Randomized, Double-blind, Placebo Controlled, Superiority Phase II Study to Evaluate the Safety, Pharmacokinetic, Efficacy of Gabapentin as add-on to Morphine in Children From 3 Months to Less Than 18 Years
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 发起方
- 主要终点
- Pain scores
研究概览
简要总结
The objective of the study is to evaluate the efficacy of gabapentin as adjunctive therapy to morphine in the treatment of severe chronic neuropathic or mixed pain in children from 3 months to less than 18 years of age assessed by the difference in average pain scores between treatment arms at the end of the treatment period.
详细描述
This paediatric trial has the objective to make gabapentin available for children with severe chronic neuropathic or mixed pain. This study will be conducted in full conformance with the ethical principles outlined in the Declaration of Helsinki, consistent with ICH-GCP (including ICH Topic E11 guideline) and applicable regulatory requirements including the Paediatric Recommendations (CE/2008).
Gabapentin has been successfully used to treat neuropathic pain in adults. In absence of specific paediatric studies it is not approved for the same condition in children.
The paediatric use of gabapentin is hampered by: a) the lack of a suitable paediatric formulation, b) the significant variability of gabapentin PK profile and c) efficacy and safety data in this specific population.
GABA-2 is a superiority trial designed to assess the potential benefit of gabapentin oral solution in augmenting the analgesic effect of morphine in children affected by severe chronic pain thus preventing or decreasing opioid tolerance, as it has been reported to happen in adults. Thus GABA-2 study is an randomized, double blind, placebo controlled, multi-centre study to evaluate the efficacy of gabapentin added to morphine in paediatric patients suffering from severe chronic pain (neuropathic or mixed with ascertained neuropathic component). The trial will include 66 patients aged from 3 months to less than 18 years affected by severe chronic neuropathic or mixed pain and in need of morphine.
Children from 3 months to <3 years of age will participate to GABA-2 on the basis of the nature of the underlying disease suggestive of a neuropathic component.
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 3 Months 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female, aged 3 months to less than 18 years at screening (V1)
- •Informed consent by parent(s) and/or legal guardian according to each country legal requirement.
- •Assent, where applicable, according to each country legal requirement.Informed (co-) consent of child, where applicable, according to each country legal requirement.
- •Subjects that meet the diagnostic criteria for neuropathic or mixed pain.
- •Subjects that present with chronic pain defined as the recurrent or continuous pain persisting more than 3 months.
- •Subject that present with severe pain as defined by average pain intensity of ≥7 /10 as assessed during a 3-day screening period
- •Stable underlying disease condition and treatment.
- •Patients with Chemotherapy Induced Peripheral Neuropathy, when in clinical remission or maintenance phase of their therapeutic protocol.
排除标准
- •Pain duration of more than 5 years.
- •Current use of gabapentin.
- •Current use of strong opioids (morphine, methadone, fentanyl, ketamine, oxycodone).
- •History of failure to respond to adequate treatment by gabapentin or opioids for neuropathic pain.
- •History of epileptic condition (except febrile seizure disorder).
- •Subjects with diagnosis of sickle cell disease.
- •Subjects that present significant cognitive impairment.
- •Subjects that present current, controlled or uncontrolled, co-morbid psychiatric diagnosis that can impair pain diagnosis and assessment such as severe depressive conditions or psychosis.
- •Subjects with history of or current suicidal ideation or behaviour.
- •Subjects with history of substance abuse in particular opioids.
- •Subjects under prohibited concomitant medication .
- •Subjects with a body mass index (BMI) for age and gender of < 5th percentile or > 95th percentile (charts provided as Appendix 3).
- •Subjects with significant renal impairment, i.e., glomerular filtration rate < 90 mL/min/1.73 m2 (Revised Schwarz equation).
- •Subjects with significant hepatic impairment or with Aspartate Transaminase (AST) or Alanine Transaminase (ALT) enzymes 3 times the upper limit of the age-specific reference range.
- •Subjects in need for corticosteroid oral treatment or corticosteroid infiltrations to treat pain caused by infiltration or compression of neural structures, e.g. peripheral nerves or spinal cord.
- •Subjects with clinically relevant abnormal ECG at the screening visit in the discretion of the Investigator/cardiologist.
- •Subjects with known allergy, hypersensibility or clinically significant intolerance to gabapentin or any component found in the study drugs.
- •Subjects with fructose intolerance, diabetes, glucose-galactose malabsorption or lactase-isomaltase deficiency.
- •Subjects participating in another clinical interventional trial.
- •Subjects scheduled for surgery or in recovery from surgery occurring within 3 months of baseline assessment.
- •Female subjects who are pregnant or currently lactating.
- •Subjects that failed screening or were previously enrolled in this study
- •Patients with Chemotherapy Induced Peripheral Neuropathy, when in induction phase of their therapeutic protocol
研究组 & 干预措施
Group 1
Gabapentin + Morphine
干预措施: Gabapentin + Morphine (Drug)
Group 2
Placebo + Morphine
干预措施: Placebo + Morphine (Drug)
结局指标
主要结局
Pain scores
时间窗: on average of 16 weeks
Pain scores in the two treatment groups assessed at baseline and at the end of the treatment by age-appropriate pain scales. FLACC (the Faces, Legs, Arms, Cry and Consolability - pts aged 3-24 months) scale composed by 5 categories. Each category is scored on the 0-2 scale, which results in a total score of 0-10, where 0=Relaxed and comfortable, 4-6=Moderate pain, 1-3=Mild discomfort, 7-10=Severe discomfort or pain or both. FPS-R scale (Faces Pain Scale - Revised - pts aged 3-7 years): score is associated with face 0, 2, 4, 6, 8, or 10, where 0 = no pain and 10=very much pain. NRS-11(Numerical Rating Scale - pts aged 8-17 years): numerical rating scale where 0=no pain and 10=worst possible pain
次要结局
- Observational assessment of pain(on average of 16 weeks)
- Extent of pain(on average of 16 weeks)
- Number of episodes of breakthrough pain(on average of 15 weeks)
- Number of pain-free days(on average of 15 weeks)
- Number of rescue interventions required during treatment period(on average of 15 weeks)
- Physical Health Summary Score from PedsQL™ scale(on average of 15 weeks)
- Percentage of responders to treatments(on average of 16 weeks)
- Self-assessment of pain for children ≥8 years of age(on average of 16 weeks)
- Participant dropouts(up to 21 weeks)
- Total Summary Score from PedsQL™ scale(on average of 15 weeks)
- Daily pain intensity(an average of 3 weeks)
- The total cumulative weight normalized dose of each rescue drug.(on average of 16 weeks)
- Psychosocial Health Summary Score from PedsQL™ scale(on average of 15 weeks)
- Clinical Global Impression of Severity of the subject's condition(an average of 15 weeks)
- Css(at week 3 or at week 4 or at week 16)
- Systemic exposure to investigational product(an average of 12 weeks)
- Global satisfaction with treatment(at week 16)
- CL/F(at week 3 or at week 4 or at week 16)
- Aggressive behaviour in children aged >6 years(an average of 15 weeks)
- Assessment of blinding(at week 16)
- Acceptability of treatment(at week 16)
- Clinical Global Impression of Improvement for pain(an average of 15 weeks)
- Vd/F(at week 3 or at week 4 or at week 16)
- ka(at week 3 or at week 4 or at week 16)
- Cmin(at week 3 or at week 4 or at week 16)
- Percentage of subjects discontinuing the Trial(up to 21 weeks)
- Patient/parent Global Impression of Change(an average of 12 weeks)
- AUC(at week 3 or at week 4 or at week 16)
- Cmax(at week 3 or at week 4 or at week 16)
- Tmax(at week 3 or at week 4 or at week 16)
- Incidence of Adverse Events(up to 21 weeks)
- Suicidal ideation/behaviour in subjects aged 6 years and older(an average of 16 weeks)