A Phase II, Dose Titration Study of CPC-201 in Patients With Dementia of Alzheimer's Type
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 28
- 试验地点
- 4
- 主要终点
- Number of Participants Who Reached the Maximum Allowed Dose (MAD) in Their Respective Cohort
研究概览
简要总结
This is a Phase II, ascending dose study of CPC-201 in patients with dementia of Alzheimer's type to determine the optimal dose titration schedule.
详细描述
This is a Phase II, ascending dose study of CPC-201 in patients with dementia of Alzheimer's type to determine the optimal dose titration schedule. The study involves a step wise cohort design in two different patient populations: Group 1 will comprise of patients who have been treated with low dose of CPC-201(5 or 10 mg/day) (given once daily) for at least 4 weeks just prior to Day1. Group 2 will consist of patients who have never been treated with CPC-201 before or who have not received any other AChEI for the past 6 months.
In this study, CPC-201 dose will be increased at weekly intervals, in accordance with the schedules given below, to its first intolerable dose (FID) or maximum allowed dose (MAD) of 60 mg/day (40mg/day for Cohort 3c) together with solifenacin 15 mg/day.
Cohort 1 1st week: 20mg 2nd week: 30mg 3rd week: 40mg 4th week: 50mg 5th week: 60mg Cohort 2* 1st week: 20mg 2nd week: 40mg 3rd week: 60mg Cohort 1b 1st - 2nd week: 10mg 3rd week: 20mg 4th week: 30mg 5th week: 40mg 6th week: 50mg 7th week: 60mg Cohort 3c* 1st week: 10mg 2nd week: 15mg 3rd week: 20mg 4th week: 25mg 5th week: 30mg 6th week: 35mg 7th week: 40mg
*: The dose titration schedule of Cohort 2 and 3 may be altered based on Cohort 1 result.
Patients will be enrolled in Cohort 2 only when patients enrolled in Cohort 1 have safely completed titration. Similary, patients will be enrolled in Cohort 3, only when patients enrolled in Cohort 2 have safely completed titration.
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
- Single (Participant)
入排标准
- 年龄范围
- 50 Years 至 89 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed an Institutional Review Board (IRB) approved informed consent document
- •Aged 50 - 89 years inclusive.
- •Meeting the diagnosis of probable AD consistent with:
- •Revised National Institute on Aging-Alzheimer's Disease Association (NIA-ADA) criteria and
- •Diagnostic and Statistical Manual of Mental Disorders (DSM IV) criteria.
- •Mild to severe severity (Mini-Mental Status Exam [MMSE] scores 7 - 24 inclusive).
- •Rosen-Modified Hachinski Ischemia Score of ≤
- •Have a suitable caregiver to supervise the at-home administration of study drugs and observe for AEs.
- •Patients treated with donepezil 5 or 10 mg/day (given once daily) for at least 4 weeks just prior to Day1 for Population (group) 1 or;
- •Patients never been treated with donepezil before (donepezil naïve) or who have not received any other AChEI for the past 6 months for Population (group)
- •Patients in generally good health as indicated by their medical history and physical examination, vital signs, electrocardiogram (ECG), and standard laboratory tests.
排除标准
- •Women of child bearing potential.
- •History or presence of a seizure disorder.
- •Current unstable peptic ulcer disease, urinary or gastric retention; asthma or obstructive pulmonary disease.
- •History or presence of bladder outflow obstruction, gastrointestinal obstructive disorder or reduced GI motility, or narrow-angle glaucoma.
- •History or presence of gastrointestinal, hepatic, or renal disease, or other condition known to interfere with the absorption, distribution, metabolism or excretion of drugs.
- •Renal and hepatic dysfunction with:
- •Total Bilirubin: >1.5 x UNL
- •AST: >2.5 x UNL
- •ALT: >2.5 x UNL
- •Serum Creatinine: >1.5 x UNL
- •Creatinine Clearance: <30 mL/min (calculated by Cockcroft and Gault equation)
- •History or presence of myasthenia.
- •History or family history of Prolonged QT Syndrome.
- •History of unexplained syncope or family history of unexplained syncope or sudden death.
- •Myocardial infarction or hospitalization for congestive heart failure within 6 months.
- •ECG findings of:
- •Complete Left Bundle Branch Block;
- •Ventricular pacing;
- •2nd degree or 3rd degree AV block;
- •Atrial fibrillation or atrial flutter;
- •HR <45 or >100;
- •PR >220 msec; or
- •QTcF >450 msec in male, >470 msec in female
- •Known hypersensitivity to donepezil, solifenacin or related drugs.
- •History of drug significant allergy.
- •History of substance abuse, known drug addiction, or positive test for drugs of abuse or alcohol.
- •Patients treated with the following medications within 8 weeks of screening
- •AChEIs (other than donepezil),
- •Peripherally acting anticholinergics (such as drugs for the treatment of overactive bladder disorder),
- •Psychoactive medications (including antipsychotics, antidepressants, anxiolytics or sedative hypnotics) having significant anticholinergic effects and/or believed to affect cognitive function.
- •Other medications are acceptable, at the investigators discretion, if dosage is held stable for at least 4 weeks prior to screening and throughout the study.
- •Patients considered unlikely to co-operate in the study, and/or poor compliance anticipated by the investigator.
- •Patients hospitalized within 4 weeks of screening.
- •Any other clinically relevant acute or chronic diseases which could interfere with patients' safety during the trial, or expose them to undue risk, or which could interfere with study objectives.
- •Patients who have participated in another clinical trial with an investigational drug within previous 30 days.
研究组 & 干预措施
Cohort 1b
Donepezil 10mg/day upward dose titration of 10mg at weekly intervals up to first intolerable dose (FID) or to maximum allowed dose (MAD) of 60mg/day with solifenacin 15 or 20mg/day.
干预措施: Solifenacin (Drug)
Cohort 1
Donepezil 20mg/day upward dose titration of 10mg at weekly intervals up to first intolerable dose (FID) or to maximum allowed dose (MAD) of 60mg/day with solifenacin 15 or 20mg/day.
干预措施: Donepezil (Drug)
Cohort 1
Donepezil 20mg/day upward dose titration of 10mg at weekly intervals up to first intolerable dose (FID) or to maximum allowed dose (MAD) of 60mg/day with solifenacin 15 or 20mg/day.
干预措施: Solifenacin (Drug)
Cohort 2
Donepezil 20mg/day upward dose titration of 20mg at weekly intervals up to first intolerable dose (FID) or to maximum allowed dose (MAD) of 60mg/day with solifenacin 15 or 20mg/day.
干预措施: Donepezil (Drug)
Cohort 2
Donepezil 20mg/day upward dose titration of 20mg at weekly intervals up to first intolerable dose (FID) or to maximum allowed dose (MAD) of 60mg/day with solifenacin 15 or 20mg/day.
干预措施: Solifenacin (Drug)
Cohort 1b
Donepezil 10mg/day upward dose titration of 10mg at weekly intervals up to first intolerable dose (FID) or to maximum allowed dose (MAD) of 60mg/day with solifenacin 15 or 20mg/day.
干预措施: Donepezil (Drug)
Cohort 3c
Donepezil 10mg/day upward dose titration of 5mg at weekly intervals up to first intolerable dose (FID) or to maximum allowed dose (MAD) of 40mg/day with solifenacin 15mg/day.
干预措施: Donepezil (Drug)
Cohort 3c
Donepezil 10mg/day upward dose titration of 5mg at weekly intervals up to first intolerable dose (FID) or to maximum allowed dose (MAD) of 40mg/day with solifenacin 15mg/day.
干预措施: Solifenacin (Drug)
结局指标
主要结局
Number of Participants Who Reached the Maximum Allowed Dose (MAD) in Their Respective Cohort
时间窗: 1-7 weeks
Of the four cohorts with different dosing schedules for CPC-201, the cohort with the greatest proportion of participants to reach the donepezil MAD was determined to be the optimal administration regimen.
次要结局
- Number of Participants With TEAEs Leading to Study Drug Discontinuation(1-7 weeks)