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

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

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.

Study Overview

• Status: Completed
• Conditions: Psoriasis; Plaque Psoriasis
• Intervention / Treatment: Drug: MK-0873 2% Cream; Drug: MK-0873 vehicle (placebo) Cream; Drug: Calcitriol Cream

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Fort Myers, Florida, United States, 33901
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    • Miramar, Florida, United States, 33025
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Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: TRIPLE

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Treatment Sequence 1; 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; 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.; Drug: MK-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.; Drug: Calcitriol 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
EXPERIMENTAL: Treatment Sequence 2; 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; 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.; Drug: MK-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.; Drug: Calcitriol 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
EXPERIMENTAL: Treatment Sequence 3; 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; 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.; Drug: MK-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.; Drug: Calcitriol 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
EXPERIMENTAL: Treatment Sequence 4; 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; 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.; Drug: MK-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.; Drug: Calcitriol 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
EXPERIMENTAL: Treatment Sequence 5; 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; 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.; Drug: MK-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.; Drug: Calcitriol 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
EXPERIMENTAL: Treatment Sequence 6; 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; 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.; Drug: MK-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.; Drug: Calcitriol 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
EXPERIMENTAL: Treatment Sequence 7; 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; 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.; Drug: MK-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.; Drug: Calcitriol 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
EXPERIMENTAL: Treatment Sequence 8; 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; 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.; Drug: MK-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.; Drug: Calcitriol 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 1, 2010
• Primary Completion (ACTUAL): April 1, 2011
• Study Completion (ACTUAL): April 1, 2011

Study Registration Dates

• First Submitted: November 4, 2010
• First Submitted That Met QC Criteria: November 4, 2010
• First Posted (ESTIMATE): November 5, 2010

Study Record Updates

• Last Update Posted (ACTUAL): February 8, 2019
• Last Update Submitted That Met QC Criteria: January 17, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Skin Diseases, Papulosquamous; Psoriasis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Micronutrients; Membrane Transport Modulators; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Phosphodiesterase Inhibitors; Vasoconstrictor Agents; Phosphodiesterase 4 Inhibitors; Calcium Channel Agonists; Calcitriol; MK 0873
• Other Study ID Numbers: 0873-022

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Study Data/Documents

1. CSR Synopsis