Open-label Safety and Pharmacokinetic Study of DUEXIS® (Ibuprofen and Famotidine) Tablets in Juvenile Idiopathic Arthritis
Condition: Juvenile Idiopathic Arthritis
MeSH terms: Arthritis; Arthritis, Juvenile
Intervention: 800 mg ibuprofen/26.6 mg famotidine
Intervention description: Oral tablet taken three time per day
Intervention MeSH terms: Ibuprofen; Famotidine
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 12.0
Sex: All
Minimum age: 10 Years
Maximum age: 16 Years
Healthy volunteers: No
Keywords: JIA; ibuprofen; famotidine; pediatrics; for > 1 month

Summary:

      The primary objective of this Phase 4, multi-center, open-label study is to evaluate the
      safety and tolerability of DUEXIS in Juvenile Idiopathic Arthritis (JIA) patients aged 10
      years to 16 years, 11 months, treated up to 24 weeks.

      The secondary objectives are to evaluate the PK characteristics of DUEXIS in JIA patients and
      to evaluate the signs and symptoms of JIA in patients aged 10 years to 16 years, 11 months
      receiving DUEXIS for up to 24 weeks.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Patient and guardian are willing to consent to undergo up to 24 weeks of treatment
             with DUEXIS (ibuprofen 800 mg/famotidine 26.6 mg) oral tablet three times daily.

          2. Patient is male or female, aged 10 years to 16 years, 11 months.

          3. Patient is diagnosed with JIA for > 1 month including oligoarthritis, polyarthritis
             rheumatoid factor (RF) +, polyarthritis RF-, psoriatic arthritis, enthesitis-related
             arthritis, or undifferentiated and systemic arthritis without systemic features in the
             past 6 months.

          4. Patient must have currently active articular disease as defined by > 1 active joint
             (i.e., presence of swelling, or if no swelling is present, limitation of motion [LOM]
             accompanied by pain, tenderness, or both).

          5. Based upon investigator judgment, given current treatment patient is receiving and
             level of disease activity, it is determined appropriate for the patient to undergo up
             to 24 weeks of treatment with DUEXIS (ibuprofen 800 mg/famotidine 26.6 mg) oral tablet
             three times daily. The investigator will use his/her clinical judgment in determining
             the duration of treatment for the patient based on the standard of care up to 24 weeks
             of treatment.

          6. Weight > 48 kg and body mass index (BMI) > 5th percentile using the Centers for
             Disease Control (CDC) BMI percentile calculator for child and teen at the screening
             visit.

          7. Patient is able to swallow a DUEXIS tablet whole.

          8. For the single dose pharmacokinetic (PK) subset, patients and guardians must be
             willing to participate in the serial blood sample collections at Day 0 and Week 4.

          9. Female patients of childbearing potential and male patients must agree to use
             medically acceptable methods of contraception, including abstinence, throughout the
             entire study period.

         10. Patient is willing and able to comply with the prescribed treatment protocol and
             evaluations.

        Exclusion Criteria:

          1. Patient has a history of or experienced any of the following:

               -  NSAID-associated and/or primary peptic ulcer disease-associated serious
                  gastrointestinal complications such as perforation of ulcers, gastric outlet
                  obstruction due to ulcers, and/or acute gastrointestinal bleeding

               -  NSAID-induced asthma exacerbation, acute renal failure, interstitial nephritis,
                  and/or hepatitis

               -  Malignant disease of the gastrointestinal tract

               -  Erosive esophagitis

               -  Coronary artery bypass graft (CABG) surgery within the 14 days prior to study Day
                  0

               -  Uncontrolled diabetes mellitus as evidenced by Hemoglobin A1c > 7%

               -  Known history of human immunodeficiency virus (HIV), hepatitis B, and/or
                  hepatitis C.

          2. Current symptoms of severe, progressive, or uncontrolled renal, hepatic,
             hematological, gastrointestinal, pulmonary, cardiac, neurological, or cerebral
             disease.

          3. JIA disease is severe as defined by either physician's or parent's global assessments
             > 90 on a 100 point scale.

          4. Systemic JIA with any of the following manifestations within the last 6 months prior
             to enrollment: intermittent fever due to JIA, rheumatoid rash, hepatosplenomegaly,
             pleuritis, pericarditis, or macrophage activation syndrome.

          5. Active uveitis.

          6. Presence of any other rheumatic disease or major chronic infectious, inflammatory,
             immunologic disease (e.g., inflammatory bowel disease, hypogammaglobulinemia, or
             systemic lupus erythematosus, etc.).

          7. Presence at screening or history of any disease other than JIA that requires the use
             of chronic systemic corticosteroids.

          8. History of clinically significant drug or alcohol abuse.

          9. Presence at screening of any of the following laboratory values:

               -  Hemoglobin < 9.0 g/dL

               -  White blood cells < 2000/mm^3 (2 x 109/L)

               -  Platelets < 150,000/mm^3 (150 x 109/L)

               -  Serum creatinine > 1.5 times upper limit of normal

               -  Serum ALT or AST > 2.0 times upper limit of normal

               -  H. pylori positive

               -  Any other lab value that in the opinion of the investigator might place the
                  patient at unacceptable risk for participation in this study.

         10. Methotrexate > 20 mg/M^2/week or > 40 mg/week.

         11. Patient currently is participating in an investigational drug study, or patient
             participated in an investigational drug study within the 30 days (or < 5 terminal
             half-lives of elimination) prior to study entry.

         12. Females who are pregnant or breast feeding.

         13. Female patient has a positive serum pregnancy test at Screening and/or a positive
             urine pregnancy test at Study Day 0.

         14. Patient has a concomitant disease or condition that, in the opinion of the
             Investigator, could interfere with the conduct of the study or could put the patient
             at unacceptable risk