Pharmacokinetics (PK) and Safety Study of XARTEMIS® XR in Postsurgical Adolescent Subjects With Moderate to Severe Acute Pain

Study Overview
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Brief Summary
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Phase 4, multicenter, open-label, multiple-dose study of the pharmacokinetics (PK) and safety of XARTEMIS XR in postsurgical adolescent subjects aged 12 to 17 years with moderate to severe acute pain. The study will assess the safety of administering multiple doses of XARTEMIS XR in this population.

Official Title
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A Phase 4, Open-Label Study of the Pharmacokinetics and Safety of XARTEMIS® XR (7.5 Oxycodone Hydrochloride/325 mg Acetaminophen) in Postsurgical Adolescent Subjects (Ages 12 to 17) With Moderate to Severe Acute Pain

Conditions
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Acute Pain

Intervention / Treatment
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* Drug: XARTEMIS XR


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Male or nonpregnant, nonlactating females between 12 and 17 years of age. Minimum weight of 100 pounds (45 kg); body mass index (BMI) >5% and <95% for their age. Moderate or severe acute pain [as determined from the Numerical Pain Rating scale (NPRS)]; must have a level of 4 or more) after surgical procedure requiring hospitalization. If, of child-bearing/reproductive potential, must abstain from unprotected sexual activity during study and 2 weeks after study exit. Females of childbearing potential must have negative pregnancy test. Subject's legally authorized representative (eg, parent, legal guardian) must sign a parental permission/informed consent and subject must sign an assent. Subject and subject's parent/legal guardian must be able to read, understand, and follow study procedures and requirements and communicate meaningfully in English. Exclusion criteria: Subject is from a vulnerable population (including mentally disabled children), other than a pediatric population. Subject requires surgery that could influence the study outcome. Abnormal electrocardiogram (ECG). Screening pulse oximetry reading of <95% while awake. Has presence of human immunodeficiency virus (HIV) or indications of hepatitis A, B or C. Lab values greater than 2 times the upper limit of normal. History of renal disease or bleeding or clotting disorders or conditions. Known or suspected alcoholism, marijuana or illicit drug abuse or misuse within 2 years before screening. Smoked or used nicotine-containing products within 6 months prior to screening. Psychiatric disorders, such as major depression disorder, anxiety disorders, or psychotic disorders within 6 months prior to screening. A history of attention deficit hyperactivity disorder requiring medication is acceptable. Diagnosis of epilepsy or other seizure disorder. Previous cardiothoracic surgery. Conditions which might be specifically contraindicated or require caution while using OC, APAP, and/or ibuprofen. Drug allergy, hypersensitivity, or intolerance including OC, APAP, ibuprofen or excipients, or any opioid drug product. Donated or had significant loss of whole blood (480 mL or more) within 30 days of or plans to donate blood or plasma during the course of the study. Pathologic, iatrogenic or surgical condition that would compromise subject's ability to swallow, absorb, metabolize, or excrete XARTEMIS XR. History of a GI event within 6 months prior to screening. Subject has used any product containing OC or APAP within 48 hours prior to the first dose of XARTEMIS XR. Any other medical condition, abnormal vital sign (blood pressure, pulse rate, respiratory rate), body temperature, pulse oximetry; or any physical examination or ECG finding at screening which would preclude safe participation in a clinical study. Received any investigational product or device within 30 days before screening, or is scheduled to receive an investigational device or another investigational drug during the course of this study.

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 17 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: XARTEMIS XR<br>All participants received XARTEMIS XR | Drug: XARTEMIS XR<br>* XARTEMIS XR [7.5 mg oxycodone hydrochloride and 325 mg acetaminophen (APAP)] Extended-Release Tablets<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Reach Steady State | The time to reach steady state in participants who received all 5 doses | within 60 hours | 
| Area Under the Concentration-time Curve (AUC) From Time Zero (AUC0) to the Time of the Last Quantifiable Plasma Sample (AUClast) | Elimination constant estimates required for the calculation of the planned AUC0-12 hours were not available. AUClast therefore provided the best available measure of exposure, effectively representing AUC0-12 hours for both moieties. While considered the best available measure, it also remains inaccurate because of the extended-release formulation and the lack of data beyond the 12.08-hour time point. | within approximately 12 hours (12.08 hours) | 
| Maximum Observed Plasma Concentration (Cmax) | The highest concentration of study drug within 12 hours. | within approximately 12 hours (12.08 hours) | 
| Apparent Plasma Terminal Drug Elimination Half-life (T1/2) | PK parameters are determined after a single administration of study drug on Day 1. Plasma concentrations that are below the level of quantification (BLQ) are set to 0 before Tmax, with the exception that a BLQ value occurring between measurable concentrations is set to missing. BLQ values that occur after Tmax are set to missing. | within approximately 12 hours (12.08 hours) | 
| Time of Maximum Observed Plasma Concentration (Tmax) | The time at which the maximum plasma concentration (Cmax) is reached. | within approximately 12 hours (12.08 hours) |