Chronic Pain
Conditions
Keywords
moderate to severe non-malignant chronic pain
Brief summary
Objectives: 1. Objective of main interest \- To assess the drop-out rate caused by adverse event\* after 6 weeks treatment 2. Further objectives * To assess the drop-out rate caused by adverse event\* after 1 week treatment * To assess the pain reduction rate after 6 weeks treatment from baseline * To assess the Euroquol (EQ-5D) quality of life * To assess physician's overall satisfaction * To assess subject's overall satisfaction * To assess safety
Detailed description
Study Design (Methodology): This will be a single center, open-label, randomised, phase IV, exploratory interventional study to compare the efficacy and tolerability of current titration patterns and slow titration pattern with Targin® (Oxycodone/Naloxone) in the treatment of moderate to severe non-malignant chronic pain patients who are dissatisfied with their current analgesic medication World Health Organisation (WHO) step II analgesics). Upon providing written informed consent, subject will be screened in the study and assessment will be performed at that time such as safety laboratory assessments, physical examination, vital sign, medical history taking, 24 hours pain intensity score. If the patient is eligible in inclusion/exclusion criteria at the time of visit 1, the patient will be randomized in a 1:1 ratio to allocate in Group A or Group B. Re-screening, study drug dose interruption is not allowed.
Interventions
Oxycodone/naloxone titration
Sponsors
Mundipharma Korea Ltd
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Male or female ≥ 20 and \<80 years of age * Patients who have non-malignant chronic pain(≥90 days) * Patients who have moderate to severe pain intensity which is not controlled with non-strong opioid * Naïve patients for Oxycodone/Naloxone (Naïve patient defined as who did not treated for 90 days) * Naïve patients for strong opioid (Naïve patient defined as who did not treated for 90 days) * Patients who signed a written informed consent form
Exclusion criteria
* Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant. * 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 * Patients with known hypersensitivity to Oxycodone/Naloxone or to any of the excipients * Patient who needs acute dose titration or whose pain intensity fluctuate significantly in a short period according to investigator's judgment * Having used other investigational drugs at the time of enrollment, or within 30 days of enrollment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Drop-out Rate Caused by Adverse Event After 6 Weeks Treatment | 6 weeks | To assess the drop-out rate caused by adverse event\* after 6 weeks treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Drop-out Rate Due to an Adverse Event After 1 Week Treatment With the Study Drug. | 1 week | The drop-out rate due to an adverse event after treatment (1 week) by treatment arm were summarized and presented as frequency and percentage, and the inter-group difference were compared by using a Chi-square test or Fisher's exact test. |
| The Change of Pain Intensity Scores(NRS) From Baseline After 6 Weeks Treatment With the Study. | 6 weeks | Change in numeric rating scales (NRS) such as score for average pain levels over the previous 24 hours, from baseline to 6weeks. NRS score was measured from 0 (No pain) to 10(worst pain imaginable). |
| Change of Quality of Life (EQ-5D) Score After 6 Weeks Treatment With the Study Drug | 6 weeks | EQ-5D to measure of health related quality of life should be answered as one of 3 levels about current condition for 5 dimensions and was calculated total average by giving a weighting on 3 level of answers (EQ-5D levels into 'no problems' (level 1) and 'problems' (level 2 and 3)). Table of scores by each level for EQ-5D items: mobility(level 1=0, level2=0.069,level 3=0.314), self care(level 1=0, level2=0.104,level 3=0.214), usual activities(level 1=0, level2=0.036,level 3=0.094), pain/discomfort (level 1=0, level2=0.,level 3=0.386) and anxiety/depression(level 1=0, level2=0.071,level 3=0.2) \*EQ-5D Total = 1 - 0.081 - (the score of the each level) - 0.269 (if at least one of level 3 presents) EQ-5D total score could be 0.919 in maximum and -0.594 in minimum if case all index indicates the level 3. So, if EQ-5D total score closed by 1 means that the healthy condition and high quality of life. |
| Assessment of Investigator's Overall Satisfaction After 6 Weeks Treatment With the Study Drug | 6 weeks | Investigator's overall satisfaction after treatment (6 weeks) (Clinical Global Impression of Change Scale(CGIC) 7 point scale) by treatment arm were summarized and presented as frequency and proportion, and the inter-group difference were compared by using a Chi-square test or Fisher's exact test. |
| Assessment of Subject's Overall Satisfaction After 6 Weeks Treatment With the Study Drug | 6weeks | At each visit, the subject assessed the overall satisfaction for efficacy by using the 7 point scale of Patient Global Impression of Change Scale(PGIC). |
Countries
South Korea
Participant flow
Recruitment details
Safety set: 261 patients were enrolled. ITT set was 258, 3 patients of the 261 patients deviated from inclusion/exclusion criteria.
Participants by arm
| Arm | Count |
|---|---|
| Start Oxycodone/Naloxone 10/5mg b.i.d Start oxycodone/naloxone 10/5mg b.i.d. titration-\>20/10mg b.i.d.-\>30/15mg b.i.d-\>40/20mg b.i.d. | 132 |
| Start Oxycodone/Naloxone 5/2.5mg b.i.d Start oxycodone/naloxone 5/2.5mg b.i.d titration-\> 10/5mg b.i.d.-\>20/10mg b.i.d.-\>30/15mg b.i.d-\>40/20mg b.i.d. | 126 |
| Total | 258 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 54 | 38 |
| Overall Study | Lack of Efficacy | 3 | 6 |
| Overall Study | Lost to Follow-up | 4 | 2 |
| Overall Study | Protocol Violation | 5 | 6 |
| Overall Study | Withdrawal by Subject | 5 | 10 |
Baseline characteristics
| Characteristic | Start Oxycodone/Naloxone 5/2.5mg b.i.d | Start Oxycodone/Naloxone 10/5mg b.i.d | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 62 Participants | 55 Participants | 117 Participants |
| Age, Categorical Between 18 and 65 years | 64 Participants | 77 Participants | 141 Participants |
| Age, Continuous | 61.15 years STANDARD_DEVIATION 11.94 | 60.63 years STANDARD_DEVIATION 9.69 | 60.88 years STANDARD_DEVIATION 10.83 |
| Region of Enrollment Korea, Republic of | 126 participants | 132 participants | 258 participants |
| Sex: Female, Male Female | 84 Participants | 81 Participants | 165 Participants |
| Sex: Female, Male Male | 42 Participants | 51 Participants | 93 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 115 / 133 | 104 / 128 |
| serious Total, serious adverse events | 0 / 133 | 2 / 128 |
Outcome results
Primary
Drop-out Rate Caused by Adverse Event After 6 Weeks Treatment
To assess the drop-out rate caused by adverse event\* after 6 weeks treatment
Time frame: 6 weeks
Population: Intent to treat analysis set: 258 patients (Last Observation Carried Forward)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Start Oxycodone/Naloxone 10/5mg b.i.d. | Drop-out Rate Caused by Adverse Event After 6 Weeks Treatment | 40.91 percentage of participants |
| Start Oxycodone/Naloxone 5/2.5mg b.i.d. | Drop-out Rate Caused by Adverse Event After 6 Weeks Treatment | 30.16 percentage of participants |
Secondary
Assessment of Investigator's Overall Satisfaction After 6 Weeks Treatment With the Study Drug
Investigator's overall satisfaction after treatment (6 weeks) (Clinical Global Impression of Change Scale(CGIC) 7 point scale) by treatment arm were summarized and presented as frequency and proportion, and the inter-group difference were compared by using a Chi-square test or Fisher's exact test.
Time frame: 6 weeks
Population: ITT analysis set: 171. Last visit(Visit 5) data was handled as LOCF. However, Missing Number as visit 3 for assessment of Investigator's overall satisfaction after 6 weeks treatment with the study drug was Group A = 50, Group B=37.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Start Oxycodone/Naloxone 10/5mg b.i.d. | Assessment of Investigator's Overall Satisfaction After 6 Weeks Treatment With the Study Drug | Minimally improved | 48 participants |
| Start Oxycodone/Naloxone 10/5mg b.i.d. | Assessment of Investigator's Overall Satisfaction After 6 Weeks Treatment With the Study Drug | Minimally worse | 0 participants |
| Start Oxycodone/Naloxone 10/5mg b.i.d. | Assessment of Investigator's Overall Satisfaction After 6 Weeks Treatment With the Study Drug | Much improved | 27 participants |
| Start Oxycodone/Naloxone 10/5mg b.i.d. | Assessment of Investigator's Overall Satisfaction After 6 Weeks Treatment With the Study Drug | Much worse | 0 participants |
| Start Oxycodone/Naloxone 10/5mg b.i.d. | Assessment of Investigator's Overall Satisfaction After 6 Weeks Treatment With the Study Drug | No change | 5 participants |
| Start Oxycodone/Naloxone 10/5mg b.i.d. | Assessment of Investigator's Overall Satisfaction After 6 Weeks Treatment With the Study Drug | very much worse | 0 participants |
| Start Oxycodone/Naloxone 10/5mg b.i.d. | Assessment of Investigator's Overall Satisfaction After 6 Weeks Treatment With the Study Drug | Very much improved | 2 participants |
| Start Oxycodone/Naloxone 5/2.5mg b.i.d. | Assessment of Investigator's Overall Satisfaction After 6 Weeks Treatment With the Study Drug | very much worse | 0 participants |
| Start Oxycodone/Naloxone 5/2.5mg b.i.d. | Assessment of Investigator's Overall Satisfaction After 6 Weeks Treatment With the Study Drug | Very much improved | 2 participants |
| Start Oxycodone/Naloxone 5/2.5mg b.i.d. | Assessment of Investigator's Overall Satisfaction After 6 Weeks Treatment With the Study Drug | Much improved | 30 participants |
| Start Oxycodone/Naloxone 5/2.5mg b.i.d. | Assessment of Investigator's Overall Satisfaction After 6 Weeks Treatment With the Study Drug | Minimally improved | 43 participants |
| Start Oxycodone/Naloxone 5/2.5mg b.i.d. | Assessment of Investigator's Overall Satisfaction After 6 Weeks Treatment With the Study Drug | No change | 14 participants |
| Start Oxycodone/Naloxone 5/2.5mg b.i.d. | Assessment of Investigator's Overall Satisfaction After 6 Weeks Treatment With the Study Drug | Minimally worse | 0 participants |
| Start Oxycodone/Naloxone 5/2.5mg b.i.d. | Assessment of Investigator's Overall Satisfaction After 6 Weeks Treatment With the Study Drug | Much worse | 0 participants |
Secondary
Assessment of Subject's Overall Satisfaction After 6 Weeks Treatment With the Study Drug
At each visit, the subject assessed the overall satisfaction for efficacy by using the 7 point scale of Patient Global Impression of Change Scale(PGIC).
Time frame: 6weeks
Population: ITT analysis set: 171. Last visit(Visit 5) data was handled as LOCF. However, Missing Number as visit 3 for assessment of Investigator's overall satisfaction after 6 weeks treatment with the study drug was Group A = 50, Group B=37.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Start Oxycodone/Naloxone 10/5mg b.i.d. | Assessment of Subject's Overall Satisfaction After 6 Weeks Treatment With the Study Drug | Minimally improved | 44 participants |
| Start Oxycodone/Naloxone 10/5mg b.i.d. | Assessment of Subject's Overall Satisfaction After 6 Weeks Treatment With the Study Drug | Minimally worse | 0 participants |
| Start Oxycodone/Naloxone 10/5mg b.i.d. | Assessment of Subject's Overall Satisfaction After 6 Weeks Treatment With the Study Drug | Much improved | 24 participants |
| Start Oxycodone/Naloxone 10/5mg b.i.d. | Assessment of Subject's Overall Satisfaction After 6 Weeks Treatment With the Study Drug | Much worse | 1 participants |
| Start Oxycodone/Naloxone 10/5mg b.i.d. | Assessment of Subject's Overall Satisfaction After 6 Weeks Treatment With the Study Drug | No change | 11 participants |
| Start Oxycodone/Naloxone 10/5mg b.i.d. | Assessment of Subject's Overall Satisfaction After 6 Weeks Treatment With the Study Drug | Very much worse | 0 participants |
| Start Oxycodone/Naloxone 10/5mg b.i.d. | Assessment of Subject's Overall Satisfaction After 6 Weeks Treatment With the Study Drug | Very much improved | 2 participants |
| Start Oxycodone/Naloxone 5/2.5mg b.i.d. | Assessment of Subject's Overall Satisfaction After 6 Weeks Treatment With the Study Drug | Very much worse | 0 participants |
| Start Oxycodone/Naloxone 5/2.5mg b.i.d. | Assessment of Subject's Overall Satisfaction After 6 Weeks Treatment With the Study Drug | Very much improved | 2 participants |
| Start Oxycodone/Naloxone 5/2.5mg b.i.d. | Assessment of Subject's Overall Satisfaction After 6 Weeks Treatment With the Study Drug | Much improved | 28 participants |
| Start Oxycodone/Naloxone 5/2.5mg b.i.d. | Assessment of Subject's Overall Satisfaction After 6 Weeks Treatment With the Study Drug | Minimally improved | 42 participants |
| Start Oxycodone/Naloxone 5/2.5mg b.i.d. | Assessment of Subject's Overall Satisfaction After 6 Weeks Treatment With the Study Drug | No change | 16 participants |
| Start Oxycodone/Naloxone 5/2.5mg b.i.d. | Assessment of Subject's Overall Satisfaction After 6 Weeks Treatment With the Study Drug | Minimally worse | 1 participants |
| Start Oxycodone/Naloxone 5/2.5mg b.i.d. | Assessment of Subject's Overall Satisfaction After 6 Weeks Treatment With the Study Drug | Much worse | 0 participants |
Secondary
Change of Quality of Life (EQ-5D) Score After 6 Weeks Treatment With the Study Drug
EQ-5D to measure of health related quality of life should be answered as one of 3 levels about current condition for 5 dimensions and was calculated total average by giving a weighting on 3 level of answers (EQ-5D levels into 'no problems' (level 1) and 'problems' (level 2 and 3)). Table of scores by each level for EQ-5D items: mobility(level 1=0, level2=0.069,level 3=0.314), self care(level 1=0, level2=0.104,level 3=0.214), usual activities(level 1=0, level2=0.036,level 3=0.094), pain/discomfort (level 1=0, level2=0.,level 3=0.386) and anxiety/depression(level 1=0, level2=0.071,level 3=0.2) \*EQ-5D Total = 1 - 0.081 - (the score of the each level) - 0.269 (if at least one of level 3 presents) EQ-5D total score could be 0.919 in maximum and -0.594 in minimum if case all index indicates the level 3. So, if EQ-5D total score closed by 1 means that the healthy condition and high quality of life.
Time frame: 6 weeks
Population: ITT analysis set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Start Oxycodone/Naloxone 10/5mg b.i.d. | Change of Quality of Life (EQ-5D) Score After 6 Weeks Treatment With the Study Drug | 0.14 units on a scale | Standard Deviation 0.26 |
| Start Oxycodone/Naloxone 5/2.5mg b.i.d. | Change of Quality of Life (EQ-5D) Score After 6 Weeks Treatment With the Study Drug | 0.07 units on a scale | Standard Deviation 0.22 |
Secondary
The Change of Pain Intensity Scores(NRS) From Baseline After 6 Weeks Treatment With the Study.
Change in numeric rating scales (NRS) such as score for average pain levels over the previous 24 hours, from baseline to 6weeks. NRS score was measured from 0 (No pain) to 10(worst pain imaginable).
Time frame: 6 weeks
Population: ITT analysis set: 258
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Start Oxycodone/Naloxone 10/5mg b.i.d. | The Change of Pain Intensity Scores(NRS) From Baseline After 6 Weeks Treatment With the Study. | -1.62 units on a scale | Standard Deviation 1.9 |
| Start Oxycodone/Naloxone 5/2.5mg b.i.d. | The Change of Pain Intensity Scores(NRS) From Baseline After 6 Weeks Treatment With the Study. | -1.48 units on a scale | Standard Deviation 1.82 |
Secondary
The Drop-out Rate Due to an Adverse Event After 1 Week Treatment With the Study Drug.
The drop-out rate due to an adverse event after treatment (1 week) by treatment arm were summarized and presented as frequency and percentage, and the inter-group difference were compared by using a Chi-square test or Fisher's exact test.
Time frame: 1 week
Population: Intent to treat analysis set: 258(Last observation Carried Forward)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Start Oxycodone/Naloxone 10/5mg b.i.d. | The Drop-out Rate Due to an Adverse Event After 1 Week Treatment With the Study Drug. | 28.79 percentage of participants |
| Start Oxycodone/Naloxone 5/2.5mg b.i.d. | The Drop-out Rate Due to an Adverse Event After 1 Week Treatment With the Study Drug. | 19.84 percentage of participants |