A Study to Evaluate and Compare the Efficacy and Pharmacokinetics of MK-0873 for the Treatment of Plaque Psoriasis (MK-0873-022)

Study Overview
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Brief Summary
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This is a within-participant comparison study to investigate the efficacy of a 28-day regimen of MK-0873 2% cream twice a day (b.i.d.) compared to MK-0873 vehicle (matching placebo) b.i.d. as well as to a positive control comparator calcitriol 0.0003% (3 µg/g) in participants with plaque psoriasis. In order to be enrolled in the study, patients need to have at least two pairs (lesions AB and CD) of approximately similar plaque lesions in severity and size of surface area involved and located in approximately symmetric regions such as the trunk or limbs of the body. Participants will be randomly assigned to apply either MK-0873 or MK-0873 vehicle to plaque A or B and will be randomly assigned to apply MK-0873 or calcitriol to plaque C or D. It is hypothesized that MK-0873 cream formulation administered to participants with psoriasis by the topical route will result in a statistically greater percent target lesion severity (TLS) reduction in plaque lesion than will MK-0873 Vehicle on Day 29.

Official Title
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A Double Blind, Active-Comparator-, and Vehicle-Controlled, Multiple-Dose Study to Evaluate the Efficacy and Pharmacokinetics of MK-0873 in Patients With Plaque Psoriasis

Conditions
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Psoriasis, Plaque Psoriasis

Intervention / Treatment
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* Drug: MK-0873 2% Cream
* Drug: MK-0873 vehicle (placebo) Cream
* Drug: Calcitriol Cream


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Is a male or female 18 to 65 years of age Female subjects of reproductive potential must have a negative serum pregnancy test at screening and agree to use and/or have their partner use two (2) acceptable methods of birth control Has a Body Mass Index (BMI) ≤36 kg/m^2 (up to 40 kg/m^2 may be enrolled, in consultation with Sponsor) Has diagnosis of plaque-type psoriasis at least 6 month prior to administration of study drug (participants with concurrent psoriatic arthritis may be enrolled) Has plaque-type psoriasis with at least two pairs of symmetrically located plaque lesions that exhibit similar baseline TLS values (TLS in each plaque ≥6 and ± 2 points difference between left and right plaque lesions) Has plaque-type psoriasis with lesion severity score ≥4 covering at least 1 to 20% of total body surface area at screening and at baseline. Is judged to be in good health based on medical history, physical examination, vital sign measurements, electrocardiogram assessment, and laboratory safety tests Exclusion Criteria Has nonplaque forms of psoriasis (e.g., Erythrodermic, guttate, or pustular). Has current drug-induced psoriasis (e.g., a new onset of psoriasis or an exacerbation of psoriasis from beta blockers, calcium channel blockers or lithium). Has received phototherapy or any systemic medications/treatments that could affect psoriasis or TLS evaluation (including but not limited to oral or injectable corticosteroids, retinoids, 1, 25-dihydroxy vitamin D3 and analogues, psoralens, sulfsalazine, hydroxyurea, fumaric acid derivatives, or herbal treatments) within 4 weeks of study drug administration. Has used topical medications/treatments that could affect psoriasis or TLS evaluation (e.g., corticosteroids, coal tar, anthralin, calcipotriene, topical vitamin D derivatives, retinoids, tazarotene, methoxsalen, trimethyl psoralens) within 2 weeks of study drug administration. Has used any systemic immunosuppressants (e.g., Methotrexate, azathioprine, cyclosporine, 6-thioguanine, mercaptopurine, mycophenolate mofetil, hydroxyurea, or tacrolimus) within 4 weeks of study drug administration or biologics (e.g., anti-tumor necrosis factor [TNF], anti-interleukins) within 3 months of study drug administration.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Sequence 1<br>Participants were randomized to receive MK-0873 on upper lesion A and vehicle on upper lesion B, and MK-0873 on lower lesion C and calcitriol on lower lesion D. | Drug: MK-0873 2% Cream<br>* Approximately 3 to 5 mg of MK-0873 2% cream per cm^2 of body area in 2 divided applications per day for 28 days. The maximum area for one treatment will be approximately 5% of body surface area.<br>Drug: MK-0873 vehicle (placebo) Cream<br>* Approximately 3 to 5 mg matching placebo to MK-0873 2% cream per cm^2 of body area in 2 divided applications per day for 28 days. The maximum area for one treatment will be approximately 5% of body surface area.<br>Drug: Calcitriol Cream<br>* Approximately 3 to 5 mg of Calcitriol 0.0003% (3 µg/g) per cm^2 of body area once daily for 28 days. The maximum area for one treatment will be approximately 5% of body surface area<br>|
| Experimental: Treatment Sequence 2<br>Participants were randomized to received MK-0873 on lower lesion A and vehicle on lower lesion B, and MK-0873 on upper lesion C and calcitriol on upper lesion D. | Drug: MK-0873 2% Cream<br>* Approximately 3 to 5 mg of MK-0873 2% cream per cm^2 of body area in 2 divided applications per day for 28 days. The maximum area for one treatment will be approximately 5% of body surface area.<br>Drug: MK-0873 vehicle (placebo) Cream<br>* Approximately 3 to 5 mg matching placebo to MK-0873 2% cream per cm^2 of body area in 2 divided applications per day for 28 days. The maximum area for one treatment will be approximately 5% of body surface area.<br>Drug: Calcitriol Cream<br>* Approximately 3 to 5 mg of Calcitriol 0.0003% (3 µg/g) per cm^2 of body area once daily for 28 days. The maximum area for one treatment will be approximately 5% of body surface area<br>|
| Experimental: Treatment Sequence 3<br>Participants were randomized to receive MK-0873 on upper lesion A and vehicle on upper lesion B, and calcitriol on lower lesion C and MK-0873 on lower lesion D. | Drug: MK-0873 2% Cream<br>* Approximately 3 to 5 mg of MK-0873 2% cream per cm^2 of body area in 2 divided applications per day for 28 days. The maximum area for one treatment will be approximately 5% of body surface area.<br>Drug: MK-0873 vehicle (placebo) Cream<br>* Approximately 3 to 5 mg matching placebo to MK-0873 2% cream per cm^2 of body area in 2 divided applications per day for 28 days. The maximum area for one treatment will be approximately 5% of body surface area.<br>Drug: Calcitriol Cream<br>* Approximately 3 to 5 mg of Calcitriol 0.0003% (3 µg/g) per cm^2 of body area once daily for 28 days. The maximum area for one treatment will be approximately 5% of body surface area<br>|
| Experimental: Treatment Sequence 4<br>Participants were randomized to receive MK-0873 on lower lesion A and vehicle on lower lesion B, and calcitriol on upper lesion C and MK-0873 on upper lesion D. | Drug: MK-0873 2% Cream<br>* Approximately 3 to 5 mg of MK-0873 2% cream per cm^2 of body area in 2 divided applications per day for 28 days. The maximum area for one treatment will be approximately 5% of body surface area.<br>Drug: MK-0873 vehicle (placebo) Cream<br>* Approximately 3 to 5 mg matching placebo to MK-0873 2% cream per cm^2 of body area in 2 divided applications per day for 28 days. The maximum area for one treatment will be approximately 5% of body surface area.<br>Drug: Calcitriol Cream<br>* Approximately 3 to 5 mg of Calcitriol 0.0003% (3 µg/g) per cm^2 of body area once daily for 28 days. The maximum area for one treatment will be approximately 5% of body surface area<br>|
| Experimental: Treatment Sequence 5<br>Participants were randomized to receive vehicle on upper lesion A and MK-0873 on upper lesion B, and MK-0873 on lower lesion C and calcitriol on lower lesion D. | Drug: MK-0873 2% Cream<br>* Approximately 3 to 5 mg of MK-0873 2% cream per cm^2 of body area in 2 divided applications per day for 28 days. The maximum area for one treatment will be approximately 5% of body surface area.<br>Drug: MK-0873 vehicle (placebo) Cream<br>* Approximately 3 to 5 mg matching placebo to MK-0873 2% cream per cm^2 of body area in 2 divided applications per day for 28 days. The maximum area for one treatment will be approximately 5% of body surface area.<br>Drug: Calcitriol Cream<br>* Approximately 3 to 5 mg of Calcitriol 0.0003% (3 µg/g) per cm^2 of body area once daily for 28 days. The maximum area for one treatment will be approximately 5% of body surface area<br>|
| Experimental: Treatment Sequence 6<br>Participants were randomized to receive vehicle on lower lesion A and MK-0873 on lower lesion B, and MK-0873 on upper lesion C and calcitriol on upper lesion D. | Drug: MK-0873 2% Cream<br>* Approximately 3 to 5 mg of MK-0873 2% cream per cm^2 of body area in 2 divided applications per day for 28 days. The maximum area for one treatment will be approximately 5% of body surface area.<br>Drug: MK-0873 vehicle (placebo) Cream<br>* Approximately 3 to 5 mg matching placebo to MK-0873 2% cream per cm^2 of body area in 2 divided applications per day for 28 days. The maximum area for one treatment will be approximately 5% of body surface area.<br>Drug: Calcitriol Cream<br>* Approximately 3 to 5 mg of Calcitriol 0.0003% (3 µg/g) per cm^2 of body area once daily for 28 days. The maximum area for one treatment will be approximately 5% of body surface area<br>|
| Experimental: Treatment Sequence 7<br>Participants were randomized to receive vehicle on upper lesion A and MK-0873 on upper lesion B, and calcitriol on lower lesion C and MK-0873 on lower lesion D. | Drug: MK-0873 2% Cream<br>* Approximately 3 to 5 mg of MK-0873 2% cream per cm^2 of body area in 2 divided applications per day for 28 days. The maximum area for one treatment will be approximately 5% of body surface area.<br>Drug: MK-0873 vehicle (placebo) Cream<br>* Approximately 3 to 5 mg matching placebo to MK-0873 2% cream per cm^2 of body area in 2 divided applications per day for 28 days. The maximum area for one treatment will be approximately 5% of body surface area.<br>Drug: Calcitriol Cream<br>* Approximately 3 to 5 mg of Calcitriol 0.0003% (3 µg/g) per cm^2 of body area once daily for 28 days. The maximum area for one treatment will be approximately 5% of body surface area<br>|
| Experimental: Treatment Sequence 8<br>Participants were randomized to receive vehicle on lower lesion A and MK-0873 on lower lesion B, and calcitriol on upper lesion C and MK-0873 on upper lesion D. | Drug: MK-0873 2% Cream<br>* Approximately 3 to 5 mg of MK-0873 2% cream per cm^2 of body area in 2 divided applications per day for 28 days. The maximum area for one treatment will be approximately 5% of body surface area.<br>Drug: MK-0873 vehicle (placebo) Cream<br>* Approximately 3 to 5 mg matching placebo to MK-0873 2% cream per cm^2 of body area in 2 divided applications per day for 28 days. The maximum area for one treatment will be approximately 5% of body surface area.<br>Drug: Calcitriol Cream<br>* Approximately 3 to 5 mg of Calcitriol 0.0003% (3 µg/g) per cm^2 of body area once daily for 28 days. The maximum area for one treatment will be approximately 5% of body surface area<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Least Squares Mean Percent Change From Baseline (Predose Day 1) of Target Lesion Severity (TLS) Score for Lesions Treated With MK-0873 and Lesions Treated With MK-0873 Vehicle | Each lesion was evaluated for 3 components: erythema, induration, and scaling. Each component was given a score using the following scale: 0=none, 1=slight, 2=moderate, 3=marked, 4=very marked, with increasing score reflecting increased lesion severity. The TLS score (range 0 to 12) is calculated as the sum of the 3 components. | Baseline and Day 29 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Least Squares Mean Percent Change From Baseline (Predose Day 1) of TLS Score for Lesions Treated With MK-0873 and Lesions Treated With Calcitriol | Each lesion was evaluated for 3 components: erythema, induration, and scaling. Each component was given a score using the following scale: 0=none, 1=slight, 2=moderate, 3=marked, 4=very marked, with increasing score reflecting increased lesion severity. The TLS score (range 0 to 12) is calculated as the sum of the 3 components. | Baseline and Day 29 | 
| Mean Maximum Plasma Concentrations at Trough of Day 8, 15, 22, and 29 Following Topical Administration of MK-0873 to Psoriatic Patients | Plasma samples were collected at 12 hours post-dose on Days 8, 15, 22, and 28 to evaluate the mean maximum plasma concentration at trough of MK-0873. | Day 8, 15, 22, 29 |