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

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)

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

Study Overview

• Status: Completed
• Conditions: Juvenile Idiopathic Arthritis (JIA)
• Intervention / Treatment: Drug: VIMOVO 250/20; Drug: VIMOVO 375/20; Drug: VIMOVO 500/20

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72202
      • Research Site
  • California
    • San Francisco, California, United States, 94143
      • Research Site
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Research Site
  • District of Columbia
    • Washington, D.C., District of Columbia, United States, 20010
      • Research Site
  • Florida
    • West Palm Beach, Florida, United States, 33407
      • Research Site
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Research Site
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Research Site
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Research Site
  • New York
    • Brooklyn, New York, United States, 11203
      • Research Site
    • New Hyde Park, New York, United States, 11040
      • Research Site
    • New York, New York, United States, 10021
      • Research Site
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Research Site
    • Cleveland, Ohio, United States, 44195
      • Research Site
    • Toledo, Ohio, United States, 43623
      • Research Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19134
      • Research Site
  • Tennessee
    • Memphis, Tennessee, United States, 38119
      • Research Site
  • Virginia
    • Fairfax, Virginia, United States, 22030
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 16 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: VIMOVO; 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; 250 mg naproxen/20 mg esomeprazole magnesium oral tablet administered twice daily for up to 6 months; Other Names: naproxen/esomeprazole; Drug: VIMOVO 375/20; 375 mg naproxen/20 mg esomeprazole magnesium oral tablet administered twice daily for up to 6 months; Other Names: naproxen/esomeprazole; Drug: VIMOVO 500/20; 500 mg naproxen/20 mg esomeprazole magnesium oral tablet administered twice daily for up to 6 months; Other Names: naproxen/esomeprazole

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Horizon Pharma Ireland, Ltd., Dublin Ireland

Publications and helpful links

General Publications

• Lovell DJ, Dare JA, Francis-Sedlak M, Ball J, LaMoreaux BD, Von Scheven E, Reinhardt A, Jerath R, Alpan O, Gupta R, Goldsmith D, Zeft A, Naddaf H, Gottlieb B, Jung L, Holt RJ. A 6-month, multicenter, open-label study of fixed dose naproxen/esomeprazole in adolescent patients with juvenile idiopathic arthritis. Pediatr Rheumatol Online J. 2018 Jun 26;16(1):41. doi: 10.1186/s12969-018-0260-y.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: April 1, 2012
• Primary Completion (Actual): February 1, 2015
• Study Completion (Actual): February 1, 2015

Study Registration Dates

• First Submitted: February 21, 2012
• First Submitted That Met QC Criteria: February 28, 2012
• First Posted (Estimate): March 5, 2012

Study Record Updates

• Last Update Posted (Actual): October 4, 2017
• Last Update Submitted That Met QC Criteria: September 7, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Juvenile; 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; Cyclooxygenase Inhibitors; Gastrointestinal Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Gout Suppressants; Esomeprazole; Naproxen
• Other Study ID Numbers: D1120C00037