Cancer
Conditions
Keywords
cancer related pain
Brief summary
Objectives: To prove non-inferiority of Targin compared to Oxycontin in terms of change of pain intensity 1. Primary objective: Change of pain intensity (NRS 0-10) score (average pain over 24 hours obtained each evening) within 4 weeks 2. Secondary objectives: Bowel Habit (worsening/no change/improving), Total dose and frequency of rescue medication, Quality of Life (QOL; EORTC QLQ-C30), Duration to need of laxative use and Adverse events
Detailed description
This will be a 4-week multicentre, randomized, open label, parallel group, active control study to evaluate efficacy and safety of Targin in comparison with Oxycontin in Korean patients with cancer pain who are administered weak opioid or naïve patients including patient not on the long term strong opioid medication within 3 months.
Interventions
Dose and administration : Upto 40mg B.I.D per daily.
DRUGOxycodone(single compound)
Dose and administration : Upto 40mg B.I.D per daily.
Sponsors
Mundipharma Korea Ltd
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female cancer patients 20 years of age or older 2. Cancer related pain that requires treatment with continuous around-the-clock strong opioid analgesic 3. Moderate to severe pain intensity(NRS pain score 4) 4. Opioid naïve patients or patients not treated with strong opioids(except PRN) within 4 weeks or patients who has been on weak opioids 5. Subject who provide signed and dated written voluntary informed consent
Exclusion criteria
1. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant. UNLESS they are: * women whose career, lifestyle, or sexual orientation precludes intercourse with a male partner * women shoes partners have been sterilized by vasectomy or other means * two birth control methods. The two methods can be a double barrier method or a barrier method plus a hormonal method. Adequate barrier methods of contraception include: diaphragm, condom (by the partner), intrauterine device (copper or hormonal), sponge or spermicide. Hormonal contraceptives include any marketed contraceptive agent that includes an estrogen and/or a progestational agent. 2. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive urine pregnancy test. 3. Have previously received treatment with Targin or Oxycontin within 4weeks(28days) of screening periods(including PRN) 4. If subjects started first cycle of chemotherapy during the 2 weeks before the screening visit or during the study, they should be excluded from the study. And If the chemotherapy regimen or dosage to be planned to change during the study, the subjects should be excluded from the study. 5. Patient who is administered laxatives with stable dose for more than 1 week 6. Patient with evidence of significant structural/functional abnormalities of GI tract which is not appropriate for oral medicine administration. Any history of hypersensitivity to Oxycodone and Naloxone 7. Patients with significant respiratory depression 8. Patients with acute or severe bronchial asthma or hypercarbia 9. Any patient who has or is suspected of having paralytic ileus 10. Severe Chronic obstructive pulmonary disease, pulmonary heart disease 11. Targin product contains lactose. Patients with rare hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption should not take 12. Patients with moderate and severe hepatic impairment 13. Abnormal aspartate aminotransferase (AST; SGOT), alanine aminotransferase (ALT; SGPT), or alkaline phosphatase levels (\>2.5 times the upper limit of normal, it is allowed \>5 times the upper limit of normal in case of transition in liver) or an abnormal total bilirubin and/or creatinine level(s) (greater than 1.5 times the upper limit of normal) 14. Any situation where opioids are contraindicated 15. Major surgery within 1 month prior to screening or planned surgery 16. Mainly pain originated other than cancer or cancer related conditions (eg. Musculoskeletal pain, inflammatory pain, diabetic polyneuropathy) 17. Patients with known or suspected unstable brain metastases or spinal cord compression that may require changes in steroid treatment throughout the duration of the study 18. Patients with uncontrolled seizures 19. Requiring interventional treatment for pain such as neurodestructive procedure or regional infusion 20. With a history of alcohol abuse within 6 months of screening 21. With a history of illicit drug abuse within 6 months of screening 22. Patients with increased intracranial pressure 23. In the investigator's opinion, subjects who are receiving hypnotics or other central nervous system (CNS) depressants that may pose a risk of additional CNS depression with opioid study medication 24. Patients with myxoedema, not adequately treated hypothyroidism or Addison's disease 25. Patients receiving opioid substitution therapy for opioid addiction (e.g. methadone or buprenorphine) 26. Patients with evidence of clinically significant gastrointestinal disease (e.g. paralytic ileus, peritoneal carcinosis), significant structural abnormalities of the gastrointestinal tract (e.g. scarring, obstruction etc) either related or not related to the underlying cancer or disease progression 27. Patients suffering from diarrhea and/or opioid withdrawal 28. With a disability that may prevent the patient from completing all study requirements and in particular, interfere with 24hrs pain intensity score 29. Clinically significant impairment of cardiovascular, respiratory and renal function 30. Patient who needs acute dose titration or whose pain intensity fluctuate significantly in a short period according to investigator's judgment 31. Having used other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives of enrollment, whichever is longer
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change of Pain Intensity From Baseline(visit1) to 4weeks.(visit3) | 4weeks | Change of pain intensity from 0(No pain) to 10(worst pain imaginable) after 4 weeks treatment . |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Bowel Habits. | 4 weeks | The change of bowel habits from baseline (Visit 1) in bowel habits at Week 4 was investigated, and was categorized as 'improved', 'unchanged', and 'worsened'. |
Countries
South Korea
Participant flow
Recruitment details
ITT set(Safety analysis) was 128(64:64) patients, but Missing primary efficacy data: 7 patients, Violation of inclusion/exclusion criteria: 4. So, FAS(Efficacy analysis) set population was 117(oxycodone/naloxone group: 58: Oxycodone: 59).
Participants by arm
| Arm | Count |
|---|---|
| Oxycodone and Naloxone Trade name is TARGIN. Daily dose can be titrated up to 40mg B.I.D. | 58 |
| Oxycodone Trade name is Oxycontin. Daily dose can be titrated up to 40mg B.I.D. | 59 |
| Total | 117 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 6 | 11 |
| Overall Study | Lack of Efficacy | 4 | 2 |
| Overall Study | missing data | 3 | 3 |
| Overall Study | Protocol Violation | 10 | 4 |
| Overall Study | Withdrawal by Subject | 2 | 8 |
Baseline characteristics
| Characteristic | Oxycodone and Naloxone | Oxycodone | Total |
|---|---|---|---|
| Age, Customized <39years | 1 participants | 3 participants | 4 participants |
| Age, Customized 40~49years | 7 participants | 5 participants | 12 participants |
| Age, Customized 50~59years | 19 participants | 17 participants | 36 participants |
| Age, Customized 60~69 years | 14 participants | 23 participants | 37 participants |
| Age, Customized 70~79 years | 17 participants | 11 participants | 28 participants |
| Region of Enrollment Korea, Republic of | 58 participants | 59 participants | 117 participants |
| Sex: Female, Male Female | 15 Participants | 20 Participants | 35 Participants |
| Sex: Female, Male Male | 43 Participants | 39 Participants | 82 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 55 / 64 | 57 / 64 |
| serious Total, serious adverse events | 15 / 64 | 28 / 64 |
Outcome results
Primary
Change of Pain Intensity From Baseline(visit1) to 4weeks.(visit3)
Change of pain intensity from 0(No pain) to 10(worst pain imaginable) after 4 weeks treatment .
Time frame: 4weeks
Population: Analysis of FAS: 117.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oxycodone and Naloxone | Change of Pain Intensity From Baseline(visit1) to 4weeks.(visit3) | 1.586 units on a scale | Standard Deviation 2.217 |
| Oxycodone | Change of Pain Intensity From Baseline(visit1) to 4weeks.(visit3) | 1.559 units on a scale | Standard Deviation 2.215 |
Secondary
Change in Bowel Habits.
The change of bowel habits from baseline (Visit 1) in bowel habits at Week 4 was investigated, and was categorized as 'improved', 'unchanged', and 'worsened'.
Time frame: 4 weeks
Population: FAS analysis, but Oxycodone/naloxone group was missed 15 patients data and Oxycodone group was missed 23 patients data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Oxycodone and Naloxone | Change in Bowel Habits. | Unchanged | 31 participants |
| Oxycodone and Naloxone | Change in Bowel Habits. | worsened | 7 participants |
| Oxycodone and Naloxone | Change in Bowel Habits. | Improved | 5 participants |
| Oxycodone | Change in Bowel Habits. | Improved | 5 participants |
| Oxycodone | Change in Bowel Habits. | Unchanged | 20 participants |
| Oxycodone | Change in Bowel Habits. | worsened | 11 participants |