An Open-label Study To Evaluate The Safety, Tolerability, And Pharmacokinetics Of Kerydin (Registered) (Tavaborole) Topical Solution, 5% In The Treatment Of Onychomycosis Of The Toenail In Pediatric Subjects Ages 6 To 16 Years And 11 Months
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 55
- 试验地点
- 12
- 主要终点
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
研究概览
简要总结
This was an open-label study to evaluate the safety and pharmacokinetics of tavaborole 5% topical solution in treating distal subungual onychomycosis (a fungal infection) of the toenail in children and adolescents (ages 6 to 16 years).
Following confirmation of eligibility, including laboratory evidence of a fungal organism in the toenail, tavaborole topical solution was applied once daily to all affected toenails for a 48-week treatment period.
Clinical assessment of the extent of infection and safety assessments were performed periodically throughout the 48-week treatment period, and again at 52 weeks (4 weeks after stopping the treatment).
A subgroup of enrolled subjects applied the topical solution to all 10 toenails and a small area of surrounding skin during the first 28 days. These subjects had blood samples analyzed to evaluate the pharmacokinetics (how the drug moves in the body) of tavaborole topical solution in children and adolescents.
详细描述
This was an open-label study to evaluate the safety, tolerability, and pharmacokinetics of tavaborole 5% topical solution in treating distal subungual onychomycosis (DSO) of the toenail in pediatric subjects aged 6 to 16 years and 11 months. An eligible subject had a target great toenail (TGT) with at least 20% involvement, with a positive potassium hydroxide (KOH) wet mount and positive fungal culture for T. rubrum or T. mentagrophytes.
Eligible subjects applied tavaborole 5% topical solution, once daily to all affected toenails (the TGT as well as all other toenails having the clinical characteristics of onychomycosis) throughout the 48 week treatment period.
Subjects were evaluated at Screening, Baseline (Day 1), and at Weeks 2, 4, 8, 16, 24, 32, 40, 48, and 52. Each evaluation included a clinical assessment of the AEs and local tolerability evaluation.
Additional procedures were performed as follows:
- Mycology sampling at Screening, Week 24, and Week 52/early termination (ET);
- Clinical disease severity of the TGT at Screening, Week 24, and Week 52/ET;
- Safety laboratory testing at Baseline, Week 24, and Week 52/ET;
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 72 Months 至 203 Months（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •males or females, ages >/= 6 years and </= 16 years and 11 months
- •clinical diagnosis of distal subungual onychomycosis affecting at least 20% of one of the great toenails (target nail); and with positive KOH and positive culture for T. rubrum or T. mentagrophytes from either great toenail
排除标准
- •the target toenail has proximal subungual onychomycosis, onychomycosis involving the nail lunula, superficial white onychomycosis, dermatophytoma, exclusively lateral disease, or yellow or brown spikes, or has co-infection with certain fungi or molds
- •anatomic abnormalities of the toes or toenail
- •current or past history of chronic moccasin-type tinea pedis
- •current or past history of psoriasis or lichen planus
- •history of significant chronic fungal disease (other than onychomycosis)
- •immunodeficiency
研究组 & 干预措施
Tavaborole 5% Topical Solution
All study participants apply study drug
干预措施: Tavaborole 5% Topical Solution (Drug)
结局指标
主要结局
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
时间窗: Baseline up to 28 days after last dose of study drug (up to Week 52)
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pre-treatment state. AEs included both serious and non-serious AEs.
Change From Baseline in Hematology Parameters (Leukocytes: Basophils, Eosinophils, Lymphocytes, Monocytes and Neutrophils) at Week 24
时间窗: Baseline, Week 24
Change From Baseline in Hematology Parameter (Hematocrit) at Week 52
时间窗: Baseline, Week 52
Change From Baseline in Hematology Parameter (Erythrocytes) at Week 24
时间窗: Baseline, Week 24
Change From Baseline in Hematology Parameter (Hematocrit) at Week 24
时间窗: Baseline, Week 24
Change From Baseline in Hematology Parameters (Leukocytes and Platelets) at Week 52
时间窗: Baseline, Week 52
Number of Participants With Local Tolerability Reactions by Severity
时间窗: Baseline up to Week 52
Local tolerability reactions consisted of burning/stinging, induration/edema, oozing and crusting, pruritus, erythema, and scaling. Here 0 indicates None, 1 (Mild), 2 (Moderate) and 3 (severe). Grading details are as follows: Burning/Stinging (0: no stinging/burning, 1: slight warm, 2: definite warm, 3: hot); Induration/Edema (0: no elevation, 1: barely perceptible elevation, 2: clearly perceptible elevation but not extensive, 3: marked and extensive elevation); Oozing and Crusting (0: absent, 1: faint signs of oozing, 2: definite oozing, 3: marked and extensive oozing); Pruritus (0: no pruritus, 1: occasional, slight itching, 2: constant itching which is not disturbing sleep, 3: severe bothersome itching/scratching which is disturbing sleep); Erythema (0: no redness present, 1: faintly detectable erythema; very light pink, 2: dull red, 3: deep/dark red); Scaling (0: no scaling, 1: barely perceptible shedding, 2: obvious but not profuse scaling, 3: heavy scale production).
Number of Participants With Adverse Events (AEs) By Severity
时间窗: Baseline up to 28 days after last dose of study drug (up to Week 52)
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. AEs were classified as mild, moderate and severe based on severity assessment by investigator and defined as: Mild = symptoms barely noticeable to the participant or does not make the participant uncomfortable; moderate = symptoms of a sufficient severity to make the participant uncomfortable; severe = symptoms of a sufficient severity to cause the participant severe discomfort.
Change From Baseline in Hematology Parameters (Leukocytes: Basophils, Eosinophils, Lymphocytes, Monocytes and Neutrophils) at Week 52
时间窗: Baseline, Week 52
Change From Baseline in Hematology Parameter (Erythrocytes) at Week 52
时间窗: Baseline, Week 52
Change From Baseline in Hematology Parameters (Hemoglobin) at Week 24
时间窗: Baseline, Week 24
Change From Baseline in Hematology Parameters (Leukocytes and Platelets) at Week 24
时间窗: Baseline, Week 24
Change From Baseline in Chemistry Parameters (Alanine Aminotransferase, Alkaline Phosphatase and Aspartate Aminotransferase) at Week 52
时间窗: Baseline, Week 52
Change From Baseline in Chemistry Parameters (Bilirubin, Creatinine, Glucose [Non-fasting] and Urea Nitrogen) at Week 24
时间窗: Baseline, Week 24
Change From Baseline in Hematology Parameters (Hemoglobin) at Week 52
时间窗: Baseline, Week 52
Change From Baseline in Chemistry Parameters (Alanine Aminotransferase, Alkaline Phosphatase and Aspartate Aminotransferase) at Week 24
时间窗: Baseline, Week 24
Change From Baseline in Chemistry Parameters (Albumin and Protein) at Week 24
时间窗: Baseline, Week 24
Change From Baseline in Chemistry Parameters (Albumin and Protein) at Week 52
时间窗: Baseline, Week 52
Change From Baseline in Chemistry Parameters (Bilirubin, Creatinine, Glucose [Non-fasting] and Urea Nitrogen) at Week 52
时间窗: Baseline, Week 52
Change From Baseline in Chemistry Parameters (Potassium and Sodium) at Week 24
时间窗: Baseline, Week 24
Change From Baseline in Chemistry Parameters (Potassium and Sodium) at Week 52
时间窗: Baseline, Week 52
Change From Baseline in Vital Sign (Pulse Rate) at Week 24
时间窗: Baseline, Week 24
Pulse rate was defined as the number of pulsations noted in a peripheral artery per minute after participant rested supine for 5 minutes.
Change From Baseline in Vital Sign (Blood Pressure) at Week 24
时间窗: Baseline, Week 24
Change From Baseline in Vital Sign (Blood Pressure) at Week 52
时间窗: Baseline, Week 52
Change From Baseline in Vital Sign (Respiratory Rate) at Week 24
时间窗: Baseline, Week 24
Respiratory rate was defined as the number of inspirations per minute.
Change From Baseline in Vital Sign (Pulse Rate) at Week 52
时间窗: Baseline, Week 52
Pulse rate was defined as the number of pulsations noted in a peripheral artery per minute after participant rested supine for 5 minutes.
Change From Baseline in Vital Sign (Respiratory Rate) at Week 52
时间窗: Baseline, Week 52
Respiratory rate was defined as the number of inspirations per minute.
Percentage of Participants With Complete Cure of Target Great Toenail (TGT) at Week 52
时间窗: Week 52
Complete cure was defined as completely clear nail, negative fungal culture and negative potassium hydroxide (KOH) wet mount.
次要结局
- Maximum Observed Plasma Concentration (Cmax) of Tavaborole(Pre-dose, 4, 6, 8, 24 hours post-dose on Day 29)
- Area Under the Plasma Concentration-Time Curve From Hour Zero to Hour 24 (AUC24) of Tavaborole(Pre-dose, 4, 6, 8, 24 hours post-dose on Day 29)
- Percentage of Participants With Negative Fungal Culture of the Target Great Toenail (TGT) at Weeks 24 and 52(Week 24, 52)
- Percentage of Participants With Mycological Cure of Target Great Toenail (TGT) at Week 24 and 52(Week 24, 52)
- Percentage of Participants With Almost Complete Cure of Target Great Toenail (TGT) at Week 24 and 52(Week 24, 52)
- Time to Maximum Observed Plasma Concentration (Tmax) of Tavaborole(Pre-dose, 4, 6, 8, 24 hours post-dose on Day 29)
- Area Under the Plasma Concentration-Time Curve Extrapolated to Infinity (AUCinf) of Tavaborole(Pre-dose, 4, 6, 8, 24 hours post-dose on Day 29)
- Elimination Rate Constant of Tavaborole(Pre-dose, 4, 6, 8, 24 hours post-dose on Day 29)
- Elimination Half-Life of Tavaborole(Pre-dose, 4, 6, 8, 24 hours post-dose on Day 29)
- Percentage of Participants With Clinical Efficacy of Target Great Toenail (TGT) at Week 24 and 52(Week 24, 52)