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

Phase 2

Completed

Conditions: Moderate to Severe Chronic Plaque Psoriasis

Interventions: Drug: Placebo
Drug: Doxercalciferol

Registration Number: NCT00601107

Lead Sponsor: Genzyme, a Sanofi Company

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 111

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Placebo matching to doxercalciferol capsules orally once daily up to Week 24.
Doxercalciferol 5 mcg/day	Doxercalciferol	Doxercalciferol 5 mcg capsules orally once daily up to Week 24.
Doxercalciferol 7.5 mcg/day	Doxercalciferol	Doxercalciferol 7.5 mcg capsules orally once daily up to Week 24.
Doxercalciferol 2.5 mcg/day	Doxercalciferol	Doxercalciferol 2.5 microgram (mcg) capsule orally once daily up to Week 24.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With at Least 50 Percent (%) Reduction in Psoriasis Area Severity Index (PASI) Score at Week 12 or Early Termination	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\[l\].

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With at Least 50 Percent (%) Reduction in Psoriasis Area Severity Index (PASI) Score at Week 24 or Early Termination	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\[l\].
Percentage of Participants With Static Physician's Global Assessment (PGA) Score of Clear or Almost Clear at Week 12, 24 or Early Termination	Week 12 or Early Termination, Week 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.