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Chronic Plaque Psoriasis Study With Topical Formulation Of GW786034

Primary Purpose

Psoriasis

Status
Completed
Phase
Phase 1
Locations
France
Study Type
Interventional
Intervention
Pazopanib
Pazopanib vehicle
Betamethasone valerate
Calcipotriol
Sponsored by
GlaxoSmithKline
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Psoriasis focused on measuring tolerability, safety, angiogenesis, vascular endothelial growth factor, pharmacodynamics, pharmacokinetics, microplaque, VEGF, GW786034

Eligibility Criteria

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

Inclusion criteria: Stable (2-3 months) chronic plaque psoriasis covering greater than 5% body surface area (as determined by PASI palm method). Other than having chronic plaque psoriasis, subject is health and ambulatory. Women will be eligible to enter the study if they are of non-child-bearing potential (i.e. physiologically incapable of becoming pregnant, including any female who is post-menopausal or surgically sterile). Must have at least two clinically similar lesions with the following characteristics as deemed by the dermatologist: Moderate to severe in elevation (thickness), erythema, and scaling (with a total score of at least 6 for each target lesion, when assessed using a 0-4 PASI score). Located on the trunk, buttocks, thighs or upper arms. Are of a sufficient size that will allow the application of three occlusive patches. Exclusion criteria: Guttate, erythrodermic, or pustular psoriasis. Psoriasis is spontaneously improving. Have had psoriasis that was unresponsive to adequately dosed (> 10 weeks) cyclosporine. Any systemic disorder or active skin disease (other than psoriasis) or subjects who present with scars, moles, tattoos, body piercings, sunburn in the test area. History of congestive heart failure (NYHA Class 3 or 4), myocardial infarction, coronary artery bypass graft, percutaneous transluminal balloon angioplasty, cerebrovascular accident, chronic or intermittent oedema. Blood pressure of greater than 150mmHg systolic and /or 95mmHg diastolic following triplicate measurements taken 5 minutes apart. Presence of unstable or severe angina or coronary insufficiency. Uncontrolled bacterial, viral, or fungal infection. Congenital or acquired immunodeficiency. History of malignancy within the last five years, except for surgically cured skin carcinoma or cervical dysplasia (CIN I-II). An unwillingness of male subjects to use a condom/spermicide in addition to having their female partner use another form of contraception if the woman could become pregnant from the time of the first dose of study medication until 5 half-lives of the drug have elapsed following removal of the last dose of study medication. An unwillingness of male subjects to abstain from sexual intercourse with pregnant or lactating women from the time of first dose of study medication until five half-lives or 5 days (whichever is longer) following removal of the last dose of study medication. Prolonged exposure to the sun (or tanning beds) during the study. Systemic anti-psoriasis therapy, including but not limited to: acitretin, cyclosporine, isotretinoin, infliximab, entercept, alefacept, oral steroids and psoralen during the 4 weeks prior to the first dose of study medication and throughout the study. Concomitant use of phototherapy or photochemotherapy. Concomitant use of lithium, antimalarials, interferons. Systemic beta-blockers are permitted provided the dose is stable for four weeks before baseline and remains stable throughout the study. Concomitant use of anti-arthritis therapies with known propensity for hepatotoxicity (i.e. diclofenac, gold, D-penicillamine, leflunomide). Use of topical or intralesional treatments for psoriasis (e.g. mid- or high-potency topical corticosteroids) within 2 weeks prior to Day 1 and throughout the study, except for class VI or VII topical steroid treatments (Desonide, or 2.5% hydrocortisone) which will be allowed on the face. Concomitant use of non-drug therapies (i.e. herbal products or alternative therapies) for psoriasis.

Sites / Locations

  • GSK Investigational Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Experimental

Experimental

Placebo Comparator

Placebo Comparator

Placebo Comparator

Arm Label

Subjects receiving treatment A

Subjects receiving treatment B

Subjects receiving treatment C

Subjects receiving treatment D

Subjects receiving treatment E

Subjects receiving treatment F

Arm Description

Eligible subjects will receive 0.1 percent pazopanib ointment.

Eligible subjects will receive 0.5 percent pazopanib ointment.

Eligible subjects will receive 1 percent pazopanib ointment.

Eligible subjects will receive pazopanib vehicle as negative control.

Eligible subjects will receive 0.1 percent betamethasone valerate ointment as steroid positive control.

Eligible subjects will receive 0.005 percent calcipotriol ointment as vitamin D agonist positive control.

Outcomes

Primary Outcome Measures

Visual assessment and clinical scoring of lesion treatment areas using modified Psoriasis Area Scoring Index (PASI) target lesion assessment scale Clinical lab tests vital signs adverse events clinical monitoring/observation

Secondary Outcome Measures

Laser doppler imaging,epidermal thickness by histology skin biopsies Primary pharmacokinetic endpoints AUC(0-t) and Cmax of GW786034 in plasma following repeat dosing

Full Information

First Posted
July 27, 2006
Last Updated
November 8, 2017
Sponsor
GlaxoSmithKline
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1. Study Identification

Unique Protocol Identification Number
NCT00358384
Brief Title
Chronic Plaque Psoriasis Study With Topical Formulation Of GW786034
Official Title
A Study to Investigate the Irritation Potential on Healthy Intact Skin and Effect on Psoriatic Skin of Topical Applications of GW786034
Study Type
Interventional

2. Study Status

Record Verification Date
November 2017
Overall Recruitment Status
Completed
Study Start Date
September 26, 2005 (Actual)
Primary Completion Date
February 24, 2006 (Actual)
Study Completion Date
February 24, 2006 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
GlaxoSmithKline

4. Oversight

5. Study Description

Brief Summary
This study is an exploratory study to evaluate the effectiveness, safety and tolerability of three concentrations of GW786034 ointment following treatment to small areas of stable psoriatic plaques. Dosing will proceed using a microplaque approach, where small volumes of ointment will be applied under full occlusion to representative psoriatic plaques. The effectiveness of topical GW786034 treatments and controls will be explored using visual intensity assessments in addition to dermal imaging and histological surrogates of disease activity.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Psoriasis
Keywords
tolerability, safety, angiogenesis, vascular endothelial growth factor, pharmacodynamics, pharmacokinetics, microplaque, VEGF, GW786034

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Allocation
Randomized
Enrollment
10 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Subjects receiving treatment A
Arm Type
Experimental
Arm Description
Eligible subjects will receive 0.1 percent pazopanib ointment.
Arm Title
Subjects receiving treatment B
Arm Type
Experimental
Arm Description
Eligible subjects will receive 0.5 percent pazopanib ointment.
Arm Title
Subjects receiving treatment C
Arm Type
Experimental
Arm Description
Eligible subjects will receive 1 percent pazopanib ointment.
Arm Title
Subjects receiving treatment D
Arm Type
Placebo Comparator
Arm Description
Eligible subjects will receive pazopanib vehicle as negative control.
Arm Title
Subjects receiving treatment E
Arm Type
Placebo Comparator
Arm Description
Eligible subjects will receive 0.1 percent betamethasone valerate ointment as steroid positive control.
Arm Title
Subjects receiving treatment F
Arm Type
Placebo Comparator
Arm Description
Eligible subjects will receive 0.005 percent calcipotriol ointment as vitamin D agonist positive control.
Intervention Type
Drug
Intervention Name(s)
Pazopanib
Intervention Description
Pazopanib will be available in dosing strengths of 0.1, 0.5 and 1 percent.
Intervention Type
Drug
Intervention Name(s)
Pazopanib vehicle
Intervention Description
Pazopanib vehicle will be given to subjects.
Intervention Type
Drug
Intervention Name(s)
Betamethasone valerate
Intervention Description
Betamethasone valerate ointment with 0.1 percent concentration will be given to subjects.
Intervention Type
Drug
Intervention Name(s)
Calcipotriol
Intervention Description
Calcipotriol ointment with 0.005 percent concentration will be given to subjects.
Primary Outcome Measure Information:
Title
Visual assessment and clinical scoring of lesion treatment areas using modified Psoriasis Area Scoring Index (PASI) target lesion assessment scale Clinical lab tests vital signs adverse events clinical monitoring/observation
Time Frame
Up to 8 weeks
Secondary Outcome Measure Information:
Title
Laser doppler imaging,epidermal thickness by histology skin biopsies Primary pharmacokinetic endpoints AUC(0-t) and Cmax of GW786034 in plasma following repeat dosing
Time Frame
Up to 8 weeks

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: Stable (2-3 months) chronic plaque psoriasis covering greater than 5% body surface area (as determined by PASI palm method). Other than having chronic plaque psoriasis, subject is health and ambulatory. Women will be eligible to enter the study if they are of non-child-bearing potential (i.e. physiologically incapable of becoming pregnant, including any female who is post-menopausal or surgically sterile). Must have at least two clinically similar lesions with the following characteristics as deemed by the dermatologist: Moderate to severe in elevation (thickness), erythema, and scaling (with a total score of at least 6 for each target lesion, when assessed using a 0-4 PASI score). Located on the trunk, buttocks, thighs or upper arms. Are of a sufficient size that will allow the application of three occlusive patches. Exclusion criteria: Guttate, erythrodermic, or pustular psoriasis. Psoriasis is spontaneously improving. Have had psoriasis that was unresponsive to adequately dosed (> 10 weeks) cyclosporine. Any systemic disorder or active skin disease (other than psoriasis) or subjects who present with scars, moles, tattoos, body piercings, sunburn in the test area. History of congestive heart failure (NYHA Class 3 or 4), myocardial infarction, coronary artery bypass graft, percutaneous transluminal balloon angioplasty, cerebrovascular accident, chronic or intermittent oedema. Blood pressure of greater than 150mmHg systolic and /or 95mmHg diastolic following triplicate measurements taken 5 minutes apart. Presence of unstable or severe angina or coronary insufficiency. Uncontrolled bacterial, viral, or fungal infection. Congenital or acquired immunodeficiency. History of malignancy within the last five years, except for surgically cured skin carcinoma or cervical dysplasia (CIN I-II). An unwillingness of male subjects to use a condom/spermicide in addition to having their female partner use another form of contraception if the woman could become pregnant from the time of the first dose of study medication until 5 half-lives of the drug have elapsed following removal of the last dose of study medication. An unwillingness of male subjects to abstain from sexual intercourse with pregnant or lactating women from the time of first dose of study medication until five half-lives or 5 days (whichever is longer) following removal of the last dose of study medication. Prolonged exposure to the sun (or tanning beds) during the study. Systemic anti-psoriasis therapy, including but not limited to: acitretin, cyclosporine, isotretinoin, infliximab, entercept, alefacept, oral steroids and psoralen during the 4 weeks prior to the first dose of study medication and throughout the study. Concomitant use of phototherapy or photochemotherapy. Concomitant use of lithium, antimalarials, interferons. Systemic beta-blockers are permitted provided the dose is stable for four weeks before baseline and remains stable throughout the study. Concomitant use of anti-arthritis therapies with known propensity for hepatotoxicity (i.e. diclofenac, gold, D-penicillamine, leflunomide). Use of topical or intralesional treatments for psoriasis (e.g. mid- or high-potency topical corticosteroids) within 2 weeks prior to Day 1 and throughout the study, except for class VI or VII topical steroid treatments (Desonide, or 2.5% hydrocortisone) which will be allowed on the face. Concomitant use of non-drug therapies (i.e. herbal products or alternative therapies) for psoriasis.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
GSK Clinical Trials
Organizational Affiliation
GlaxoSmithKline
Official's Role
Study Director
Facility Information:
Facility Name
GSK Investigational Site
City
Paris
ZIP/Postal Code
75015
Country
France

12. IPD Sharing Statement

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Chronic Plaque Psoriasis Study With Topical Formulation Of GW786034

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