NCT03044249

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

Terminated Phase 2 Results posted Last updated 1 April 2021

What this trial tests

Phase 2 trial testing MP-101 in Psychosis in 81 participants. Terminated before completion.

Timeline

4 May 2017

Primary endpoint
30 January 2020

30 January 2020

Quick facts

Lead sponsor	Mediti Pharma Inc.
Phase	Phase 2
Status	Terminated
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	triple
Primary purpose	treatment
Enrollment	81
Start date	4 May 2017
Primary completion	30 January 2020
Estimated completion	30 January 2020
Sites	20 locations across Canada, United States

Drugs / interventions tested

• MP-101 — full drug profile →
• Placebo

Conditions studied

• Psychosis — all drugs for Psychosis →
• Dementia — all drugs for Dementia →
• Aggression — all drugs for Aggression →
• Agitation — all drugs for Agitation →

Sponsor

Mediti Pharma Inc. — full company profile →

Who can join

50 and older, any sex, with Psychosis or Dementia. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percentage of Participants With 30% Improvement From Baseline in the Neuropsychiatric Inventory (NPI) - Psychosis Subscale or Aggression/Agitation Subscale Score Primary · 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)

Group	Value	95% CI
Placebo	58
MP-101	62

Percentage of Participants With Improvement From Baseline in the Clinical Global Impression of Improvement (CGI-I) at Week 10 Secondary · 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.

Very much improved

Group	Value	95% CI
Placebo	0
MP-101	8.0

Much improved

Group	Value	95% CI
Placebo	25.0
MP-101	28.0

Minimally improved

Group	Value	95% CI
Placebo	34.4
MP-101	28.0

No change

Group	Value	95% CI
Placebo	21.9
MP-101	16.0

Minimally worse

Group	Value	95% CI
Placebo	15.6
MP-101	12.0

Much worse

Group	Value	95% CI
Placebo	3.1
MP-101	8.0

Very much worse

Group	Value	95% CI
Placebo	0
MP-101	0

Change From Baseline in NPI Total Score Secondary · 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.

Group	Value	95% CI
Placebo	-3.43	± 2.34
MP-101	-8.70	± 2.66

Change From Baseline in NPI Core Total Score Secondary · 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 in

Group	Value	95% CI
Placebo	-3.46	± 1.15
MP-101	-5.05	± 1.31

Number of Participants With NPI Caregiver Distress Secondary · 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.

Week 10 Delusions ( Not at all)

Group	Value	95% CI
Placebo	0
MP-101	0

Week 10 Delusions ( Minimally)

Group	Value	95% CI
Placebo	1
MP-101	1

Week 10 Delusions (Mildly)

Group	Value	95% CI
Placebo	9
MP-101	5

Week 10 Delusions (Moderately)

Group	Value	95% CI
Placebo	7
MP-101	3

Week 10 Delusions (severely)

Group	Value	95% CI
Placebo	1
MP-101	2

Week 10 Delusions (Very Severely or extremely)

Group	Value	95% CI
Placebo	1
MP-101	0

Week 10 Hallucinations ( Not at all)

Group	Value	95% CI
Placebo	3
MP-101	1

Week 10 Hallucinations ( Minimally)

Group	Value	95% CI
Placebo	3
MP-101	3

Change From Baseline in NPI Domains - Anxiety Secondary · 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

Group	Value	95% CI
Placebo	-0.1	± 3.53
MP-101	-0.6	± 2.69

Number of Participants With Any Treatment Emergent Adverse Event Secondary · 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.

Group	Value	95% CI
Placebo	24
MP-101	24

Change From Baseline in the Unified Parkinson's Disease Rating Scale (UPDRS) Part III Secondary · 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.

Group	Value	95% CI
Placebo	-0.29	± 0.76
MP-101	-0.37	± 0.87

Population Pharmacokinetics (PK): Plasma Levels of MP-101 and Metabolite Secondary · 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.

Week 2: 4-8 hours

Group	Value	95% CI
MP-101	7.9	± 1.11
LY2812223 (MP-101 Metabolite)	429.8	± 1.00

Week 4: Predose

Group	Value	95% CI
LY2812223 (MP-101 Metabolite)	85.0	± 1.01

Week 4: 0-2 hours

Group	Value	95% CI
MP-101	11.4	± 1.09
LY2812223 (MP-101 Metabolite)	249	± 1.01

Week 6: 8-12 hours

Group	Value	95% CI
MP-101	4.1	± 1.36
LY2812223 (MP-101 Metabolite)	808.4	± 1.00

Week 10: 2- 4 hours

Group	Value	95% CI
MP-101	9.3	± 1.12
LY2812223 (MP-101 Metabolite)	929	± 1.00

Early Termination

Group	Value	95% CI
MP-101	NA	± NA
LY2812223 (MP-101 Metabolite)	13.0	± 1.24

Adverse events — posted to ClinicalTrials.gov

Time frame: Baseline Up To 10 Weeks. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo

Serious: 4/42 (10%)

Deaths: 0/42

MP-101

Serious: 4/39 (10%)

Deaths: 1/39

Serious adverse events (11 terms)

Reaction	System	Placebo	MP-101
Pneumonia	Infections and infestations	—	—
Sepsis	Infections and infestations	—	—
Fall	Injury, poisoning and procedural complications	—	—
Hip fracture	Injury, poisoning and procedural complications	—	—
Dementia	Nervous system disorders	—	—
Unresponsive to stimuli	Nervous system disorders	—	—
Abnormal behaviour	Psychiatric disorders	—	—
Mental status changes	Psychiatric disorders	—	—
Psychotic disorder	Psychiatric disorders	—	—
Suicidal ideation	Psychiatric disorders	—	—
Acute kidney injury	Renal and urinary disorders	—	—

Other adverse events (8 terms — click to expand)

Reaction	System	Placebo	MP-101
Confusional state	Psychiatric disorders	—	—
Nausea	Gastrointestinal disorders	—	—
Vomiting	Gastrointestinal disorders	—	—
Dizziness	Nervous system disorders	—	—
Fatigue	General disorders	—	—
Fall	Injury, poisoning and procedural complications	—	—
Contusion	Injury, poisoning and procedural complications	—	—
Headache	Nervous system disorders	—	—

Most-reported serious reactions: Pneumonia, Sepsis, Fall, Hip fracture, Dementia, Unresponsive to stimuli, Abnormal behaviour, Mental status changes.

Data from ClinicalTrials.gov NCT03044249 adverse events section.

Sponsor's own description

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

Publications & conference data

7 peer-reviewed publications reference this trial (live from Europe PMC):

1. Alzheimer's disease drug development pipeline: 2019.
   Cummings J, Lee G, Ritter A, Sabbagh M, et al · · 2019 · cited 485× · PMID 31334330 · DOI 10.1016/j.trci.2019.05.008
2. Alzheimer's disease drug development pipeline: 2018.
   Cummings J, Lee G, Ritter A, Zhong K. · · 2018 · cited 402× · PMID 29955663 · DOI 10.1016/j.trci.2018.03.009
3. Pharmacotherapy of Behavioral and Psychological Symptoms of Dementia: State of the Art and Future Progress.
   Magierski R, Sobow T, Schwertner E, Religa D. · · 2020 · cited 76× · PMID 32848775 · DOI 10.3389/fphar.2020.01168
4. Challenges and opportunities for improving the landscape for Lewy body dementia clinical trials.
   Goldman JG, Forsberg LK, Boeve BF, Armstrong MJ, et al · · 2020 · cited 44× · PMID 33121510 · DOI 10.1186/s13195-020-00703-5
5. Psychosis in Alzheimer's Disease.
   Ballard C, Kales HC, Lyketsos C, Aarsland D, et al · · 2020 · cited 38× · PMID 33048274 · DOI 10.1007/s11910-020-01074-y
6. Management of Dementia-Related Psychosis, Agitation and Aggression: A Review of the Pharmacology and Clinical Effects of Potential Drug Candidates.
   Marcinkowska M, Śniecikowska J, Fajkis N, Paśko P, et al · · 2020 · cited 37× · PMID 32052375 · DOI 10.1007/s40263-020-00707-7
7. Pharmacological treatment trials of agitation in Alzheimer's disease: A systematic review of ClinicalTrials.gov registered trials.
   Liu KY, Borissova A, Mahmood J, Elliott T, et al · · 2021 · cited 11× · PMID 33816763 · DOI 10.1002/trc2.12157