“…OC-02 (simpinicline solution) nasal spray was well tolerated, with no changes in key optical parameters and few adverse events reported, and the safety profile was consistent with the newer OC-01 (varenicline solution) nasal spray. 25 In agreement with published studies of OC-01 (varenicline solution) nasal spray, 25 , 26 our findings suggest that agonist stimulation of nAChRs on the trigeminal parasympathetic nerve in the nasal cavity is a valid and effective mechanism to elicit natural tear production in patients with dry eye disease. Given the Phase II nature of this study, the data may be used to inform future clinical trials on nAChR agonists for dry eye disease and other ophthalmic diseases.…”
Section: Discussionsupporting
confidence: 91%
“…Therefore, we anticipate that OC-02 (simpicline solution) nasal spray would be effective with repeated doses, similar to OC-01 (vareniciline solution) nasal spray. 25 The clinical implications of the study are limited by the single-dose assessments of OC-02 nasal spray, and a longer-term clinical trial will be needed to assess whether OC-02 (simpinicline solution) nasal spray is a suitable treatment for patients with dry eye disease in the real world. In addition, the trial was limited by study design because the order of assessments was not randomized.…”
“…OC-02 (simpinicline solution) nasal spray was well tolerated, with no changes in key optical parameters and few adverse events reported, and the safety profile was consistent with the newer OC-01 (varenicline solution) nasal spray. 25 In agreement with published studies of OC-01 (varenicline solution) nasal spray, 25 , 26 our findings suggest that agonist stimulation of nAChRs on the trigeminal parasympathetic nerve in the nasal cavity is a valid and effective mechanism to elicit natural tear production in patients with dry eye disease. Given the Phase II nature of this study, the data may be used to inform future clinical trials on nAChR agonists for dry eye disease and other ophthalmic diseases.…”
Section: Discussionsupporting
confidence: 91%
“…Therefore, we anticipate that OC-02 (simpicline solution) nasal spray would be effective with repeated doses, similar to OC-01 (vareniciline solution) nasal spray. 25 The clinical implications of the study are limited by the single-dose assessments of OC-02 nasal spray, and a longer-term clinical trial will be needed to assess whether OC-02 (simpinicline solution) nasal spray is a suitable treatment for patients with dry eye disease in the real world. In addition, the trial was limited by study design because the order of assessments was not randomized.…”
“…The efficacy of varenicline solution nasal spray in the treatment of DED was evaluated in three randomized, double-masked, placebo (vehicle)-controlled trials: the short-term (4-week/28-day) ONSET-1 [ 25 ] and -2 [ 26 ] studies, which were conducted at multiple centres in the USA (Sect. 3.1 ; Fig.…”
Section: Therapeutic Efficacy Of Varenicline Solutionmentioning
confidence: 99%
“… Fig. 1 Trial design of the randomized, double-masked, vehicle-controlled, multicentre, phase IIb ONSET-1 and phase III ONSET-2 trials in adults with dry eye disease [ 25 , 26 ], with further information available in Table 1 . Efficacy results for the intranasal varenicline solution dosage approved in the USA are reported in the animated figure (available online).…”
Section: Therapeutic Efficacy Of Varenicline Solutionmentioning
Increasing endogenous tear film production via pharmacological neuroactivation of the nasolacrimal reflex [NLR; also known as the trigeminal parasympathetic pathway (TPP)] is a novel therapeutic approach to treating dry eye disease (DED). An intranasal formulation of the water-soluble, small-molecule, nicotinic acetylcholine receptor (nAChR) agonist varenicline (Tyrvaya™) has been approved in the USA for the treatment of DED. Twice-daily administration of varenicline solution nasal spray resulted in rapid, statistically significant and clinically meaningful improvements in the signs and symptoms of DED over a period of 4 weeks in two pivotal studies (ONSET-1 and -2). The efficacy of varenicline solution was maintained over a longer-term period of 12 weeks in a third study (MYSTIC). Consistent with the nasal route of delivery, the most common adverse events reported by varenicline solution recipients were non-ocular in nature (mild and transient sneezing and cough). Thus, varenicline solution nasal spray is a rapidly-acting, effective and generally well tolerated treatment for DED that offers several potentially useful advantages over existing topical ocular therapies in terms of increasing endogenous tear secretion and reducing ophthalmic treatment burden.
Supplementary Information
The online version contains supplementary material available at 10.1007/s40265-022-01782-4.
“…It is hypothesized that the primary nAChR subtypes instigating the trigeminal parasympathetic pathway (TPP) are the α 4 β 2 and α 4 α 6 β 2 nAChRs located on the trigeminal nerve endings in the nasal mucosa. When delivered as a nasal spray, varenicline activates the TPP and stimulates lacrimal functional units (LFU) to promote natural tear film production, improving the signs and symptoms of DED ( Nau et al, 2021 ; Quiroz-Mercado et al, 2021 ; Wirta et al, 2021 ). To date, several clinical studies of OC-01 nasal spray have been conducted to evaluate the safety, efficacy, and pharmacokinetic (PK) of OC-01 in DED treatment ( ClinicalTrials.gov, 2021a ; ClinicalTrials.gov, 2021b ; ClinicalTrials.gov, 2021c ; ClinicalTrials.gov, 2021d ; ClinicalTrials.gov, 2021e ; ClinicalTrials.gov, 2021f ).…”
This study aimed to build a nasal semi-physiologically based pharmacokinetic (PBPK) model to predict the intranasal pharmacokinetic (PK) of the OC-01(varenicline) nasal spray and accelerate the development of this drug. Based on the physiology of the human upper respiratory system, the semi-PBPK model was established and validated using systemic plasma PK data of varenicline previously observed in Americans and Chinese. Drug concentrations, both in respiratory tissue and plasma circulation system, were well simulated, and it was indicated that local concentration at the target site (nasal cavity) was significantly higher than that of plasma when OC-01 nasal spray was administered. The nasal semi-PBPK model successfully depicted the absorption and distribution of intranasal varenicline in the respiratory tissues and provided an alternative to clinical PK study of OC-01 nasal spray in Chinese. Meanwhile the current study presented a viable framework for predicting respiratory concentrations for other novel nasal spray drugs by semi-PBPK modeling.
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