An Open Label, Phase 1, Pharmacokinetics, Maximal Usage Pharmacokinetics, Safety, and Efficacy Study of ARQ-151 Cream 0.15% or ARQ-151 Cream 0.05% Administered QD in Adolescent and Pediatric Subjects With Mild to Moderate Atopic Dermatitis
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 101
- 试验地点
- 10
- 主要终点
- Maximum Plasma Concentration (Cmax) of roflumilast and its N-oxide metabolite
研究概览
简要总结
This is a research study where all subjects will receive study medication to understand how the body processes the study medication, and to determine the PK, safety and efficacy of ARQ-151 cream 0.15% or 0.05% in adolescent and pediatric subjects with mild to moderate AD. At entry, subjects in Cohorts 1-3 will have 1.5-35% Body Surface Area involvement (excluding the scalp, palms, soles) and mild or moderate atopic dermatitis (AD) based on vIGA-AD. Cohort 2 and Cohort 3 will be performed in parallel and may commence after results are available from ARQ-151-212, a Phase 2 study evaluating ARQ-151 cream 0.05% and 0.15% administered once a day for 4 weeks in adolescents and adults with mild to moderate AD affecting 1.5% to 35% BSA.
For the maximal usage PK study (Cohorts 4-8), subjects will have BSA involvement (excluding the scalp, palms, soles) of ≥ 35% in subjects 3 months old to 11 years old (inclusive) or ≥25% in subjects 12 to <17 years old with mild or moderate AD .
Seven groups will be evaluated, including:
- Cohort 1: ARQ-151 cream 0.15% in adolescents (12-17 years old; inclusive)
- Cohort 2: ARQ-151 cream 0.15% in children 6-11 years old (inclusive)
- Cohort 3: ARQ-151 cream 0.15% in children 2-5 years old (inclusive; will be performed in parallel with Cohort 2)
- Cohort 4: ARQ-151 cream 0.15% in adolescents 12 to <17 years old
- Cohort 5: ARQ-151 cream 0.15% in children 6-11 years old (inclusive)
- Cohort 6: ARQ-151 cream 0.15% in children 2-5 years old (inclusive)
- Cohort 7: ARQ-151 cream 0.05% in children 2-5 years old (inclusive)
- Cohort 8: ARQ-151 cream 0.05% in children 3 months old to less than 2 years old
Subjects will apply ARQ-151 cream 0.15% or 0.05% once a day for 28 days to all AD affected areas and any newly appearing AD lesions that arise during the study, except on the scalp.
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
- 3 Months 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Informed consent of parent(s) or legal guardian, and, if age appropriate, assent by the subject, as required by local laws.
- •Males or females, 12-17 years old (inclusive; Cohort 1), or 6-11 years old (inclusive; Cohort 2), or 2-5 years old (inclusive; Cohort 3), and in the maximal usage PK study subjects aged 12 to <17 years old (Cohort 4), 6 to 11 years old (Cohort 5), 2-5 years old (Cohort 6 and Cohort 7), or 3 months to less than 2 years old (Cohort 8).
- •Clinical diagnosis of active atopic dermatitis for at least 3 months (2 weeks for Cohort 8).
- •EASI Score ≥
- •vIGA-AD score of 'Mild' ('2') or 'Moderate ('3').
- •Has AD involvement of 1.5 to 35% BSA (Cohorts 1-3) or ≥25% BSA (Cohorts 4-7), all excluding the scalp, palms, soles; or for Cohort 8 ≥35% BSA excluding the scalp, perioral, and below wrists/ankles .
- •Females of childbearing potential must have a negative serum pregnancy test at Screening and, if sexually active, agree to use birth control throughout the trial.
- •In good health as judged by the Investigator, based on medical history, physical examination, and clinical tests.
排除标准
- •Subjects with any serious medical or psychiatric condition or clinically significant physical examination or test abnormality that would prevent study participation or place the subject at significant risk.
- •Subjects with unstable AD or any consistent requirement for high potency topical steroids to manage AD signs or symptoms.
- •Subjects who cannot discontinue the use of strong P-450 cytochrome inducers or inhibitors.
- •Subjects who are unwilling to refrain from prolonged sun exposure and from using a tanning bed or other artificial light emitting devices (LEDs) for 4 weeks prior to Baseline/Visit 2 and during the study.
- •Subjects who cannot discontinue systemic and/or topical therapies.
- •Current or a history of cancer within 5 years with the exception of fully treated skin basal cell carcinoma, cutaneous squamous cell carcinoma or carcinoma in situ of the cervix.
- •Subjects with actively infected AD or any infection that required oral or intravenous administration of antibiotics, antifungal or antiviral agents
- •Known or suspected:
- •severe renal insufficiency or moderate to severe hepatic disorders (Child-Pugh B or C)
- •history of chronic infectious disease (e.g., hepatitis B, hepatitis C, or human immunodeficiency virus (HIV))
- •hypersensitivity to component(s) of the investigational product
- •history of severe depression, suicidal ideation, Baseline/Screening C-SSRS indicative of suicidal ideation, whether lifetime or recent/current
- •Females who are pregnant, wishing to become pregnant during the study, or are breast-feeding.
- •Subjects (12 to 17 years old, inclusive) with modified PHQ-A score ≥10 at Screening or Baseline visits.
- •Subjects (6 to 11 years old, inclusive) with a CDI-2 (parent report) raw score >20 at Screening/Baseline
- •Subjects with a history of a major surgery within 4 weeks prior to Baseline/Visit 1 or subjects who have a major surgery planned during the study.
- •Subjects with prior exposure to ARQ-151
- •Subjects 3 to <12 months old who were premature at birth
- •Subject is nursing and subject's mother requires high dose systemic steroids
研究组 & 干预措施
ARQ-151 cream 0.15% or 0.05%
Open-label study of 0.15% or 0.05% active concentration
干预措施: ARQ-151 cream 0.15% (Drug)
ARQ-151 cream 0.15% or 0.05%
Open-label study of 0.15% or 0.05% active concentration
干预措施: ARQ-151 cream 0.05% (Drug)
结局指标
主要结局
Maximum Plasma Concentration (Cmax) of roflumilast and its N-oxide metabolite
时间窗: 4 weeks
Maximum observed plasma concentration of drug in plasma
Area under the plasma concentration-time curve within a dosing interval (AUC) for roflumilast and its N-oxide metabolite
时间窗: 4 weeks
The area under the plasma concentration-time curve (AUC) is a method of measurement of the total exposure of a drug in plasma.
Treatment Emergent Adverse Events (TEAE)
时间窗: 4 weeks
Number of participants with adverse events during treatment will be assessed.
次要结局
- Eczema Area and Severity Index (EASI) Total Score Change and Percent Change in Total Score(Baseline, Week 2, and Week 4)
- Eczema Area and Severity Index Score 100%, 90%, 75%, and 50% Improvement (EASI100, EASI90, EASI75, and EASI50)(Baseline, Week 2, and Week 4)
- Achievement of a Validated Investigator Global Assessment scale for Atopic Dermatitis (vIGA-AD) score of 'clear' or 'almost clear' at each study visit, or 'clear' or 'almost clear' with a 2-point improvement from baseline at each study visit(Baseline, Week 2, Week 4)
- Change from baseline in vIGA-AD score at each study visit(Baseline, Week 2, Week 4)
- Body Surface Area (BSA) Involvement Change(Baseline, Week 2, Week 4)
- Worse Itch Numerical Rating Score (WI-NRS) Pruritis Score Change(Baseline, Week 2, Week 4)
- WI-NRS Pruritus Score Improvement(Baseline, Week 2, Week 4)