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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01235728
First received: November 4, 2010
Last updated: May 13, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
Psoriasis
Plaque Psoriasis
Drug: MK-0873 2% Cream
Drug: MK-0873 vehicle (placebo) Cream
Drug: Calcitriol Cream
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • 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 [ Time Frame: Baseline and Day 29 ] [ Designated as safety issue: No ]
    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 Outcome Measures:
  • Least Squares Mean Percent Change From Baseline (Predose Day 1) of TLS Score for Lesions Treated With MK-0873 and Lesions Treated With Calcitriol [ Time Frame: Baseline and Day 29 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 8, 15, 22, 29 ] [ Designated as safety issue: No ]
    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.


Enrollment: 24
Study Start Date: November 2010
Study Completion Date: April 2011
Primary Completion Date: April 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01235728

Locations
United States, Florida
Call for Information
Fort Myers, Florida, United States, 33901
Call for Information
Miramar, Florida, United States, 33025
Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Director Merck Sharp & Dohme Corp.
  More Information

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01235728     History of Changes
Other Study ID Numbers: 0873-022
Study First Received: November 4, 2010
Results First Received: May 13, 2014
Last Updated: May 13, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Psoriasis
Skin Diseases, Papulosquamous
Skin Diseases
Calcitriol
Calcium Channel Agonists
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Vasoconstrictor Agents
Cardiovascular Agents
Therapeutic Uses
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs
Bone Density Conservation Agents

ClinicalTrials.gov processed this record on August 27, 2014