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

Primary Purpose

Psoriasis, Plaque Psoriasis

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
MK-0873 2% Cream
MK-0873 vehicle (placebo) Cream
Calcitriol Cream
Sponsored by
Merck Sharp & Dohme LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Psoriasis

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Call for Information
  • Call for Information

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Treatment Sequence 1

Treatment Sequence 2

Treatment Sequence 3

Treatment Sequence 4

Treatment Sequence 5

Treatment Sequence 6

Treatment Sequence 7

Treatment Sequence 8

Arm Description

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.

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.

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.

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.

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.

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.

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.

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.

Outcomes

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
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
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
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.

Full Information

First Posted
November 4, 2010
Last Updated
January 17, 2019
Sponsor
Merck Sharp & Dohme LLC
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1. Study Identification

Unique Protocol Identification Number
NCT01235728
Brief Title
A Study to Evaluate and Compare the Efficacy and Pharmacokinetics of MK-0873 for the Treatment of Plaque Psoriasis (MK-0873-022)
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
Study Type
Interventional

2. Study Status

Record Verification Date
January 2019
Overall Recruitment Status
Completed
Study Start Date
November 1, 2010 (Actual)
Primary Completion Date
April 1, 2011 (Actual)
Study Completion Date
April 1, 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck Sharp & Dohme LLC

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Psoriasis, Plaque Psoriasis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
24 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment Sequence 1
Arm Type
Experimental
Arm Description
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.
Arm Title
Treatment Sequence 2
Arm Type
Experimental
Arm Description
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.
Arm Title
Treatment Sequence 3
Arm Type
Experimental
Arm Description
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.
Arm Title
Treatment Sequence 4
Arm Type
Experimental
Arm Description
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.
Arm Title
Treatment Sequence 5
Arm Type
Experimental
Arm Description
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.
Arm Title
Treatment Sequence 6
Arm Type
Experimental
Arm Description
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.
Arm Title
Treatment Sequence 7
Arm Type
Experimental
Arm Description
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.
Arm Title
Treatment Sequence 8
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
MK-0873 2% Cream
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
MK-0873 vehicle (placebo) Cream
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Calcitriol Cream
Intervention Description
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
Primary Outcome Measure Information:
Title
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
Description
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
Secondary Outcome Measure Information:
Title
Least Squares Mean Percent Change From Baseline (Predose Day 1) of TLS Score for Lesions Treated With MK-0873 and Lesions Treated With Calcitriol
Description
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
Title
Mean Maximum Plasma Concentrations at Trough of Day 8, 15, 22, and 29 Following Topical Administration of MK-0873 to Psoriatic Patients
Description
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Merck Sharp & Dohme LLC
Official's Role
Study Director
Facility Information:
Facility Name
Call for Information
City
Fort Myers
State/Province
Florida
ZIP/Postal Code
33901
Country
United States
Facility Name
Call for Information
City
Miramar
State/Province
Florida
ZIP/Postal Code
33025
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
IPD Sharing URL
http://engagezone.msd.com/ds_documentation.php
Available IPD and Supporting Information:
Available IPD/Information Type
CSR Synopsis
Available IPD/Information URL
http://www.merck.com/clinical-trials/study.html?id=0873-022&kw=0873-022&tab=access

Learn more about this trial

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

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