Tolerability, Pharmacokinetics, and Efficacy of MP-101 in the Treatment of Patients With Dementia-Related Psychosis and/or Agitation and Aggression
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 81
- 试验地点
- 19
- 主要终点
- Percentage of Participants With 30% Improvement From Baseline in the Neuropsychiatric Inventory (NPI) - Psychosis Subscale or Aggression/Agitation Subscale Score
研究概览
简要总结
A ten-week study to assess MP-101 in Dementia-Related Psychosis and/or Agitation and Aggression
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 50 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Females must be of non-childbearing potential, defined as women greater than or equal to (≥) 60 years of age, postmenopausal women ≥50 and less than (<) 60 years of age who have had a cessation of menses for at least 12 months, or women who are congenitally or surgically sterile
- •Males must agree to use 2 forms of highly effective birth control with female partners of childbearing potential while enrolled in the study, and for at least 28 days following the last dose
- •Ambulatory (with or without walking device) with a stable gait
- •Have a Mini-Mental State Examination (MMSE) score of 10 to 24
- •Meet clinical criteria for one of the following disorders: dementia associated with Parkinson's disease, dementia with Lewy bodies, possible or probable Alzheimer's disease, frontotemporal degeneration spectrum disorders, vascular dementia
- •Able to communicate verbally
- •Have an NPI score of ≥4 on either individual item (delusions or hallucinations) or ≥6 on the Psychosis Subscale (combined delusions and hallucinations), or an NPI score of ≥4 on agitation/aggression domain
- •Have a reliable caregiver who provides written informed consent to participate and who is in frequent contact with the patient (defined as spending at least 4 hours/day at least 4 days/week with the patient and who is knowledgeable about the patient's daytime and nighttime behaviors). The caregiver must be able to communicate with site personnel, and opinion of the investigator, must understand the written protocol-specified questionnaires. If a caregiver cannot continue, one replacement caregiver will be allowed if the above criterion is met
- •Must be on a stable dose of cholinesterase inhibitor and/or memantine, if applicable
- •If taking antipsychotic drugs or any drug intended to treat psychosis, must be on a stable treatment regimen for ≥1 month prior to the study
- •Have venous access sufficient to allow for blood sampling per the protocol
- •Have clinical laboratory test results within normal reference range for the population or investigative site
- •Are capable of participating in all study assessments
- •Are able and willing to provide consent (patients and caregivers)
排除标准
- •Have a history of significant psychotic disorders (including, schizophrenia, delusional disorder, substance abuse psychosis that lasted over 6 months, major depressive disorder or bipolar disorder with psychotic episodes)
- •Has a history of ischemic stroke within the last 12 months or any evidence of hemorrhagic stroke
- •Have renal impairment as defined by Estimated Glomerular Filtration Rate (eGFR) <45 milliliters per minute per 1.73 square meters (ml/min/1.73m2)
- •Have significant cardiovascular, respiratory, gastrointestinal, renal, hematologic, or oncologic comorbidities that could impact patient safety and study participation over 10 weeks
- •Have a history of seizures or other condition that would place the patient at increased risk of seizures.
- •Are, in the investigator's judgment, at risk for suicide, or as indicated by the Columbia Suicide Severity Rating Scale (C-SSRS)
- •Have a Fridericia's corrected QT interval (QTcF) greater than (>) 450 milliseconds (ms) for males or 470 ms for females
- •Are currently enrolled in any other clinical trial involving an investigational product or any other type of medical research judged not to be scientifically or medically compatible with this study
- •Have participated, within the last 30 days, in a clinical trial involving an investigational product. If the previous investigational product has a long half-life, at least 3 months (or more) must have passed
- •In the opinion of the investigator or sponsor, are unsuitable for inclusion in the study
研究组 & 干预措施
MP-101
Week 0:
Participants received 20 milligrams (mg) MP-101 orally QD (1 x 20-mg caps) and 2 placebo caps.
Week 1:
Participants received 40 mg MP-101 orally QD (2 x 20-mg caps) and 1 placebo caps.
Week 2 through Week 9:
Participants received 60 mg MP-101 orally QD (3 x 20-mg caps ).
干预措施: MP-101 (Drug)
Placebo
Participants received 3 capsules (caps) of placebo orally once daily (QD) during Week 0, Week 1, and Week 2 through Week 9.
干预措施: Placebo (Drug)
结局指标
主要结局
Percentage of Participants With 30% Improvement From Baseline in the Neuropsychiatric Inventory (NPI) - Psychosis Subscale or Aggression/Agitation Subscale Score
时间窗: Week 10
The NPI is a questionnaire that quantifies behavioral changes in dementia. For each of 12 domains there are 4 scores: Frequency (scale:1=occasionally to 4=very frequently), Severity (scale:1=Mild to 3=Severe), Total (frequency x severity), Caregiver distress (scale: 0=not at all distressing to 5=extremely distressing). An NPI response was defined as at least a 30% improvement from baseline on the NPI Psychosis sub-score (for participants with a psychosis diagnosis (Delusions and Hallucinations)) or the NPI Aggression/Agitation sub-score (for participants with an agitation/aggression diagnosis). The delusions, hallucinations, and aggression/agitation domain scores were added together to form a core total score with score range of 0 to 36. Lower score=less severity. A negative change score from baseline indicates improvement.
次要结局
- Change From Baseline in NPI Total Score(Baseline, Week 10)
- Change From Baseline in NPI Core Total Score(Baseline, Week 10)
- Number of Participants With NPI Caregiver Distress(Week 10)
- Percentage of Participants With Improvement From Baseline in the Clinical Global Impression of Improvement (CGI-I) at Week 10(Week 10)
- Change From Baseline in NPI Domains - Anxiety(Baseline, 10 Weeks)
- Population Pharmacokinetics (PK): Plasma Levels of MP-101 and Metabolite(Week 2: 4-8 hours post-dose; Week 4: Predose, 0-2 hours postdose; Week 6: 8-12 hours postdose; Week 10: 2- 4 hours;Early Termination)
- Number of Participants With Any Treatment Emergent Adverse Event(Baseline Up to 10 Weeks)
- Change From Baseline in the Unified Parkinson's Disease Rating Scale (UPDRS) Part III(Baseline, Week 10)