A Study to Evaluate the Safety and Effectiveness of Doxercalciferol Capsules in Participants With Moderate to Severe Psoriasis

Study Overview
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Brief Summary
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The purpose of this study was to evaluate the safety and effectiveness of an investigational drug called doxercalciferol in participants with moderate to severe chronic plaque psoriasis, in comparison with a placebo (sugar pill). All study related care was provided including doctor visits, physical exams, laboratory tests and study medication. Total length of participation was 28 weeks.

Detailed Description
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This was a multicenter, randomized, double-blind, placebo-controlled, dose-ranging, parallel group study to evaluate the efficacy and safety of doxercalciferol given orally, once daily for 24 weeks to participants with moderate to severe chronic plaque psoriasis. Participants were randomized and stratified by site and Psoriasis Area Severity Index (PASI) score to one of three active treatment groups or to the placebo group.

Official Title
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A Multicenter, Double-Blind, Placebo-Controlled, Dose-Ranging Study to Assess the Efficacy and Safety of Doxercalciferol Capsules in the Treatment of Subjects With Moderate to Severe Chronic Plaque Psoriasis

Conditions
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Moderate to Severe Chronic Plaque Psoriasis

Intervention / Treatment
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* Drug: Doxercalciferol
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant had moderate to severe chronic plaque psoriasis defined by a body surface area (BSA) involvement greater than or equal to (>=) 10 percent (%) and plaques with at least a slight elevation above the surrounding normal skin at the Day 1 visit Participant had a static Physician's Global Assessment (PGA) of moderate or severe at the Day 1 visit Participant had a minimum PASI score of 10 at the Day 1 visit Participant was a candidate to receive systemic psoriasis therapy in the opinion of the Investigator Participant of childbearing potential, was willing to use an effective contraceptive method throughout the study, which included barrier methods, hormones, or intrauterine devices Exclusion Criteria: Used vitamin D analogues, multivitamin supplements containing greater than (>) 400 international unit (IU) vitamin D, topical retinoids, topical pimecrolimus, and topical tacrolimus within 14 days prior to the Day 1 visit Used drugs known to influence serum calcium (such as lithium, digoxin, thiazide diuretics, teriparatide, bisphosphonates, and calcitonin) and multivitamin supplements containing calcium and/or calcium-containing antacids exceeding a total of 1 gram/day within 14 days prior to the Day 1 visit Used keratolytics or coal tar (except shampoo containing coal tar or salicylic acid) within 14 days prior to the Day 1 visit Used low potency topical corticosteroids (Classes VI and VII), except on the groin, scalp, palms, soles and face, within 14 days prior to the Day 1 visit Used medium potency topical corticosteroids (Classes III - V) or high potency topical corticosteroids (Classes I and II) within 14 days prior to the Day 1 visit Used systemic retinoids, systemic corticosteroids, methotrexate, cyclosporine, azathioprine, thioguanine or other systemic immunosuppressant agents within 28 days prior to the Day 1 visit Used phototherapy, including Ultraviolet B within 14 days or Psoralen plus Ultraviolet A within 28 days prior to the Day 1 visit Used a biological agent (including, but not limited to, etanercept, adalimumab, efalizumab, infliximab, or alefacept) within 5 half-lives of the drug prior to the Day 1 visit Used systemic antibiotics within 14 days prior to the Day 1 visit. Antibiotic treatment of infections during the Treatment Period was not excluded Used investigational drugs within 28 days prior to the Day 1 visit Current erythrodermic, guttate, generalized pustular, unstable psoriasis or other chronic active skin conditions that may interfere with the study Screening visit laboratory result exceeded the following limits: alanine transaminase (ALT) or aspartate transaminase (AST) >1.5 times the upper limit of normal (ULN); bilirubin >ULN; serum creatinine, calcium, or phosphorus >ULN; spot urine calcium/creatinine ratio >0.4 History of nephrolithiasis Chronic kidney disease as evidenced by a calculated glomerular filtration rate (GFR) less than (<) 60 milliliter/minute/1.73 square meter (mL/min/1.73 m^2) at the screening visit Symptomatic coronary or cerebral vascular disease, human immunodeficiency virus, active viral hepatitis, or any other clinically significant, unstable medical condition that would interfere with the completion of the study Clinically significant electrocardiogram (EKG) abnormality at screening Any evidence of active malignancy except for basal cell carcinoma of the skin. A history of malignancy was not an exclusion Active ethanol or drug abuse, excluding tobacco use Active severe psychiatric illness that could interfere with the conduct of the study Pregnant or breast-feeding women Known allergy or hypersensitivity to vitamin D or other ingredients in the study drug formulation

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Doxercalciferol 2.5 mcg/day<br>Doxercalciferol 2.5 microgram (mcg) capsule orally once daily up to Week 24. | Drug: Doxercalciferol<br> <br> * Other names: Hectorol®;|
| Experimental: Doxercalciferol 5 mcg/day<br>Doxercalciferol 5 mcg capsules orally once daily up to Week 24. | Drug: Doxercalciferol<br> <br> * Other names: Hectorol®;|
| Experimental: Doxercalciferol 7.5 mcg/day<br>Doxercalciferol 7.5 mcg capsules orally once daily up to Week 24. | Drug: Doxercalciferol<br> <br> * Other names: Hectorol®;|
| Placebo Comparator: Placebo<br>Placebo matching to doxercalciferol capsules orally once daily up to Week 24. | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With at Least 50 Percent (%) Reduction in Psoriasis Area Severity Index (PASI) Score at Week 12 or Early Termination | PASI score: range: 0 (no disease) to 72 (maximal disease). Body was divided into head (h), trunk (t), upper (u) and lower (l) extremities. For each section, percent area of skin involved (A) was estimated: 1 (<10%) to 6 (90% - 100%), and severity was estimated by clinical signs: (erythema [E], induration [I], and desquamation [D]) on a scale: 0=no symptoms, 4=very marked. PASI score= 0.1 (E[h] + I[h] + D[h]) A[h] + 0.2 (E[u] + I[u] + D[u]) A[u] + 0.3 (E[t] + I[t] + D[t]) A[t] + 0.4 (E[l] + l[I] + D[l]) A[l]. | Week 12 or Early Termination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With at Least 50 Percent (%) Reduction in Psoriasis Area Severity Index (PASI) Score at Week 24 or Early Termination | PASI score: range: 0 (no disease) to 72 (maximal disease). Body was divided into head (h), trunk (t), upper (u) and lower (l) extremities. For each section, percent area of skin involved (A) was estimated: 1 (<10%) to 6 (90% - 100%), and severity was estimated by clinical signs: (erythema [E], induration [I], and desquamation [D]) on a scale: 0=no symptoms, 4=very marked. PASI score= 0.1 (E[h] + I[h] + D[h]) A[h] + 0.2 (E[u] + I[u] + D[u]) A[u] + 0.3 (E[t] + I[t] + D[t]) A[t] + 0.4 (E[l] + l[I] + D[l]) A[l]. | Week 24 or Early Termination | 
| Percentage of Participants With Static Physician's Global Assessment (PGA) Score of Clear or Almost Clear at Week 12, 24 or Early Termination | Static PGA of psoriasis is scored on a 5-point scale (0 = clear to 4 = severe), reflecting a global consideration of the erythema, induration and scaling across all psoriatic lesions. Clear (erythema: no, scale: no, induration: no thickness); Almost Clear (erythema: light pink, scale: fine scale, induration: barely palpable); Mild (erythema: light red, scale: coarse scale on most lesions, induration: slight but visible elevation, indistinct edges); Moderate (erythema: red, scale: coarse adherent scale predominates, induration: moderate elevation with edges); and Severe (erythema: dark red to purple, scale: thickened adherent scale, induration: marked thickness distinct and pronounced edges). Percentage of participants with static PGA score of clear or almost clear are reported. | Week 12 or Early Termination, Week 24 or Early Termination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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psoriasis, psoriasis vulgaris, plaque psoriasis, chronic plaque psoriasis