Randomized, Double-blind, Double-dummy, Active Controlled, Multicentre, Non-inferiority Phase-III Study to Compare Gabapentin Liquid Formulation to Tramadol in Children Experiencing Moderate to Severe Chronic Neuropathic or Mixed Pain
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 发起方
- 入组人数
- 2
- 试验地点
- 2
- 主要终点
- Pain score
研究概览
简要总结
This study evaluates the efficacy and safety of gabapentin relative to tramadol for the treatment of chronic, neuropathic or mixed pain in the paediatric population. Children from 3 months to less than 18 years of age experiencing moderate to severe chronic pain will receive either gabapentin or tramadol for 15 weeks. The difference in average pain scores between treatment arms at the end of the treatment period will be assessed.
详细描述
Gabapentin is indicated for the treatment of peripheral neuropathic pain in adults. In the 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 pharmacokinetics profile and c) efficacy and safety data in this specific population.
The GABA-1 study is designed to demonstrate the efficacy of gabapentin oral solution relative to tramadol and to document the Pharmacokinetic and safety profile of gabapentin in this indication.
GABA-1 is a non-inferiority trial because gabapentin is expected to be equally effective but better tolerated than tramadol, thus providing a clinical benefit to affected children.
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.
- •Informed consent by parent(s) and/or legal guardian according to each country legal requirement.
- •Assent by the patient, 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. Duration of pain will be determined from the date of the first pain experienced.
- •Subjects that present with at least moderate pain as defined by average pain intensity of ≥4/10 as assessed during a 3-day screening period
- •Stable underlying disease condition and treatment.
- •In presence of malignant diseases, subjects in clinical remission and/or no expected changes in their therapeutic protocol during participation to the present study.
排除标准
- •Pain duration of more than 5 years.
- •Current use of gabapentin or tramadol.
- •History of failure to respond to adequate treatment by gabapentin or tramadol/opioids for neuropathic pain.
- •History of epileptic condition except febrile seizure disorder.
- •Subjects with sleeping apnoea syndrome of any origin or subjects with history of severe respiratory impairment.
- •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 suicidal ideation or behaviour.
- •History of substance abuse in particular opioids.
- •Subjects under prohibited concomitant medication
- •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 born prematurely at ≤ 36 weeks gestational age, if recruited during the first year of age.
- •Subjects with a body mass index (BMI) for age and gender of < 5th percentile or > 95th percentile.
- •Subjects with glomerular filtration rate < 90 mL/min/1.73 m2 (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 with known allergy, hypersensitivity or clinically significant intolerance to gabapentin or tramadol or any component found in the study drugs.
- •Subjects with fructose intolerance, diabetes, glucose-galactose malabsorption or lactase-isomaltase deficiency.
- •Subjects with clinically relevant abnormal ECG at the screening visit in the discretion of the Investigator/cardiologist.
- •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.
研究组 & 干预措施
gabapentin / placebo tramadol
gabapentin 75 mg/ml syrup / placebo tramadol, 3 times/day for 15 weeks.
干预措施: gabapentin (Drug)
gabapentin / placebo tramadol
gabapentin 75 mg/ml syrup / placebo tramadol, 3 times/day for 15 weeks.
干预措施: placebo tramadol (Other)
tramadol / placebo gabapentin
tramadol oral drops 100 mg/ml / placebo gabapentin, 3 times/day for 15 weeks.
干预措施: tramadol (Drug)
tramadol / placebo gabapentin
tramadol oral drops 100 mg/ml / placebo gabapentin, 3 times/day for 15 weeks.
干预措施: placebo gabapentin (Other)
结局指标
主要结局
Pain score
时间窗: an average of 16 weeks
Pain score (0-10) measured at baseline (before starting the therapy) and at the end of the treatment in: patients aged 3-24 months using FLACC pain scale, patients aged 3-7 years using FPS-R scale, patients aged 8-17 years using NRS-11. The FLACC (the Faces, Legs, Arms, Cry and Consolability) scale is 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 (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
- Number of rescue interventions(an average of 15 weeks)
- Percentage of responders to treatment(an average of 16 weeks)
- Physical Health Summary Score from PedsQL™ scale(an average of 15 weeks)
- Number of participant dropouts(up to 21 weeks)
- Extent of pain(an average of 16 weeks)
- Percentage of subjects discontinuing the trial due to treatment-emergent adverse events.(up to 21 weeks)
- Global satisfaction with treatment(at week 15)
- Clinical Global Impression of Severity of the subject's condition(an average of 15 weeks)
- Clinical Global Impression of Improvement for pain(an average of 15 weeks)
- Self-assessment of pain for children ≥8 years of age(an average of 16 weeks)
- Number of episodes of breakthrough pain(an average of 16 weeks)
- Incidence of Adverse Events at all visits(up to 21 weeks)
- Daily pain intensity(an average of 3 weeks)
- Observational assessment of pain(an average of 16 weeks)
- CL/F(at week 3 or at week 4 or at week 16)
- ka(at week 3 or at week 4 or at week 16)
- Css(at week 3 or at week 4 or at week 16)
- Number of pain-free days(an average of 15 weeks)
- The total cumulative weight normalized dose of each rescue drug(up to 21 weeks)
- Total Summary Score from PedsQL™ scale(an average of 15 weeks)
- Psychosocial Health Summary Score from PedsQL™ scale(an average of 15 weeks)
- Acceptability of treatment(at week 16)
- Vd/F(at week 3 or at week 4 or at week 16)
- Cmax(at week 3 or at week 4 or at week 16)
- Systemic exposure to investigational products during maintenance period(an average of 12 weeks)
- Aggressive behaviour in children aged >6 years(an average of 15 weeks)
- Patient/parent Global Impression of Change(an average of 12 weeks)
- AUC(at week 3 or at week 4 or at week 16)
- Cmin(at week 3 or at week 4 or at week 16)
- Assessment of blinding(at week 16)
- Tmax(at week 3 or at week 4 or at week 16)
- Suicidal ideation/behaviour in subjects aged 6 years and older(an average of 16 weeks)