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

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

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.

Study Overview

• Status: Completed
• Conditions: Delirium
• Intervention / Treatment: Drug: Suvorexant; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 203
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Fukuoka, Japan, 810-8563
    • National Hospital Organization Kyushu Medical Center ( Site 8532)
  • Gifu, Japan, 500-8513
    • Gifu Municipal Hospital ( Site 8555)
  • Hiroshima, Japan, 730-8518
    • Hiroshima City Hiroshima Citizens Hospital ( Site 8505)
  • Kumamoto, Japan, 860-0008
    • National Hospital Organization Kumamoto Medical Center ( Site 8511)
  • Kyoto, Japan, 602-8026
    • Japanese Red Cross Kyoto Daini Hospital ( Site 8533)
  • Kyoto, Japan, 615-8256
    • Kyoto Katsura Hospital ( Site 8539)
  • Miyazaki, Japan, 880-8510
    • Miyazaki Prefectural Miyazaki Hospital ( Site 8543)
  • Niigata, Japan, 950-1197
    • Niigata City General Hospital ( Site 8544)
  • Okayama, Japan, 700-8511
    • Okayama Saiseikai General Hospital ( Site 8549)
  • Okayama, Japan, 7008558
    • Okayama University Hospital ( Site 8510)
  • Osaka, Japan, 534-0021
    • Osaka City General Hospital ( Site 8518)
  • Osaka, Japan, 540-0006
    • National Hospital Organization Osaka National Hospital ( Site 8536)
  • Osaka, Japan, 543-8555
    • Japanese Red Cross Osaka Hospital ( Site 8523)
  • Osaka, Japan, 550-0006
    • Nippon Life Hospital ( Site 8552)
  • Osaka, Japan, 553-0003
    • Japan Community Health care Organization Osaka Hospital ( Site 8545)
  • Osaka, Japan, 558-8558
    • Osaka General Medical Center ( Site 8538)
  • Saga, Japan, 840-8571
    • Saga-Ken Medical Centre Koseikan ( Site 8526)
  • Tokushima, Japan, 770-8539
    • Tokushima Prefectural Central Hospital ( Site 8509)
  • Tokyo, Japan, 104-0045
    • National Cancer Center Hospital ( Site 8520)
  • Tokyo, Japan, 152-8902
    • National Hospital Organization Tokyo Medical Center ( Site 8529)
  • Tokyo, Japan, 162-8666
    • Tokyo Women's Medical University Hospital ( Site 8527)
  • Tokyo, Japan, 177-8521
    • Juntendo University Nerima Hospital ( Site 8501)
  • Tokyo, Japan
    • Tokyo Medical and Dental University Hospital ( Site 8503)
  • Chiba
    • Ichikawa, Chiba, Japan, 272-8516
      • Kohnodai Hospital, National Center for Global Health and Medicine ( Site 8522)
  • Fukuoka
    • Iizuka, Fukuoka, Japan
      • Iizuka Hospital ( Site 8540)
    • Kitakyushu, Fukuoka, Japan, 802-8555
      • Kokura Memorial Hospital ( Site 8537)
  • Gunma
    • Maebashi, Gunma, Japan, 371-0811
      • Maebashi Red Cross Hospital ( Site 8548)
  • Hiroshima
    • Fukuyama, Hiroshima, Japan, 721-8511
      • Fukuyama City Hospital ( Site 8528)
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 060-0004
      • Tonan Hospital ( Site 8512)
  • Hyogo
    • Amagasaki, Hyogo, Japan, 660-8511
      • Kansai Rosai Hospital ( Site 8550)
  • Ishikawa
    • Kahoku-gun, Ishikawa, Japan, 920-0293
      • Kanazawa Medical University Hospital ( Site 8514)
    • Kanazawa, Ishikawa, Japan, 920-8650
      • National Hospital Organization Kanazawa Medical Center ( Site 8554)
  • Kagawa
    • Kita-gun, Kagawa, Japan, 761-0793
      • Kagawa University Hospital ( Site 8519)
    • Takamatsu, Kagawa, Japan, 760-0017
      • TAKAMATSU Red Cross Hospital ( Site 8547)
  • Kanagawa
    • Kawasaki, Kanagawa, Japan, 211-8533
      • Nippon Medical School Musashi Kosugi Hospital ( Site 8502)
    • Yokohama, Kanagawa, Japan, 224-8503
      • Showa University Northern Yokohama Hospital ( Site 8534)
    • Yokohama, Kanagawa, Japan, 232-0024
      • Yokohama City University Medical Center ( Site 8516)
    • Yokohama, Kanagawa, Japan, 234-8503
      • Saiseikai Yokohamashi Nanbu Hospital ( Site 8541)
    • Yokohama, Kanagawa, Japan, 2360064
      • Yokohama City University Hospital ( Site 8515)
    • Yokohama, Kanagawa, Japan, 245-8575
      • National Hospital Organization Yokohama Medical Center ( Site 8531)
  • Kyoto
    • Maizuru-shi, Kyoto, Japan, 625-8502
      • National Hospital Organization Maizuru Medical Center ( Site 8535)
  • Nagano
    • Matsumoto, Nagano, Japan, 390-8510
      • Aizawa Hospital ( Site 8542)
  • Osaka
    • Moriguchi, Osaka, Japan, 570-8540
      • Matsushita Memorial Hospital ( Site 8556)
    • Suita, Osaka, Japan, 565-0871
      • Osaka University Hospital ( Site 8524)
    • Toyonaka, Osaka, Japan, 560-8565
      • Toyonaka Municipal Hospital ( Site 8521)
  • Shimane
    • Izumo, Shimane, Japan, 693-8555
      • Shimane Prefectural Central Hospital ( Site 8530)
  • Tochigi
    • Kanuma, Tochigi, Japan, 322-8550
      • Kamitsuga General Hospital ( Site 8546)
    • Sano, Tochigi, Japan, 327-8511
      • SANO KOSEI GENERAL HOSPITAL ( Site 8551)
    • Shimotsuke, Tochigi, Japan, 329-0498
      • Jichi Medical University Hospital ( Site 8525)
  • Yamaguchi
    • Ube, Yamaguchi, Japan, 755-8505
      • Yamaguchi University Hospital ( Site 8517)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years to 90 years (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start (Actual): October 22, 2020
• Primary Completion (Actual): December 23, 2022
• Study Completion (Actual): December 23, 2022

Study Registration Dates

• First Submitted: September 25, 2020
• First Submitted That Met QC Criteria: September 25, 2020
• First Posted (Actual): October 1, 2020

Study Record Updates

• Last Update Posted (Actual): January 4, 2023
• Last Update Submitted That Met QC Criteria: January 2, 2023
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Neurologic Manifestations; Confusion; Neurobehavioral Manifestations; Neurocognitive Disorders; Delirium; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Hypnotics and Sedatives; Sleep Aids, Pharmaceutical; Orexin Receptor Antagonists; Suvorexant
• Other Study ID Numbers: 4305-085; MK-4305-085 (Other Identifier: Merck); jRCT2031200149 (Registry Identifier: jRCT)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No