Efficacy and Safety of Suvorexant (MK-4305) for Reducing Incidence of Delirium in Japanese Participants at High Risk of Delirium (MK-4305-085)

Study Overview
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Brief Summary
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The goal of this study is to evaluate the efficacy and safety of suvorexant (MK-4305) for reducing the incidence of delirium in Japanese participants who are at high risk of delirium. The primary hypothesis is that suvorexant reduces the proportion of participants with delirium compared with placebo as assessed by the diagnostic and statistical manual of mental disorders 5th edition (DSM-5) criteria.

Official Title
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A Phase 3 Multicenter, Randomized, Placebo-controlled, Double-blind Clinical Study to Evaluate the Efficacy and Safety of MK-4305 (Suvorexant) for Reducing Incidence of Delirium in Japanese Participants at High Risk of Delirium

Conditions
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Delirium

Intervention / Treatment
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* Drug: Suvorexant
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Is hospitalized for (1) acute disease with severe disease state or decreased daily living function or (2) elective surgery requiring general anesthesia scheduled on the day after or 2 days after admission/Day 1 Has (1) mild cognitive impairment or mild dementia and/or (2) a history of delirium in any prior hospitalization Requires hospitalization for 6 days for acute disease, with treatment starting on day of admission; or 7 days, with treatment starting the day after admission OR Requires hospitalization for 6 days for elective surgery scheduled on the day after admission; or for 7 days for elective surgery scheduled 2 days after admission Is able to take study medications orally Exclusion Criteria: Has moderate or severe dementia Has a history of epilepsy or Parkinson's disease Currently uses psychotropic agents or has a mental condition including schizophrenia, other mental disorders, bipolar disorder and major depression Has a history of drug or alcohol abuse in the 5 years prior to start of study or has alcoholic disease such as alcoholic liver disease or gastritis alcoholic Has a history of narcolepsy or cataplexy Has used hypnotics, antipsychotics, mood stabilizers, antidepressants, anxiolytics, psychostimulants, anticonvulsants or tiapride within 2 weeks prior to randomization Has delirium as assessed by DSM-5 or DRS-R-98 (total score ≥14.5) before the first dose of study medication

Ages Eligible for Study
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Minimum Age: 65 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Suvorexant<br>Participants will receive 15 mg of suvorexant orally once daily (QD) for 5 to 7 days. | Drug: Suvorexant<br>* Suvorexant administered at a dose of 15 mg QD via oral tablet<br>* Other names: MK-4305;|
| Placebo Comparator: Placebo<br>Participants will receive suvorexant-matching placebo orally QD for 5 to 7 days. | Drug: Placebo<br>* Suvorexant-matching placebo administered QD via oral tablet<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants with delirium as assessed by diagnostic and statistical manual of mental disorders 5th edition (DSM-5) criteria | DSM-5 is the gold standard for diagnosis of delirium. DSM-5 criteria will be used for clinician assessment of delirium. The percentage of participants with delirium per DSM-5 criteria will be presented. | Up to  8 days | 
| Number of participants who experience one or more adverse events (AEs) | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who experience one or more AEs will be presented. | Up to  21 days | 
| Number of participants who discontinue study treatment due to an AE | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who discontinue study treatment due to an AE will be presented. | Up to  7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum daily total score on Delirium Rating Scale-Revised-98 (DRS-R-98) | DRS-R-98 is a diagnostic and assessment tool used for evaluation of delirium. It is a 16-item clinician-rated scale with 13 items measuring delirium severity and 3 diagnostic items. The total DRS-R-98 score can range from 0 (lowest) to 46 (highest). Higher scores indicate worsening or more severe delirium. The maximum daily total score on DRS-R-98 will be presented. | Up to  8 days | 
| Percentage of participants with delirium as assessed by DRS-R-98 | DRS-R-98 is a diagnostic and assessment tool used for evaluation of delirium. It is a 16-item clinician-rated scale with 13 items measuring delirium severity and 3 diagnostic items. The total DRS-R-98 score can range from 0 (lowest) to 46 (highest). Higher scores indicate worsening or more severe delirium. Optimized cutoff score for delirium diagnosis in Japanese translated DRS-R-98 has been determined as ≥14.5. The percentage of participants with delirium as assessed by DRS-R-98, defined as the percentage of participants with total score ≥14.5 per DRS-R-98, will be presented. | Up to  8 days |