Pharmacokinetics and Safety of ORF Tablets in Pediatric Patients

An Open-label Study to Characterize the Pharmacokinetics and Safety of Oxycodone Hydrochloride q12h Controlled-Release (ORF) Tablets in Pediatric Patients Aged 6 to 16 Years Inclusive, Who Require Opioid Analgesia

The purpose of this study is to characterize the pharmacokinetics (PK) of single-dose ORF tablets in pediatric patients aged 6 to 16 years, inclusive.

Inclusion Criteria:

• Written informed consent provided by the parent or legal guardian and patient assent, when appropriate.
• Children of either gender, aged 6 to 16 years, inclusive.
• Have or are expected to have moderate to severe pain for an extended period of time requiring inpatient opioid analgesic treatment for at least 12 hours as this is the minimum duration of study period treatment.
• In order to receive the first oral dose, patients must have respiratory stability, including a sustained SpO2 of at least 92% with or without supplemental oxygen during the 15 minute period just prior to dosing.
• Must be inpatient for the treatment period of the study.
• The patient's anticipated opioid analgesic requirement over the first 12 hours that will follow administration of ORF must be equivalent to at least 10 mg of intravenous (IV) morphine.
• Have adequate pain control during the 6 hours prior to study drug administration, based on appropriate clinical assessment.
• Must be sufficiently alert to communicate and complete the faces pain scales-revised (FPS-R) or 100-mm visual analogue scale (VAS).
• Females who are of child bearing potential must be using an adequate and reliable method of contraception (e.g., barrier with additional spermicidal foam or jelly, intra-uterine device, hormonal contraception) or be abstinent.
• If female, must have a negative pregnancy test and be non-lactating.
• Must be able to swallow tablets whole.
• Must have stable vital signs.
• Must have vascular access to facilitate blood draws.
• Must be willing and able to participate in all aspects of this study involving use of oral medications, patient evaluation, and phlebotomy, as evidenced by written informed consent from the parent or legal guardian and written patient assent when required by the local IRB/EC.
• Must be willing to have up to 10 milliliters (mL) of blood collected for blood analysis (7 mL for primary PK and 3 mL for secondary PK analysis); and up to 10 mL of blood for pre-specified safety laboratory tests, without safety concerns.
• Must be treated with an opioid for a minimum of 96 hours prior to first dose of ORF.

Exclusion Criteria:

• Any history of hypersensitivity or medical contraindication for the use of oxycodone (this does not exclude patients with a history of expected opioid-related adverse events (AEs), such as light-headedness, dizziness, sedation, nausea, or vomiting).
• Any current history of medical or surgical conditions that might significantly interfere with the gastrointestinal absorption, distribution, metabolism, or excretion of oxycodone (this includes any history of serious disease+ of the gastrointestinal tract, liver, kidneys, and/or blood-forming organs).
• Received oxycodone in the 24 hours prior to study drug administration. .
• Received epidural (or regional) anesthesia < 12 hours prior to the first oral dose of ORF.
• A current history of malabsorption syndrome.
• A current diagnosis of sleep apnea within the last year.
• Reduced renal function (serum creatinine > 1.8 X the upper limit of normal for age).
• Hepatic impairment as evidenced by serum alanine amino transferase (ALT) or serum aspartate amino transferase (AST) > 5 times the upper limit of normal (ULN) for age.
• Currently taking any medications which are CYP3A4 inhibitors.
• Impaired respiratory reserve including severe acute or chronic lung disease, or patients receiving mechanical respiratory support, including mechanical ventilation, BIPAP, or CPAP 6 hours prior to the first oral dose and during the entire oral treatment period.
• Impaired cardiovascular stability (e.g., the day of surgery for cardiac surgery patients).
• Participated in a clinical drug study within 30 days preceding the initial dose in this study.
• Patients who have had surgery within 96 hours prior to the day of the first dose of study drug.
• Deemed to be unsuitable by the investigator for reason(s) not specifically stated in the exclusion criteria.