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A Study of MP-101 in Dementia-Related Psychosis and/or Agitation and Aggression

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03044249
Recruitment Status : Terminated (Statistical futility; totality of evidence suggests study unlikely to meet endpoint)
First Posted : February 6, 2017
Results First Posted : April 1, 2021
Last Update Posted : April 1, 2021
Sponsor:
Information provided by (Responsible Party):
Mediti Pharma Inc.

Brief Summary:
A ten-week study to assess MP-101 in Dementia-Related Psychosis and/or Agitation and Aggression

Condition or disease Intervention/treatment Phase
Psychosis Dementia Aggression Agitation Alzheimer Dementia Drug: MP-101 Drug: Placebo Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 81 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Tolerability, Pharmacokinetics, and Efficacy of MP-101 in the Treatment of Patients With Dementia-Related Psychosis and/or Agitation and Aggression
Actual Study Start Date : May 4, 2017
Actual Primary Completion Date : January 30, 2020
Actual Study Completion Date : January 30, 2020


Arm Intervention/treatment
Experimental: 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 ).

Drug: MP-101
Capsules
Other Names:
  • LY2979165
  • LY2812223

Placebo Comparator: Placebo
Participants received 3 capsules (caps) of placebo orally once daily (QD) during Week 0, Week 1, and Week 2 through Week 9.
Drug: Placebo
Capsules




Primary Outcome Measures :
  1. Percentage of Participants With 30% Improvement From Baseline in the Neuropsychiatric Inventory (NPI) - Psychosis Subscale or Aggression/Agitation Subscale Score [ Time Frame: 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.


Secondary Outcome Measures :
  1. Percentage of Participants With Improvement From Baseline in the Clinical Global Impression of Improvement (CGI-I) at Week 10 [ Time Frame: Week 10 ]
    The CGI rating scale, which measures symptom severity, treatment response and the efficacy of treatments, is used in clinical studies on mental disorders. CGI Improvement scale is a 7 point scale that requires the clinician to assess how much the participant's illness has improved or worsened relative to a baseline state at the beginning of the intervention: 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; 7=very much worse.

  2. Change From Baseline in NPI Total Score [ Time Frame: Baseline, 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). The NPI Total Score is calculated by adding the Individual Item Scores for all 12 domains, to yield a possible NPI Total Score of 0 to 144. Lower score=less severity. A negative change score from baseline indicates improvement.

  3. Change From Baseline in NPI Core Total Score [ Time Frame: Baseline, Week 10 ]
    The NPI is a questionnaire that quantifies behavioral changes in dementia. For each of 12 behavioral 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). The NPI CoreTotal Score is calculated by adding the Individual Item Scores for all 3 domains (hallucinations, delusions, and agitation/aggression) to yield a possible NPI Core Total Score of 0 to 36. Lower score=less severity. A negative change score from baseline indicates improvement.

  4. Number of Participants With NPI Caregiver Distress [ Time Frame: 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). The NPI Psychosis Subscale Caregiver Distress Score is calculated by adding Individual Item Scores for the domains of Delusions and Hallucinations, to yield a possible total score of 0 to 10. Lower score=less severity. A negative change score from baseline=improvement.

  5. Change From Baseline in NPI Domains - Anxiety [ Time Frame: Baseline, 10 Weeks ]
    The 12 individual items in NPI that quantify changes in dementia are delusions, hallucinations, agitation, depression, anxiety, apathy, disinhibition, irritability, euphoria, aberrant motor behavior, nighttime behaviors, and appetite. For each of 12 behavioral 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). The NPI Psychosis Subscale Anxiety consists of anxiety item to yield a possible NPI Score of 0 to 12. Lower score=less severity. A negative change score from baseline indicates improvement.

  6. Number of Participants With Any Treatment Emergent Adverse Event [ Time Frame: Baseline Up to 10 Weeks ]
    Number of participants with untoward medical occurrences that emerge during the treatment period, having been absent pretreatment, or worsen relative to the pretreatment state, which do not necessarily have a causal relationship with this treatment. A summary of serious adverse events (SAEs) and other non-serious adverse events (AEs) is located in the reported adverse events module.

  7. Change From Baseline in the Unified Parkinson's Disease Rating Scale (UPDRS) Part III [ Time Frame: Baseline, Week 10 ]
    Part III of the UPDRS is an investigator-scored scale used to assess the motor symptoms of patients with Parkinson's disease. The investigator rates the patient on 14 items based on observation or the performance of a task the patient performs (even in the context of any comorbidities) on a 5-point scale. The scores range from 0 to 4, with higher scores indicating greater impairment. The total UPDRS score was calculated as the sum of all items, ranging from 0 to 56 with higher scores indicating greater impairment. If any individual item was missing, the UPDRS score was be set to missing.

  8. Population Pharmacokinetics (PK): Plasma Levels of MP-101 and Metabolite [ Time Frame: 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 ]
    Summary statistics of sparse blood concentration samples at weeks 2, 4, 6, 10 and Early Termination obtained utilizing a population PK approach.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   50 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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)

Exclusion Criteria:

  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03044249


Locations
Show Show 20 study locations
Sponsors and Collaborators
Mediti Pharma Inc.
Investigators
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Study Director: Mediti Pharma Mediti Pharma Inc.
  Study Documents (Full-Text)

Documents provided by Mediti Pharma Inc.:
Study Protocol  [PDF] February 13, 2018
Statistical Analysis Plan  [PDF] November 20, 2018

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Responsible Party: Mediti Pharma Inc.
ClinicalTrials.gov Identifier: NCT03044249    
Other Study ID Numbers: MP-101-01
First Posted: February 6, 2017    Key Record Dates
Results First Posted: April 1, 2021
Last Update Posted: April 1, 2021
Last Verified: March 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Mediti Pharma Inc.:
Psychotic Disorders
Additional relevant MeSH terms:
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Dementia
Alzheimer Disease
Psychomotor Agitation
Psychotic Disorders
Mental Disorders
Aggression
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurocognitive Disorders
Tauopathies
Neurodegenerative Diseases
Schizophrenia Spectrum and Other Psychotic Disorders
Dyskinesias
Neurologic Manifestations
Psychomotor Disorders
Neurobehavioral Manifestations
Behavioral Symptoms