Study to Assess the Injection Site Pain Associated With a New Etanercept Formulation in Adults With Rheumatoid Arthritis or Psoriatic Arthritis

Study Overview
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Brief Summary
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The primary objective was to assess the injection site pain associated with the new formulation of etanercept compared with commercial etanercept in adults with rheumatoid arthritis (RA) or psoriatic arthritis (PsA) as measured by a visual analog scale (VAS).

Detailed Description
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This is a phase 3b, multicenter, randomized, double-blind, 2-period, 2-sequence crossover study in adults with RA or PsA who are naive to etanercept. The study will evaluate injection site pain associated with the commercial formulation of etanercept and the new formulation of etanercept immediately after injection of each formulation.The study will consist of a screening period of up to 14 days, a 2 week treatment period with a 30 day post treatment safety follow-up. Each dose will follow the recommended label dosing for adults with RA and PsA: 50 mg weekly (scheduled approximately 7 days apart).

Official Title
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A Multicenter, Randomized, Double-blind, Crossover Study to Assess the Injection Site Pain Associated With a Modified Etanercept Formulation in Adult Subjects With Either Rheumatoid Arthritis or Psoriatic Arthritis

Conditions
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Arthritis, Rheumatoid; Arthritis, Psoriatic

Intervention / Treatment
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* Drug: Commercial Formulation Etanercept
* Drug: New Formulation Etanercept


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Subject has provided informed consent prior to initiation of any study specific activities/procedures. Male or female subject is 18 years of age or older at time of signing the informed consent form. Subject has a diagnosis of RA or PsA and indicated for treatment with etanercept per the current label, based on investigator judgment. Subject is naïve to etanercept. Subject is able to self-inject etanercept. Exclusion Criteria Subject is diagnosed with Felty's syndrome. Subject has active erythrodermic, pustular, guttate psoriasis, or medication induced psoriasis, or other skin conditions. Subject has a history of clinically significant skin allergies Subject has a history of alcoholic hepatitis, nonalcoholic steatohepatitis or immunodeficiency syndromes. Subject has any active infection for which anti-infectives were indicated within 4 weeks prior to screening. Subject has had a serious infection, defined as requiring hospitalization or intravenous anti-infectives within 8 weeks prior to first dose of investigational product. Subject had prosthetic joint infection within 5 years of screening or native joint infection within 1 year of screening. Subject has known alcohol addiction or dependency. Subject has positive hepatitis B surface antigen, hepatitis B core antibody (confirmed by hepatitis B virus deoxyribonucleic acid (DNA) test) or hepatitis C virus antibody serology at screening, or a positive medical history for hepatitis B or C. (Subjects with a history of hepatitis B vaccination without history of hepatitis B are allowed to enroll). Subject has any active malignancy, including evidence of cutaneous basal or squamous cell carcinoma or melanoma. Subject has known history of active tuberculosis. Subject has used biologic disease modifying agent (DMARD) less than or equal to 3 months prior to screening. If subject is receiving continuous treatment with acetaminophen, non-steroidal anti-inflammatory drug or tramadol, hydrocodone, oxycodone, codeine, and/or propoxyphene and the dose is within 4 hours before study visit and dose is not stable for ≥ 2 weeks before first dose of investigational product For subjects not on continuous analgesics, subject has taken the following within 4 hours before screening: acetaminophen, non-steroidal anti-inflammatory drugs, hydrocodone, codeine, tramadol, propoxyphene, and/or oxycodone (unless in the form of OxyContin). For subjects not on continuous analgesics, subject has taken OxyContin within 24 hours before screening. Subject has received live vaccines less than or equal to 4 weeks prior to first dose of investigational product. Subject has laboratory abnormalities during screening. Estimated creatinine clearance less than 50 mL/min. Subject has any other laboratory abnormality, which, in the opinion of the investigator poses a safety risk, will prevent the subject from completing the study, or will interfere with the interpretation of the study results. Subject is currently receiving treatment in another investigational device or drug study, or less than 30 days since ending treatment on another investigational device or drug study(s). Other investigational procedures while participating in this study. Women who are pregnant or breastfeeding, or planning to become pregnant or breastfeed during treatment and/or within 4 weeks after the last dose of etanercept. Women of child-bearing potential with a positive pregnancy test. Women of child-bearing potential who are unwilling to practice true sexual abstinence or unwilling to use 1 of the following effective birth control methods during treatment and for an additional 4 weeks after the last dose of etanercept.

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: Supportive Care
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sequence AB<br>Participants received a single 50 mg subcutaneous (SC) dose of the commercial formulation etanercept in a prefilled SureClick autoinjector on day 1 (Treatment A) followed by a single 50 mg SC dose of the new formulation of etanercept in a prefilled SureClick autoinjector on day 8 (Treatment B). | Drug: Commercial Formulation Etanercept<br>* Etanercept was supplied in a single-use SureClick autoinjector as a sterile, preservative-free solution for SC injection containing 0.98 mL of 50 mg/mL etanercept in the commercial formulation.<br>* Other names: Enbrel;Drug: New Formulation Etanercept<br>* Etanercept was supplied in a single-use SureClick autoinjector as a sterile, preservative-free solution for SC injection containing 0.98 mL of 50 mg/mL etanercept in the new formulation.<br>|
| Experimental: Sequence BA<br>Participants received a single 50 mg SC dose of the new formulation of etanercept in a prefilled SureClick autoinjector on day 1 (Treatment B) followed by a single 50 mg SC dose of the commercial formulation etanercept in a prefilled SureClick autoinjector on day 8 (Treatment A). | Drug: Commercial Formulation Etanercept<br>* Etanercept was supplied in a single-use SureClick autoinjector as a sterile, preservative-free solution for SC injection containing 0.98 mL of 50 mg/mL etanercept in the commercial formulation.<br>* Other names: Enbrel;Drug: New Formulation Etanercept<br>* Etanercept was supplied in a single-use SureClick autoinjector as a sterile, preservative-free solution for SC injection containing 0.98 mL of 50 mg/mL etanercept in the new formulation.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Injection Site Pain | Injection site pain was assessed using a 100 mm visual analog scale (VAS), from 0 mm (No Pain At All) to 100 mm (Worst Pain Imaginable). Participants were asked to indicate the severity of their pain at the injection site by placing a vertical line on the scale. | Immediately following injection of each study drug on day 1 and day 8 of this crossover study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Injection Site Pain by Disease Indication | Injection site pain was assessed using a 100 mm visual analog scale (VAS), from 0 mm (No Pain At All) to 100 mm (Worst Pain Imaginable). Participants were asked to indicate the severity of their pain at the injection site by placing a vertical line on the scale. | Immediately following injection of each study drug on day 1 and day 8 of this crossover study | 
| Number of Participants With Adverse Events | The severity of each adverse event was graded by the investigator using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. | From first dose of etanercept to 30 days after the last dose; 38 days. |