A Safety Study of VIMOVO in Adolescents With Juvenile Idiopathic Arthritis (JIA)

Study Overview
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Brief Summary
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A 6-month study of the safety of VIMOVO in adolescents aged 12 to 16 years with JIA.

Official Title
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A 6-month, Multicenter, Open-label, Safety Study of VIMOVO (250 mg/20 mg, 375 mg/20 mg, and 500 mg/20 mg Naproxen/Esomeprazole) in Adolescents Aged 12 to 16 Years, Inclusive, With Juvenile Idiopathic Arthritis (JIA)

Conditions
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Juvenile Idiopathic Arthritis (JIA)

Intervention / Treatment
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* Drug: VIMOVO 250/20
* Drug: VIMOVO 375/20
* Drug: VIMOVO 500/20


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Parent or legal guardian is able to provide written informed consent and patient is able to provide written assent if appropriate. Male and female adolescents aged 12 to 16 years at the time of enrollment. Diagnosed with JIA, including all the International League of Associations for Rheumatology JIA subtypes: oligoarthritis, polyarthritis (both rheumatoid factor [RF]+ and RF-), psoriatic arthritis, enthesitis-related arthritis, undifferentiated arthritis, and systemic arthritis. Based upon investigator judgment, it is determined appropriate for the patient to undergo 6 months of continuous treatment with VIMOVO. Body weight > 31 kg (68.2 lbs) and within the 5th to 95th percentile of body mass index for age. Exclusion Criteria: In systemic JIA patients, presence of systemic features (ie, fever, rheumatoid rash, serositis, lymphadenopathy, macrophage activation syndrome) within 6 months prior to start of study drug. Currently taking (ie, within 4 weeks prior to start of drug) naproxen > 20 mg/kg/day or > 1000 mg total daily dose. Hemoglobin ≤ 8.5 g/dL. Individuals who have cardiovascular or cerebrovascular disease, based on history or risk factors. Any significant hepatic, renal, pulmonary, ophthalmologic, neurologic, or any other medical conditions indicated by medical/surgical history, physical, or laboratory examination that might put the patient at greater risk during the study.

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 16 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: VIMOVO<br>Three VIMOVO strengths will be used in this study: 250 mg naproxen/20 mg esomeprazole magnesium (VIMOVO 250/20), 375 mg naproxen/20 mg esomeprazole magnesium (VIMOVO 375/20), and 500 mg naproxen/20 mg esomeprazole magnesium (VIMOVO 500/20). The VIMOVO strength allocated to each participant will be determined by the participant's weight at baseline and based on investigator's discretion. The target dose of the naproxen component will be within the range of 10-20 mg/kg/day divided twice daily (BID) with a maximum daily dose of 1000 mg. | Drug: VIMOVO 250/20<br>* 250 mg naproxen/20 mg esomeprazole magnesium oral tablet administered twice daily for up to 6 months<br>* Other names: naproxen/esomeprazole;Drug: VIMOVO 375/20<br>* 375 mg naproxen/20 mg esomeprazole magnesium oral tablet administered twice daily for up to 6 months<br>* Other names: naproxen/esomeprazole;Drug: VIMOVO 500/20<br>* 500 mg naproxen/20 mg esomeprazole magnesium oral tablet administered twice daily for up to 6 months<br>* Other names: naproxen/esomeprazole;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Reporting Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and TEAEs Leading to Discontinuation (DC) of Study Drug | An AE is defined as the development of an undesirable medical condition or the deterioration of a preexisting medical condition, whether or not considered causally related to treatment. An SAE is defined as an AE occurring during any study phase (ie, run-in, treatment, washout, follow-up), that fulfils one or more of the following criteria: results in death; is immediately life-threatening; requires in-patient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability or incapacity; is a congenital abnormality or birth defect; is an important medical event that may jeopardize the participant or may require medical intervention to prevent one of the outcomes listed above. AEs were considered treatment-emergent if they occurred after the first dose of study drug. Events were categorized as mild, moderate, and severe; participants were represented only with the maximum reported intensity. | SAEs were collected from signing of informed consent through Month 6 (or end of treatment) plus 14 days. AEs were collected from administration of VIMOVO through Month 6 (or end of treatment) plus 14 days. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK) of Esomeprazole: Area Under the Concentration-Time Curve From the Time of Dosing to the Last Measurable Concentration (AUC[0-t]) |  | pre-dose, and up to 3 hours post-dose | 
| PK of Esomeprazole: Oral Plasma Clearance (CL/F) |  | pre-dose, and up to 3 hours post-dose | 
| PK of Esomeprazole: Absorption Rate Constant (Ka) |  | pre-dose, and up to 3 hours post-dose | 
| PK of Esomeprazole: Oral Volume of Distribution (V/F) |  | pre-dose, and up to 3 hours post-dose | 
| PK of Naproxen: Trough Plasma Concentrations | Trough concentration was defined as lowest plasma concentration from pre-dose to 3 hours post-dose, for each individual participant. | Month 1 and Month 3: pre-dose, and up to 3 hours post-dose |