An Open-label, Multicenter Study of the Safety of Twice Daily Oxycodone Hydrochloride Controlled-release Tablets in Opioid Experienced Children from Ages 6 to 16 Years Old, Inclusive, with Moderate to Severe Malignant and/or Nonmalignant Pain Requiring Opioid Analgesics
This is a phase 3, multicenter, open-label clinical trial in 135 opioid tolerant pediatric patients at approximately 75 study centers worldwide. eligible patients may be outpatients or inpatients at the time of enrollment. inpatients may continue in the study upon hospital discharge. The study includes a 0-48 hour screening period, treatment period of up to 4 weeks and a follow-up period of 7 to 10 days, including a total of up to 3 clinic visits/evaluations and additional telephone interviews and unscheduled visits if necessary.
Screening procedures will be performed at visit 1. at visit 1, after written informed consent is obtained, patients will undergo a complete evaluation for study eligibility and blood and urine samples will be collected for clinical laboratory tests. Laboratory results must be reviewed to ensure inclusion criteria are met prior to administering the first dose of study drug.
Patients must be opioid tolerant, ie, have been treated with opioids for at least the 5 consecutive days prior to dosing and with at least 20 mg of oxycodone daily and no more than 240 mg daily during at least the last 48 hours before the start of study drug dosing. eligible post-operative patients cannot be dosed with study drug until at least 120 hours after surgery. During treatment, patients will receive 20 to 240 mg total daily dose of oxycodone HCl CR tablets administered in divided doses every 12 hours. upward or downward dose titration should be performed until the most effective and safe dose is established. Dose titrations may occur at any time during the study. upward titration can only occur after 48 hours of study drug treatment at a particular dose. Patients will have four to six PK samples collected throughout the study. PK samples will be collected after the first dose on day 1 (one sample 2-4 hours after the dose and one sample 4-6 hours after the dose with 2 hours between the samples). in addition, at Visit 2 and/or Visit 3, one sample will be collected immediately prior to dosing and one sample will be collected 2-4 hours after that dose. Blood samples for pharmacokinetic analyses should be collected at Visit 2 (Week 2) if, in the judgment of the investigator, the patient is not expected to complete 4 weeks of study drug dosing.if only 1 PK sample is collected at Visit 2, and the patient continues treatment then every attempt should be made to obtain 2 PK samples at the final visit (Visit 3) for a total of 5 samples. if 2 PK samples are collected at Visit 2, then the sampling at Visit 3 is not required. However, if the patient does complete 4 weeks of treatment, then 2 additional PK samples may be collected at Visit 3 if deemed appropriate by the investigator and acceptable to the patient, for a total of 6 samples. if a patient discontinues the study prior to Visit 3, a PK sample should be collected at the time of discontinuation.Supplemental opioid and nonopioid pain medication, with the exception oxycodone products, will be permitted during the study within appropriate dose ranges for patient age and weight. The investigator will evaluate the information provided by the parent/caregiver for consideration of a change in oxycodone HCl CR tablet dose to achieve adequate pain control or for tolerability or safety purposes.
During the study, patients will have a visit or evaluation at week 2 (visit 2) and week 4 (visit 3) or at early discontinuation from the study. Phone calls will be made to the parent/caregiver every 48 hours for outpatients to assess the safety of the patient and efficacy of oxycodone HCl CR. unscheduled visits may occur at any time to assess safety, for drug resupply following a dose titration, or for other reasons. all patients will have a follow-up phone call or visit 7 to 10 days after their last dose of oxycodone HCl CR tablets for a safety follow-up evaluation.
1) Male and female patient aged 6 to 16 years, inclusive, who are expected to require ongoing around-the-clock opioid treatment equivalent to at least 20 mg daily dose of oxycodone for at least 2 weeks for management of moderate to severe (based on the investigator[?]s judgment) malignant or nonmalignant pain;
2) Patients must be opioid tolerant, ie, have been treated with opioids for at least the 5 consecutive days prior to dosing and with at least 20 mg daily of oxycodone or the equivalent during at least the last 48 hours prior to thestart of study drug dosing and have tolerated the therapy, as demonstrated at the start of study drug dosing by:
(a) A normal respiratory rate for age,
(b) Pulse oximetry (SpO2) 92% on room air, and
(c) No significant (grade 3 or 4) opioid-induced somnolence based on the University of Michigan Sedation Scale (UMSS) and the investigator[?]s judgment;
Patients who are currently using transdermal fentanyl should have been on the patch for at least 3 days before removing the patch and oxycodone HCl CR treatment can only be initiated at least 18 hours following the removal of the transdermal fentanyl patch.
3) Patients must not require more than a 240 mg total daily dose of oxycodone HCl CR tablets;
4) Patients must be willing and able to swallow the oxycodone HCl CR tablets whole;
5) Patients must be able to understand and complete the age appropriate scale to rate pain intensity, ie, patients must not have a cognitive developmental delay or any other condition that would preclude them from completing age appropriate pain scale;
6) Patients must have a parent/caregiver who can perform study assessments, including the assessment of UMSS, Functional Disability Inventory (FDI), and Parent/Caregiver-Assessed Global Impression of Change (PGIC) record the assessment scores, each dose of oxycodone HCl CR tablets, and each dose of supplemental pain medication;
7) Female patients of childbearing age must have a negative pregnancy test within 24 hours prior to study drug administration and be nonlactating;
8) Female patients who are sexually active must be using an acceptable method of birth control;
9) Patients and parents/caregivers who are willing and able to be compliant with the protocol, are capable of patient evaluation, are able to read and understand questionnaires, are willing and able to use a diary, and are able to read, understand, and sign the written informed consent and/or assent