Cancer
Conditions
Keywords
Cancer Pain
Brief summary
The efficacy of dose titration of OxyNorm™(Oxycodone) immediate-release capsules versus morphine immediate-release tablets in the treatment of cancer pain.
Detailed description
To compare the efficacy of dose titration of OxyNorm™(Oxycodone) immediate-release capsules versus morphine immediate-release tablets in the treatment of cancer pain.
Interventions
DRUGOxycodone
dosage: 5mg, l0mg and 20mg dosage form: capsule frequency: every 6h, duration: 5-8 days
DRUGMorphine
Morphine tablets 10mg and 20mg, oral every 4-6 hours
Sponsors
Mundipharma (China) Pharmaceutical Co. Ltd
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Patients of either sex aged 18 to 80 years inclusive, who with cancers of all type. 2. Patients with moderate to severe cancer pain, whose pain intensity Numeric Rating Scale ≥4. 3. Patients who can understand and are able to complete Numeric Rating Scale and Brief Pain Inventory assessment. 4. Patients who have given written informed consent to participate in the study.
Exclusion criteria
1. Patients who are pregnant, or lactating. 2. Patients who are unable to manage their pain effectively with opioids. 3. Patient who need ≥120mg morphine or equivalent for treatment of pain at time of study entry; 4. Patients who are receiving chemotherapy, or still under the responsive period of chemotherapy (patients who are at the interval period of chemotherapy can be enrolled into study. That is to say, patients who completed chemotherapy for more than 2 weeks can enrolled, or patients has completed chemotherapy for at least one week could be enrolled at the discretion of the investigator). 5. Patients who have received radio-therapy for bony metastasis, patients receiving radiotherapy within the 4 week period before study entry (patient receiving radiotherapy for area other than pain area can be enrolled) , or patients who were scheduled to receive radiotherapy for pain area during study period. 6. Patients are receiving or should receive anti-convulsion drugs/anti- depression drugs considered by investigator for the treatment of neuropathy pain. Patients are receiving or should receive any analgesic other than study medicine, which including NSAIDs. 7. Patients with other unstable disease, or with dysfunction of important organ. 8. Patients with an ongoing infection, abscess or fever. 9. Patient with serious abnormal liver/ renal function (ALT/Aspartate Transaminase/creatinine/urea nitrogen) which is higher than 3 times of upper limit; 10. Paralytic or mechanical ileus; 11. Persistent asthma, chronic obstructive diseases, and cor pulmonary; 12. Intracranial neoplasms, and intracranial hypertension with central respiratory depression risk. 13. Monoamine oxidase inhibitors (MAOIs) or same type drugs have been administered in last 2 weeks; 14. Patients who are currently taking active treatment for epilepsy or arrhythmias. 15. Patients with known sensitivity or record of specific or allergic reaction to oxycodone or morphine. 16. Patients excluded by the contra-indications, adverse drug reaction (ADRs) and drug interactions of oxycodone or morphine as detailed in the data sheet, summary of product characteristics or investigator's brochure. 17. Patients with a history of drug or alcohol abuse. 18. Patients who participated in another clinical research study involving a new chemical entity within one month prior to study entry. 19. Patients whose concomitant medication is likely to be changed within the study period, with the exception of treatment for opioid side effects. 20. Patients who, in the opinion of the investigator, are unsuitable to participate in the study for any other reason not mentioned in the inclusion and
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Numerical Rating Scale (NRS) | baseline up to 5-8 days (double blind period) | The numerical rating scale is the tool to assess pain level using a numerical rating scale. The primary outcome measurement is the average change of NRS score after double blind treatment between the two treatment groups. The NRS evaluates the pain level using number scale from 0 to 10. 0 means not painful and 10 means extremely painful. 1 to 3 is lightly pain, 4-6 is moderate pain and 7 to 10 is severe pain. There is no subscales used for NRS reporting. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Brief Pain Inventory (BPI) Change From Baseline to After Double Blind Period | baseline up to 5-8 days (double blind period) | The secondary outcome measurement is the change between BPI score at baseline and after completion of double blind treatment between the two treatment groups. The Brief Pain Inventory (BPI) rapidly assesses the severity of pain and its impact on functioning. This tool measures the worst/least pain in the passed 24 hours, and the average/current pain in last 24 hours. The scale is numerically from 0 to 10. 0 means not painful, 10 means extremely painful. The BPI is the average number of above 4 BPI Pain Items. |
| Times of Breakthrough Pain Occurrence | Within 8 days after baseline | the times of breakthrough pain occurrence during double blind treatment phase between the two treatment groups |
| Patient Assessments of Satisfaction for Pain Management | baseline up to 19-22 days (open label treatment) | the number of patients of satisfaction for pain management between the two treatment groups at the end of double blind treatment and the open label treatment period. |
| The Average Dose of Study Medicine Used During Double Blind Treatment Period | baseline up to 5-8 days (double blind period) | the average dose of study medicine used during double blind treatment period between the two treatment groups. |
| Brief Pain Inventory (BPI) Change From Baseline to Open Label Treatment | baseline up to 19-22 days (open label treatment) | The secondary outcome measurement is the change of BPI score from baseline to the end of open label treatment between the two treatment groups. The Brief Pain Inventory (BPI) rapidly assesses the severity of pain and its impact on functioning. This tool measures the worst/least pain in passed 24 hours, and the average/current pain in last 24 hours. The scale is numerically from 0 to 10. 0 means not painful, 10 means extremely painful. The BPI is the average number of above 4 BPI Pain Items. |
| the Total Dose of Rescue Medicine for Breakthrough Pain. | baseline up to 22 days (double blind period) | the total dose of rescue medicine for breakthrough pain during double blind phase between the two treatment groups |
| Degree of Pain Relief Within 24hrs After Treatment | baseline up to 5-8 days (double blind period) | Brief Pain Inventory (BPI) Change From Baseline to After Double Blind Period. The BPI is the average number of above 4 BPI Pain Items. For the degree of pain relief within 24hrs after treatment, 0 means zero relief and 100 means completely relief with unit of percentage(%). |
| Average Number of Titrations | baseline up to 1-3 days(double blind period) | the average times to change the dose in order to find the proper dose between two treatment groups |
Participant flow
Recruitment details
A total of 242 subjects were enrolled from 20 centers in which 192 subjects completed the study and 50 subjects did not completed the study. All the subjects were recruited from medical clinic.The recruitment period is from 2011 Jan to 2012 Mar.
Pre-assignment details
Patients with moderate to severe cancer pain requiring oral opioid therapy were screened. All the patients who meets the inclusion/exclusion criteria were enrolled to double blind treatment phase. No wash our or run-in period required by protocol.
Participants by arm
| Arm | Count |
|---|---|
| Oxycodone Capsules for Cancer Pain Oxycodone: dosage: 5mg, l0mg and 20mg dosage form: capsule frequency: every 6h, duration: 5-8 days | 120 |
| Morphine Tablets for Cancer Pain Morphine: Morphine tablets 10mg and 20mg, oral every 4-6 hours | 118 |
| Total | 238 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 12 | 10 |
| Overall Study | Lack of Efficacy | 2 | 4 |
| Overall Study | Lost to Follow-up | 1 | 3 |
| Overall Study | Other | 5 | 4 |
| Overall Study | Protocol Violation | 4 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 2 |
Baseline characteristics
| Characteristic | Oxycodone Capsules for Cancer Pain | Morphine Tablets for Cancer Pain | Total |
|---|---|---|---|
| Age, Continuous | 56.62 years STANDARD_DEVIATION 12.96 | 57.05 years STANDARD_DEVIATION 12.07 | 56.83 years STANDARD_DEVIATION 12.5 |
| height | 164.5 centimeter STANDARD_DEVIATION 7.45 | 164.99 centimeter STANDARD_DEVIATION 8.2 | 164.74 centimeter STANDARD_DEVIATION 7.82 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 119 Participants | 117 Participants | 236 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment China | 120 Participants | 118 Participants | 238 Participants |
| Sex: Female, Male Female | 58 Participants | 59 Participants | 117 Participants |
| Sex: Female, Male Male | 62 Participants | 59 Participants | 121 Participants |
| weight | 58.64 kg STANDARD_DEVIATION 10.79 | 58.34 kg STANDARD_DEVIATION 11.01 | 58.49 kg STANDARD_DEVIATION 10.88 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 120 | 2 / 118 |
| other Total, other adverse events | 76 / 120 | 75 / 118 |
| serious Total, serious adverse events | 4 / 120 | 2 / 118 |
Outcome results
Primary
Numerical Rating Scale (NRS)
The numerical rating scale is the tool to assess pain level using a numerical rating scale. The primary outcome measurement is the average change of NRS score after double blind treatment between the two treatment groups. The NRS evaluates the pain level using number scale from 0 to 10. 0 means not painful and 10 means extremely painful. 1 to 3 is lightly pain, 4-6 is moderate pain and 7 to 10 is severe pain. There is no subscales used for NRS reporting.
Time frame: baseline up to 5-8 days (double blind period)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oxycodone Capsules for Cancer Pain | Numerical Rating Scale (NRS) | 3.91 scores on a scale | Standard Deviation 2.31 |
| Morphine Tablets for Cancer Pain | Numerical Rating Scale (NRS) | 3.87 scores on a scale | Standard Deviation 2.22 |
Secondary
Average Number of Titrations
the average times to change the dose in order to find the proper dose between two treatment groups
Time frame: baseline up to 1-3 days(double blind period)
Population: Dosing change frequency for complete titration
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oxycodone Capsules for Cancer Pain | Average Number of Titrations | 8.25 dose changes | Standard Deviation 4.52 |
| Morphine Tablets for Cancer Pain | Average Number of Titrations | 7.89 dose changes | Standard Deviation 3.43 |
Secondary
Brief Pain Inventory (BPI) Change From Baseline to After Double Blind Period
The secondary outcome measurement is the change between BPI score at baseline and after completion of double blind treatment between the two treatment groups. The Brief Pain Inventory (BPI) rapidly assesses the severity of pain and its impact on functioning. This tool measures the worst/least pain in the passed 24 hours, and the average/current pain in last 24 hours. The scale is numerically from 0 to 10. 0 means not painful, 10 means extremely painful. The BPI is the average number of above 4 BPI Pain Items.
Time frame: baseline up to 5-8 days (double blind period)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oxycodone Capsules for Cancer Pain | Brief Pain Inventory (BPI) Change From Baseline to After Double Blind Period | Highest pain intensity in 24 hrs | 4.25 scores on a scale | Standard Deviation 1.98 |
| Oxycodone Capsules for Cancer Pain | Brief Pain Inventory (BPI) Change From Baseline to After Double Blind Period | Lowest pain intensity in 24 hrs | 2.62 scores on a scale | Standard Deviation 2.08 |
| Oxycodone Capsules for Cancer Pain | Brief Pain Inventory (BPI) Change From Baseline to After Double Blind Period | Average pain intensity in 24 hrs | 3.39 scores on a scale | Standard Deviation 1.8 |
| Oxycodone Capsules for Cancer Pain | Brief Pain Inventory (BPI) Change From Baseline to After Double Blind Period | Current Pain intensity | 3.78 scores on a scale | Standard Deviation 1.94 |
| Morphine Tablets for Cancer Pain | Brief Pain Inventory (BPI) Change From Baseline to After Double Blind Period | Current Pain intensity | 3.70 scores on a scale | Standard Deviation 1.88 |
| Morphine Tablets for Cancer Pain | Brief Pain Inventory (BPI) Change From Baseline to After Double Blind Period | Highest pain intensity in 24 hrs | 4.03 scores on a scale | Standard Deviation 2.2 |
| Morphine Tablets for Cancer Pain | Brief Pain Inventory (BPI) Change From Baseline to After Double Blind Period | Average pain intensity in 24 hrs | 3.35 scores on a scale | Standard Deviation 1.73 |
| Morphine Tablets for Cancer Pain | Brief Pain Inventory (BPI) Change From Baseline to After Double Blind Period | Lowest pain intensity in 24 hrs | 2.53 scores on a scale | Standard Deviation 1.98 |
Secondary
Brief Pain Inventory (BPI) Change From Baseline to Open Label Treatment
For the degree of pain relief within 24hrs after treatment, 0 means zero relief and 100 means completely relief with unit of percentage(%).
Time frame: baseline up to 19-22 days (open label treatment)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oxycodone Capsules for Cancer Pain | Brief Pain Inventory (BPI) Change From Baseline to Open Label Treatment | 32.31 percentage of pain relief | Standard Deviation 30.8 |
| Morphine Tablets for Cancer Pain | Brief Pain Inventory (BPI) Change From Baseline to Open Label Treatment | 31.64 percentage of pain relief | Standard Deviation 29.73 |
Secondary
Brief Pain Inventory (BPI) Change From Baseline to Open Label Treatment
The secondary outcome measurement is the change of BPI score from baseline to the end of open label treatment between the two treatment groups. The Brief Pain Inventory (BPI) rapidly assesses the severity of pain and its impact on functioning. This tool measures the worst/least pain in passed 24 hours, and the average/current pain in last 24 hours. The scale is numerically from 0 to 10. 0 means not painful, 10 means extremely painful. The BPI is the average number of above 4 BPI Pain Items.
Time frame: baseline up to 19-22 days (open label treatment)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oxycodone Capsules for Cancer Pain | Brief Pain Inventory (BPI) Change From Baseline to Open Label Treatment | Highest pain intensity in 24 hrs | 3.98 scores on a scale | Standard Deviation 2.09 |
| Oxycodone Capsules for Cancer Pain | Brief Pain Inventory (BPI) Change From Baseline to Open Label Treatment | Lowest pain intensity in 24 hrs | 2.57 scores on a scale | Standard Deviation 2.05 |
| Oxycodone Capsules for Cancer Pain | Brief Pain Inventory (BPI) Change From Baseline to Open Label Treatment | Average pain intensity in 24 hrs | 3.33 scores on a scale | Standard Deviation 1.83 |
| Oxycodone Capsules for Cancer Pain | Brief Pain Inventory (BPI) Change From Baseline to Open Label Treatment | Current Pain intensity | 3.62 scores on a scale | Standard Deviation 1.87 |
| Morphine Tablets for Cancer Pain | Brief Pain Inventory (BPI) Change From Baseline to Open Label Treatment | Current Pain intensity | 3.71 scores on a scale | Standard Deviation 1.57 |
| Morphine Tablets for Cancer Pain | Brief Pain Inventory (BPI) Change From Baseline to Open Label Treatment | Highest pain intensity in 24 hrs | 3.95 scores on a scale | Standard Deviation 1.92 |
| Morphine Tablets for Cancer Pain | Brief Pain Inventory (BPI) Change From Baseline to Open Label Treatment | Average pain intensity in 24 hrs | 3.48 scores on a scale | Standard Deviation 1.57 |
| Morphine Tablets for Cancer Pain | Brief Pain Inventory (BPI) Change From Baseline to Open Label Treatment | Lowest pain intensity in 24 hrs | 2.64 scores on a scale | Standard Deviation 1.98 |
Secondary
Degree of Pain Relief Within 24hrs After Treatment
Brief Pain Inventory (BPI) Change From Baseline to After Double Blind Period. The BPI is the average number of above 4 BPI Pain Items. For the degree of pain relief within 24hrs after treatment, 0 means zero relief and 100 means completely relief with unit of percentage(%).
Time frame: baseline up to 5-8 days (double blind period)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oxycodone Capsules for Cancer Pain | Degree of Pain Relief Within 24hrs After Treatment | 35.23 percentage of pain relief | Standard Deviation 28.27 |
| Morphine Tablets for Cancer Pain | Degree of Pain Relief Within 24hrs After Treatment | 34.19 percentage of pain relief | Standard Deviation 30.85 |
Secondary
Patient Assessments of Satisfaction for Pain Management
the number of patients of satisfaction for pain management between the two treatment groups at the end of double blind treatment and the open label treatment period.
Time frame: baseline up to 19-22 days (open label treatment)
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Oxycodone Capsules for Cancer Pain | Patient Assessments of Satisfaction for Pain Management | Satisfied | 64 Participants |
| Oxycodone Capsules for Cancer Pain | Patient Assessments of Satisfaction for Pain Management | Dissatisfied | 1 Participants |
| Oxycodone Capsules for Cancer Pain | Patient Assessments of Satisfaction for Pain Management | Neutral | 9 Participants |
| Oxycodone Capsules for Cancer Pain | Patient Assessments of Satisfaction for Pain Management | Missing | 11 Participants |
| Oxycodone Capsules for Cancer Pain | Patient Assessments of Satisfaction for Pain Management | Very satisfied | 35 Participants |
| Morphine Tablets for Cancer Pain | Patient Assessments of Satisfaction for Pain Management | Missing | 11 Participants |
| Morphine Tablets for Cancer Pain | Patient Assessments of Satisfaction for Pain Management | Very satisfied | 37 Participants |
| Morphine Tablets for Cancer Pain | Patient Assessments of Satisfaction for Pain Management | Satisfied | 61 Participants |
| Morphine Tablets for Cancer Pain | Patient Assessments of Satisfaction for Pain Management | Neutral | 5 Participants |
| Morphine Tablets for Cancer Pain | Patient Assessments of Satisfaction for Pain Management | Dissatisfied | 4 Participants |
Secondary
The Average Dose of Study Medicine Used During Double Blind Treatment Period
the average dose of study medicine used during double blind treatment period between the two treatment groups.
Time frame: baseline up to 5-8 days (double blind period)
Population: The average total dosage during double-blind treatment was defined as a primary efficacy endpoint in the protocol, but this study was a non-inferiority study, and non-inferiority analysis could not be performed in average total dosage in data processing and statistics.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oxycodone Capsules for Cancer Pain | The Average Dose of Study Medicine Used During Double Blind Treatment Period | Average total dosage during double-blind titration | 83.29 mg | Standard Deviation 82.87 |
| Oxycodone Capsules for Cancer Pain | The Average Dose of Study Medicine Used During Double Blind Treatment Period | Ave. total dosage during double-blind maintenance | 167.41 mg | Standard Deviation 103.92 |
| Morphine Tablets for Cancer Pain | The Average Dose of Study Medicine Used During Double Blind Treatment Period | Average total dosage during double-blind titration | 141.61 mg | Standard Deviation 112.1 |
| Morphine Tablets for Cancer Pain | The Average Dose of Study Medicine Used During Double Blind Treatment Period | Ave. total dosage during double-blind maintenance | 308.63 mg | Standard Deviation 189.93 |
Secondary
the Total Dose of Rescue Medicine for Breakthrough Pain.
the total dose of rescue medicine for breakthrough pain during double blind phase between the two treatment groups
Time frame: baseline up to 22 days (double blind period)
Population: The double-blind titration period was the dose adjusting phase, so breakthrough pain occurrences in this period were not included in statistical analysis. After titration was completed, subjects entered into maintenance treatment with the titrated dose.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oxycodone Capsules for Cancer Pain | the Total Dose of Rescue Medicine for Breakthrough Pain. | the total dose of rescue medicine-day4 | 20.00 mg | Standard Deviation 8.94 |
| Oxycodone Capsules for Cancer Pain | the Total Dose of Rescue Medicine for Breakthrough Pain. | the total dose of rescue medicine-day5 | 11.00 mg | Standard Deviation 10.84 |
| Oxycodone Capsules for Cancer Pain | the Total Dose of Rescue Medicine for Breakthrough Pain. | the total dose of rescue medicine -day6 | 0 mg | Standard Deviation 0 |
| Oxycodone Capsules for Cancer Pain | the Total Dose of Rescue Medicine for Breakthrough Pain. | the total dose of rescue medicine after day6 | 5.00 mg | Standard Deviation 0 |
| Oxycodone Capsules for Cancer Pain | the Total Dose of Rescue Medicine for Breakthrough Pain. | the total dose of rescue medicine -day1 | 10.63 mg | Standard Deviation 7.76 |
| Oxycodone Capsules for Cancer Pain | the Total Dose of Rescue Medicine for Breakthrough Pain. | the total dose of rescue medicine -day2 | 10.00 mg | Standard Deviation 8.29 |
| Oxycodone Capsules for Cancer Pain | the Total Dose of Rescue Medicine for Breakthrough Pain. | the total dose of rescue medicine-day3 | 10.63 mg | Standard Deviation 8.21 |
| Morphine Tablets for Cancer Pain | the Total Dose of Rescue Medicine for Breakthrough Pain. | the total dose of rescue medicine-day4 | 7.86 mg | Standard Deviation 3.93 |
| Morphine Tablets for Cancer Pain | the Total Dose of Rescue Medicine for Breakthrough Pain. | the total dose of rescue medicine -day1 | 7.00 mg | Standard Deviation 4.83 |
| Morphine Tablets for Cancer Pain | the Total Dose of Rescue Medicine for Breakthrough Pain. | the total dose of rescue medicine-day5 | 6.67 mg | Standard Deviation 4.08 |
| Morphine Tablets for Cancer Pain | the Total Dose of Rescue Medicine for Breakthrough Pain. | the total dose of rescue medicine-day3 | 6.82 mg | Standard Deviation 2.52 |
| Morphine Tablets for Cancer Pain | the Total Dose of Rescue Medicine for Breakthrough Pain. | the total dose of rescue medicine -day6 | 5.00 mg | Standard Deviation 0 |
| Morphine Tablets for Cancer Pain | the Total Dose of Rescue Medicine for Breakthrough Pain. | the total dose of rescue medicine -day2 | 6.00 mg | Standard Deviation 2.07 |
| Morphine Tablets for Cancer Pain | the Total Dose of Rescue Medicine for Breakthrough Pain. | the total dose of rescue medicine after day6 | 5.00 mg | Standard Deviation 0 |
Secondary
Times of Breakthrough Pain Occurrence
the times of breakthrough pain occurrence during double blind treatment phase between the two treatment groups
Time frame: Within 8 days after baseline
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Oxycodone Capsules for Cancer Pain | Times of Breakthrough Pain Occurrence | 15 breakthrough pain events |
| Morphine Tablets for Cancer Pain | Times of Breakthrough Pain Occurrence | 20 breakthrough pain events |