A Randomized, Double-Masked, Single-Center, Placebo-Controlled Single and Multiple Ascending Dose Study to Assess Safety, Tolerability, Pharmacokinetics, and Efficacy of SJP-0132 in Subjects With Dry Eye Disease
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 89
- 试验地点
- 1
- 主要终点
- Accumulation Ratio (Rac) After Multiple Dosing
研究概览
简要总结
This is the first study in humans to evaluate the effectiveness of SJP-0132 in the treatment of dry eye disease. This study will evaluate the safety, tolerability, efficacy, and pharmacokinetics of single- and multiple-dose regimens of SJP-0132 in subjects with dry eye disease
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Body mass index (BMI) within 18.5 to 30.0 kg/m2 (inclusive) and body weight between 45 kg and 100 kg
- •Generally healthy as determined by medical history, physical examinations, clinical laboratory examination, and ophthalmologic examinations performed at Screening
- •Have a subject reported history of Dry Eye Disease in both eyes for at least 6 months prior to Screening
- •Non-smoker or ex-smoker for >12 months
排除标准
- •Have clinically significant systemic or ophthalmic disease
- •Has a positive serum pregnancy test at Screening or urine pregnancy test
- •Have had significant blood loss or have donated or received one or more units (450 mL) of blood or plasma within 30 days before randomization
- •Have used or anticipates use of any prescription or over-the-counter medication, including topical medications such as ophthalmic solutions, nasal drops or spray, vitamins, alternative and complementary medicines (including herbal formulations) within 14 days or 5 half-lives (whichever is longer) before randomization or at any time during the study
- •Use or anticipates use of prescribed dry eye medications within 28 days prior to randomization or at any time during the study
- •Have used or anticipates use CYP3A4 inducers, such as St. John's Wort, within 14 days before randomization or at any time during the study.
- •Have consumed red wine, grapefruit or grapefruit juice, Seville oranges, star fruit, or any products containing these items, or any foods that may inhibit CYP3A4, within 48 hours before randomization and throughout the duration of the study
- •Have a positive urine alcohol or urine drug test at Screening or Day -1
- •Contact lens wearers who cannot discontinue the wear over the trial period
- •Have undergone eye surgery (including laser surgery) within the last 12 months or whom the Investigator considers unsuitable
- •Have a best corrected visual acuity (BCVA) worse than 20/100 in either eye
- •History of permanent punctal occlusion (cautery or laser) or current use of punctal plugs
- •Any corneal abnormality or disease which might impact normal tear film spreading
- •Active or history of significant corneal disease
- •Known allergy or sensitivity to fluorescein, lissamine green or any of the study medications
- •Other protocol-defined Inclusion/Exclusion Criteria may apply
研究组 & 干预措施
Cohort 1-4: Placebo
Single dose of placebo
干预措施: Placebo (Drug)
Cohort 5-6: SJP-0132
Cohort 5 SJP-0132 will receive the second maximum acceptable dose from Cohorts 1-4 for 4 weeks. Cohort 6 SJP-0132 will receive the maximum acceptable dose from Cohorts 1-4 for 4 weeks
干预措施: SJP-0132 (Drug)
Cohort 1-4: SJP-0132
Each cohort will receive a single dose of 1 of 4 strengths of SJP-0132
干预措施: SJP-0132 (Drug)
Cohort 5-6: Placebo
Multiple dose placebo for 4 weeks
干预措施: Placebo (Drug)
结局指标
主要结局
Accumulation Ratio (Rac) After Multiple Dosing
时间窗: Day 2, 4, 8
Plasma were collected at 0, 0.25, 0.5, 1, 2, and 4 hours after dosing on Day 1, pre-dose on Day 2, Day 4 and Day 8. Accumulation ratios calculated as (predose plasma concentration \[Ctrough\] on Day 4) / (Ctrough on Day 2) and (Ctrough on Day 8) / (Ctrough on Day 2)
Number of Participants With Adverse Events by Severity in Each Cohort
时间窗: Day 2 for cohort 1-4, Day 29 for cohort 5-6
Number of participants with adverse events by severity are summarize in each cohort. Adverse events are reported as Treatment-Emergent Adverse Events (TEAEs), which are defined as any event not present before exposure to the study drug or any event already presented that worsened in either intensity or frequency after exposure to the study drug.
Number of Subjects With Abnormal Changes in Laboratory Parameters, Vital Signs, and/or Physical and Ophthalmologic Observations in Each Cohort
时间窗: Day 2 for cohort 1-4, Day 29 for cohort 5-6
Clinical laboratory parameters include hematology, clinical chemistry, urinalysis, and serology. Vital signs include diastolic blood pressure, systolic blood pressure, heart rate, respiratory rate, and body temperature. Ophthalmologic observations include examination of visual acuity, slit lamp biomicroscopy, Schirmer I, intraocular pressure, and ophthalmoscopy.
Change From Baseline in Corneal Fluorescein Staining (CFS) Score at the Central Zone on Day 29
时间窗: Day 29
Change from baseline of central zone CFS score at the central zone on Day 29. CFS score at the central zone ranged from 0 to 5, where '0' represents no fluorescein staining, and '5' represents severe staining on the cornea. The higher scores mean worse outcomes. Results from the study eye are reported.
Maximum Plasma Concentration (Cmax)
时间窗: Day 1
The results are from the maximum plasma concentration (Cmax) on Day 1. The blood for pharmacokinetics assessment was collected at 0, 0.25, 0.5, 1, 2, 4, 8, and 12 hours after dosing on Day 1 for Cohorts 1 to 4. The blood for pharmacokinetics assessment was collected at 0, 0.25, 0.5, 1, 2, and 4 hours after dosing on Day 1 for Cohorts 5 and 6.
Area Under the Plasma Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration (AUC0-last)
时间窗: Day 1
Area under the plasma concentration-time curves (AUCs) for Cohorts 1 to 4 were calculated using the plasma collected at 0, 0.25, 0.5, 1, 2, 4, 8, and 12 hours after dosing on Day 1, and those for Cohorts 5 and 6 were calculated using the plasma collected at 0, 0.25, 0.5, 1, 2, and 4 hours after dosing on Day 1.
Change From Baseline in Eye Dryness Symptom (VAS) at 4hour on Day 29
时间窗: Day 29
Visual analog scale (VAS): "0" mean none, and "100" mean the worst imaginable for the symptom question.
次要结局
- Change From Baseline in Eye Dryness Symptom by Visual Analog Scale (VAS) in Each Timepoints(Day 29)
- Change From Baseline in Ocular Surface Disease Index (OSDI)(Day 8, 15, 22, 29)
- Change From Baseline in Conjunctival Lissamine Green Staining (CLGS) Score at Total Zone in Each Timepoints(Day 8, 15, 22, 29)
- Change in Matrix Metalloproteinase-9 (MMP-9)(Day 29)
- Change From Baseline in Corneal Fluorescein Staining (CFS) Score at Total Zone in Each Timepoints(Day 8, 15, 22, 29)
- Change From Baseline in Lid Wiper Epitheliopathy Score in Each Timepoints(Day 8, 15, 22, 29)
- Change From Baseline in Tear Film Break-up Time (TFBUT) in Each Timepoints(Day 8, 15, 22, 29)
- Change From Baseline in Dry Eye Questionnaire 5 (DEQ-5) Scores(Day 29)