Plaque Psoriasis, Psoriasis
Conditions
Brief summary
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.
Interventions
DRUGMK-0873 2% Cream
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.
DRUGMK-0873 vehicle (placebo) Cream
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.
DRUGCalcitriol Cream
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
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Baseline and Day 29 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Least Squares Mean Percent Change From Baseline (Predose Day 1) of TLS Score for Lesions Treated With MK-0873 and Lesions Treated With Calcitriol | Baseline and Day 29 | 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. |
| Mean Maximum Plasma Concentrations at Trough of Day 8, 15, 22, and 29 Following Topical Administration of MK-0873 to Psoriatic Patients | Day 8, 15, 22, 29 | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| MK-0873 Participants were randomized to receive MK-0873 on upper or lower lesion C or D and calcitriol on the opposing lesion D or C. The lesion receiving calcitriol was evaluated. | 24 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Protocol Violation | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | MK-0873 |
|---|---|
| Age, Continuous | 43.3 Years |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 8 / 24 |
| serious Total, serious adverse events | 0 / 24 |
Outcome results
Primary
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.
Time frame: Baseline and Day 29
Population: The population consisted of all participants that received treatment, had no major protocol violations, and had TLS scores available at baseline and Day 29.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| MK-0873 | 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 | -47.37 Percent Change |
| MK-0873 Vehicle | 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 | -42.71 Percent Change |
Secondary
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.
Time frame: Baseline and Day 29
Population: The population consisted of all participants that received treatment, had no major protocol violations, and had TLS scores available at baseline and Day 29
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| MK-0873 | Least Squares Mean Percent Change From Baseline (Predose Day 1) of TLS Score for Lesions Treated With MK-0873 and Lesions Treated With Calcitriol | -57.24 Percent Change |
| MK-0873 Vehicle | Least Squares Mean Percent Change From Baseline (Predose Day 1) of TLS Score for Lesions Treated With MK-0873 and Lesions Treated With Calcitriol | -47.89 Percent Change |
Secondary
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.
Time frame: Day 8, 15, 22, 29
Population: The population consisted of all participants that received treatment, had no major protocol violations, and had MK-0873 plasma trough values available for the Day 8, 15, 22, and 28 treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MK-0873 | Mean Maximum Plasma Concentrations at Trough of Day 8, 15, 22, and 29 Following Topical Administration of MK-0873 to Psoriatic Patients | 3.6 nM | Standard Deviation 3.1 |