Tolerability and Analgesic Efficacy of Loxapine in Patients With Refractory, Chemotherapy-induced Neuropathic Pain
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 4
- 试验地点
- 1
- 主要终点
- Loxapine dosage with the lowest incidence of events.
研究概览
简要总结
Loxapine is an antipsychotic drug approved for the treatment of schizophrenia in several countries including the United States. In animal studies in mice, loxapine reduced neuropathic pain. Hence, in a proof-of-principle and dose-escalating study the tolerability and analgesic efficacy of loxapine will be evaluated in patients with neuropathic pain.
详细描述
In this dose-escalating study, 12 patients with refractory, chemotherapy-induced neuropathic pain (including mixed pain) will receive loxapine during four 14-days treatment episodes. The dosage for episode 1 (Days 1-14) will be 10 mg b.i.d., dosages for episodes 2, 3, and 4 will be defined by taking into account tolerability and analgesic efficacy of the former episode. In case of an acceptable tolerability and if a clinically relevant analgesic efficacy is not reached, loxapine dosage will be increased (2nd Episode 10 mg t.i.d, 3rd Episode 20 mg b.i.d., 4th episode 20 mg t.i.d.). In case of an acceptable tolerability and if a clinically relevant analgesic efficacy is reached, loxapine dosage will not be changed. If clinically relevant (serious) adverse events ((S)AEs) occur, loxapine dosage will be reduced or the treatment will be interrupted or stopped irrespective of the analgesic efficacy. A clinically relevant pain reduction / analgesic efficacy is defined by an at least 30% decrease or an absolute decrease of two scale units compared to baseline using 11-point numeric pain rating scale. Patients will receive loxapine as add-on treatment to their usual (analgesic) care.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
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
- •Primarily chemotherapy-induced neuropathic pain (including mixed pain) for at least 3 months refractory to at least one analgesic compound
- •Neuropathic pain >= 4 (11-point numeric pain scale) at screening visit (including mixed pain)
- •Age >= 18 years
- •Body weight between 50 and 150 kg
- •Given written informed consent
排除标准
- •Participation in other interventional clinical studies (currently or within the last 3 months)
- •Parkinson's disease, movement disorders (extrapyramidal signs and symptoms) associated with antipsychotics, neuroleptic malignant syndrome, other syndromes associated with antipsychotics
- •Severe hypotension with a syncope in history, glaucoma, urinary retention, epilepsy or other seizure disorders in history, severe dementia, dementia-related psychosis in history, malignancies with a life expectancy of less than 6 months, breast cancer in history, other life-threatening conditions
- •Corrected QT interval (QTc) > 460 ms (females) or > 450 ms (males)
- •Known alcohol and/or drug abuse
- •Concomitant intake of antipsychotics, dopamine agonists (Levodopa, bromocriptine, lisuride, pergolide, ropinirole, cabergoline, pramipexole, apomorphine), alpha-receptor blocking compounds
- •Compounds with a strong evidence for a clinically relevant QT interval prolongation or torsade de pointes risk increase
- •Strong inhibitors of CYP1A2, CYP2D6, or CYP3A4
- •Known CYP2D6 Poor metabolizer status
- •Pregnancy or lactation period
- •Missing or insufficient contraception in pre- or perimenopausal women
- •Close Affiliation with the investigational site
研究组 & 干预措施
Loxapine
Loxapine Capsules 10 mg Day 1- 14: 10 mg b.i.d Day 15-28: 10 mg t.i.d Day 29-42: 20 mg b.i.d. Day 43-56: 20 mg t.i.d. Dosages will be escalated according to analgesic efficacy and tolerability.
干预措施: Loxapine (Drug)
结局指标
主要结局
Loxapine dosage with the lowest incidence of events.
时间窗: After each of the four 14 days study episodes (Day 15, Day 29, Day 43, Day 57)
The primary endpoint is defined as the first occurrence of a (serious) adverse event ((S)AE) leading to dose reduction or withdrawal of loxapine ("event"). The loxapine dosage with the lowest incidence of events will be identified.
次要结局
- Individual (study participant-related) changes in pain severity (NRS scale)(After each of the four 14 days study episodes (Day 15, Day 29, Day 43, Day 57))
- Individual (study participant-related) changes in anxiety and depression (HADS-D scale)(After each of the four 14 days study episodes (Day 15, Day 29, Day 43, Day 57))
- Individual (study participant-related) incidence of individual (S)AEs(After each of the four 14 days study episodes (Day 15, Day 29, Day 43, Day 57))
- Association between event pattern and QoL (SF-12v2)(After each of the four 14 days study episodes (Day 15, Day 29, Day 43, Day 57))
- Association between event pattern and analgesic co-medication(After each of the four 14 days study episodes (Day 15, Day 29, Day 43, Day 57))
- Cumulative incidence rates for (S)AE pattern of study participants(After each of the four 14 days study episodes (Day 15, Day 29, Day 43, Day 57))
- Individual (study participant-related) changes in pain severity (painDETECT)(After each of the four 14 days study episodes (Day 15, Day 29, Day 43, Day 57))
- Number, type, and severity of (serious) adverse events ((S)AEs)(After each of the four 14 days study episodes (Day 15, Day 29, Day 43, Day 57))
- Association between event pattern and individual pain level (NRS scale)(After each of the four 14 days study episodes (Day 15, Day 29, Day 43, Day 57))
- Association between event pattern and individual pain level (painDETECT)(After each of the four 14 days study episodes (Day 15, Day 29, Day 43, Day 57))
- Individual (study participant-related) changes in QoL (SF-12v2)(After each of the four 14 days study episodes (Day 15, Day 29, Day 43, Day 57))
- Association between event pattern and anxiety and depression (HADS-D scale)(After each of the four 14 days study episodes (Day 15, Day 29, Day 43, Day 57))