An Open Label 24-Week, Flexible Dose Trial to Assess the Safety and Efficacy of Galantamine in Patients With Dementia With Lewy Bodies
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 50
- 试验地点
- 10
- 主要终点
- NPI-12
研究概览
简要总结
TRIAL SUMMARY:
This is an open-label, 24-week, investigator initiated study to evaluate the safety and efficacy of galantamine (16 8 to 24 mg/day; flexible dosing) in the treatment of Dementia with Lewy bodies. The primary efficacy variables will be the NPI -12, the COGDRAS tests of attention and visuospatial orientation, and the ADCS-CGIC. The secondary efficacy variables will be the MMSE, ADCS-ADL-Inventory, ADAS-Cog, PSQI, and the use of concomitant rescue antipsychotic medication. PET scanning will be obtained on 10 patients at one site. An interim analysis will also be performed. Safety outcome measures will be adverse event reports, vital signs, physical examinations, ECG, laboratory parameters and the UPDRS (motor subscale).
详细描述
TRIAL DESIGN
- Rationale
In a previously published study of DLB treated with rivastigmine, efficacy was seen to be maximized at 20 weeks in multiple parameters compared to placebo. The efficacy was seen in the NPI - 4 as well as the NPI -10, MMSE and a Computerized Cognitive Assessment Systems Score5. There was no change in UPDRS score. The efficacy of rivastigmine for patients with DLB responding greater than 30 percent in behavioral measures was equal to or better than most studies of antipsychotic medications used for behavioral abnormalities in DLB and AD patients.
Since the titration for galantamine involves less time than the titration for rivastigmine, an interim analysis may show efficacy at 12 weeks. However, for complete efficacy and safety evaluations, a 24-week treatment for galantamine is preferable. Since the cholinergic deficits in DLB patients is more profound than that for AD patients, the dose range of 16 8 to 24 mg/day for DLB patients should be sufficient to show efficacy. Since galantamine has previously been shown to be efficacious in the domains of behavior, cognition, ADL's and global assessment in AD patients, we expect efficacy to be shown similarly and perhaps to a greater extent in DLB patients.
TREATMENT OF SUBJECTS
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 51 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female subjects (>50 years old) diagnosed with Dementia with Lewy bodies, in accordance with the consensus criteria for probable Dementia with Lewy bodies (McKeith et al., 1996) viii.
- •NPI score ≥ 8 at screening
- •MMSE ≥ 7 at screening
- •Subjects living at home or in a residential or community care home. Subjects who live with or have regular daily visits from a responsible caregiver. Subjects must be able to read, write, and fully understand the language of the scales used in this trial.
- •Subjects must exhibit sufficient visual, hearing, and communication capabilities
- •The Informed Consent must be given by the subject and the subject's legally acceptable representative.
- •The informed consent must also be signed by the caregiver.
- •CT or MRI within last 12 months - to be performed if not done
排除标准
- •Neurodegenerative disorders such as Alzheimer's disease, Frontotemporal dementia, including Pick's disease, Korsakoff's syndrome, Huntington's chorea, Down's syndrome, Creutzfeldt-Jacob disease and causes of Parkinsonism other than DLB.
- •One of the following conditions possibly resulting in cognitive impairment:
- •Acute cerebral trauma, subdural hematoma and injuries secondary to chronic trauma (such as boxing).
- •Hypoxic cerebral damage whether or not due to acute or chronic cerebral hypoperfusion,
- •Vitamin deficiency state such as folate, vitamin B12 and other B complex deficiencies, e.g., thiamine deficiency in Korsakoff's syndrome. Note: subjects taking regular B12 and folate are not necessarily excluded (treatment must be stable, ongoing for at least 4 weeks prior to entry).
- •Infection such as cerebral abscess, neurosyphilis, meningitis or encephalitis.
- •Primary or metastatic cerebral neoplasia.
- •Significant endocrine or metabolic disease e
- •Mental retardation or oligophrenia. Multi-infarct dementia or clinically active cerebrovascular disease
- •Subjects with the following co-existing medical condition:
- •Any history of epilepsy or convulsions except for febrile convulsions during childhood.
- •Current clinically significant psychiatric disease, as judged by DSM-IV criteria, in particular current major depression or schizophrenia.
- •Peptic ulcer: if the ulcer is to be considered still "active", i.e., treatment for this condition started <3 months ago or if treatment is not successful (still symptoms present), the subject is not eligible.
- •Clinically significant hepatic, renal, pulmonary, metabolic or endocrine disturbances.
- •Current, clinically significant cardiovascular disease that would be expected to limit the subject's ability to participate in and complete a 7-month trial.
- •Any agent being used for the treatment of dementia (approved, experimental or over the counter agents),
- •History of drug or alcohol abuse within the last year or prior prolonged history.
- •Female subject of childbearing potential without adequate contraception. Females who are breast-feeding are also excluded.
- •Subjects who, in the opinion of the investigator, are otherwise unsuitable for a trial of this type.
- •History of severe drug allergy or hypersensitivity; including recorded hypersensitivity to cholinesterase inhibitors, choline agonists or similar agents, bromide or the components of the drug under study.
- •Subjects who have previously been enrolled in other galantamine HBr trials. Subjects who were screened for previous galantamine studies but not enrolled may be re-screened for this study.
- •Subjects on antipsychotics other than Risperdal® (risperidone), Zyprexa® (olanzapine), Seroquel® (quetiapine), Geodon® (ziprasidone).
- •Conditions that could interfere with the absorption of the compound or with the evaluation of the disease.
结局指标
主要结局
NPI-12
ADCS-CGIC
COGDRAS
次要结局
- ADCS-ADL
- MMSE
- ADAS-Cog
- PSQI
- Concomitant Antipsychotic Medication use