Maximal Usage Pharmacokinetics and Safety of ARQ-151 in Adolescents and Adults With Chronic Plaque Psoriasis

Study Overview
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Brief Summary
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This is a phase 1, open label, single arm study in which ARQ-151 cream 0.3% is applied QD for 2 weeks to adolescent subjects with chronic plaque psoriasis involving at least 10% body surface area (BSA) and adult subjects with chronic plaque psoriasis involving at least 20% BSA (excluding scalp). The objectives of this study are to evaluate the exposure and characterize the plasma pharmacokinetic profile and to assess the safety and tolerability of ARQ-151 cream 0.3% administered once daily for 2 weeks to adolescent and adult subjects with chronic plaque psoriasis.

Official Title
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An Open Label, Phase 1, Maximal Usage Pharmacokinetics and Safety Study of ARQ-151 Cream 0.3% Administered QD in Adolescent and Adult Subjects With Chronic Plaque Psoriasis

Conditions
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Plaque Psoriasis

Intervention / Treatment
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* Drug: ARQ-151- cream 0.3%


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants legally competent to sign and give informed consent or for adolescents assent with consent of a parent or legal guardian. Males and females ages 12 years and older (inclusive) at the time of consent/assent. Clinical diagnosis of psoriasis vulgaris of at least 3 months duration as determined by the Investigator or through subject interview. Stable disease for the past 4 weeks. Psoriasis vulgaris on the face, extremities, trunk, and/or intertriginous areas involving at least 10% of BSA in adolescents and at least 20% of BSA in adults (excluding the scalp). An Investigator Global Assessment of disease severity of at least Moderate ('3') at Baseline. Females of childbearing potential (FOCBP) must have a negative serum pregnancy test at Screening (Visit 1) and a negative urine pregnancy test at Baseline (Visit 2). In addition, sexually active FOCBP must agree to use at least one form of highly effective contraception throughout the trial. Females of non-childbearing potential should be premenarchal, post-menopausal with spontaneous amenorrhea for at least 12 months or have undergone surgical sterilization. Subjects in good health as judged by the Investigator, based on medical history, physical examination, vital signs, 12-lead electrocardiogram, serum chemistry labs, hematology values, and urinalysis. Subjects are considered reliable and capable of adhering to the Protocol and visit schedule, according to the judgment of the Investigator. Exclusion Criteria: Subjects who cannot discontinue medication and treatments prior to the Baseline visit and during the study according to Excluded Medications and Treatments (Table 1). Planned excessive exposure of treated area(s) to either natural or artificial sunlight, tanning bed or other light emitting diode (LED). Subjects currently taking lithium or antimalarial drugs. Planned initiation or changes to concomitant medication that could, in the opinion of the Investigator, affect psoriasis vulgaris (e.g. beta blockers, ACE inhibitors). Current diagnosis of non-plaque form of psoriasis (e.g., guttate, erythrodermic/exfoliative, or pustular psoriasis). Current diagnosis of drug-induced psoriasis. Subjects with any condition on the treatment area which, in the opinion of the Investigator, could confound efficacy measurements. Known allergies to excipients in ARQ-151 cream Subjects who cannot discontinue the use of systemic strong P 450 cytochrome inhibitors (e.g., indinavir, nelfinavir, ritonavir, clarithromycin, itraconazole, ketoconazole, fluconazole, nefazodone, saquinavir, suboxone and telithromycin) for two weeks prior to the Baseline visit and during the study period. Subjects who cannot discontinue the use of systemic strong P 450 cytochrome inducers (e.g., efavirenz, nevirapine, glucocorticoids, barbiturates (including phenobarbital), phenytoin, rifampin and carbamazepine) for two weeks prior to the Baseline visit and during the study period. Females who are pregnant, wishing to become pregnant during the study, or are breast-feeding. Subjects who have received oral roflumilast (Daliresp®, Daxas®) or other PDE4 inhibitors (apremilast) within the past 4 weeks. Known or suspected: severe renal insufficiency or moderate to severe liver impairment (Child-Pugh B or C) known HIV infection hypersensitivity to component(s) of the investigational products history of severe depression, suicidal ideation, Baseline/Screening C-SSRS indicative of suicidal ideation, whether lifetime or recent/current Adult subjects with PHQ-8 ≥10 or adolescent subjects with modified PHQ-A ≥10 at Screening or Baseline visits. Subjects with a history of chronic alcohol or drug abuse within 6 months of initiation of investigational product. Subjects with a history of a major surgery within 4 weeks prior to Baseline (Visit 2) or has a major surgery planned during the study. Subjects who are unable to communicate, read or understand the local language, or who display another condition, which in the Investigator's opinion, makes them unsuitable for clinical study participation. For adolescent subjects; parent(s)/legal guardian(s) who are unable to communicate, read, or understand the local language. Subjects who are family members of the clinical study site, clinical study staff, or Sponsor. Subjects with any serious medical condition or laboratory abnormality that would prevent study participation or place the subject at significant risk, as determined by the Investigator. 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 active infection that required oral or intravenous administration of antibiotics, antifungal or antiviral agents within 7 days of Baseline/Day 1.

Ages Eligible for Study
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Minimum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ARQ-151 cream 0.3%<br>Open label study of ARQ-151 cream 0.3% applied once daily for 2 weeks | Drug: ARQ-151- cream 0.3%<br>* ARQ-151 cream 0.3% applied to chronic plaque psoriasis lesions once a day for 2 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum concentration (Cmax) of roflumilast and its major N-oxide metabolite | Maximum observed concentration of drug in plasma metabolite | 5 weeks | 
| Area under the plasma concentration-time curve until the last quantifiable timepoint (AUC) for roflumilast and its N-oxide metabolite | The area under the plasma concentration-time curve (AUC) is a method of measurement of the total exposure of a drug in plasma. | 5 weeks | 
| Time of maximum concentration (Tmax) of roflumilast and its major N-oxide metabolite | Tmax is the time that a drug achieves maximum concentration in plasma | 5 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subject incidence of adverse events | Number of participants with adverse events during treatment will be assessed | 5 weeks | 
| Incidence of application site reactions | Number of subjects that experience an application site skin reaction by investigator assessment and application site reactions reported as adverse events will be assessed | 5 weeks | 
| Incidence of application site reactions | Percentage of subjects that experience an application site skin reaction by investigator assessment and application site reactions reported as adverse events will be assessed | 5 weeks | 
| The incidence of suicide ideation as measured by the Columbia Suicide Severity Rating Scale (C-SSRS) | The C-SSRS is a tool used to assess suicide risk, the severity and immediacy of that risk. The C-SSRS is made up of ten categories and includes questions that require binary responses (yes/no) to indicate a presence or absence of the behavior and follow-up questions for any behavior that is endorsed (yes) to collect additional information. | 5 weeks | 
| The incidence of changes from baseline in the Patient Health Questionnaire (PHQ-8) Depression Scale | The PHQ-8 is an instrument used for screening, diagnosing, monitoring and measuring the severity of depression in adults. The score for the PHQ-8 ranges from 0-24 with a higher score reflecting a higher severity category of depression. | 5 weeks | 
| The incidence of changes from baseline in the Patient Health Questionnaire for Adolescents (PHQ-A) Depression Scale | The PHQ-A is an instrument used for screening, diagnosing, monitoring and measuring the severity of depression in adolescents. The score for the PHQ-A ranges from 0-24 with a higher score reflecting a higher severity category of depression. | 5 weeks |