Dose Ranging Study of the Safety and Efficacy of R115966 in Plaque Psoriasis

A Randomized, Evaluator-Blind, Placebo-Controlled, Parallel-Group Dose-Ranging Study of the Safety and Efficacy of Oral R115866 and R115866 Placebo in the Treatment of Plaque Psoriasis

Eligible subjects will be randomly assigned to one of three dose regimens of oral R115866 or placebo for the treatment of severe plaque psoriasis for 12 twelve weeks. The safety and efficacy of R115866 will be evaluated during the treatment period and the 8-week post treatment follow-up period.

Study Overview

• Status: Completed
• Conditions: Psoriasis
• Intervention / Treatment: Drug: Talarozole

• Study Type: Interventional
• Enrollment (Actual): 176
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Augsburg, Germany
    • GSK Investigational Site
  • Berlin, Germany
    • GSK Investigational Site
  • Dresden, Germany
    • GSK Investigational Site
  • Frankfurt, Germany
    • GSK Investigational Site
  • Hamburg, Germany
    • GSK Investigational Site
  • Salzwedel, Germany
    • GSK Investigational Site
• Ireland
  • Cork, Ireland
    • GSK Investigational Site
• Netherlands
  • Maastricht, Netherlands
    • GSK Investigational Site
  • Nijmegen, Netherlands
    • GSK Investigational Site
• Russian Federation
  • Korolev, Russian Federation
    • GSK Investigational Site
  • Lipetsk, Russian Federation
    • GSK Investigational Site
  • Moscow, Russian Federation
    • GSK Investigational Site
  • Novgorod, Russian Federation
    • GSK Investigational Site
  • Smolensk, Russian Federation
    • GSK Investigational Site
  • St. Petersburg, Russian Federation
    • GSK Investigational Site
  • Yaroslavl, Russian Federation
    • GSK Investigational Site
• United Kingdom
  • Aberdeen, United Kingdom
    • GSK Investigational Site
  • Amersham, United Kingdom
    • GSK Investigational Site
  • Coventry, United Kingdom
    • GSK Investigational Site
  • Glasgow, United Kingdom
    • GSK Investigational Site
  • Manchester, United Kingdom
    • GSK Investigational Site
  • Norwich, United Kingdom
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Plaque Psoriasis with PASI greater than or equal to 10
• Male or a female who was NOT of childbearing potential (i.e., post- menopausal for greater than 12 months or had a complete hysterectomy);

Exclusion Criteria:

• Spontaneously improving or rapidly deteriorating plaque psoriasis
• Guttate, pustular, erythrodermic, or other non-plaque form of psoriasis
• Subject was under treatment for a heart disorder or had a history of cardiovascular disease (excluding effectively controlled hypertension)
• Any acute psychiatric condition, including an increased risk for suicide attempt, based on medical and psychiatric history
• Previous use of a psoriasis vaccine or had participated in an investigational study of a psoriasis vaccine
• Previous use of systemic immunomodulatory therapy known to affect psoriasis and to typically decrease immune cell populations
• Previous use of any systemic immunomodulatory therapy known to affect psoriasis and NOT typically to decrease immune cell populations
• Previous use of any photo-therapy (including laser), photo-chemotherapy, or systemic psoriasis therapy (such as systemic corticosteroids, methotrexate, retinoids, or cyclosporine) within the previous four weeks
• Pregnant or a nursing mother
• Significant coexisting hepatic, renal, or bone marrow disease, hyperlipidemia, chronic pancreatitis, osteoporosis, cancer (except non-melanoma skin cancer), a positive test for human immunodeficiency virus (HIV), a history indicating adrenal cortex dysfunction

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: A; Talarozole 0.5 mg	Drug: Talarozole; Oral Capsule Once Daily; Other Names: Rambazole; R115866
Active Comparator: B; Talarozole 1.0 mg	Drug: Talarozole; Oral Capsule Once Daily; Other Names: Rambazole; R115866
Active Comparator: C; Talarozole 2.0 mg	Drug: Talarozole; Oral Capsule Once Daily; Other Names: Rambazole; R115866
Placebo Comparator: D; Talarozole matching Placebo	Drug: Talarozole; Oral Capsule Once Daily; Other Names: Rambazole; R115866

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Psoriasis Area Severity Index (PASI)75 Success at Visit 6	PASI75 success at Visit 6 was defined as number of participants who achieved at least 75% reduction in PASI scores at Visit 6 compared to Visit 2 (Baseline). The PASI score was determined through evaluation of body surface area (BSA) covered by plaque psoriasis in four regions (head/neck, upper extremities, trunk and lower extremities). This assessment included a combination of both degree of involvement (assessed as per the % of affected body area using a 7-point scale that ranged as 0 (0% involvement), 1 = 1-9%, 2 = 10-29%, 3 = 30-49%, 4 = 50-69%, 5 = 70-89% and 6 = 90-100%) and severity (evaluated individually using a 5-point scale that ranged as 0 = No evidence of sign, 1 = slight evidence of sign, 2 = moderate evidence of sign, 3 = marked evidence of sign and 4 = very marked, most severe evidence of sign) of erythema, induration and desquamation in each of the same four regions. PASI score ranged from 0 to 72 in 0.1-unit intervals; higher scores indicating worse psoriasis.	Week 12 (Visit 6)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PASI50 Success (the Reduction in PASI Score at Each Visit of at Least 50 Percent Relative to Visit 2) at Each Post Baseline Visit	PASI50 success was defined as number of participants who achieved at least 50% reduction in PASI scores at each post baseline visit (Visit 3 to 8) compared to Visit 2 (Baseline). The PASI score was determined through evaluation of BSA covered by plaque psoriasis in four regions (head/neck, upper extremities, trunk and lower extremities). This assessment included a combination of both degree of involvement (assessed as per the % of affected body area using a 7-point scale that ranged as 0 (0% involvement), 1 = 1-9%, 2 = 10-29%, 3 = 30-49%, 4 = 50-69%, 5 = 70-89% and 6 = 90-100%) and severity (evaluated individually using a 5-point scale that ranged as 0 = No evidence of sign, 1 = slight evidence of sign, 2 = moderate evidence of sign, 3 = marked evidence of sign and 4 = very marked, most severe evidence of sign) of erythema, induration and desquamation in each of the same four regions. PASI score ranged from 0 to 72 in 0.1-unit intervals; higher scores indicating worse psoriasis.	Week 1 to Week 20 (Visit 3 to Visit 8)
Investigator's Global Assessment (IGA) at Each Post Baseline Visit	The IGA was used to assess the overall severity of a participant's plaque psoriasis at a particular time point and the evaluation took into consideration the three individual characteristics of plaque psoriasis (scaling, plaque elevation, and erythema). The IGA was recorded using a scale that ranged from 0 (clear), 1 = almost clear, 2 = mild, 3 = moderate to 4 (severe) in whole-unit increments; higher scores indicating worse psoriasis. Investigators did not refer to previous evaluations when conducting the IGA assessment. At every study visit, the investigator evaluated each participant's plaque psoriasis and recorded the one integer grade that best described the average, overall severity of the condition. Investigators were trained not to refer to previous assessments of the IGA, and not to base the IGA scores on any component of the PASI. Individual body regions were not assessed (as in the PASI), but rather a global evaluation for each participant at each visit was determined.	Week 1 to Week 20 (Visit 3 to Visit 8)
PASI75 at Each Post Baseline Visit Except Visit 6	PASI75 success was defined as number of participants who achieved at least 75% reduction in PASI scores at each post baseline visit (Visit 3 to Visit 8) except Visit 6. The PASI score was determined through evaluation of BSA covered by plaque psoriasis in four regions (head/neck, upper extremities, trunk and lower extremities). This assessment included a combination of both degree of involvement (assessed as per the % of affected body area using a 7-point scale that ranged as 0 (0% involvement), 1 = 1-9%, 2 = 10-29%, 3 = 30-49%, 4 = 50-69%, 5 = 70-89% and 6 = 90-100%) and severity (evaluated individually using a 5-point scale that ranged as 0 = No evidence of sign, 1 = slight evidence of sign, 2 = moderate evidence of sign, 3 = marked evidence of sign and 4 = very marked, most severe evidence of sign) of erythema, induration and desquamation in each of the same four regions. PASI score ranged from 0 to 72 in 0.1-unit intervals; higher scores indicating worse psoriasis.	Week 1 to Week 20 (Visit 3 to Visit 8) except Week 12 (Visit 6)

Collaborators and Investigators

• Sponsor: Stiefel, a GSK Company
• Collaborators: GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start: June 1, 2006
• Primary Completion (Actual): May 1, 2007
• Study Completion (Actual): May 1, 2007

Study Registration Dates

• First Submitted: July 15, 2008
• First Submitted That Met QC Criteria: July 15, 2008
• First Posted (Estimate): July 16, 2008

Study Record Updates

• Last Update Posted (Actual): January 29, 2018
• Last Update Submitted That Met QC Criteria: June 28, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: Psoriasis
• Additional Relevant MeSH Terms: Skin Diseases; Skin Diseases, Papulosquamous; Psoriasis; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Cytochrome P-450 Enzyme Inhibitors; R 115866
• Other Study ID Numbers: BT0720-201-INT