Clinical trial NCT01961271: Evaluation Of Efficacy And Safety Of Norspan In Moderate To Severe Pain Due To Osteoarthritis, Rheumatoid Arthritis, Joint/Muscle Pain
Official title: Multicentre Study To Evaluate Efficacy And Safety Of Buprenorphine Transdermal Patch (Norspan) In Chronic Non-Malignant Pain Of Moderate To Severe Intensity Due To Osteoarthritis, Rheumatoid Arthritis, Lower Back Pain And Joint / Muscle Pain, When Opioid Is Needed For Analgesia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Osteoarthritis
Rheumatoid Arthritis
Lower Back Pain
Joint Pain
Muscle Pain
Keywords: Norspan
buprenorphine
transdermal
patch
chronic pain
non-malignant
osteoarthritis
rheumatoid arthritis
lower back pain
joint pain
muscle pain
opioid
analgesic
painkiller
Mundipharma
Lead sponsor: Mundipharma Pte Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Mundipharma Korea Ltd
name: Mundipharma (Hong Kong) Ltd
name: Mundipharma Distribution GmBH (Philippine Branch)
First posted: 2013-10-11
Enrollment: 114
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Efficacy According to BS-11 Pain Score Reduction
timeFrame: Maximum 17 weeks starting from enrolment
Secondary outcomes:
measure: 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
timeFrame: approximately 17 weeks starting from enrolment
measure: Treatment-emergent Adverse Events (TEAE's) as Measured by Number of Subjects With at Least 1 TEAE
timeFrame: From time of enrolment up to 7 days after completion / discontinuation visit (up to 140 days)
measure: Secondary Efficacy Outcome as Measured by Number of Subjects Requiring at Least 1 Breakthrough (Rescue) Pain Medication
timeFrame: Approximately 17 weeks starting from enrolment
measure: 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
timeFrame: At visit 6 (anywhere between Day 91 to 119 after enrolment depending on how long titration took)
measure: Secondary Efficacy Outcome -- Incidence of Early Treatment Discontinuation Due to Lack of Efficacy.
timeFrame: From time of enrolment to Visit 6 (ie. up to119 days from enrolment)
Other outcomes:
Locations:
city: Yuen Long
country: Hong Kong
facility: Pok Oi Hospital
state: New Territories
city: Gascoigne Road
country: Hong Kong
facility: Queen Elizabeth Hospital
city: Pokfulam Road
country: Hong Kong
facility: Queen Mary Hospital (Dept of Anaesthesiology)
city: Pokfulam Road
country: Hong Kong
facility: Queen Mary Hospital (Dept of Rheumatology)
city: Shatin
country: Hong Kong
facility: Prince of Wales Hospital
city: Tuen Mun
country: Hong Kong
facility: Tuen Mun Hospital
city: Gangnam-Gu
country: Korea, Republic of
facility: Samsung Medical Center
state: Seoul
city: Jongno-gu
country: Korea, Republic of
facility: Seoul National University Hospital (Dept of Neurology)
state: Seoul
city: Jongno-gu
country: Korea, Republic of
facility: Seoul National University Hospital (Dept of Orthopedics)
state: Seoul
city: Seocho-gu
country: Korea, Republic of
facility: Seoul St. Mary's Hospital
state: Seoul
city: Seodaemun-gu
country: Korea, Republic of
facility: Severance Hospital
state: Seoul
city: Songpa-Gu
country: Korea, Republic of
facility: Asan Medical Center
state: Seoul
city: Makati City
country: Philippines
facility: Makati Medical Center
city: Manila
country: Philippines
facility: Philippine General Hospital
city: Manila
country: Philippines
facility: University of Santo Tomas Hospital
city: Quezon City
country: Philippines
facility: St. Luke's Medical Center
Study officials:
References:
citation: Yoon DH, Bin SI, Chan SK, Chung CK, In Y, Kim H, Lichauco JJ, Mok CC, Moon YW, Ng TK, Penserga EG, Shin DA, You D, Moon H. Effectiveness and tolerability of transdermal buprenorphine patches: a multicenter, prospective, open-label study in Asian patients with moderate to severe chronic musculoskeletal pain. BMC Musculoskelet Disord. 2017 Aug 4;18(1):337. doi: 10.1186/s12891-017-1664-4.