Pharmacokinetics & Safety of Diclofenac Potassium Oral Solution in Ped. Subjects (2-12 Yrs) With Mild-Mod. Acute Pain

Study Overview
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Brief Summary
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As part of the Pediatric Research Equity Act (PREA) commitment, the objectives of the study are to characterize the pharmacokinetic (PK) profile and to determine the safety and tolerability of diclofenac potassium oral solution in pediatric subjects experiencing mild to moderate acute pain.

Detailed Description
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This is an open-label study with pediatric subjects, ages 2-12 years, who will be dosed with diclofenac potassium oral solution, based on weight, every 6 hours as needed for the treatment of mild to moderate acute pain for up to 4 days. PK samples will be collected through 6 hours after the first dose. Safety data will be collected throughout the study.

Official Title
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A Phase 4, Open-Label Study of the Pharmacokinetics and Safety of Diclofenac Potassium Oral Solution in Pediatric Subjects (Ages 2-12 Years) With Mild to Moderate Acute Pain

Conditions
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Pain

Intervention / Treatment
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* Drug: diclofenac potassium oral solution


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female subjects between 2-12 years of age. Subjects must be post-op, having mild or moderate acute pain. Other inclusions apply. Exclusion Criteria: Subject has a known history of allergic reaction, hypersensitivity to diclofenac, aspirin, acetaminophen, or reaction to the non-active ingredients of the study medication. Subject has been taking analgesics for 48-72 hours prior to Screening. Subject has a history of any GI event greater than 6 months before Screening. Subject is currently receiving any medication that is contraindicated for use concomitantly with diclofenac or acetaminophen. Subject is requiring treatment for pre-existing hypertension. Other exclusions apply.

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 12 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: diclofenac potassium oral solution<br>5 mg/mL, liquid form, weight-based dosing, every 6 hours, for up to 4 days. | Drug: diclofenac potassium oral solution<br>* Administration of diclofenac potassium oral solution, taken by mouth, as needed for mild to moderate acute pain.<br>* Other names: diclofenac;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To Characterize the Pharmacokinetic (PK) Profile of a Single Dose of Diclofenac Potassium Oral Solution, With Weight-based Dosing, in Pediatric Subjects, Ages 2-12 Years Experiencing Mild to Moderate Acute Pain (1 of 8). | • Cmax: maximum concentration (ng/mL) | 6 hours (pre-dose, 15, 30, and 60 min, and 2, 4, and 6 hrs post-dose) | 
| To Characterize the Pharmacokinetic (PK) Profile of a Single Dose of Diclofenac Potassium Oral Solution, With Weight-based Dosing, in Pediatric Subjects, Ages 2-12 Years Experiencing Mild to Moderate Acute Pain (2 of 8). | • Tmax: time to maximum concentration (hr) | 6 hours (pre-dose, 15, 30, and 60 min, and 2, 4, and 6 hrs post-dose) | 
| To Characterize the Pharmacokinetic (PK) Profile of a Single Dose of Diclofenac Potassium Oral Solution, With Weight-based Dosing, in Pediatric Subjects, Ages 2-12 Years Experiencing Mild to Moderate Acute Pain (3 of 8). | • λz: elimination rate constant (1/hr) | 6 hours (pre-dose, 15, 30, and 60 min, and 2, 4, and 6 hrs post-dose) | 
| To Characterize the Pharmacokinetic (PK) Profile of a Single Dose of Diclofenac Potassium Oral Solution, With Weight-based Dosing, in Pediatric Subjects, Ages 2-12 Years Experiencing Mild to Moderate Acute Pain (4 of 8). | • t1/2: terminal elimination half-life (hr) | 6 hours (pre-dose, 15, 30, and 60 min, and 2, 4, and 6 hrs post-dose) | 
| To Characterize the Pharmacokinetic (PK) Profile of a Single Dose of Diclofenac Potassium Oral Solution, With Weight-based Dosing, in Pediatric Subjects, Ages 2-12 Years Experiencing Mild to Moderate Acute Pain (5 of 8). | • AUC 0-t: area under the concentration-time curve from time 0 to last time point (t) where diclofenac could be measured (hr*ng/mL) | 6 hours (pre-dose, 15, 30, and 60 min, and 2, 4, and 6 hrs post-dose) | 
| To Characterize the Pharmacokinetic (PK) Profile of a Single Dose of Diclofenac Potassium Oral Solution, With Weight-based Dosing, in Pediatric Subjects, Ages 2-12 Years Experiencing Mild to Moderate Acute Pain (6 of 8). | • AUC 0-∞: area under the concentration-time curve from time 0 to infinity (∞) (hr*ng/mL) | 6 hours (pre-dose, 15, 30, and 60 min, and 2, 4, and 6 hrs post-dose) | 
| To Characterize the Pharmacokinetic (PK) Profile of a Single Dose of Diclofenac Potassium Oral Solution, With Weight-based Dosing, in Pediatric Subjects, Ages 2-12 Years Experiencing Mild to Moderate Acute Pain (7 of 8). | • CL/F: apparent clearance (mL/hr). | 6 hours (pre-dose, 15, 30, and 60 min, and 2, 4, and 6 hrs post-dose) | 
| To Characterize the Pharmacokinetic (PK) Profile of a Single Dose of Diclofenac Potassium Oral Solution, With Weight-based Dosing, in Pediatric Subjects, Ages 2-12 Years Experiencing Mild to Moderate Acute Pain (8 of 8). | • Vz/F: apparent volume of distribution (mL). | 6 hours (pre-dose, 15, 30, and 60 min, and 2, 4, and 6 hrs post-dose) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To Determine the Safety and Tolerability of Diclofenac Potassium Oral Solution in Pediatric Subjects, Ages 2-12 Years Experiencing Mild to Moderate Acute Pain (1 of 7). | • Treatment emergent AEs (TEAEs) | 4 weeks (first dose of study drug and up to 30 days after the date of the last dose of study drug) | 
| To Determine the Safety and Tolerability of Diclofenac Potassium Oral Solution in Pediatric Subjects, Ages 2-12 Years Experiencing Mild to Moderate Acute Pain (2 of 7). | • Serious adverse events (SAEs) | 4 weeks (signed informed consent/assent to 30 days after the last dose of study drug) | 
| To Determine the Safety and Tolerability of Diclofenac Potassium Oral Solution in Pediatric Subjects, Ages 2-12 Years Experiencing Mild to Moderate Acute Pain (3 of 7). | • Withdrawals due to AEs | 4 weeks (signed informed consent/assent to 30 days after the last dose of study drug) | 
| To Determine the Safety and Tolerability of Diclofenac Potassium Oral Solution in Pediatric Subjects, Ages 2-12 Years Experiencing Mild to Moderate Acute Pain (4 of 7). | • Deaths | 4 weeks (signed informed consent/assent to 30 days after the last dose of study drug) | 
| To Determine the Safety and Tolerability of Diclofenac Potassium Oral Solution in Pediatric Subjects, Ages 2-12 Years Experiencing Mild to Moderate Acute Pain (5.1 of 7). | • Changes in vital sign measurements: Temperature (degrees C). | 4 weeks (signed informed consent/assent to the final visit) | 
| To Determine the Safety and Tolerability of Diclofenac Potassium Oral Solution in Pediatric Subjects, Ages 2-12 Years Experiencing Mild to Moderate Acute Pain (5.2 of 7). | • Changes in vital sign measurements: Pulse Rate (beats/min). | 4 weeks (signed informed consent/assent to the final visit) | 
| To Determine the Safety and Tolerability of Diclofenac Potassium Oral Solution in Pediatric Subjects, Ages 2-12 Years Experiencing Mild to Moderate Acute Pain (5.3 of 7). | • Changes in vital sign measurements: Respiratory Rate (breaths/min). | 4 weeks (signed informed consent/assent to the final visit) | 
| To Determine the Safety and Tolerability of Diclofenac Potassium Oral Solution in Pediatric Subjects, Ages 2-12 Years Experiencing Mild to Moderate Acute Pain (5.4 of 7). | • Changes in vital sign measurements: Systolic Blood Pressure (mmHg). | 4 weeks (signed informed consent/assent to the final visit) | 
| To Determine the Safety and Tolerability of Diclofenac Potassium Oral Solution in Pediatric Subjects, Ages 2-12 Years Experiencing Mild to Moderate Acute Pain (5.5 of 7). | • Changes in vital sign measurements: Diastolic Blood Pressure (mmHg). | 4 weeks (signed informed consent/assent to the final visit) | 
| To Determine the Safety and Tolerability of Diclofenac Potassium Oral Solution in Pediatric Subjects, Ages 2-12 Years Experiencing Mild to Moderate Acute Pain (6.1 of 7). | • Changes in clinical laboratory results: Hematology - Hematocrit (L/L). | 4 weeks (signed informed consent/assent to the final visit) | 
| To Determine the Safety and Tolerability of Diclofenac Potassium Oral Solution in Pediatric Subjects, Ages 2-12 Years Experiencing Mild to Moderate Acute Pain (6.2 of 7). | • Changes in clinical laboratory results: Hematology - Hemoglobin (g/L). | 4 weeks (signed informed consent/assent to the final visit) | 
| To Determine the Safety and Tolerability of Diclofenac Potassium Oral Solution in Pediatric Subjects, Ages 2-12 Years Experiencing Mild to Moderate Acute Pain (6.3 of 7). | • Changes in clinical laboratory results: Hematology - Platelet Count (10^9/L). | 4 weeks (signed informed consent/assent to the final visit) | 
| To Determine the Safety and Tolerability of Diclofenac Potassium Oral Solution in Pediatric Subjects, Ages 2-12 Years Experiencing Mild to Moderate Acute Pain (6.4 of 7). | • Changes in clinical laboratory results: Hematology - White Blood Cells (10^9/L). | 4 weeks (signed informed consent/assent to the final visit) | 
| To Determine the Safety and Tolerability of Diclofenac Potassium Oral Solution in Pediatric Subjects, Ages 2-12 Years Experiencing Mild to Moderate Acute Pain (6.5 of 7). | • Changes in clinical laboratory results: Hematology - Basophils (%). | 4 weeks (signed informed consent/assent to the final visit) | 
| To Determine the Safety and Tolerability of Diclofenac Potassium Oral Solution in Pediatric Subjects, Ages 2-12 Years Experiencing Mild to Moderate Acute Pain (6.6 of 7). | • Changes in clinical laboratory results: Hematology - Eosinophils (%). | 4 weeks (signed informed consent/assent to the final visit) | 
| To Determine the Safety and Tolerability of Diclofenac Potassium Oral Solution in Pediatric Subjects, Ages 2-12 Years Experiencing Mild to Moderate Acute Pain (6.7 of 7). | • Changes in clinical laboratory results: Hematology - Neutrophils (%). | 4 weeks (signed informed consent/assent to the final visit) | 
| To Determine the Safety and Tolerability of Diclofenac Potassium Oral Solution in Pediatric Subjects, Ages 2-12 Years Experiencing Mild to Moderate Acute Pain (6.8 of 7). | • Changes in clinical laboratory results: Hematology - Lymphocytes (%). | 4 weeks (signed informed consent/assent to the final visit) | 
| To Determine the Safety and Tolerability of Diclofenac Potassium Oral Solution in Pediatric Subjects, Ages 2-12 Years Experiencing Mild to Moderate Acute Pain (6.9 of 7). | • Changes in clinical laboratory results: Hematology - Monocytes (%). | 4 weeks (signed informed consent/assent to the final visit) | 
| To Determine the Safety and Tolerability of Diclofenac Potassium Oral Solution in Pediatric Subjects, Ages 2-12 Years Experiencing Mild to Moderate Acute Pain (6.10 of 7). | • Changes in clinical laboratory results: Chemistry - Albumin (g/L). | 4 weeks (signed informed consent/assent to the final visit) | 
| To Determine the Safety and Tolerability of Diclofenac Potassium Oral Solution in Pediatric Subjects, Ages 2-12 Years Experiencing Mild to Moderate Acute Pain (6.11 of 7). | • Changes in clinical laboratory results: Chemistry - Alkaline Phosphatase (U/L). | 4 weeks (signed informed consent/assent to the final visit) | 
| To Determine the Safety and Tolerability of Diclofenac Potassium Oral Solution in Pediatric Subjects, Ages 2-12 Years Experiencing Mild to Moderate Acute Pain (6.12 of 7). | • Changes in clinical laboratory results: Chemistry - ALT (SGPT) (U/L). | 4 weeks (signed informed consent/assent to the final visit) | 
| To Determine the Safety and Tolerability of Diclofenac Potassium Oral Solution in Pediatric Subjects, Ages 2-12 Years Experiencing Mild to Moderate Acute Pain (6.13 of 7). | • Changes in clinical laboratory results: Chemistry - AST (SGOT) (U/L). | 4 weeks (signed informed consent/assent to the final visit) | 
| To Determine the Safety and Tolerability of Diclofenac Potassium Oral Solution in Pediatric Subjects, Ages 2-12 Years Experiencing Mild to Moderate Acute Pain (6.14 of 7). | • Changes in clinical laboratory results: Chemistry - Bicarbonate (CO2) (mmol/L). | 4 weeks (signed informed consent/assent to the final visit) | 
| To Determine the Safety and Tolerability of Diclofenac Potassium Oral Solution in Pediatric Subjects, Ages 2-12 Years Experiencing Mild to Moderate Acute Pain (6.15 of 7). | • Changes in clinical laboratory results: Chemistry - Bilirubin Total (umol/L). | 4 weeks (signed informed consent/assent to the final visit) | 
| To Determine the Safety and Tolerability of Diclofenac Potassium Oral Solution in Pediatric Subjects, Ages 2-12 Years Experiencing Mild to Moderate Acute Pain (6.16 of 7). | • Changes in clinical laboratory results: Chemistry - BUN (Urea) (mmol/L). | 4 weeks (signed informed consent/assent to the final visit) | 
| To Determine the Safety and Tolerability of Diclofenac Potassium Oral Solution in Pediatric Subjects, Ages 2-12 Years Experiencing Mild to Moderate Acute Pain (6.17 of 7). | • Changes in clinical laboratory results: Chemistry - Chloride (mmol/L). | 4 weeks (signed informed consent/assent to the final visit) | 
| To Determine the Safety and Tolerability of Diclofenac Potassium Oral Solution in Pediatric Subjects, Ages 2-12 Years Experiencing Mild to Moderate Acute Pain (6.18 of 7). | • Changes in clinical laboratory results: Chemistry - Creatinine (umol/L). | 4 weeks (signed informed consent/assent to the final visit) | 
| To Determine the Safety and Tolerability of Diclofenac Potassium Oral Solution in Pediatric Subjects, Ages 2-12 Years Experiencing Mild to Moderate Acute Pain (6.19 of 7). | • Changes in clinical laboratory results: Chemistry - Glucose (mmol/L). | 4 weeks (signed informed consent/assent to the final visit) | 
| To Determine the Safety and Tolerability of Diclofenac Potassium Oral Solution in Pediatric Subjects, Ages 2-12 Years Experiencing Mild to Moderate Acute Pain (6.20 of 7). | • Changes in clinical laboratory results: Chemistry - LDH (U/L). | 4 weeks (signed informed consent/assent to the final visit) | 
| To Determine the Safety and Tolerability of Diclofenac Potassium Oral Solution in Pediatric Subjects, Ages 2-12 Years Experiencing Mild to Moderate Acute Pain (6.21 of 7). | • Changes in clinical laboratory results: Chemistry - Potassium (mmol/L). | 4 weeks (signed informed consent/assent to the final visit) | 
| To Determine the Safety and Tolerability of Diclofenac Potassium Oral Solution in Pediatric Subjects, Ages 2-12 Years Experiencing Mild to Moderate Acute Pain (6.22 of 7). | • Changes in clinical laboratory results: Chemistry - Sodium (mmol/L). | 4 weeks (signed informed consent/assent to the final visit) | 
| To Determine the Safety and Tolerability of Diclofenac Potassium Oral Solution in Pediatric Subjects, Ages 2-12 Years Experiencing Mild to Moderate Acute Pain (6.23 of 7). | • Changes in clinical laboratory results: Urinalysis - pH. | 4 weeks (signed informed consent/assent to the final visit) | 
| To Determine the Safety and Tolerability of Diclofenac Potassium Oral Solution in Pediatric Subjects, Ages 2-12 Years Experiencing Mild to Moderate Acute Pain (6.24 of 7). | • Changes in clinical laboratory results: Urinalysis - Specific Gravity. | 4 weeks (signed informed consent/assent to the final visit) | 
| To Determine the Safety and Tolerability of Diclofenac Potassium Oral Solution in Pediatric Subjects, Ages 2-12 Years Experiencing Mild to Moderate Acute Pain (7 of 7). | • Physical examination findings including abnormal clinically significant findings | 4 weeks (signed informed consent/assent to the final visit) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pain, moderate pain, mild pain, acute pain, mild acute pain, moderate acute pain, mild or moderate acute pain, NSAID, nonsteroidal anti-inflammatory drug