Osteoarthritis, Rheumatoid Arthritis, Lower Back Pain, Joint Pain, Muscle Pain
Conditions
Keywords
Norspan, buprenorphine, transdermal, patch, chronic pain, non-malignant, osteoarthritis, rheumatoid arthritis, lower back pain, joint pain, muscle pain, opioid, analgesic, painkiller, Mundipharma
Brief summary
The purpose of this study is to assess the efficacy of the buprenorphine transdermal patch (Norspan® or Sovenor® transdermal patch) in patients with chronic non-malignant pain of moderate to severe intensity due to osteoarthritis, rheumatoid arthritis, lower back pain and joint/muscle pain, who are not adequately responding to non-opioid painkillers.
Detailed description
Baseline assessment (Visit 1) includes medical history, physical examination, vital signs. At Visit 2 \[7 days ( ± 3 days) after Visit 1\] and subsequent optional titration visits up to (Visit 1 + 42 days) , patients will be titrated up to an effective and tolerated dose of Norspan® or Sovenor® transdermal patch and continue rescue analgesic, if necessary. Titration period is dependent on time to achieving optimal pain control as determined by the investigator. The up-titration regime is planned on a weekly basis. Earlier dose titration (i.e. minimum 3 days after the patch application) is permitted at the investigator's discretion if the pain is uncontrolled. Effective and tolerated dose is assessed by data recorded in the case report form and patient diary. According to country label, all patients will begin treatment with Norspan® or Sovenor® transdermal patch 5mg and will then be up-titrated, if necessary, to a maximum of Norspan® or Sovenor® transdermal patch 40mg or according to country label to achieve stable pain control. Patients that require oral opioid at any time during the study should be discontinued from the trial.
Interventions
Please see Arm Description.
Sponsors
Mundipharma Korea Ltd
Mundipharma (Hong Kong) Ltd
Mundipharma Distribution GmBH (Philippine Branch)
Mundipharma Pte Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Males and females aged 18-80 years (both inclusive) at the time of recruitment. 2. Clinical diagnosis of osteoarthritis, rheumatoid arthritis, lower back pain or joint / muscle pain. 3. Having non-malignant pain of moderate or severe intensity requiring an opioid for adequate analgesia (according to local label of Norspan® or Sovenor®). This is to be determined using BS-11 scores, where the cut-off point is ≥4. 4. Patients with chronic uncontrolled pain and is assessed to require opioid treatment but have not been treated with opioids (including tramadol, morphine etc.) within 4 weeks or more before study entry.
Exclusion criteria
1. Pregnant and lactating females. 2. Patients with chronic condition(s), in addition to osteoarthritis, that require(s) frequent analgesic treatment (e.g. frequent headaches, frequent migraine, and gout). 3. Patients who are awaiting a scheduled operation or other surgical procedure during study period or 3 months or less post-operative. 4. Prior history of being on opioids in the preceding 1 month prior to the study for the management of chronic non-malignant pain. 5. Prior history of buprenorphine transdermal system use. 6. Patients with history of allergic reactions against paracetamol/ acetaminophen, NSAIDs and/or opioids. 7. Patients with allergies or other contraindications to transdermal systems or patch adhesives. 8. Patients with dermatological disorders who may have problems applying patch or rotating patch placement area. 9. Patients with cancer (except for basal cell carcinoma) or history of cancer who have been diagnosed within five years prior to the first study visit (except for treated basal cell carcinoma). 10. Patients with conditions such as brain tumour, brain injury or raised intracranial pressure. 11. Patients with history of psychiatric disorder, uncontrollable epilepsy, untreated depression or other psychiatric disorders of a type that would make participation in the study an unacceptable risk to the patient. 12. Patients with any conditions causing poor cognitive function as assessed by the participating physician. 13. Patients with history of alcohol and drug abuse or patients who have demonstrated behaviour that suggests a dependency or drug abuse. 14. Patients currently taking hypnotics or other central nervous system depressants that may pose a risk of additional central nervous system depression with study medication. 15. Patients who are currently being administered monoamine oxidase inhibitors (MAOIs) or have taken MAOIs within 2 weeks before screening. 16. Patients requiring dose titration of adjuvant analgesics i.e. antidepressants (e.g. amitriptyline, amoxapine, clomipramine, selective serotonin re-uptake inhibitors (SSRIs)) and anticonvulsants (e.g. gabapentin, pregabalin). Patients will be allowed to enter the study as long as they are on the stable doses of adjuvant analgesics at screening and do not have dose adjustments during the study. 17. Patients who have received steroid treatment (intra-articular, intramuscular, oral, intravenous, epidural or other corticosteroid injections) within 6 weeks prior to clinical study or planned steroid treatment during the clinical study period. 18. Patients who have to use heating facility (examples: heating lamp, electric blanket, sauna, warm compresses, heated saline baths, etc.). 19. Patients who cannot or do not wish to remove hair growing at body surface where the patch can be placed. 20. Patients who are currently on disability claims or in the process of applying for disability claims. 21. Patients at child-bearing age who are planning to conceive a child during the study period and are not practicing adequate contraception. 22. Patients with known severe hepatic impairment as determined by liver function test within the past one year. 23. Patients who are currently in or have participated in other clinical trials within the last 30 days prior to study recruitment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy According to BS-11 Pain Score Reduction | Maximum 17 weeks starting from enrolment | The primary efficacy outcome analysis is the pre- and post-intervention change in BS-11 pain score. The reduction in scores were calculated by subtracting the post-intervention score from the baseline score. BS-11 is known as Box scale-11; it is an 11-point scale measuring pain intensity. It ranges from 0 to 10, whereby 0 represents no pain and 10 represents the worst imaginable pain. Subjects selected a number based on the pain intensity they were feeling at that time. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Secondary Efficacy Outcome Determined by Change in Percentage of Subjects Who Met Criteria on EQ5D-3L Quality of Life Questionnaire From Pre- to Post-intervention | approximately 17 weeks starting from enrolment | Pre-intervention: Visit 1 Post-intervention: Visit 6 There are 5 dimensions in the EQ5D-3L questionnaire answered by the subjects, classified into 5 categories here: Mobility -- change in % of subjects who have no problem in walking around Self-care -- change in % of subjects who have no problem in self-care Usual activities -- change in % of subjects who have no problem with performing their usual activities Pain/ discomfort -- change in % of subjects who do not experience pain or discomfort Anxiety/ depression -- change in % of subjects who do not feel anxious or depressed |
| Treatment-emergent Adverse Events (TEAE's) as Measured by Number of Subjects With at Least 1 TEAE | From time of enrolment up to 7 days after completion / discontinuation visit (up to 140 days) | Side effects of the transdermal patch treatment will be analysed. |
| Secondary Efficacy Outcome as Measured by Number of Subjects Requiring at Least 1 Breakthrough (Rescue) Pain Medication | Approximately 17 weeks starting from enrolment | Daily use of breakthrough pain medication from visits 1-6, assessed from patient diaries. |
| Secondary Efficacy Outcome on Physicians' and Patients' Treatment Satisfaction Assessed Using Physician's Global Impression of Change Scale and Patient's Global Impression of Change Scale Respectively | At visit 6 (anywhere between Day 91 to 119 after enrolment depending on how long titration took) | The overall assessment of the change in pain intensity from baseline is measured at Visit 6. Physician's Global Impression of Change scale: Investigator's opinion on a scale of 1 to 7 where 1 is very much improved and 7 is very much worse Patient's Global Impression of Change scale: Subject's opinion on a scale of 1 to 7 where 1 is very much improved and 7 is very much worse |
| Secondary Efficacy Outcome -- Incidence of Early Treatment Discontinuation Due to Lack of Efficacy. | From time of enrolment to Visit 6 (ie. up to119 days from enrolment) | — |
Countries
Hong Kong, Philippines, South Korea
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Buprenorphine Transdermal Patch Subjects will be on either 5mg, 10mg, 15mg, 20mg, 25mg, 30mg or 40mg doses for 17 weeks. Dose titration will occur every week for the first 6 weeks, and will be maintained for the next 11 weeks.
Buprenorphine transdermal patch: Please see Arm Description. | 114 |
| Total | 114 |
Baseline characteristics
| Characteristic | Buprenorphine Transdermal Patch |
|---|---|
| Age, Continuous | 57 years STANDARD_DEVIATION 13.4 |
| Region of Enrollment Hong Kong | 26 participants |
| Region of Enrollment Korea, Republic of | 62 participants |
| Region of Enrollment Philippines | 26 participants |
| Sex: Female, Male Female | 86 Participants |
| Sex: Female, Male Male | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 89 / 114 |
| serious Total, serious adverse events | 1 / 114 |
Outcome results
Primary
Efficacy According to BS-11 Pain Score Reduction
The primary efficacy outcome analysis is the pre- and post-intervention change in BS-11 pain score. The reduction in scores were calculated by subtracting the post-intervention score from the baseline score. BS-11 is known as Box scale-11; it is an 11-point scale measuring pain intensity. It ranges from 0 to 10, whereby 0 represents no pain and 10 represents the worst imaginable pain. Subjects selected a number based on the pain intensity they were feeling at that time.
Time frame: Maximum 17 weeks starting from enrolment
Population: Subjects of the analysis population met the eligibility criteria. It consists of subjects who completed the study and who withdrew for any reason.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Buprenorphine Transdermal Patch | Efficacy According to BS-11 Pain Score Reduction | 2.7 units on a scale | Standard Deviation 2.4 |
Secondary
Secondary Efficacy Outcome as Measured by Number of Subjects Requiring at Least 1 Breakthrough (Rescue) Pain Medication
Daily use of breakthrough pain medication from visits 1-6, assessed from patient diaries.
Time frame: Approximately 17 weeks starting from enrolment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Buprenorphine Transdermal Patch | Secondary Efficacy Outcome as Measured by Number of Subjects Requiring at Least 1 Breakthrough (Rescue) Pain Medication | 26 participants |
Secondary
Secondary Efficacy Outcome Determined by Change in Percentage of Subjects Who Met Criteria on EQ5D-3L Quality of Life Questionnaire From Pre- to Post-intervention
Pre-intervention: Visit 1 Post-intervention: Visit 6 There are 5 dimensions in the EQ5D-3L questionnaire answered by the subjects, classified into 5 categories here: Mobility -- change in % of subjects who have no problem in walking around Self-care -- change in % of subjects who have no problem in self-care Usual activities -- change in % of subjects who have no problem with performing their usual activities Pain/ discomfort -- change in % of subjects who do not experience pain or discomfort Anxiety/ depression -- change in % of subjects who do not feel anxious or depressed
Time frame: approximately 17 weeks starting from enrolment
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Buprenorphine Transdermal Patch | Secondary Efficacy Outcome Determined by Change in Percentage of Subjects Who Met Criteria on EQ5D-3L Quality of Life Questionnaire From Pre- to Post-intervention | Mobility | 25.8 percentage of subjects |
| Buprenorphine Transdermal Patch | Secondary Efficacy Outcome Determined by Change in Percentage of Subjects Who Met Criteria on EQ5D-3L Quality of Life Questionnaire From Pre- to Post-intervention | Self-care | 20.2 percentage of subjects |
| Buprenorphine Transdermal Patch | Secondary Efficacy Outcome Determined by Change in Percentage of Subjects Who Met Criteria on EQ5D-3L Quality of Life Questionnaire From Pre- to Post-intervention | Usual Activities | 19.4 percentage of subjects |
| Buprenorphine Transdermal Patch | Secondary Efficacy Outcome Determined by Change in Percentage of Subjects Who Met Criteria on EQ5D-3L Quality of Life Questionnaire From Pre- to Post-intervention | Pain/Discomfort | 14.3 percentage of subjects |
| Buprenorphine Transdermal Patch | Secondary Efficacy Outcome Determined by Change in Percentage of Subjects Who Met Criteria on EQ5D-3L Quality of Life Questionnaire From Pre- to Post-intervention | Anxiety/ Depression | 18 percentage of subjects |
Secondary
Secondary Efficacy Outcome -- Incidence of Early Treatment Discontinuation Due to Lack of Efficacy.
Time frame: From time of enrolment to Visit 6 (ie. up to119 days from enrolment)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Buprenorphine Transdermal Patch | Secondary Efficacy Outcome -- Incidence of Early Treatment Discontinuation Due to Lack of Efficacy. | 3 participants |
Secondary
Secondary Efficacy Outcome on Physicians' and Patients' Treatment Satisfaction Assessed Using Physician's Global Impression of Change Scale and Patient's Global Impression of Change Scale Respectively
The overall assessment of the change in pain intensity from baseline is measured at Visit 6. Physician's Global Impression of Change scale: Investigator's opinion on a scale of 1 to 7 where 1 is very much improved and 7 is very much worse Patient's Global Impression of Change scale: Subject's opinion on a scale of 1 to 7 where 1 is very much improved and 7 is very much worse
Time frame: At visit 6 (anywhere between Day 91 to 119 after enrolment depending on how long titration took)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Buprenorphine Transdermal Patch | Secondary Efficacy Outcome on Physicians' and Patients' Treatment Satisfaction Assessed Using Physician's Global Impression of Change Scale and Patient's Global Impression of Change Scale Respectively | Physician Impression | 2.62 units on a scale | Standard Deviation 0.84 |
| Buprenorphine Transdermal Patch | Secondary Efficacy Outcome on Physicians' and Patients' Treatment Satisfaction Assessed Using Physician's Global Impression of Change Scale and Patient's Global Impression of Change Scale Respectively | Patient Impression | 2.66 units on a scale | Standard Deviation 0.81 |
Secondary
Treatment-emergent Adverse Events (TEAE's) as Measured by Number of Subjects With at Least 1 TEAE
Side effects of the transdermal patch treatment will be analysed.
Time frame: From time of enrolment up to 7 days after completion / discontinuation visit (up to 140 days)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Buprenorphine Transdermal Patch | Treatment-emergent Adverse Events (TEAE's) as Measured by Number of Subjects With at Least 1 TEAE | 89 participants |