A Study to Compare the Titration Efficacy and Safety of Control-released Oxycodone and Immediate-released Oxycodone in Patients With Moderate to Severe Cancer Pain

Study Overview
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Brief Summary
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This study is to evaluate the efficacy and safety of a titration method by selects 10 mg control-released (CR) oxycodone tablet as background drug in combined with immediate-released (IR) oxycodone, compared to conventional titration method with immediate-released (IR) oxycodone in patients with moderate to severe cancer pain in Taiwan.

Detailed Description
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This is an interventional, open label, randomized controlled study carrying in multi-centers. Eighty opioid-naive patients with moderate to severe cancer pain (≥ 4) in outpatient department (OPD), who agreed and signed informed consent will be randomly assigned in a 1:1 ratio to receive CR + IR oxycodone or conventional IR oxycodone groups. The study is to compare the titration efficacy and safety of CR with IR oxycodone (experimental group) comparing IR oxycodone (control group) in cancer patients suffered with moderate to severe pain. The study last 14 days. Patients begin the study by the first day visit of the clinic and received the study medication (Baseline). Following visits on cycle 1 (day 3 or 4 depends on the available clinics), cycle 2 (day 7±1), cycle 3 (day 10±1), and cycle 4 (day 14±1). In the experimental group, 10 mg CR oxycodone tablet will be selected as background dose of titration, and patients will be administered once every 12 hrs. Meanwhile, the titration with IR oxycodone will be added according to the pain intensity, e.g. if patient receiving 6 tablets of 10 mg CR oxycodone (giving in Q12H frequency for 3 days), 12 capsules of 5mg IR oxycodone will be dispensed for managing acute pain (rescue use) for the first cycle. In the control group, the conventional titration with IR oxycodone will be conducted according to pain intensity, using 5 mg as initial dose, e.g. 12 capsules of 5mg IR oxycodone (giving in Q6H frequency for 3 days), 12 capsules of 5mg IR oxycodone will be dispensed for rescue use upon to the first cycle. Patient will record their pain score (4 times in Q6H frequency and before taking the drug), 24hr total dose (total tablets/capsule number), number of breakthrough pain and PRN time and dosage used onto the patient diary. The background dose of each patient will be titrated after cycle 1 by investigators. Titration cycles will be recorded and evaluated pain assessments on cycle 2 (day 7±1), cycle 3 (Day 10±1), cycle 4 (day 14±1). During study, the study nurse will follow patient's daily records, drug use condition every second day by telephone or other contact methods to keep close monitor of patient's condition. The telephone contact for cycle 1 and cycle 3 is acceptable for this study. If the telephone contact is conducted for patient, the 1-week quantities of oxycodone should be dispensed to patient. The safety for individual patient will be followed during study up to end of treatment (EOT) or early termination (ET). All adverse events (AE(s)) and serious adverse events (SAE(s)) occurred during the study period will be followed until resolution or the event is considered stable.

Official Title
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An Interventional, Open Label, and Randomized Controlled Study to Compare the Titration Efficacy and Safety of Control-released Oxycodone and Immediate-released Oxycodone in Opioid-naive Patients With Moderate to Severe Cancer Pain

Conditions
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Cancer, Pain

Intervention / Treatment
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* Drug: Oxycodone
* Drug: Oxycodone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Cancer patients aged 20 years old and over Patients with background cancer pain more than or equal to NRS 4 during previous 24 hours, or receive more than or equal to 3 times/day for breakthrough pain medication management ECOG ≤ 2 Opioid-naive patients who are not administrated any strong opioid for at least one month prior to the index treatments, who currently with poor pain control and intended to be treated for pain relief with strong opioids. The FDA identifies opioid-naive as who not receiving the following treatment for a week or longer of strong opioids: 1) ≥ 60 mg of morphine daily 2) ≥25 mcg transdermalfentanyl/hour 3) ≥ 8 mg of oral hydromorphone daily or 4) an equianalgesic dose of another opioid 5) Patients who will not be treated with radiotherapy within 7 days prior to randomization and during study 6) Patients who need chemotherapy, long term administration of hormone, targeted therapy, or bisphosphonates therapy should undergo a stable anti-tumor therapy prior to randomization. 7) Patients or his/her caregivers who are able to fill out the diary and questionnaire forms Exclusion Criteria: Patients diagnosed with non-cancer pain or unexplained pain Patients suffered with post-op pain Patients who cannot be applicable for oral administration Patients who have severe constipation defined by CTCAE grade 3 and above Patients with any disease that may easily lead to respiratory depression Monoamine oxidase inhibitor (MAOI) was administrated one week before randomization There are abnormal lab results, with obvious clinical significance, such as the creatinine ≥ 2 fold of upper limit of normal value, or ALT or AST ≥ 2.5 fold of upper limit of normal value (≥ 5 fold, to the patients with liver metastasis or primary liver cancer), or liver function of Child C grade Patients who have potential risk for surgical operation, which may lead to gastrointestinal stenosis, blind loop or gastrointestinal obstruction; or patient is unable to effectively absorb oral medication through gastrointestinal tract Patients who are drug or alcohol abuse Patients with moderate to severe psychiatric problems Patients who have hypersensitivity to oxycodone Patients who are pregnant or lactating Patients who are clinically unstable or have a life expectancy of less than three months making completion of the trial unlikely

Ages Eligible for Study
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Minimum Age: 20 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Control-released oxycodone<br>Control-released oxycodone Q12H, initial daily dose is 20 mg + immediate-released oxycodone for PRN | Drug: Oxycodone<br>* Every 12 hours for control-released oxycodone (OxyContin®)<br>|
| Active Comparator: Immediate-released oxycodone<br>Immediate-released oxycodone Q6H, initial daily dose is 20mg + immediate-released oxycodone for PRN | Drug: Oxycodone<br>* Every 6 hours for immediate-released oxycodone (OxyNorm®)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the variable change of NRS pain score and the number of breakthrough pain to obtain pain control after treatment | The change from baseline of NRS pain score and the daily number of breakthrough pain | Up to 14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the percentage of patients in each titration cycle | The percentage of patients in each titration cycle | Up to 14 days | 
| To evaluate the number of patients who switched/discontinued therapy due to serious adverse events or lack of pain control | The number of patients who switched/discontinued therapy due to serious adverse events or lack of pain control | Up to 14 days | 
| The total opioid taken within 24hrs daily from baseline to day 14 | The total opioid taken within 24 hrs daily from baseline to day 14 | Up to 14 days | 
| To evaluate the mean daily NRS score of subjects from baseline to day 14 | Mean daily NRS score of patients from baseline to day 14 | Up to 14 days | 
| To evaluate the total daily rescue dose taken (immediate-released oxycodone capsule) for treatment of breakthrough pain among patients from baseline to day 14 | The total daily rescue dose taken (immediate-released oxycodone capsule) for treatment of breakthrough pain among patients from baseline to day 14 | Up to 14 days | 
| To evaluate the tolerability and safety of Oxycodone CR and IR in cancer pain patient | The occurrence rate of adverse events and physical examination status | Up to 28 days | 
| To evaluate the change from baseline in questionnaire | The change from baseline in questionnaire | Up to 14 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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control-released oxycodone, immediate-released oxycodone, cancer pain, opioid-naive