment for Dry Eye Disease is being evaluated to see if it will help releive the pain and irritation of patients who suffer from this disease. The treatment involves stimulating nerves in a very particular way to create a soothing effect."

Dry Eye Disease • Ophthalmology

COMET-2: Study Evaluating the Safety and Efficacy of AR-15512 (clinicaltrials.gov) - P3 | N=460 | Recruiting | Sponsor: Aerie Pharmaceuticals | Trial completion date: Feb 2023 ➔ Aug 2023 | Trial primary completion date: Feb 2023 ➔ Aug 2023

Trial completion date • Trial primary completion date • Dry Eye Disease • Ophthalmology

Study Evaluating the Safety and Efficacy of AR-15512 (COMET-3) (clinicaltrials.gov) - P3 | N=460 | Recruiting | Sponsor: Aerie Pharmaceuticals | Trial completion date: May 2023 ➔ Oct 2023 | Trial primary completion date: May 2023 ➔ Oct 2023

Trial completion date • Trial primary completion date • Dry Eye Disease • Ophthalmology

COMET-4: A Long-Term Safety Study Evaluating the Safety and Systemic Exposure of AR-15512 (clinicaltrials.gov) - P3 | N=275 | Active, not recruiting | Sponsor: Aerie Pharmaceuticals | Recruiting ➔ Active, not recruiting

Enrollment closed • Dry Eye Disease • Ophthalmology

COMET-4: A Long-Term Safety Study Evaluating the Safety and Systemic Exposure of AR-15512 (clinicaltrials.gov) - P3 | N=270 | Recruiting | Sponsor: Aerie Pharmaceuticals | Not yet recruiting ➔ Recruiting

Enrollment open • Dry Eye Disease • Ophthalmology

'A randomized, vehicle-controlled, Phase 2b study of two concentrations of the TRPM8 receptor agonist AR-15512 in the treatment of dry eye disease (COMET-1). (PubMed, Ocul Surf) - "Although predefined co-primary study endpoints were not met, AR-15512 demonstrated statistically significant improvements in DED signs, symptoms, and disease-related QoL."

Journal • P2b data • Anesthesia • Dry Eye Disease • Ophthalmology • Pain