A Double-blind, Double-dummy, Parallel Group, Randomised Study to Compare the Efficacy & Tolerability of Oxycodone/Naloxone Prolonged Release (OXN PR) & Codeine/Paracetamol in the Treatment of Moderate to Severe Chronic Low Back Pain or Pain Due to Osteoarthritis
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 247
- 主要终点
- Average Daily Pain Score Box Scale-11 (BS-11) Recorded at Week 12 (Average Pain Over Last 24 Hours)
研究概览
简要总结
The purpose of this study is to compare oxycodone/naloxone combination tablet and codeine/paracetamol tablets in the treatment of moderate to severe chronic low back pain or pain due to osteoarthritis.
详细描述
This is a randomised, double-blind, double-dummy, parallel group, 12-week study to assess the efficacy and tolerability of oxycodone/naloxone compared to codeine/paracetamol tablets in the treatment of moderate to severe chronic low back pain or moderate to severe pain due to OA of the hip and /or knee.
The screening period will be 3 - 7 days duration. If a subject meets all the screening criteria they may enter the Run-in Period.
During the screening period subjects will continue to take their pre-study pain medication.
The run-in period will be 7 - 14 days duration. During the run-in period subjects will continue to take their pre-study pain medication.
Visit 3 will occur at the end of the Run-in Period (7-14 days after Visit 2). To qualify for entry into the treatment period of the study, subjects must have uncontrolled pain as shown by average daily pain scores of >5 on 4 of the last 7 days of the run in period.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female subjects at least 18 years or older.
- •Female subjects less than one year post-menopausal must have a negative urine pregnancy test recorded prior to the first dose of study medication, be non-lactating, and willing to use adequate and reliable contraception throughout the study. A highly effective method of birth control is defined as those which result in a low failure rate (i.e. less than 1% per year) when used consistently and correctly such as sterilization, implants, injectables, combined oral contraceptives, some IUDs, sexual abstinence or vasectomised partner.
- •Subjects with a clinical diagnosis of degenerative or primary OA whose primary pain site is of the hip(s) and/or knee(s) and that require around-the-clock opioid therapy in which the diagnosis may be supported by evidence such as one of the following: MRI, CAT, arthroscopy or x-ray. The clinical imaging of OA may include one or more of the following features: joint space narrowing, degenerative changes, osteophyte formation or subchondral cysts. Subjects will identify the most painful joint (hip or knee) for documentation of OA. Pain measurement will be done at this joint only.
- •Subjects with moderate to severe chronic low back pain e.g osteoarthritis, spinal stenosis, spondylolisthesis, failed back surgery, scoliosis, discogenic disorders such as herniated disc.
- •Subjects who are currently receiving codeine/paracetamol combination tablets up to a maximum dose of 120 mg codeine per day or tramadol up to a maximum dose of 100 mg/day or dihydrocodeine / paracetamol tablets up to a maximum dose of 120 mg dihydrocodeine per day.
- •Subjects willing and able to participate in all aspects of the core study, including use of oral medication, completion of subjective evaluations, attending scheduled clinic visits, completing telephone contacts, and compliance with protocol requirements as evidenced by providing written, informed consent.
- •Subjects in which the pre-study, non-opioid analgesics, and all other concomitant medications, including those medications for the treatment of depression are anticipated to remain stable throughout the treatment phase of the study.
排除标准
- •Any history of hypersensitivity to oxycodone, naloxone, codeine, ibuprofen, bisacodyl or related products and ingredients.
- •Any contraindication to oxycodone, naloxone, codeine, paracetamol or ibuprofen.
- •Subjects with evidence of significant structural abnormalities of the GI tract (e.g., bowel obstruction, strictures) or any diseases/conditions that affect bowel transit (e.g., ileus, hypothyroidism).
- •Subjects with cancer associated pain.
- •Subjects with secondary osteoarthritis (e.g. fracture, septic, acromegaly etc.).
- •Active alcohol or drug abuse and/or history of opioid abuse.
- •Subjects with Rheumatoid Arthritis.
- •Subjects with non opioid induced constipation.
- •Subjects with evidence of clinically unstable disease, as determined by medical history, clinical laboratory tests, ECG results, and physical examination that, in the investigator's opinion, preclude entry into the study.
- •Subjects with evidence of impaired liver/kidney function upon entry into the study defined as: Aspartate aminotransferase, alanine aminotransferase, or alkaline phosphatase levels >3 times the upper limit of normal; Gamma glutamyl transpeptidase ≥5 times the upper limit of normal; Total bilirubin level outside of the reference range unless the value is associated with pre documented Gilbert's Syndrome; Creatinine level outside of the reference range or > 2 mg/dl unless after discussion with the Medical Monitor it is confirmed the subject does not have renal impairment that would preclude the subject's inclusion in the study; In the investigator's opinion the subject has liver and/or kidney impairment to the extent that the subject should not participate in this study.
- •Subjects who have required treatment for the diagnosis of IBS.
- •Subjects receiving hypnotics or other CNS depressants that, in the investigator's opinion, may pose a risk of additional CNS depression with opioid study medication.
- •Subjects with a history of depression or other psychiatric disorder that in the opinion of the investigator is significant enough to exclude the subject from the study.
- •Subjects who are currently involved in legal action regarding their pain condition or subjects in which their pain condition may be of a psychiatric nature.
- •Subjects receiving opioid substitution therapy for opioid addiction (e.g., methadone or buprenorphine).
- •Subjects presently taking, or who have taken naloxone or naltrexone within 30 days of study entry (defined as the start of the Screening Period).
- •Surgery within 2 months prior to the start of the Screening Period, or planned surgery during the12-week treatment period that may affect GI motility or pain levels.
- •Subjects who have received a new chemical entity or an experimental drug within 30 days of study entry (define as the start of the Screening Period).
研究组 & 干预措施
Oxycodone/Naloxone Tablets
Oxycodone/Naloxone combination
干预措施: Oxycodone/Naloxone (Drug)
Codeine/Paracetamol Tablets
Codeine/Paracetamol combination
干预措施: Codeine/Paracetamol (Drug)
结局指标
主要结局
Average Daily Pain Score Box Scale-11 (BS-11) Recorded at Week 12 (Average Pain Over Last 24 Hours)
时间窗: Average daily pain over last 24 hours (at Week 12)
The primary objective was to demonstrate non inferiority of Oxycodone/Naloxone Prolonged Release (OXN PR) compared to codeine/paracetamol in moderate to severe pain as assessed by BS-11 average daily pain scores. The Box Scale-11 is a scale from 0 to 10 (i.e. 0, 1, 2...10), where the subject records their daily pain over the previous 24 hours, by circling the relevant box, where 0 = no pain and 10 = pain as bad as you can imagine. This value is the value recorded at week 12 (average pain over the last 24 hours)
次要结局
- Number of Intakes of Rescue Medication (Ibuprofen) Between Visit 8 and Visit 9 for the 2 Groups.(Between visit 8 and 9)