NCT04764669已完成2 期
An Open-Label Study To Evaluate the Pharmacodynamic Effects, Efficacy, Safety, and Tolerability of E2027 in Subjects With Dementia With Lewy Bodies or Parkinson's Disease Dementia With or Without Amyloid Copathology
适应症
干预措施
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Eisai Inc.
- 入组人数
- 34
- 试验地点
- 14
- 主要终点
- Percent Change From Baseline in Cerebrospinal Fluid (CSF) Cyclic Guanosine Monophosphate (cGMP) at Week 9
研究概览
简要总结
The purpose of study is to demonstrate the pharmacodynamic (PD) effects of E2027 on cerebrospinal fluid (CSF) cyclic guanosine monophosphate (cGMP) in participants with DLB and PDD with and without amyloid copathology after 9 weeks of treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 50 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female, age 50 to 85 years, inclusive at time of consent
- •Meet criteria for probable DLB (as defined by the 4th report of the DLB Consortium) or meet criteria for probable PDD (as defined by the task force of the Movement Disorder Society).
- •Mini-mental state examination (MMSE) greater than (>) 14 and less than (<) 26 at Screening Visit
- •For DLB participants, have experienced visual hallucinations since onset of their DLB
- •If receiving acetylcholinesterase inhibitors (AChEIs), must have been on a stable dose for at least 12 weeks before Screening Visit, with no plans for dose adjustment during the study. Treatment naive participants can be entered into the study but there should be no plans to initiate treatment with AChEIs from Screening to the end of the study.
- •If receiving memantine, must have been on a stable dose for at least 12 weeks before Screening Visit, with no plans for dose adjustment during the study. Treatment naive participants can be entered into the study but there should be no plans to initiate treatment with memantine from Screening to the end of the study.
- •If receiving Parkinson's disease medications, must have been on a stable dose for at least 4 weeks before Screening Visit, with no plans for dose adjustment during the study.
- •Must have an identified caregiver or informant who is willing and able to provide follow up information on the participant throughout the course of the study.
- •Provide written informed consent.
排除标准
- •Any neurological condition that may be contributing to cognitive impairment above and beyond those caused by the participant's DLB or PDD, including any comorbidities detected by clinical assessment or magnetic resonance imaging (MRI) (identification of amyloid copathology is not exclusionary)
- •History of transient ischemic attacks or stroke within 12 months of Screening
- •Modified Hachinski Ischemic Scale >4
- •Parkinsonian (extrapyramidal) features with Hoehn and Yahr Scale (HYS) stage 4 or higher
- •Any major psychiatric diagnosis, including schizophrenia, bipolar disorder and current major depressive disorder as per Diagnostic and Statistical Manual of Mental Disorders Fifth Edition
- •Geriatric Depression Scale (GDS) score >8
- •Severe visual or hearing impairment that may interfere with the participant study assessments including cognitive testing
- •Any contraindications to lumbar puncture
- •History of deep brain stimulation or other neurosurgical procedure for Parkinson's disease
- •Has thyroid stimulating hormone (TSH) above normal range
- •Abnormally low serum vitamin B12 levels (< the lower limit of normal [LLN]) for the testing laboratory
- •Contraindications to MRI scanning
- •Evidence of other clinically significant lesions that suggest a dementia diagnosis other than DLB or PDD on brain MRI at Screening
- •Other significant pathological findings on brain MRI at Screening
- •Hypersensitivity to E2027 or any of the excipients
- •A prolonged corrected QT interval calculated using Fridericia's formula (QTcF) as demonstrated by triplicate ECG at the Screening or Baseline Visit (that is, mean value >450 millisecond [msec])
- •Had symptomatic orthostatic hypotension or symptomatic orthostatic tachycardia which resulted in hospitalization or urgent medical review in hospital in the past 12 months before Screening
- •Any other clinically significant abnormalities in vital signs, ECG and laboratory values that in the opinion of the investigator, require further investigation or treatment or that may interfere with study procedures or safety
- •Malignant neoplasms within 3 years of Screening (except for basal or squamous cell carcinoma of the skin, or localized prostate cancer in male participants). Participants who had malignant neoplasms but who have had at least 3 years of documented uninterrupted remission before Screening need not be excluded.
- •Has a "yes" answer to C-SSRS suicidal ideation Type 4 or 5, or any suicidal behavior assessment within 6 months before Screening, at Screening, or at the Baseline Visit, or has been hospitalized or treated for suicidal behavior in the past 5 years before Screening
- •Known or suspected history of drug or alcohol dependency or abuse within 2 years before Screening, current use of recreational drugs or a positive urine drug test at Screening.
- •Any other medical conditions (example, cardiac, respiratory, gastrointestinal, renal disease) which are not stably and adequately controlled, or which in the opinion of the investigator may affect the participant's safety or interfere with the study assessments
- •Taking any of the prohibited medications or not meeting the requirements regarding stable doses of permitted medications
- •Participation in a clinical study involving any investigational drug/device for DLB or PDD within 6 months before Screening or any other investigational drug/device in the 8 weeks or 5 half-lives (whichever is longer) of the study medication before Screening unless it can be documented that the participant was in a placebo treatment arm
- •Planned surgery which requires general, spinal or epidural anesthesia that will take place during the study.
- •Males who have not had a successful vasectomy (confirmed azoospermia) if their female partners are of childbearing potential and are not willing to use a highly effective contraceptive method throughout the study period and for 98 days after study drug discontinuation. No sperm donation is allowed during the study period and for 98 days after study drug discontinuation.
- •Females who are breastfeeding or pregnant at Screening or Baseline
- •Females of childbearing potential who:
- •Within 28 days before study entry, did not use a highly effective method of contraception
- •Do not agree to use a highly effective method of contraception throughout the entire study period and for 28 days after study drug discontinuation
研究组 & 干预措施
DLB Without Amyloid Copathology
Experimental
Participants with DLB (without amyloid copathology) will receive E2027 50 milligram (mg) capsules, orally, once daily up to 12 weeks.
干预措施: E2027 (Drug)
DLB With Amyloid Copathology
Experimental
Participants with DLB (with amyloid copathology) will receive E2027 50 mg capsules, orally, once daily up to 12 weeks.
干预措施: E2027 (Drug)
PDD Without Amyloid Copathology
Experimental
Participants with PDD (without amyloid copathology) will receive E2027 50 mg capsules, orally, once daily up to 12 weeks.
干预措施: E2027 (Drug)
PDD With Amyloid Copathology
Experimental
Participants with PDD (with amyloid copathology) will receive E2027 50 mg capsules, orally, once daily up to 12 weeks.
干预措施: E2027 (Drug)
结局指标
主要结局
Percent Change From Baseline in Cerebrospinal Fluid (CSF) Cyclic Guanosine Monophosphate (cGMP) at Week 9
时间窗: Baseline, Week 9
cGMP was measured in CSF samples using a validated liquid chromatography with tandem mass spectrometry (LC-MS/MS) method with a lower limit of quantitative at 0.500 nanogram per milliliter (ng/ml). Evaluation of cGMP following dosing of E2027 was based on relative percent change from baseline.
次要结局
- Number of Participants With Treatment Emergent Orthostatic Hypotension(Week 3, Week 6, Week 9, Week 12 and Week 16)
- Number of Participants With Markedly Abnormal Laboratory Values(From first dose of study drug up to Week 16)
- Change From Baseline in Total Score of Unified Parkinson's Disease Rating Scale Part III: Motor Examination (UPDRS-III)(Baseline, Week 12 and Week 16)
- Number of Participants With Treatment Emergent Adverse Events (TEAEs), Severe TEAEs, Serious TEAEs, Adverse Events (AEs) Resulting in Study Discontinuation(From first dose of study drug up to Week 16)
- Number of Participants With Post Baseline Treatment Emergent Orthostatic Tachycardia(From first dose of study drug up to Week 16)
- Number of Participants With Post-Baseline Abnormal Electrocardiogram (ECG) Findings(From first dose of study drug up to Week 16)
- Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS)(From first dose of study drug up to Week 16)
研究者
研究点 (14)
Loading locations...
相似试验
终止
2 期
A Study to Evaluate the Pharmacodynamic Activity of E2730 in Adult Participants With Photosensitive EpilepsyPhotosensitive EpilepsyNCT03603639Eisai Inc.6
终止
1 期
Dose Response Relationship of Oxytocin on Irritability in YouthsIrritable MoodNCT03863288University of Nebraska60
终止
2 期
A Study to Evaluate the Pharmacodynamic Activity of E2082 in Adult Participants With Photosensitive EpilepsyPhotosensitive EpilepsyNCT03686033Eisai Inc.8
已完成
1 期
Study in Pediatric Subjects Evaluating Pharmacokinetics and Safety of EXPARELPostoperative Pain ManagementNCT03485014Pacira Pharmaceuticals, Inc15
已完成
2 期
Phase 2a RDEA3170 and Allopurinol Combination Study in Gout SubjectsGoutNCT02498652Ardea Biosciences, Inc.41