Clinical trial NCT01563185: Open-label Safety and Pharmacokinetic Study of DUEXIS® (Ibuprofen and Famotidine) Tablets in Juvenile Idiopathic Arthritis
Official title: A Multicenter, Open-label Safety and Pharmacokinetic Study of DUEXIS® (Ibuprofen and Famotidine) Tablets in Juvenile Idiopathic Arthritis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Juvenile Idiopathic Arthritis
Keywords: JIA
ibuprofen
famotidine
pediatrics
for > 1 month
Lead sponsor: Amgen
Sponsor class: INDUSTRY
Collaborators: name: Pediatric Rheumatology Collaborative Study Group
First posted: 2012-03-26
Enrollment: 12
Sex: ALL
Minimum age (years): 10
Maximum age (years): 16
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed description: Approximately 30 JIA patients who meet all eligibility criteria and who are expected to require daily administration of an NSAID for up to 24 weeks will be enrolled. A subset of approximately 6 patients will participate in a single dose PK study at Day 0 with an abbreviated PK profile performed at Week 4 if possible. Multiple dose PK sampling will occur in all enrolled patients.

Study with completed results acquired from Horizon in 2024

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

Primary outcomes:
measure: Number of Participants Reporting Treatment Emergent Adverse Events (TEAEs)
timeFrame: Day 0 through Week 26/ET (adverse event data was collected at every visit, including telephone visits)
Secondary outcomes:
measure: Childhood Health Questionnaire Parent Form 50 (CHQ-PF50) Scores
timeFrame: Baseline to Endpoint (Endpoint is the last post-baseline value obtained, as two subjects did not complete the study up until week 24).
measure: American College of Rheumatology (ACR) Pediatric Core Measures: Physician's Global Assessment of Disease Activity and Parent's Assessment of Overall Well-being
timeFrame: Baseline to Endpoint (Endpoint is the last post-baseline value obtained, as two subjects did not complete the study up until week 24).
measure: American College of Rheumatology (ACR) Pediatric Core Measures: CHAQ - Disability Index
timeFrame: Baseline to Endpoint (Endpoint is the last post-baseline value obtained, as two subjects did not complete the study up until week 24).
measure: ACR Pediatric Components by Time Point: Number of Joints With Active Arthritis and the Number of Joints With Limited Range of Motion Number of Joints With Active Arthritis
timeFrame: Baseline to Endpoint (Endpoint is the last post-baseline value obtained, as two subjects did not complete the study up until week 24).
measure: American College of Rheumatology (ACR) Pediatric Core Measures: Serum C Reactive Protein (CRP) Concentration
timeFrame: Baseline to Endpoint (Endpoint is the last post-baseline value obtained, as two subjects did not complete the study up until week 24).
measure: Single Dose Pharmacokinetic Characteristics of DUEXIS in JIA Patients: Time of Maximum Observed Concentration (Tmax)
timeFrame: Pre-dose, 0.5, 1, 2, 4, 8 hours post-dose
measure: Single Dose Pharmacokinetic Characteristics of DUEXIS in JIA Patients: Maximum Observed Concentration (Cmax)
timeFrame: Pre-dose, and 0.5, 1, 2, 4, 8 hours post-dose
measure: Single Dose Pharmacokinetic Characteristics of DUEXIS in JIA Patients: Area Under the Concentration-time Curve From the Time of Dosing to the Last Measurable Concentration (AUC(0-t))
timeFrame: Pre-dose, and 0.5, 1, 2, 4, 8 hours post-dose
measure: Multiple Dose Pharmacokinetic Characteristics of DUEXIS in JIA Patients: Individual Oral Clearance (CL/F)
timeFrame: Pre-dose and 0.5, 1, 2, 4, and 8 hours post-dose in the single dose group; sparse samples at random times in the multiple dose group
measure: Multiple Dose Pharmacokinetic Characteristics of DUEXIS in JIA Patients: Volume Distribution (V/F)
timeFrame: Pre-dose and 0.5, 1, 2, 4, and 8 hours post-dose in the single dose group; sparse samples at random times in the multiple dose group
Other outcomes:
Locations:
city: New Orleans
country: United States
facility: Children's Hospital
state: Louisiana
city: Boston
country: United States
facility: Floating Hospital for Children @ Tufts Medical Center
state: Massachusetts
city: Worcester
country: United States
facility: UMASS Memorial Children's Medical Center
state: Massachusetts
city: Duncansville
country: United States
facility: Altoona Center for Clinical Research Altoona Arthritis
state: Pennsylvania
city: Austin
country: United States
facility: Dell Children's Medical Center of Central Texas
state: Texas
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References: