Business decision

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.

Inclusion criteria:

1. Male or nonpregnant, nonlactating females between 12 and 17 years of age.
2. Minimum weight of 100 pounds (45 kg); body mass index (BMI) >5% and <95% for their age.
3. 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.
4. If, of child-bearing/reproductive potential, must abstain from unprotected sexual activity during study and 2 weeks after study exit.
5. Females of childbearing potential must have negative pregnancy test.
6. Subject's legally authorized representative (eg, parent, legal guardian) must sign a parental permission/informed consent and subject must sign an assent.
7. 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:

1. Subject is from a vulnerable population (including mentally disabled children), other than a pediatric population.
2. Subject requires surgery that could influence the study outcome.
3. Abnormal electrocardiogram (ECG).
4. Screening pulse oximetry reading of <95% while awake.
5. Has presence of human immunodeficiency virus (HIV) or indications of hepatitis A, B or C.
6. Lab values greater than 2 times the upper limit of normal.
7. History of renal disease or bleeding or clotting disorders or conditions.
8. Known or suspected alcoholism, marijuana or illicit drug abuse or misuse within 2 years before screening.
9. Smoked or used nicotine-containing products within 6 months prior to screening.
10. 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.
11. Diagnosis of epilepsy or other seizure disorder.
12. Previous cardiothoracic surgery.
13. Conditions which might be specifically contraindicated or require caution while using OC, APAP, and/or ibuprofen.
14. Drug allergy, hypersensitivity, or intolerance including OC, APAP, ibuprofen or excipients, or any opioid drug product.
15. 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.
16. Pathologic, iatrogenic or surgical condition that would compromise subject's ability to swallow, absorb, metabolize, or excrete XARTEMIS XR.
17. History of a GI event within 6 months prior to screening.
18. Subject has used any product containing OC or APAP within 48 hours prior to the first dose of XARTEMIS XR.
19. 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.
20. 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.

The Safety population included all participants who enrolled in the study and received any quantity of XARTEMIS XR.

Up to 17 months.

A treatment-emergent adverse event (TEAE) is defined as an evat that emerges during treatment having been absent pre-treatment or worsens relative to the pre-treatment state. Any TEAE determined as possibly related or related to the study drug is considered a treatment-related TEAE. All serious adverse events are reported, as well as all treatment-related TEAEs.