A Double-Masked, Randomized, Placebo-Controlled Dose Escalation Study of the Safety and Tolerability of P 321 Ophthalmic Solution in Subjects With Dry Eye Disease
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 53
- 试验地点
- 1
- 主要终点
- Changes from baseline at 28 days in ophthalmoscopy for Cohort 4 only.
研究概览
简要总结
The purpose of this study is to assess the safety and tolerability of P-321 Ophthalmic Solution in subjects with mild to moderate dry eye disease.
详细描述
This is a single-center, dose escalation, randomized, double-masked, placebo-controlled, Phase 1/2a trial designed to evaluate the safety and tolerability of P-321 Ophthalmic Solution in subjects with mild to moderate dry eye for up to 4-weeks of treatment and up to 8 scheduled in clinic visits. This study will conduct a consecutive dose escalation of the following concentrations of P-321 Ophthalmic Solution given two times a day via ocular instillation: 0.0005% (Cohort 1), 0.0015% (Cohort 2), 0.005% (Cohort 3), and 0.01% (Cohort 4). Up to 48 subjects will be enrolled in four consecutive cohorts. Subjects will be randomized to P-321 Ophthalmic Solution or placebo in a 3:1 ratio.
Safety and tolerability assessments, drug plasma concentrations and drug urine concentrations will be evaluated throughout the study in all cohorts.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Individuals of both genders and any race will be eligible for study participation if they:
- •Provide written informed consent.
- •Are 18 - 80 years of age.
- •Corneal fluorescein staining score ≥2/15 on the NEI/Industry scale
- •Conjunctival lissamine staining score of ≥ 2/18 on the NEI/Industry scale
- •Schirmer <10mm/5min
- •Are willing and able to follow instructions and can be present for the required study visits for the duration of the study.
- •Female patients of child bearing potential must have a negative urine pregnancy test at Screening and agree to use a medically acceptable form of birth control. Male subjects who are sexually active must be willing to use highly effective contraception (i.e., less than 1% failure rate) during heterosexual intercourse from Day 1 through completion of the study.
- •Have a history of Dry Eye Disease in both eyes supported by a previous clinical diagnosis or have a self-reported history of subjective complaints for at least 4 months prior to Screening, low tear volume, and ocular staining.
- •Have documented history of topical lubricants at least daily or the desire to use topical lubricants in the past 4 months.
- •Have normal lid anatomy
排除标准
- •Individuals are not eligible for study participation if:
- •Have anterior segment eye disease except primary dry eye.
- •Patients with an identifiable or suspected secondary dry eye, i.e., a documented or likely systemic, ocular, pharmacologic, post-traumatic, post-surgical, or external cause for dry eye symptoms or ocular surface staining.
- •Patients with current punctal plugs, punctal occlusion, or history of nasolacrimal duct obstruction are excluded.
- •Have a history of glaucoma or intraocular pressure (IOP) > 25 mmHg at the Screening Visit (Visit 1) or a history of elevated IOP within the past year prior to Visit 1
- •Contact lenses wear in the previous 30 days or during the Treatment Phase of the study.
- •Use of lid scrubs (including baby shampoos)
- •Known hypersensitivity to the study investigational medicinal product, or formulation excipients, including amiloride or related drugs or allergies to the components of the study drug.
- •Any significant chronic illness that, in the opinion of the Principal Investigator (PI), could interfere with the study parameters.
- •Use of any investigational product or device within 30 days prior to the Screening Visit or during the study.
- •Those unable in the opinion of the PI to comply fully with the study requirements or complete the study.
研究组 & 干预措施
P-321
P-321 Ophthalmic Solution
干预措施: P-321 Ophthalmic Solution (Drug)
P-321 Ophthalmic Solution Placebo
P-321 Ophthalmic Solution Placebo
干预措施: P-321 Ophthalmic Solution placebo (Drug)
结局指标
主要结局
Changes from baseline at 28 days in ophthalmoscopy for Cohort 4 only.
时间窗: Changes from baseline at 28 days
Changes from baseline at 28 days in ophthalmoscopy for Cohort 4 only.
Changes from baseline at 14 days in ophthalmoscopy.
时间窗: Changes from baseline at 14 days
Changes from baseline at 14 days in ophthalmoscopy.
Number of subjects with adverse events
时间窗: Days 0, 1, 2, 8, 15, 22 and 28
One primary objective of this trial is to assess the safety of P-321 Ophthalmic Solution versus placebo in subjects with moderate dry eye disease at 14 days (Cohorts 1-4) and 28 days (Cohort 4 only).
Changes from baseline at 14 days in conjunctival staining.
时间窗: Changes from baseline at 14 days
Changes from baseline at 14 days in conjunctival staining.
Changes from baseline at 28 days in conjunctival staining for Cohort 4 only.
时间窗: Changes from baseline at 28 days
Changes from baseline at 28 days in conjunctival staining for Cohort 4 only.
Changes from baseline in 14 days in visual acuity.
时间窗: Change from baseline at 14 days.
Change from baseline at 14 days in visual acuity.
Changes from baseline at 28 days in intraocular pressure. for Cohort 4 only.
时间窗: Changes from baseline at 28 days
Changes from baseline at 28 days in intraocular pressure. for Cohort 4 only.
Change from baseline at 28 days in visual acuity for Cohort 4 only.
时间窗: Change from baseline at 28 days in visual acuity.
Change from baseline at 28 days in visual acuity for Cohort 4 only.
Changes from baseline at 14 days in corneal staining.
时间窗: Changes from baseline at 14 days.
Changes from baseline at 14 days in corneal staining.
Changes from baseline at 28 days in corneal staining for cohort 4 only.
时间窗: Changes from baseline at 28 days.
Changes from baseline at 28 days in corneal staining for cohort 4 only.
Changes from baseline at 14 days in intraocular pressure.
时间窗: Changes from baseline at 14 days.
Changes from baseline at 14 days in intraocular pressure.
次要结局
- Measure plasma P-321 concentrations(Pre-dose 0.5, 1, 2, 4, and 6 hours post dosing on Days 1 and Day 15 and pre-dose on Day 8.)
- Measure urine concentrations of P-321(At multiple timepoints throughout the study)
- Measure tear concentrations of P-321(pre-dose 0.5, 1, 2, 4, and 6 hours post dosing on Day 1 and Day 15 and pre-dose on Day 8.)
- Measure urine concentrations of P-321 in Cohort 4(Day 28)
- Measure plasma P-321 concentrations in Cohort 4(pre-dose on Day 8 and Day 22, and pre-dose, 0.5, 1, 2, 4, 6, 8, and 24 hours post-dose on Day 28)
- Measure tear concentrations of P-321 in Cohort 4(pre-dose on Day 8 and Day 22, and pre-dose, 0.5, 1, 2, 4, 6, 8, and 24 hours post-dose on Day 28)