A Randomized Withdrawal, Active- and Placebo-controlled, Double-blind, Multi-center Phase III Trial Assessing Safety and Efficacy of Oral CG5503 (Tapentadol) Prolonged Release (PR*) in Subjects With Moderate to Severe Chronic Malignant Tumor-related Pain. *Prolonged Release and is the Recommended Nomenclature for Use in the European Union (EU). ER Means Extended Release and is the Recommended Nomenclature for Use in the United States of America (USA). "PR" is Synonymous With "ER" and is Interchangeable.
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 136
- 试验地点
- 37
- 主要终点
- Responder Rates in Maintenance Period
研究概览
简要总结
The purpose of this study is to determine whether CG5503 (tapentadol) is effective and safe in the treatment of chronic tumor related pain compared to placebo.
详细描述
Normally chronic tumor related pain is controlled when subjects receive repeated doses of opioid analgesics. However, opioid therapy is commonly associated with side effects such as nausea, vomiting, sedation, constipation, addiction, tolerance, and respiratory depression. Tapentadol, a newly synthesized drug with an Prolonged Release (ER) formulation, also acts as a centrally acting pain reliever but has a dual mode of action.
The aim of this trial is to investigate the effectiveness (level of pain control) and safety (side effects) of Tapentadol Prolonged Release (ER) compared to a tablet with no active ingredient drug (placebo) and a corresponding dose of Morphine (an opioid commonly used to treat tumor related pain). This trial is a randomized, double-blind (neither investigator nor patient will know which treatment was received), active- and placebo-controlled, parallel-group, randomized-withdrawal, multicenter trial. To maintain the blind all subjects were re-randomized at the start of the maintenance period. To maintain the blind all tapentadol subjects were re-randomized at the start of the maintenance period. Subjects that received morphine in the titration period continued in the maintenance period on morphine.
The trial includes a 2 week titration phase starting with either 45 mg Morphine Sulfate Controlled Release (CR) twice daily or 100 mg tapentadol ER taken twice daily (bid). Based on effectiveness and side effects participants can up-titrate in steps of 50 mg Tapentadol ER or 15 mg Morphine Sulfate CR to a maximal dose of 250 mg Tapentadol ER bid or 90 mg Morphine Sulfate CR twice daily respectively. If subjects meet the stabilization criteria at the end of the titration phase they will be re-randomized to either placebo or active treatment and will continue 4 weeks at the last dose level in the maintenance phase.
Assessments of pain relief, defined as a responder include the pain intensity numeric rating scale (NRS). The Patient Global Impression of Change scale (PGIC) will also be used as a secondary efficacy endpoint. Safety evaluations include monitoring of adverse events, physical examinations, and clinical laboratory tests. Venous blood samples will be collected for the determination of serum concentrations of tapentadol.
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
- •A signed informed consent document.
- •Male and non-pregnant, non-lactating female subjects.
- •Female subjects must be post menopausal, surgically sterile, or practicing an effective method of birth control and continue to do so throughout the trial.
- •At least 18 years of age.
- •Have chronic malignant tumor-related pain
- •Are opioid-naïve or have been pretreated with an equianalgesic dose range equivalent of up to 160 mg oral morphine per day and are dissatisfied with prior treatment.
- •Have a mean pain intensity of at least 5 points on an 11-point Numeric Rating Scale (where 0 indicates no pain and 10 indicates worst possible pain).
- •Have an expected course of the disease such that the pain that will permit compliance with the trial protocol over the entire trial period.
排除标准
- •Have a life-long history of seizure disorder or epilepsy.
- •Have had any of the following within one year: mild/moderate traumatic brain injury, stroke, and transient ischemic attack.
- •Have had severe traumatic brain injury within 15 years (consisting of ≥ 1 of the following: brain contusion, intracranial hematoma, and either unconsciousness or post-traumatic amnesia lasting for more than 24 hours) or residual sequelae suggesting transient changes in consciousness.
- •Have a known history and/or presence of cerebral metastases.
- •Have moderately or severely impaired hepatic function.
- •Have laboratory values reflecting inadequate hepatic function.
- •Have thrombopenia, leucopenia or hypercalcemia
- •Have severely impaired renal function.
- •Having uncontrolled hypertension
- •Having clinically relevant history of hypersensitivity, allergy or contraindications to morphine or any of the excipients.
- •Have chronic hepatitis B or hepatitis C, or Human Immunodeficiency Virus (HIV).
- •Subjects currently undergoing the following concomitant therapy: radiotherapy, pain inducing chemotherapy, anti-parkinsonian drugs, neuroleptics, monoamine oxidase inhibitors, serotonin norepinephrine re-uptake inhibitors (SNRI) or any other analgesic therapy than investigational medication or rescue medication during the trial. Selective serotonin re-uptake inhibitor (SSRI) treatments are allowed if taken for at least 30 days before the screening period of the trial at an unchanged dose.
研究组 & 干预措施
Matching Placebo
Oral Tapentadol 100 mg to 250 mg twice daily. Followed by matching placebo in the maintenance (i.e. randomized withdrawal phase).
干预措施: Matching Placebo in the Maintenance Phase after Tapentadol in the Titration Phase (Drug)
Morphine Controlled Release
Oral Morphine 45 mg to 90 mg twice daily.
干预措施: Morphine in the Maintenance Phase (Drug)
Morphine Controlled Release
Oral Morphine 45 mg to 90 mg twice daily.
干预措施: Morphine in the Titration Phase (Drug)
Tapentadol Extended Release
Oral Tapentadol 100 mg to 250 mg twice daily.
干预措施: Tapentadol in the Titration Phase (Drug)
Tapentadol Extended Release
Oral Tapentadol 100 mg to 250 mg twice daily.
干预措施: Tapentadol in the Maintenance Phase (Drug)
结局指标
主要结局
Responder Rates in Maintenance Period
时间窗: End of the 4 week Maintenance Phase (Day 43)
A "responder" is a participant in the study that: 1. completed 28 days of the maintenance phase 2. had a numeric rating scale score below 5 on the 11 point scale (where 0 indicates no pain and 10 indicates worst possible pain. This twice daily current pain score was averaged over Day 18 to Day 43. 3. did not use more than 30 mg of rescue medication per day on average in the 28 day (excluding the first 3 days) maintenance period (from Day 18 to Day 43). A participant that met all 3 of the above-mentioned criteria is counted as a responder, in other words the participant benefited from the assigned drug treatment. A participant that fails to meet at least 1 of the 3 criteria is not counted as a responder.
次要结局
- Patient Global Impression of Change (PGIC)(Day 15 corresponds with PGIC at end of titration phase; Day 43 corresponds with PGIC at end of maintenance phase)