NCT03305809已完成2 期
Effect of LY3154207 on Cognition in Mild-to-Moderate Dementia Due to Lewy Body Dementia (LBD) Associated With Idiopathic Parkinson's Disease (PD) or Dementia With Lewy Bodies (DLB)
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 344
- 试验地点
- 76
- 主要终点
- Change From Baseline in the Continuity of Attention (CoA) Composite Score of the Cognitive Drug Research Computerized Cognition Battery (CDR-CCB)
研究概览
简要总结
A randomized placebo-controlled trial to evaluate the safety and efficacy of three doses of study drug LY3154207 treated for 12 weeks in participants with mild-to-moderate dementia associated with LBD (PDD or DLB).
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 40 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Have dementia as defined by a decline in cognitive function, which in the opinion of the investigator has resulted in functional impairment.
- •Meet diagnostic criteria for PD per MDS criteria or DLB per 4th Consensus Report of the DLB Consortium.
- •Have a score on the MoCA of 10 -
- •Are Modified Hoehn and Yahr Stages 0 -
- •Have a blood pressure (BP) or pulse rate at screening and randomization, as determined by three sequential BP/pulse rate measurements in a seated position:
- •Participants <60 years old:
- •A mean systolic BP less than or equal to 140 millimeters of mercury (mmHg), a mean diastolic BP less than or equal to 90 mmHg and a mean pulse rate less than or equal 90 beats/minute in a seated position.
- •Each of the 3 systolic BP measurement must be less than 180 mmHg
- •Participants ≥60 years old:
- •A mean systolic BP less than or equal to 150 mmHg, a mean diastolic BP less than or equal to 90 mmHg and a mean pulse rate less than or equal to 90 beats/min in a seated position.
- •Each of the 3 systolic BP measurement must be less than 180 mmHg
- •If on anti-parkinsonian agents, participants must be on stable dosage for at least 3 weeks prior to screening, and should remain on stable doses during the course of the study.
- •If on medications affecting cognition (rivastigmine, galantamine, donepezil, memantine), participants must be on stable dosage for at least 3 weeks prior to screening and should remain at a stable dosage during the course of the study.
- •If on antidepressant medications, participants must be on stable dosage for at least 3 weeks prior to screening and should remain at a stable dosage during the course of the study.
- •If on clozapine, quetiapine, and pimavanserin to address drug induced or disease related psychosis, participants must be on stable dosage for 3 weeks prior to screening and should remain at a stable dosage during the course of the study.
- •If on antihypertensive medications, participants must be on stable dosage for at least 3 weeks prior to screening.
- •Men should use appropriate contraception.
- •All participants must have a reliable caregiver who is in frequent contact with the participant (defined as at least 10 hours per week) and will accompany the participant to screening, baseline, day 7, day 42, day 84 and follow-up.
排除标准
- •Are women of childbearing potential.
- •Have significant central nervous system or psychiatric disease, other than PD or DLB, that in the investigator's opinion may affect cognition or the ability to complete the study.
- •Have a history in the last 6 months of transient ischemic attacks or ischemic stroke.
- •Have a history of intra cerebral hemorrhage due to hypertension.
- •Have a history of hypertensive encephalopathy.
- •Have atypical or secondary parkinsonism due to drugs (e.g., antipsychotics) or disease (such as progressive supranuclear palsy, essential tremor, multiple system atrophy (e.g. striatonigral degeneration, olivopontocerebellar atrophy), or postencephalitic parkinsonism).
- •Have a current implantable intracranial stimulator or history of intracranial ablation surgery (e.g., subthalamic, globus pallidus-internal segment [GPi]).
- •Have a history of substance abuse within the past 1 year (drug categories defined by the Diagnostic and Statistical Manual of Mental Disorder, 5th Edition [DSM-5], and/or substance dependence within the past 1 year, not including caffeine and nicotine.
- •Have a serious or unstable medical illness, other than idiopathic LBD (PDD or DLB), including cardiovascular, hepatic, respiratory, hematologic, endocrinologic, neurologic, or renal disease, or clinically significant laboratory or electrocardiogram (ECG) abnormality as determined by the investigator.
- •Have a history in the last 6 months of exertional angina, unstable angina, myocardial infarction, and acute coronary syndrome.
- •Have a history of heart failure of either New York Heart Association Class III or IV.
- •A history of additional risk factors for Torsades de Pointes (TdP; [e.g., chronic hypokalemia, family history of Long QT Syndrome]).
- •Participants with acute liver disease (e.g. acute viral hepatitis, alcoholic hepatitis); participants with a known chronic liver disease (e.g. hepatitis B, C, alcoholic liver disease, cirrhosis); alanine aminotransferase (ALT) or aspartate aminotransferase (AST) equal to or higher than 2X upper limit of normal (ULN); total bilirubin (TBL) equal to or higher than 1.5X ULN; (except for participants with Gilbert's syndrome); or alkaline phosphatase (ALP) equal to or higher than 2X ULN.
- •Participants have answered 'yes' to either Question 4 (Active Suicidal Ideation with Some Intent to Act, Without Specific Plan) or Question 5 (Active Suicidal Ideation with Specific Plan and Intent) on the "Suicidal Ideation" portion of the Columbia Suicide Severity Rating Scale (C-SSRS)- Children's version, or answer "yes" to any of the suicide-related behaviors (actual attempt, interrupted attempt, aborted attempt).
- •Have used antipsychotic medications, with the exception of clozapine, quetiapine, pimavanserin in the 6 months prior to screening and at any time during the course of the study.
- •Have used anticholinergics trihexyphenidyl and benztropine in the 4 weeks prior to screening and at any time during the course of the study.
- •Have motor conditions for which the antiparkinsonian treatment is expected to change during the course of the study, as well as unpredictable motor fluctuations that in the investigator's opinion would interfere with administering assessments.
- •Are taking any medications or food, herbal or dietary supplements that are inhibitors (e.g., ketoconazole, grapefruit juice), or strong/moderate inducers of cytochrome P450 3A4 (CYP3A4) (e.g., rifampicin) or are unable or unwilling to discontinue usage of them 4 weeks prior to first dose of study drug.
研究组 & 干预措施
Placebo
Placebo Comparator
Participants received placebo administered orally once a day (QD).
干预措施: Placebo (Drug)
10 milligram (mg) LY3154207
Experimental
Participants received 10 mg LY3154207 administered orally QD.
干预措施: LY3154207 (Drug)
30 mg LY3154207
Experimental
Participants received 30 mg LY3154207 administered orally QD.
干预措施: LY3154207 (Drug)
75 mg LY3154207
Experimental
Participants received 75 mg LY3154207 administered orally QD.
干预措施: LY3154207 (Drug)
结局指标
主要结局
Change From Baseline in the Continuity of Attention (CoA) Composite Score of the Cognitive Drug Research Computerized Cognition Battery (CDR-CCB)
时间窗: Baseline, Week 12
The CDR-CCB tests is designed to evaluate the effects of novel compounds on the quality of cognitive functioning which includes tests of attention (simple and choice reaction time, digit vigilance), working memory (spatial and numeric) and episodic memory (word recognition, picture recognition). Continuity of attention measures speed and accuracy and is calculated from 3 attentional tasks on the CDR computerized battery tests. For continuity of attention, the score range is -999 to 35. A high score reflects someone able to keep his/her mind on a single task for a prolonged period. A negative change from baseline reflects impairment compared to baseline. Data presented are model-based bayesian posterior mean response rates with 95% credible interval.
次要结局
- Change From Baseline in Pulse Rate to Week 12(Baseline, Week 12)
- Change From Baseline on the Alzheimer's Disease Cooperative Study-Clinician Global Impression of Change (ADCS-CGIC) Score(Baseline, Week 12)
- Change From Baseline on the CDR-CCB Power of Attention (PoA) Composite Score(Baseline, Week 12)
- Change From Baseline in the 13-item Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog13)(Baseline, Week 12)
- Change From Screening in the Montreal Cognitive Assessment (MoCA) Score(Screening (Baseline), Week 12)
- Change From Baseline in the Neuropsychiatric Inventory (NPI) Total Score and Individual Item Scores(Baseline, Week 12)
- Change From Baseline in the Epworth Sleepiness Scale (ESS) Score(Baseline, Week 12)
- Change From Baseline in the Movement Disorder Society's Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Total Score (Sum of Parts I-III)(Baseline, Week 12)
- Change From Baseline in the Penn Parkinson's Daily Activities Questionnaire-15 (PDAQ-15) Total Score(Baseline, Week 12)
- Change From Baseline in Delis-Kaplan Executive Function System (D-KEFS) Verbal Fluency Test Score(Baseline, Week 12)
- Change in MDS-UPDRS Parts II (Motor Experiences of Daily Living) and III (Motor Exam) From Baseline to Week 12(Baseline, Week 12)
- Number of Participants Who Met the Potentially Clinically Significant Vital Signs Criteria at 3 Consecutive Time Points at Visit 3(Visit 3 (Day 1 stopping rules))
- Change From Baseline in Clinic Blood Pressure (BP) to 8 Hours Post Dose(Baseline, 8 Hours Post Dose)
- Change From Baseline in Pulse Rate to 8 Hours Post Dose(Baseline, 8 Hours Post Dose)
- Change From Baseline In-clinic BP to Week 12(Baseline, Week 12)
- Change in Home Blood Pressure Measurement (HBPM), for SBP, DBP From Baseline to Week 12(Baseline, Week 12)
- Change in HBPM for Pulse Rate From Baseline to Week 12(Baseline, Week 12)
- Change From Baseline in the Physician Withdrawal Checklist (PWC)-20 Total Score From Week 12 to In-Clinic Follow-up Visit(Week 12, Follow-up (2 Weeks after Week 12))
- Pharmacokinetics (PK): Steady-State Trough Plasma Concentrations of LY3154207(Day 1: 1-3 hours post-dose; Day 7, Day 14 and Day 42: post-dose; Day 84: pre-dose)
研究者
研究点 (76)
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