- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00456092
Phase II Study of Apremilast (CC-10004) in Adults With in Psoriatic Arthritis
A Phase II, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group, Efficacy and Safety Study of Two Dose Regimens of CC-10004 in Subjects With Active Psoriatic Arthritis
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Brussels, Belgium, 1020
- CHU Brugmann
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Diepenbeek, Belgium, 3590
- Universiteit Hasselt
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Leuven, Belgium, 3000
- University Hospital
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Merksem, Belgium, 2170
- Jan Palfijn Ziekenhuis
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British Columbia
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Vancouver, British Columbia, Canada, V5Z 1L7
- The Arthritis Research Centre of Canada
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Victoria, British Columbia, Canada, V8P4Y3
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Newfoundland and Labrador
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St Johns, Newfoundland and Labrador, Canada, A1B 3E1
- Nexus Clinical Research
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Ontario
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Burlington, Ontario, Canada, L7R 4B7
- Burlington Rheumatology and Osteoporosis Clinic
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Hamilton, Ontario, Canada, L8N 2B6
- MAC Research Inc.
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Kitchener, Ontario, Canada, N2M 5N6
- K-W Musculoskeletal Research Inc.
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Mississauga, Ontario, Canada, L5M 2V8
- Credit Valley Rheumatology
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Newmarket, Ontario, Canada, L3Y 3R7
- Arthritis Program Research Group Inc
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Ottawa, Ontario, Canada, K1H 1A2
- Rheumatology Research Associates
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Toronto, Ontario, Canada, M5T 3L9
- Mount Sinai Hospital
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Toronto, Ontario, Canada, M5T 2S8
- Center for Prognosis Studies in the Rheumatic Diseases University Health Network, Toronto Western Hospital
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Waterloo, Ontario, Canada, N2J1C4
- Probity Medical
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Windsor, Ontario, Canada, N8X 5A6
- Clinical Research and Arthritis Centre
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Quebec
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Pointe-Claire, Quebec, Canada
- West Island Rheumatology Research Associates
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Saskatchewan
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Saskatoon, Saskatchewan, Canada, S7K 0H6
- Saskatoon Osteoporosis Center
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Bad Brückenau, Germany, 97769
- Capio Franz von Prümmer Klinik
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Berlin, Germany, 10117
- Free University of Berlin
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Frankfurt, Germany, 60590
- Universitaetsklinikum Frankfurt
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Hamburg, Germany, 22081
- Klinikum Eilbek
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Heidelberg, Germany, 69120
- Universitaet Heidelberg
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Herne, Germany, 44652
- Rheumazentrum Ruhrgebiet
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Koeln, Germany, 50924
- Universitaetsklinik Koeln
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Leipzig, Germany, 04103
- Universitaetsklinikum Leipzig
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Leipzig, Germany, 04103
- Universitaet Leipzig
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Munich, Germany, 80336
- University of Munich
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Munster, Germany, 48149
- Klinikum der Universität Munster
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Nuremberg, Germany, 91054
- Friedrich-Alexander University, Erlangen
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Den Haag, Netherlands, 2454 CH
- HagaZiekenhuis
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Leiden, Netherlands, 2300
- Leiden University Medical Centre
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Nijmegen, Netherlands, 6500
- Radboud University
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Leeds, United Kingdom, LS7 4SA
- Chapel Allerton Hospital
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Newcastle-upon-Tyne, United Kingdom, NE7 7DN
- Freeman Hospital
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Manchester
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Salford, Manchester, United Kingdom, M6 8HD
- Hope Hospital
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Staffs
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Stoke on Trent, Staffs, United Kingdom, ST6 7AG
- Haywood Hospital
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Diagnosis of psoriatic arthritis (Moll and Wright Criteria), including symmetrical or asymmetrical peripheral joint involvement for at least 6 months
- Active psoriatic arthritis at the time of screening and baseline as defined by: 3 or more swollen joints AND 3 or more tender joints
- Negative rheumatoid factor (RF)
- If using methotrexate, be on methotrexate for at least 168 days (24 weeks) and be on a stable dose for at least 56 days prior to screening and throughout the study
- If using oral corticosteroids, be on a stable dose of prednisone ≤ 10 mg/day or equivalent for at least 28 days prior to screening and throughout the study
- If using nonsteroidal anti-inflammatory drug (NSAID) therapy, be on a stable dose for at least 14 days prior to screening and throughout the study
Must meet the following laboratory criteria:
- Hemoglobin ≥ 9 g/dL
- Hematocrit ≥ 27%
- White blood cell (WBC) count ≥ 3000/μL (≥ 3.0 X 10^9/L) and < 20,000/μL (< 20 X 10^9/L)
- Neutrophils ≥ 1500 /μL (≥ 1.5 X 10^9/L)
- Platelets ≥ 100,000 /μL (≥ 100 X 10^9/L)
- Serum creatinine ≤ 1.5 mg/dL (≤ 132.6 μmol/L)
- Total bilirubin ≤ 2.0 mg/dL
- Aspartate transaminase (AST [serum glutamic oxaloacetic transaminase, SGOT]) and alanine transaminase (ALT [serum glutamate pyruvic transaminase, SGPT]) ≤ 1.5x upper limit of normal (ULN)
- Females of childbearing potential (FCBP) must have a negative urine pregnancy test at screening (Visit 1). In addition, sexually active FCBP must agree to use TWO adequate forms of contraception while on study medication. A FCBP must agree to have pregnancy tests every 28 days while on study medication
- Males (including those who have had a vasectomy) must agree to use barrier contraception (latex condoms) when engaging in reproductive sexual activity with FCBP while on study medication and for at least 84 days after taking the last dose of study medication
Exclusion Criteria:
History of any clinically significant cardiac, endocrinologic, pulmonary, neurologic, psychiatric, hepatic, renal, hematologic, immunologic, or other major diseases
- Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study
- Pregnant or lactating female
- History of active Mycobacterium tuberculosis infection (any subspecies) within 3 years prior to the screening visit. Infections that occurred > 3 years prior to entry must have been effectively treated.
- History of incompletely treated latent Mycobacterium tuberculosis infection (as indicated by a positive Purified Protein Derivative [PPD] skin test or in vitro test [T SPOT®.TB, QuantiFERON Gold®])
- Clinically significant abnormality on the chest x-ray (CXR) at screening
- Current erythrodermic, guttate, or pustular forms of psoriasis
- History of infected joint prosthesis within the past 5 years
- Systemic therapy for psoriasis and/or psoriatic arthritis (except for methotrexate, ≤ 10 mg/day prednisone or equivalent, and NSAIDs) including, but not limited to, sulfasalazine, leflunomide, chloroquine, hydroxychloroquine, gold compounds, parenteral corticosteroids (including intra-articular), penicillamine, cyclosporine, oral retinoids, mycophenolate mofetil, thioguanine, hydroxyurea, sirolimus, tacrolimus, azathioprine, and fumaric acid esters within 28 days of randomization and throughout the study
- Topical therapy for the treatment of psoriasis including, but not limited to topical steroids, topical vitamin A or D analog preparations, tacrolimus, pimecrolimus, or anthralin within 14 days of randomization (Note: Topical background therapy for treatment of psoriasis is allowed, except within 24 hours of a study visit, as follows: mild or moderate potency corticosteroids for treatment of the palms, face, scalp, axillae, plantar surfaces, and groin in accordance with the manufacturer's suggested usage. Nonmedicated emollients [eg, Eucerin®] and tar shampoo are also allowed.)
- Phototherapy (ultraviolet light A [UVA], narrow-band ultraviolet light B [NB-UVB], psoralens and long-wave ultraviolet radiation [PUVA]) within 28 days prior to randomization
- Etanercept use within 56 days prior to randomization
- Adalimumab, efalizumab, or infliximab use within 84 days prior to randomization
- Alefacept use within 168 days (24 weeks) prior to randomization
- Use of intra-articular corticosteroids within 28 days prior to randomization
- Use of any investigational medication within 28 days prior to randomization or 5 half-lives if known (whichever is longer)
- Any clinically significant abnormality on 12-lead electrocardiogram (ECG) at screening
- High-risk factor(s) for, or a history of, human immunodeficiency virus (HIV), hepatitis B, or hepatitis C virus infection
- History of malignancy within previous 5 years (except for treated basal-cell skin carcinoma(s) and/or fewer than 3 treated squamous-cell skin carcinomas)
- Evidence of skin conditions at the time of screening visit that would interfere with evaluations of the effect of study medication on psoriasis
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Apremilast 40 mg QD
Participants received 40 mg apremilast orally once a day (QD) for 12 weeks in the Treatment Phase. Participants who entered the Extension Phase continued to receive 40 mg apremilast QD for an additional 12 weeks. The dose of apremilast was titrated starting at 10 mg QD during Days 1 to 3 followed by 20 mg QD during Days 4 to 7 and then 40 mg QD thereafter. A single dose reduction to 20 mg per day was allowed for participants who experienced intolerable adverse effects from study medication. |
Capsules for oral administration
Other Names:
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Experimental: Apremilast 20 mg BID
Participants received 20 mg apremilast orally twice a day (BID) for 12 weeks in the Treatment Phase.
Participants who entered the Extension Phase continued to receive 20 mg apremilast BID for an additional 12 weeks.
The dose of apremilast was titrated starting at 10 mg QD during Days 1 to 3 followed by 20 mg QD during Days 4 to 7 and then 20 mg BID thereafter.
A single dose reduction to 20 mg per day was allowed for participants who experienced intolerable adverse effects from study medication.
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Capsules for oral administration
Other Names:
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Placebo Comparator: Placebo
Participants received matching placebo to apremilast orally BID for 12 weeks during the Treatment Phase.
Participants who entered the Extension Phase were re-randomized on Day 85 to receive either 40 mg apremilast QD or 20 mg apremilast BID for 12 weeks.
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Capsules for oral administration
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Percentage of Participants With a Modified American College of Rheumatology 20% (ACR 20) Response at Week 12
Time Frame: Baseline and Week 12
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A modified American College of Rheumatology 20% (ACR 20) response was defined as a participant who met the following 3 criteria for improvement from Baseline: • ≥ 20% improvement in 78 tender joint count (includes 10 additional joints often involved in psoriatic arthritis: the first carpometacarpal [CMC] and the distal interphalangeal [DIP] joints of the fingers); • ≥ 20% improvement in 76 swollen joint count; and • ≥ 20% improvement in at least 3 of the 5 following parameters: ◦ Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]); ◦ Patient's global assessment of disease activity (measured on a 100 mm VAS); ◦ Physician's global assessment of disease activity (measured on a 100 mm VAS); ◦ Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [HAQ-DI]); ◦ C-reactive protein.
Participants with no post-baseline ACR scores were considered non-responders.
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Baseline and Week 12
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Number of Participants With Adverse Events During the Treatment Phase
Time Frame: 12 weeks
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The severity of each adverse event (AE) was graded based upon the participant's symptoms according to National Cancer Institute (NCI) Common Toxicity Criteria (CTCAE, Version 3.0), on a scale from 1 (Mild AE) to 5 (Death due to AE).
Severe AEs are defined as NCI CTCAE grade 3 or higher.
AEs related to study drug are those determined by the investigator as suspected to be related to study drug where a temporal relationship of the adverse event to study drug administration made a causal relationship possible, and other medications, therapeutic interventions, or underlying conditions did not provide a sufficient explanation for the observed event.
A serious adverse event (SAE) is any AE which: - Resulted in death - Was life-threatening - Required inpatient hospitalization or prolongation of existing hospitalization - Resulted in persistent or significant disability/incapacity - Was a congenital anomaly/birth defect - Constituted an important medical event.
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12 weeks
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Percentage of Participants With a Psoriatic Arthritis Response Criteria (PsARC) Response at Week 12
Time Frame: Baseline and Week 12
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A PsARC response is defined as improvement from Baseline in at least 2 of the following 4 measures, at least 1 of which must be tender joint count or swollen joint count, and no worsening in any of the 4 measures, according to the following: • At least 30% improvement in the 78 tender joint count, • At least 30% improvement in the 76 swollen joint count, • At least 20% improvement in the patient global assessment of disease activity, measured on a 100 mm visual analog scale (VAS), where 0 mm = lowest disease activity and 100 mm = highest; • At least 20% improvement in the physician global assessment of disease activity, measured on a 100 mm VAS, where 0 mm = lowest disease activity and 100 mm = highest.
Participants with no post-baseline PsARC scores were considered non-responders.
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Baseline and Week 12
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Percentage of Participants With a Modified ACR 50 Response at Week 12
Time Frame: Baseline and Week 12
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A modified American College of Rheumatology 50% (ACR 50) response was defined as a participant who met the following 3 criteria for improvement from Baseline: • ≥ 50% improvement in 78 tender joint count (includes 10 additional joints often involved in psoriatic arthritis: the first carpometacarpal [CMC] and the distal interphalangeal [DIP] joints of the fingers); • ≥ 50% improvement in 76 swollen joint count; and • ≥ 50% improvement in at least 3 of the 5 following parameters: ◦ Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]); ◦ Patient's global assessment of disease activity (measured on a 100 mm VAS); ◦ Physician's global assessment of disease activity (measured on a 100 mm VAS); ◦ Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [HAQ-DI]); ◦ C-reactive protein.
Participants with no post-baseline ACR scores were considered non-responders.
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Baseline and Week 12
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Percentage of Participants With a Modified ACR 70 Response at Week 12
Time Frame: Baseline and Week 12
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A modified American College of Rheumatology 70% (ACR 70) response was defined as a participant who met the following 3 criteria for improvement from Baseline: • ≥ 70% improvement in 78 tender joint count (includes 10 additional joints often involved in psoriatic arthritis: the first carpometacarpal [CMC] and the distal interphalangeal [DIP] joints of the fingers); • ≥ 70% improvement in 76 swollen joint count; and • ≥ 70% improvement in at least 3 of the 5 following parameters: ◦ Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]); ◦ Patient's global assessment of disease activity (measured on a 100 mm VAS); ◦ Physician's global assessment of disease activity (measured on a 100 mm VAS); ◦ Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); ◦ C-reactive protein.
Participants with no post-baseline ACR scores were considered non-responders.
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Baseline and Week 12
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Percentage of Participants With Good or Moderate European League Against Rheumatism (EULAR) Response Based on Disease Activity Score (DAS28)-CRP(4) at Week 12
Time Frame: Baseline and Week 12
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The DAS28 measures the severity of disease at a specific time.
DAS28-CRP(4) is derived from the following 4 variables: • 28 tender joint count, (TJC; does not include the DIP joints, the hip joint, or the joints below the knee) • 28 swollen joint count (SJC) • C-reactive protein (CRP) • Patient's global assessment of disease activity (GH) according to the formula: DAS28-CRP(4) = 0.56*√(TJC28) + 0.28*(SJC28) + 0.36*ln(CRP+1) + 0.014*GH + 0.96.
DAS28 scores range from 0 to 9.4, where higher scores indicate more disease activity.
A EULAR response reflects an improvement in disease activity based on the DAS-28 score.
A Good Response is defined as an improvement (decrease) in the DAS28 > 1.2 from Baseline and a DAS28 score ≤ 3.2.
A Moderate Response is defined as either: • an improvement (decrease) in the DAS28 > 0.6 and ≤ 1.2 and a DAS28 score ≤ to 5.1 or, • an improvement (decrease) in the DAS28 > 1.2 and a DAS28 score > 3.2
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Baseline and Week 12
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Percentage of Participants With Good or Moderate EULAR Response Based on DAS28-CRP(3) at Week 12
Time Frame: Baseline and Week 12
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The DAS28 measures the severity of disease at a specific time.
DAS28-CRP(3) is derived from the following 3 variables: • 28 tender joint count, (does not include the DIP joints, the hip joint, or the joints below the knee) • 28 swollen joint count • C-reactive protein (CRP) according to the formula: DAS28-CRP(3) = [0.56*√(TJC28)
+ 0.28*√(SJC28) + 0.36*ln(CRP+1)] * 1.10 + 1.15.
DAS28 scores range from 0 to 9.4, where higher scores indicate more disease activity.
A EULAR response reflects an improvement in disease activity based on the DAS-28 score.
A Good Response is defined as an improvement (decrease) in the DAS28 > 1.2 from Baseline and attainment of a DAS28 score ≤ 3.2.
A Moderate Response is defined as either: • an improvement (decrease) in the DAS28 > 0.6 and ≤ 1.2 and a DAS28 score ≤ to 5.1 or, • an improvement (decrease) in the DAS28 > 1.2 and a DAS28 score > 3.2
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Baseline and Week 12
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Percentage of Participants With DAS28-CRP(4) Score of Mild Disease Activity or In Remission at Week 12
Time Frame: Week 12
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The DAS28-CRP(4) measures the severity of disease derived from the following 4 variables: • 28 tender joint count, (does not include the DIP joints, the hip joint, or the joints below the knee) • 28 swollen joint count • C-reactive protein (CRP) • Patient's global assessment of disease activity.
DAS28-CRP(4) scores range from 0 to 9.4, where higher scores indicate more disease activity.
Mild disease severity is defined as a DAS28-CRP(4) score of ≤ 3.2.
In remission is defined as a DAS28-CRP(4) score of ≤ 2.6.
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Week 12
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Percentage of Participants With DAS28-CRP(3) Score of Mild Disease Activity or In Remission at Week 12
Time Frame: Week 12
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The DAS28-CRP(3) measures the severity of disease derived from the following 3 variables: • 28 tender joint count (does not include the DIP joints, the hip joint, or the joints below the knee) • 28 swollen joint count • C-reactive protein (CRP) DAS28-CRP(3) scores range from 0 to 9.4, where higher scores indicate more disease activity.
Mild disease severity is defined as a DAS28-CRP(3) score of ≤ 3.2.
In remission is defined as a DAS28-CRP(3) score of ≤ 2.6.
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Week 12
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Number of Participants Who Withdrew Prematurely Due to Lack of Efficacy
Time Frame: Baseline to Week 12
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The number of participants who withdrew prematurely from the treatment phase due to lack of efficacy, including flare of psoriasis, flare of psoriatic arthritis or worsening or not responding to study treatment.
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Baseline to Week 12
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Number of Participants With Adverse Events Leading to a Dose Reduction
Time Frame: Baseline to Week 12
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The number of participants who were dose reduced during the treatment phase due to adverse events.
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Baseline to Week 12
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Maximal ACR Response During the Treatment Phase
Time Frame: ACR was measured at Baseline and Weeks 2, 4, 6, 8, 10, and 12
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The ACR-N index score was calculated for each participant at each time point in the study according to the following definition: ACR-N = the lowest of the following 3 values: - percent improvement from Baseline in the 76 swollen joint count, - percent improvement from Baseline in the 78 tender joint count - median percent improvement from Baseline in the following 5 measures ◦ Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]); ◦ Patient's global assessment of disease activity (measured on a 100 mm VAS); ◦ Physician's global assessment of disease activity (measured on a 100 mm VAS); ◦ Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [HAQ-DI]); ◦ C-reactive protein.
The maximal ACR-N for each participant during the 12-week treatment period was calculated, and represents the maximal ACR response achieved.
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ACR was measured at Baseline and Weeks 2, 4, 6, 8, 10, and 12
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Time to ACR 20 Response During the Treatment Phase
Time Frame: Baseline to Week 12
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The Kaplan-Meier estimates of time to ACR 20 response was calculated for participants who had an ACR 20 response at any time during the treatment phase.
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Baseline to Week 12
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Time to ACR 50 Response During the Treatment Phase
Time Frame: Baseline to Week 12
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The Kaplan-Meier estimates of time to ACR 50 response was calculated for participants who had an ACR 50 response at any time during the treatment phase.
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Baseline to Week 12
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Time to ACR 70 Response During the Treatment Phase
Time Frame: Baseline to Week 12
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The Kaplan-Meier estimates of time to ACR 70 response was calculated for participants who had an ACR 70 response at any time during the treatment phase.
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Baseline to Week 12
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Change From Baseline in Dactylitis Severity Score at Week 12
Time Frame: Baseline and Week 12
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Dactylitis is characterized by swelling of the entire finger or toe.
Each digit on the hands and feet was rated on a scale from 0 (no dactylitis) to 3 (severe dactylitis).
The dactylitis severity score is the sum of the individual scores for each digit and ranges from 0 to 60.
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Baseline and Week 12
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Percentage of Participants With Enthesitis
Time Frame: Baseline and Week 12
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Enthesitis is inflammation of the entheses, the sites where tendons or ligaments insert into the bone.
Enthesitis is characterized by swelling, pain, and tenderness around the calcaneous, and occasionally by effusion in the bursa associated with this joint.
The enthesitis assessment is an evaluation of inflammation at the insertions of the Achilles tendon into the calcaneous and of the plantar fascia into the calcaneous.
Inflammation at 1 or more insertions on either the right or left side constituted a positive assessment.
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Baseline and Week 12
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Time to Relapse of Psoriatic Arthritis During the Observational Follow-up Phase
Time Frame: From Week 12 to end of 28-day observational follow-up (1) and from the date of maximal ACR during the 12-week Treatment Phase until the end of the 28-day observational follow-up phase (2).
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Relapse of psoriatic arthritis was defined as a 50% loss of the maximal ACR improvement during the Observation Phase in participants who received apremilast and achieved at least an ACR 20 at their Final Treatment Phase/Early Termination Visit.
The time to relapse during the Observational Phase was calculated from the time of maximum ACR reduction and from the date of the Final Treatment Phase visit.
Participants classified as responders who did not relapse were censored at the day of the last follow-up.
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From Week 12 to end of 28-day observational follow-up (1) and from the date of maximal ACR during the 12-week Treatment Phase until the end of the 28-day observational follow-up phase (2).
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Number of Participants Who Relapsed During the Observational Follow-up Phase
Time Frame: 28-day observational follow-up period following Week 12
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Relapse of psoriatic arthritis was defined as a 50% loss of the maximal ACR improvement during the Observation Phase in participants who received apremilast and achieved at least an ACR 20 at their Final Treatment Phase/Early Termination Visit.
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28-day observational follow-up period following Week 12
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Change From Baseline in Short Form 36 (SF-36) Summary Physical and Mental Component Scores at Week 12
Time Frame: Baseline and Week 12
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The Medical Outcome SF 36-Item Health Survey, Version 2 is a self-administered instrument that measures the impact of disease on overall quality of life and consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health).
The summary physical health score included the following subscales: physical functioning, role-physical, bodily pain, and general health.
The summary mental health score included other subscales: vitality, social functioning, role-emotional, and mental health.
Norm-based scores were used in analyses, calibrated so that 50 is the average score and the standard deviation equals 10, where higher scores are associated with better functioning/quality of life.
Each domain is scored by summing the individual items and transforming the scores into a 0 to 100 scale.
A higher change from baseline indicates an improvement in better health results or functioning.
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Baseline and Week 12
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Change From Baseline in Dermatology Life Quality Index (DLQI) at Week 12
Time Frame: Baseline and Week 12
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The DLQI is a validated, self-administered, 10-item questionnaire that measures the impact of skin disease on participants' quality of life, based on recall over the past week.
Domains include symptoms, feelings, daily activities, leisure, work, personal relationships, and treatment.
Each question is answered on a scale from 0 (not at all) to 3 (very much).
The total score ranges from 0 to 30 where a higher score indicates that a participant's dermatological condition has a greater impact on their daily life.
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Baseline and Week 12
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Change From Baseline in the Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 12
Time Frame: Baseline and Week 12
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The HAQ-DI is a self-administered instrument consisting of 20 questions in eight categories of functioning which represent a comprehensive set of functional activities - dressing, rising, eating, walking, hygiene, reach, grip, and usual activities.
Each item asks over the past week whether a particular task can be performed.
For each item, there is a four-level difficulty scale that is scored from 0 to 3, representing normal (no difficulty) (0), some difficulty (1), much difficulty (2), and unable to do (3).
The eight category scores are averaged into an overall HAQ-DI score on a scale from zero (no disability) to three (completely disabled).
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Baseline and Week 12
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Change From Baseline in the Functional Assessment of Chronic Illness Therapy for Fatigue (FACIT-F) at Week 12
Time Frame: Baseline and Week 12
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The FACIT-Fatigue is a 13 item self-administered questionnaire that assesses both the physical and functional consequences of fatigue based on recall during the past 7 days.
Each question is answered on a 5-point scale, where 0 means "not at all," and 4 means "very much."
The total score ranges from 0 to 52 with higher scores representing less fatigue.
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Baseline and Week 12
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Number of Participants With Adverse Events During the Extension Phase
Time Frame: Weeks 12 to 24 (Extension Phase)
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The severity of each adverse event (AE) was graded based upon the participant's symptoms according to National Cancer Institute (NCI) Common Toxicity Criteria (CTCAE, Version 3.0), on a scale from 1 (Mild AE) to 5 (Death due to AE).
Severe AEs are defined as NCI CTCAE grade 3 or higher.
AEs related to study drug are those determined by the investigator as suspected to be related to study drug where a temporal relationship of the adverse event to study drug administration made a causal relationship possible, and other medications, therapeutic interventions, or underlying conditions did not provide a sufficient explanation for the observed event.
A serious adverse event (SAE) is any AE which: - Resulted in death - Was life-threatening - Required inpatient hospitalization or prolongation of existing hospitalization - Resulted in persistent or significant disability/incapacity - Was a congenital anomaly/birth defect - Constituted an important medical event.
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Weeks 12 to 24 (Extension Phase)
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Percentage of Participants With a Psoriatic Arthritis Response Criteria (PsARC) Response at Week 24
Time Frame: Baseline and Week 24
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A PsARC response is defined as improvement from Baseline in at least 2 of the following 4 measures, at least 1 of which must be tender joint count or swollen joint count, and no worsening in any of the 4 measures: • At least 30% improvement in the 78 tender joint count, • At least 30% improvement in the 76 swollen joint count, • At least 20% improvement in the patient global assessment of disease activity, measured on a 100 mm visual Analog scale (VAS), where 0 mm = lowest disease activity and 100 mm = highest; • At least 20% improvement in the physician global assessment of disease activity, measured on a 100 mm VAS, where 0 mm = lowest disease activity and 100 mm = highest.
Participants with missing data were considered non-responders.
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Baseline and Week 24
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Percentage of Participants With a Modified ACR 20 Response at Week 24
Time Frame: Baseline (Day 1), Week 12 (Day 85) and Week 24
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A modified ACR 20 response was defined as a participant who met the following 3 criteria for improvement: • ≥ 20% improvement in 78 tender joint count (includes 10 additional joints often involved in psoriatic arthritis: the first carpometacarpal [CMC] and the distal interphalangeal [DIP] joints of the fingers); • ≥ 20% improvement in 76 swollen joint count; and • ≥ 20% improvement in at least 3 of the 5 following parameters: ◦ Patient's assessment of pain (measured on a 100 mm VAS); ◦ Patient's global assessment of disease activity (measured on a 100 mm VAS); ◦ Physician's global assessment of disease activity (measured on a 100 mm VAS); ◦ Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [HAQ-DI]); ◦ C-reactive protein.
Response at Week 24 was measured as improvement from Baseline (Day 1) and from Week 12 (Day 85).
Participants with no post-baseline ACR scores were considered non-responders.
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Baseline (Day 1), Week 12 (Day 85) and Week 24
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Percentage of Participants With a Modified ACR 50 Response at Week 24
Time Frame: Baseline (Day 1), Week 12 (Day 85) and Week 24
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A modified ACR 50 response was defined as a participant who met the following 3 criteria for improvement: • ≥ 50% improvement in 78 tender joint count (includes 10 additional joints often involved in psoriatic arthritis: the first carpometacarpal [CMC] and the distal interphalangeal [DIP] joints of the fingers); • ≥ 50% improvement in 76 swollen joint count; and • ≥ 50% improvement in at least 3 of the 5 following parameters: ◦ Patient's assessment of pain (measured on a 100 mm VAS); ◦ Patient's global assessment of disease activity (measured on a 100 mm VAS); ◦ Physician's global assessment of disease activity (measured on a 100 mm VAS); ◦ Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [HAQ-DI]); ◦ C-reactive protein.
Response at Week 24 was measured as improvement from Baseline (Day 1) and from Week 12 (Day 85).
Participants with no post-baseline ACR scores were considered non-responders.
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Baseline (Day 1), Week 12 (Day 85) and Week 24
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Percentage of Participants With a Modified ACR 70 Response at Week 24
Time Frame: Baseline (Day 1) and Week 24
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A modified ACR 70 response was defined as a participant who met the following 3 criteria for improvement: • ≥ 70% improvement in 78 tender joint count (includes 10 additional joints often involved in psoriatic arthritis: the first carpometacarpal [CMC] and the distal interphalangeal [DIP] joints of the fingers); • ≥ 70% improvement in 76 swollen joint count; and • ≥ 70% improvement in at least 3 of the 5 following parameters: ◦ Patient's assessment of pain (measured on a 100 mm VAS); ◦ Patient's global assessment of disease activity (measured on a 100 mm VAS); ◦ Physician's global assessment of disease activity (measured on a 100 mm VAS); ◦ Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [HAQ-DI]); ◦ C-reactive protein.
Response at Week 24 was measured as improvement from Baseline (Day 1).
Participants with no post-baseline ACR scores were considered non-responders.
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Baseline (Day 1) and Week 24
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Percentage of Participants With Good or Moderate EULAR Response Based on DAS28-CRP(4) at Week 24
Time Frame: Baseline and Week 24
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The DAS28 measures the severity of disease at a specific time.
DAS28-CRP(4) is derived from the following 4 variables: • 28 tender joint count, (does not include the DIP joints, the hip joint, or the joints below the knee) • 28 swollen joint count • C-reactive protein • Patient's global assessment of disease activity according to the formula: DAS28-CRP(4) = 0.56*√(TJC28) + 0.28*(SJC28) + 0.36*ln(CRP+1) + 0.014*GH + 0.96.
DAS28 scores range from 0 to 9.4, where higher scores indicate more disease activity.
A EULAR response reflects an improvement in disease activity based on the DAS-28 score.
A Good Response is defined as an improvement (decrease) in the DAS28 > 1.2 from Baseline and attainment of a DAS28 score ≤ 3.2.
A Moderate Response is defined as either: • an improvement (decrease) in the DAS28 > 0.6 and ≤ 1.2 and a DAS28 score ≤ to 5.1 or, • an improvement (decrease) in the DAS28 > 1.2 and a DAS28 score > 3.2
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Baseline and Week 24
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Percentage of Participants With Good or Moderate EULAR Response Based on DAS28-CRP(3) at Week 24
Time Frame: Baseline and Week 24
|
The DAS28 measures the severity of disease at a specific time.
DAS28-CRP(3) is derived from the following 3 variables: • 28 tender joint count, (does not include the DIP joints, the hip joint, or the joints below the knee) • 28 swollen joint count • C-reactive protein (CRP) according to the formula: DAS28-CRP(3) = [0.56*√(TJC28)
+ 0.28*√(SJC28) + 0.36*ln(CRP+1)] * 1.10 + 1.15.
DAS28 scores range from 0 to 9.4, where higher scores indicate more disease activity.
A EULAR response reflects an improvement in disease activity based on the DAS-28 score.
A Good Response is defined as an improvement (decrease) in the DAS28 > 1.2 from Baseline and attainment of a DAS28 score ≤ 3.2.
A Moderate Response is defined as either: • an improvement (decrease) in the DAS28 > 0.6 and ≤ 1.2 and a DAS28 score ≤ to 5.1 or, • an improvement (decrease) in the DAS28 > 1.2 and a DAS28 score > 3.2
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Baseline and Week 24
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Maximal ACR Response During the Extension Period
Time Frame: ACR was measured at Baseline and Weeks 16, 20 and 24
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The ACR-N index score was calculated for each participant at each time point in the study according to the following definition: ACR-N = the lowest of the following 3 values: • percent improvement from Baseline in the 76 swollen joint count, • percent improvement from Baseline in the 78 tender joint count • median percent improvement from Baseline in the following 5 measures ◦ Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]); ◦ Patient's global assessment of disease activity (measured on a 100 mm VAS); ◦ Physician's global assessment of disease activity (measured on a 100 mm VAS); ◦ Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [HAQ-DI]); ◦ C-reactive protein.
The maximal ACR-N for each participant during the 12-week extension period was calculated, and represents the maximal ACR response achieved.
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ACR was measured at Baseline and Weeks 16, 20 and 24
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Time to ACR 20 Response During the Study
Time Frame: Baseline to Week 24
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Time to ACR 20 was measured from the first dose of apremilast to the first time a participant achieved an ACR 20 response in the treatment or extension phase.
The Kaplan-Meier estimates of time to ACR 20 response were calculated for participants who had an ACR 20 response at any time during the study.
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Baseline to Week 24
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Time to ACR 50 Response During the Treatment and Extension Phase
Time Frame: Baseline to Week 24
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Time to ACR 50 response was measured from the first dose of apremilast to the first time a participant achieved an ACR 50 response in the treatment or extension phase.
The Kaplan-Meier estimates of time to ACR 50 response were calculated for participants who had an ACR 50 response at any time during the study.
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Baseline to Week 24
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Time to ACR 70 Response During the Treatment and Extension Phase
Time Frame: Baseline to Week 24
|
Time to ACR 70 response was measured from the first dose of apremilast to the first time a participant achieved an ACR 70 response in the treatment or extension phase.
The Kaplan-Meier estimates of time to ACR 70 response were calculated for participants who had an ACR 70 response at any time during the study.
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Baseline to Week 24
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Change From Baseline and Week 12 in Dactylitis Severity Score at Week 24
Time Frame: Baseline, Week 12 and Week 24
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Dactylitis is characterized by swelling of the entire finger or toe.
Each digit on the hands and feet was rated on a scale from 0 (no dactylitis) to 3 (severe dactylitis).
The dactylitis severity score is the sum of the individual scores for each digit and ranges from 0 to 60. Change in the dactylitis severity score was assessed from Baseline (Day 1) and from Week 12 (Day 85).
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Baseline, Week 12 and Week 24
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Percentage of Participants With Enthesitis in the Extension Phase
Time Frame: Week 12 and Week 24
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Enthesitis is inflammation of the entheses, the sites where tendons or ligaments insert into the bone.
Enthesitis is characterized by swelling, pain, and tenderness around the calcaneous, and occasionally by effusion in the bursa associated with this joint.
The enthesitis assessment is an evaluation of inflammation at the insertions of the Achilles tendon into the calcaneous and of the plantar fascia into the calcaneous.
Inflammation at 1 or more insertions on either the right or left side constituted a positive assessment.
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Week 12 and Week 24
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Time to Relapse of Psoriatic Arthritis After Extension Phase
Time Frame: From Week 24 to the end of the 28-day follow-up (1) and from the date of maximal ACR until the end of the 28-day follow-up phase (2).
|
Relapse of psoriatic arthritis was defined as a 50% loss of the maximal ACR improvement during the Follow-up Phase in participants who achieved at least an ACR 20 at their Final Extension Phase (Week 24)/Early Termination Visit.
The time to relapse during the Follow-up Phase was calculated from the time of maximum ACR reduction and from the date of the Final Extension Phase visit.
Participants classified as responders who did not relapse were censored at the day of the last follow-up.
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From Week 24 to the end of the 28-day follow-up (1) and from the date of maximal ACR until the end of the 28-day follow-up phase (2).
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Number of Participants Who Relapsed After the Extension Phase
Time Frame: Week 24 to Week 28 (28-day follow-up period)
|
Relapse of psoriatic arthritis was defined as a 50% loss of the maximal ACR improvement during the Follow-up Phase in participants who achieved at least an ACR 20 at their Final Extension Phase/Early Termination Visit.
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Week 24 to Week 28 (28-day follow-up period)
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Change From Baseline and Week 12 in SF-36 at Week 24
Time Frame: Baseline (Day 1), Week 12 (Day 85) and Week 24
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The Medical Outcome SF 36-Item Health Survey, Version 2 is a self-administered instrument that measures the impact of disease on overall quality of life and consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health).
The summary physical health score included the following subscales: physical functioning, role-physical, bodily pain, and general health.
The summary mental health score included other subscales: vitality, social functioning, role-emotional, and mental health.
Norm-based scores were used in analyses, calibrated so that 50 is the average score and the standard deviation equals 10, where higher scores are associated with better functioning/quality of life.
Each domain is scored by summing the individual items and transforming the scores into a 0 to 100 scale.
A higher change from baseline indicates an improvement in better health results or functioning.
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Baseline (Day 1), Week 12 (Day 85) and Week 24
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Change From Baseline and Week 12 in Dermatology Life Quality Index (DLQI) at Week 24
Time Frame: Baseline (Day 1), Week 12 (Day 85) and Week 24
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The DLQI is a validated, self-administered, 10-item questionnaire that measures the impact of skin disease on participants' quality of life, based on recall over the past week.
Domains include symptoms, feelings, daily activities, leisure, work, personal relationships, and treatment.
Each question is answered on a scale from 0 (not at all) to 3 (very much) The total score ranges from 0 to 30 where a higher score indicates that a participant's dermatological condition has a greater impact on their daily life.
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Baseline (Day 1), Week 12 (Day 85) and Week 24
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Change From Baseline and Week 12 in the Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 24
Time Frame: Baseline (Day 1), Week 12 (Day 85) and Week 24
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The HAQ-DI is a self-administered instrument consisting of 20 questions in eight categories of functioning which represent a comprehensive set of functional activities - dressing, rising, eating, walking, hygiene, reach, grip, and usual activities.
Each item asks over the past week whether a particular task can be performed.
For each item, there is a four-level difficulty scale that is scored from 0 to 3, representing normal (no difficulty) (0), some difficulty (1), much difficulty (2), and unable to do (3).
The eight category scores are averaged into an overall HAQ-DI score on a scale from zero (no disability) to three (completely disabled).
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Baseline (Day 1), Week 12 (Day 85) and Week 24
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Change From Baseline in the Functional Assessment of Chronic Illness Therapy for Fatigue (FACIT-F) at Week 24
Time Frame: Baseline (Day 1), Week 12 (Day 85) and Week 24
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The FACIT-Fatigue is a 13 item self-administered questionnaire that assesses both the physical and functional consequences of fatigue based on recall during the past 7 days.
Each question is answered on a 5-point scale, where 0 means "not at all," and 4 means "very much."
The total score ranges from 0 to 52 with higher scores representing less fatigue.
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Baseline (Day 1), Week 12 (Day 85) and Week 24
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Collaborators and Investigators
Sponsor
Publications and helpful links
General Publications
- Schett G, Wollenhaupt J, Papp K, Joos R, Rodrigues JF, Vessey AR, Hu C, Stevens R, de Vlam KL. Oral apremilast in the treatment of active psoriatic arthritis: results of a multicenter, randomized, double-blind, placebo-controlled study. Arthritis Rheum. 2012 Oct;64(10):3156-67. doi: 10.1002/art.34627.
- Strand V, Schett G, Hu C, Stevens RM. Patient-reported Health-related Quality of Life with apremilast for psoriatic arthritis: a phase II, randomized, controlled study. J Rheumatol. 2013 Jul;40(7):1158-65. doi: 10.3899/jrheum.121200. Epub 2013 Apr 15.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Skin Diseases
- Joint Diseases
- Musculoskeletal Diseases
- Skin Diseases, Papulosquamous
- Spinal Diseases
- Bone Diseases
- Spondylarthropathies
- Spondylarthritis
- Spondylitis
- Psoriasis
- Arthritis
- Arthritis, Psoriatic
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Peripheral Nervous System Agents
- Enzyme Inhibitors
- Analgesics
- Sensory System Agents
- Anti-Inflammatory Agents, Non-Steroidal
- Analgesics, Non-Narcotic
- Anti-Inflammatory Agents
- Antirheumatic Agents
- Phosphodiesterase Inhibitors
- Phosphodiesterase 4 Inhibitors
- Apremilast
Other Study ID Numbers
- CC-10004-PSA-001
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Time Frame
IPD Sharing Access Criteria
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
- SAP
- ICF
- CSR
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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