Safety and efficacy of twice daily administration of KPI-121 1% for ocular inflammation and pain following cataract surgery

Kim, Terry; Sall, Kenneth; Holland, Edward J.; Brazzell, Romulus K.; Coultas, Susan; Gupta, Preeya K.

doi:10.2147/opth.s185800

Cited by 24 publications

(17 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Likewise, the differences relative to vehicle in the proportion of subjects with complete resolution of ocular pain at day 8 reported with LE gel 0.38% TID and LE gel 0.5% QID were 25.6% and 30.5%, respectively. Findings were also comparable to those of another newly developed LE formulation—a suspension formulation with comparable smaller LE drug particles (0.2–0.4 µm vs 0.4–0.6 µm), but with a 2.6-fold higher drug concentration (1% vs 0.38%) approved with BID dosing 22,23. In this study, differences relative to vehicle in the proportion of LE suspension 1%-treated subjects with complete resolution of AC cells and ocular pain, respectively, at day 8 and maintained through day 15 were 10.9% and 19.9%.…”

Section: Discussionsupporting

confidence: 72%

<p>Loteprednol etabonate (submicron) ophthalmic gel 0.38% dosed three times daily following cataract surgery: integrated analysis of two Phase III clinical studies</p>

Fong

Cavet²,

DeCory³

et al. 2019

OPTH

View full text Add to dashboard Cite

Purpose To evaluate the efficacy and safety of a submicron formulation of loteprednol etabonate (LE) gel 0.38% instilled three times daily (TID) compared with vehicle for the treatment of inflammation and pain following cataract surgery with intraocular lens implantation, integrated across two multicenter, double-masked, randomized, parallel-group, Phase III studies. Patients and methods Subjects ≥18 years of age with anterior chamber (AC) cells ≥grade 2 (6–15 cells) on day 1 after cataract surgery were randomized to receive 1 drop of LE gel 0.38% TID, twice daily (not reported/analyzed herein), or vehicle instilled in the study eye for 14 days. Primary endpoints were the proportion of subjects with resolution of AC cells and grade 0 (no) pain at postoperative day 8. Safety outcomes included adverse events (AEs), ocular signs, fundoscopy results, visual acuity, intraocular pressure (IOP), and tolerability (drop comfort and ocular symptoms). Results The integrated intent-to-treat population included 742 subjects (LE gel 0.38% TID, n=371; vehicle, n=371). Significantly more subjects in the LE gel 0.38% TID group compared with the vehicle group had complete resolution of AC cells (29.6% vs 15.1%) and grade 0 pain (74.4% vs 48.8%) at day 8 ( P <0.0001 for both). LE gel 0.38% TID was safe and well tolerated, with only 1 LE-treated subject experiencing an IOP elevation ≥10 mm Hg. Most treatment-related AEs were mild and occurred less frequently with LE gel 0.38% than with vehicle. The majority (>75%) of subjects in each treatment group reported no drop discomfort. There were no reports of blurred vision with LE gel. Conclusion The results of this integrated analysis indicate that LE (submicron) gel 0.38% administered TID is safe and effective for the treatment of ocular inflammation and pain following cataract surgery, with minimal risk of IOP elevation.

show abstract

Section: Discussionsupporting

confidence: 72%

<p>Loteprednol etabonate (submicron) ophthalmic gel 0.38% dosed three times daily following cataract surgery: integrated analysis of two Phase III clinical studies</p>

Fong

Cavet²,

DeCory³

et al. 2019

OPTH

View full text Add to dashboard Cite

show abstract

“… 32 Each study achieved the primary efficacy endpoints of complete resolution of ocular inflammation by slit-lamp biomicroscopy and complete resolution of subject-rated ocular pain. 32 …”

Section: Kpi-121 Clinical Developmentmentioning

confidence: 99%

“…31 Two phase-3, randomized, double-masked, vehiclecontrolled, parallel-group trials (ClinicalTrials.gov identifiers, NCT02163824 and NCT02793817) compared 14 days of twice-daily administration of KPI-121 1% or vehicle for treatment of patients with postsurgical inflammation and pain following cataract surgery. 32 Each study achieved the primary efficacy endpoints of complete resolution of ocular inflammation by slit-lamp biomicroscopy and complete resolution of subject-rated ocular pain. 32 KPI-121 0.25% was approved by the FDA in 2020 for short-term treatment (up to 2 weeks) of the signs and symptoms of DED (EYSUVIS ® , Kala Pharmaceuticals, Inc.).…”

Section: Kpi-121 Clinical Developmentmentioning

confidence: 99%

The role of KPI-121 0.25% in the treatment of dry eye disease: penetrating the mucus barrier to treat periodic flares

Gupta

Venkateswaran

2021

Ophthalmol Eye Dis

Self Cite

View full text Add to dashboard Cite

The tear film, which includes mucins that adhere to foreign particles, rapidly clears allergens and pathogens from the ocular surface, protecting the underlying tissues. However, the tear film’s ability to efficiently remove foreign particles during blinking can also pose challenges for topical drug delivery, as traditional eye drops (solutions and suspensions) are cleared from the ocular surface before the drug can penetrate into the conjunctival and corneal epithelium. In the past 15 years, there has been an increase in the development of nanoparticles with specialized coatings that have reduced affinity to mucins and are small enough in size to pass through the mucus barrier. These mucus-penetrating particles (MPPs) have been shown to efficiently penetrate the mucus barrier and reach the ocular surface tissues. Dry eye disease (DED) is a common inflammatory ocular surface disorder that often presents with periodic flares (exacerbations). However, currently approved immunomodulatory treatments for DED are intended for long-term use. Thus, there is a need for effective short-term treatments that can address intermittent flares of DED. Loteprednol etabonate, an ocular corticosteroid, was engineered to break down rapidly after administration to the ocular surface tissues and thereby reduce risks associated with other topical steroids. KPI-121 is an ophthalmic suspension that uses the MPP technology to deliver loteprednol etabonate more efficiently to the ocular tissues, achieving in animal models a 3.6-fold greater penetration of loteprednol etabonate to the cornea than traditional loteprednol etabonate ophthalmic suspensions. In clinical trials, short-term treatment with KPI-121 0.25% significantly reduced signs and symptoms of DED compared with its vehicle (placebo). Recently approved KPI-121 0.25%, with its novel drug delivery design and ease of use, has the potential to effectively treat periodic flares of DED experienced by many patients.

show abstract

“…One product utilizing MPP technology (trademarked by Kala Pharmaceuticals, Inc. as AMPPLIFY ® Drug Delivery Technology), INVELTYS ® (LE ophthalmic suspension 1%), has already been approved by the U.S. FDA. 58 , 63 It is the first twice-daily ocular corticosteroid indicated for the treatment of postoperative inflammation and pain after ocular surgery. Another program (KPI-121 0.25% ophthalmic suspension for temporary relief of the signs and symptoms of dry eye disease) has completed Phase 3 trials and is currently undergoing an NDA review.…”

Section: Discussionmentioning

confidence: 99%

Mucus-Penetrating Particles and the Role of Ocular Mucus as a Barrier to Micro- and Nanosuspensions

Попов

2020

Journal of Ocular Pharmacology and Therapeutics

View full text Add to dashboard Cite

The ocular surface is naturally covered with a layer of mucus. Along with other functions, this mucus layer serves to trap and eliminate foreign substances, such as allergens, pathogens, and debris. In playing this pivotal role, mucus can also hinder topical delivery of therapeutics to the eye. Recent studies provide evidence that drugs formulated as traditional micro-or nanoparticles are susceptible to entrapment and rapid clearance by ocular mucus. Mucus-penetrating particles (MPPs) is a nanoparticle technology that emerged over the past decade. With a muco-inert surface and a particle size smaller than the mucus mesh size, MPPs can diffuse in ex vivo mucus essentially freely. Preclinical studies have shown that, compared with particles lacking the mucus-penetrating attributes, MPPs can improve the uniformity of drug particle distribution on mucosal surfaces and enhance drug delivery to ocular tissues.

show abstract

Safety and efficacy of twice daily administration of KPI-121 1% for ocular inflammation and pain following cataract surgery

Cited by 24 publications

References 24 publications

<p>Loteprednol etabonate (submicron) ophthalmic gel 0.38% dosed three times daily following cataract surgery: integrated analysis of two Phase III clinical studies</p>

<p>Loteprednol etabonate (submicron) ophthalmic gel 0.38% dosed three times daily following cataract surgery: integrated analysis of two Phase III clinical studies</p>

The role of KPI-121 0.25% in the treatment of dry eye disease: penetrating the mucus barrier to treat periodic flares

Mucus-Penetrating Particles and the Role of Ocular Mucus as a Barrier to Micro- and Nanosuspensions

Contact Info

Product

Resources

About