Efficacy and Safety of MK-8189 in Participants With an Acute Episode of Schizophrenia (MK-8189-008)

A Phase 2B Randomized, Double-Blind, Placebo- and Active-Controlled Trial of the Efficacy and Safety of MK-8189 in Participants Experiencing an Acute Episode of Schizophrenia

The purpose of this study is to evaluate the efficacy and safety of MK-8189 at a range of doses (8 mg, 16 mg, and 24 mg once daily) in adult participants who have an acute episode of schizophrenia according to Diagnostic and Statistical Manual of Mental Disorders 5th Edition (DSM-5) criteria. The primary hypotheses are the following: (1) MK-8189 24 mg is superior to placebo in reducing the Week 6 mean change from baseline in Positive and Negative Syndrome Scale (PANSS) total score (2) MK-8189 16 mg is superior to placebo in reducing the Week 6 mean change from baseline in PANSS total score.

With Amendment 4, enrollment was changed to approximately 500 participants with removal of the MK-8189 8 mg treatment arm. Participants enrolled before Amendment 4 that have been assigned to 8 mg MK-8189 will remain on 8 mg MK-8189 per protocol.

Study Overview

• Status: Active, not recruiting
• Conditions: Schizophrenia
• Intervention / Treatment: Drug: MK-8189; Drug: Placebo to risperidone; Drug: Risperidone; Drug: Placebo to MK-8189

• Study Type: Interventional
• Enrollment (Estimated): 500
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Toll Free Number; Phone Number: 1-888-577-8839; Email: Trialsites@merck.com

Study Locations

• Bulgaria
  • Burgas, Bulgaria, 8001
    • Mental Health Center Prof. Dr. Ivan Temkov - Burgas EOOD ( Site 3002)
  • Kardzhali, Bulgaria, 6600
    • State Psychiatric Hospital - Kardzhali ( Site 3005)
  • Ruse, Bulgaria, 7000
    • Mental Health Center - Ruse, EOOD ( Site 3003)
  • Sofia, Bulgaria, 1000
    • Center for Mental Health Prof. Nikola Shipkovenski Ltd ( Site 3000)
  • Veliko Tarnovo, Bulgaria, 5000
    • Mental Health Center - Veliko Tarnovo ( Site 3006)
  • Sofia
    • Novi Iskar, Sofia, Bulgaria, 1282
      • State Psychiatric Hospital "Sv. Ivan Rilski", Novi Iskar ( Site 3001)
• Croatia
  • Grad Zagreb
    • Zagreb, Grad Zagreb, Croatia, 10090
      • Klinika za psihijatriju Vrapce ( Site 4000)
    • Zagreb, Grad Zagreb, Croatia, 10090
      • Klinika za psihijatriju Vrapce ( Site 4001)
  • Primorsko-goranska Zupanija
    • Rijeka, Primorsko-goranska Zupanija, Croatia, 51000
      • Klinicki bolnicki centar Rijeka ( Site 4005)
  • Zagrebacka Zupanija
    • Zagreb, Zagrebacka Zupanija, Croatia, 10090
      • Klinika za psihijatriju Sveti Ivan ( Site 4003)
• Japan
  • Chiba, Japan, 260-8677
    • Chiba University Hospital ( Site 2024)
  • Fukuoka, Japan, 815-0074
    • Inokuchi Noma Hospital ( Site 2030)
  • Fukuoka, Japan, 819-0037
    • Kuramitsu Hospital ( Site 2014)
  • Kumamoto, Japan, 861-8002
    • Yuge Hospital ( Site 2018)
  • Tokyo, Japan, 121-8515
    • Seijin Hospital ( Site 2026)
  • Tokyo, Japan, 175-0091
    • Narimasu Kosei Hospital ( Site 2006)
  • Aichi
    • Toyoake, Aichi, Japan, 470-1168
      • Seishinkai Okehazama Hospital Fujita Kokoro Care Center ( Site 2011)
  • Chiba
    • Ichikawa, Chiba, Japan, 272-8516
      • Kohnodai Hospital, National Center for Global Health and Medicine ( Site 2005)
  • Fukuoka
    • Kitakyushu, Fukuoka, Japan, 808-0139
      • Wakato Hospital ( Site 2031)
    • Omuta, Fukuoka, Japan, 8360004
      • Shiranui Hospital ( Site 2043)
  • Gunma
    • Tomioka, Gunma, Japan, 3702455
      • Seimou Hospital ( Site 2004)
  • Kanagawa
    • Atsugi, Kanagawa, Japan, 243-0201
      • Soushu Hospital ( Site 2008)
    • Hadano, Kanagawa, Japan, 259-1304
      • Tanzawa Hospital ( Site 2037)
    • Yokohama-Shi, Kanagawa, Japan, 233-0006
      • Kanagawa Psychiatric Center ( Site 2035)
  • Nagano
    • Komoro, Nagano, Japan, 384-8540
      • Komoro Kogen Hospital ( Site 2046)
  • Okinawa
    • Kunigamigun, Okinawa, Japan, 904-1201
      • National Hospital Organization Ryukyu Hospital ( Site 2019)
    • Naha, Okinawa, Japan, 900-0005
      • Amekudai Hospital ( Site 2020)
  • Saga
    • Kanzaki-gun, Saga, Japan, 8420192
      • National Hospital Organization Hizen Psychiatric Medical Center ( Site 2017)
    • Karatsu, Saga, Japan, 847-0031
      • Rainbow and Sea Hospital ( Site 2016)
  • Tokyo
    • Hachioji, Tokyo, Japan, 192-0153
      • Ongata Hospital ( Site 2007)
    • Kita-ku, Tokyo, Japan, 114-0024
      • Nishigahara Hospital ( Site 2042)
    • Kodaira, Tokyo, Japan, 187-8551
      • National Center of Neurology and Psychiatry ( Site 2023)
• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital ( Site 0600)
  • Pusan-Kwangyokshi
    • Busan, Pusan-Kwangyokshi, Korea, Republic of, 47392
      • Inje University Busan Paik Hospital ( Site 0604)
  • Taegu-Kwangyokshi
    • Daegu, Taegu-Kwangyokshi, Korea, Republic of, 41944
      • Kyungpook National University Hospital ( Site 0601)
• Latvia
  • Daugavpils, Latvia, 5417
    • Daugavpils Psihoneirologiska Slimnica ( Site 8005)
  • Liepaja, Latvia, 3401
    • Piejuras Slimnica Psihiatriska Klinika ( Site 8001)
• Poland
  • Lodzkie
    • Lodz, Lodzkie, Poland, 91-229
      • Specjal. Psychiatryczny ZOZ w Lodzi, Szpital im. Babinskiego ( Site 0905)
  • Mazowieckie
    • Pruszkow, Mazowieckie, Poland, 05-802
      • Klinika Psychiatryczna Wydzialu Nauki o Zdrowiu WUM ( Site 0900)
    • Warsaw, Mazowieckie, Poland, 00-665
      • Samodzielny Wojewódzki Zespół Publicznych Zakładów Psychiatrycznej Opieki Zdrowotnej w Warszawie ( S
  • Pomorskie
    • Gdansk, Pomorskie, Poland, 80-211
      • Uniwersyteckie Centrum Kliniczne ( Site 0902)
  • Wielkopolskie
    • Poznań, Wielkopolskie, Poland, 61-485
      • Centrum Medyczne HCP ( Site 0913)
• Romania
  • Bucuresti
    • Bucharest, Bucuresti, Romania, 041914
      • Prof. Dr. Alexandru Obregia Psychiatry Hospital ( Site 0815)
    • Bucharest, Bucuresti, Romania, 041914
      • Prof. Dr. Alexandru Obregia Psychiatry Hospital ( Site 0816)
    • Bucharest, Bucuresti, Romania, 041914
      • Prof. Dr. Alexandru Obregia Psychiatry Hospital ( Site 0817)
    • Bucharest, Bucuresti, Romania, 041914
      • Prof. Dr. Alexandru Obregia Psychiatry Hospital ( Site 0818)
  • Iasi
    • Iași, Iasi, Romania, 700282
      • Institutul de Psihiatrie Socola ( Site 0810)
    • Iași, Iasi, Romania, 700282
      • Institutul de Psihiatrie Socola ( Site 0814)
• Russian Federation
  • Arkhangel Skaya Oblast
    • Arkhangelsk, Arkhangel Skaya Oblast, Russian Federation, 163530
      • Arkhangelsk Regional Psychiatric Clinical Hospital ( Site 6020)
  • Leningradskaya Oblast
    • Leningrad Region, Leningradskaya Oblast, Russian Federation, 188820
      • SGHI Leningrad Region Psyconeurology Dispensary ( Site 6017)
  • Lipetskaya Oblast
    • Lipetsk, Lipetskaya Oblast, Russian Federation, 399083
      • Lipetsk Regional Psychoneurology Hospital ( Site 6021)
  • Moskva
    • Moscow, Moskva, Russian Federation, 107076
      • Moscow Scientific Research Institute for Psychiatry ( Site 6013)
    • Moscow, Moskva, Russian Federation, 107076
      • Psychiatric Clinical Hospital 4 named after PB Gannushkin ( Site 6016)
    • Moscow, Moskva, Russian Federation, 107076
      • Psychiatric Clinical Hospital 4 named after PB Gannushkin-Psychiatric department 4 ( Site 6023)
    • Moscow, Moskva, Russian Federation, 127083
      • Central Moscow Regional Clinical Psychiatric Hospital ( Site 6018)
  • Sankt-Peterburg
    • Saint Petersburg, Sankt-Peterburg, Russian Federation, 192019
      • Bekhterev Research Institute for Psychoneurology ( Site 6008)
    • St. Petersburg, Sankt-Peterburg, Russian Federation, 197341
      • SPb City Psychiatric Hospital #3 na II Skvortsov-Stepanov ( Site 6000)
    • St. Petersburg, Sankt-Peterburg, Russian Federation, 197341
      • SPb City Psychiatric Hospital #3 na II Skvortsov-Stepanov ( Site 6001)
    • St. Petersburg, Sankt-Peterburg, Russian Federation, 197341
      • SPb City Psychiatric Hospital #3 na II Skvortsov-Stepanov ( Site 6002)
  • Stavropol Skiy Kray
    • Stavropol, Stavropol Skiy Kray, Russian Federation, 357034
      • Stavropol Region Psychiatric Hospital #2 ( Site 6005)
  • Tomskaya Oblast
    • Tomsk, Tomskaya Oblast, Russian Federation, 634014
      • Federal State Scientific Institution Research Institute of Mental Health ( Site 6014)
  • Yaroslavskaya Oblast
    • Yaroslavl, Yaroslavskaya Oblast, Russian Federation, 150003
      • Yaroslavl Regional Clinical Psychiatry Hospital ( Site 6022)
• Serbia
  • Beograd
    • Belgrade, Beograd, Serbia, 11000
      • Clinical Center of Serbia ( Site 5101)
    • Belgrade, Beograd, Serbia, 11000
      • Clinical Center of Serbia ( Site 5107)
    • Belgrade, Beograd, Serbia, 11000
      • Institut za mentalno zdravlje ( Site 5105)
    • Belgrade, Beograd, Serbia, 11000
      • University Clinical Hospital Center "Dr. Dragisa Misovic - Dedinje" ( Site 5104)
  • Sumadijski Okrug
    • Kragujevac, Sumadijski Okrug, Serbia, 34000
      • Clinical Center Kragujevac ( Site 5100)
    • Kragujevac, Sumadijski Okrug, Serbia, 34000
      • Clinical Center Kragujevac ( Site 5102)
    • Kragujevac, Sumadijski Okrug, Serbia, 34000
      • Clinical Center Kragujevac ( Site 5106)
  • Vojvodina
    • Kovin, Vojvodina, Serbia, 26220
      • Special Hospital for Psychiatric Diseases Kovin ( Site 5108)
    • Kovin, Vojvodina, Serbia, 26220
      • Special Hospital for Psychiatric Diseases Kovin ( Site 5109)
• Taiwan
  • Taichung, Taiwan, 404
    • China Medical University Hospital ( Site 9006)
  • Taipei, Taiwan, 100
    • National Taiwan University Hospital ( Site 9001)
  • Taipei, Taiwan, 110
    • Taipei City Hospital, Songde Branch ( Site 9004)
  • Taipei, Taiwan, 11217
    • Taipei Veterans General Hospital ( Site 9000)
  • Taoyuan, Taiwan, 333
    • Chang Gung Memorial Hospital - Linkou Branch ( Site 9002)
• Ukraine
  • Cherkaska Oblast
    • Smila, Cherkaska Oblast, Ukraine, 20708
      • CNE Cherkasy reg. psychiatric hospital of Cherkasy regional council ( Site 7009)
  • Dnipropetrovska Oblast
    • Dnipro, Dnipropetrovska Oblast, Ukraine, 49005
      • Dnepropetrovsk Regional Clinical Hospital Mechnikov-Regional Centre of Psychosomatic Disorders base
  • Ivano-Frankivska Oblast
    • Ivano-Frankivsk, Ivano-Frankivska Oblast, Ukraine, 76014
      • CNE "Precarpathian Regional Clinical Center of Mental Health of Ivano-Frankivsk Regional Council"" (
  • Kharkivska Oblast
    • Kharkiv, Kharkivska Oblast, Ukraine, 61068
      • CNE of Kharkiv Reg. Council Reg. Clinical Psychiatric Hospital Nub 3 ( Site 7012)
    • Kharkiv, Kharkivska Oblast, Ukraine, 61068
      • Institute of Neurology,Psychiatry and Narcology AMS Ukraine ( Site 7011)
  • Khersonska Oblast
    • Kherson, Khersonska Oblast, Ukraine, 73488
      • CNE. Kherson Regional Psychiatric Hospital ( Site 7004)
  • Kyivska Oblast
    • Kyiv, Kyivska Oblast, Ukraine, 02192
      • Kyiv City Psychoneurological Hospital 2 ( Site 7008)
    • Kyiv, Kyivska Oblast, Ukraine, 04080
      • CNE Clinical Hospital PSYCHIATRY of executive body of Kyiv City Council -Kyiv City State Admin ( Sit
    • Kyiv, Kyivska Oblast, Ukraine, 08631
      • MNE of KRC-Regional psychiatric and narcological medical association ( Site 7005)
  • Vinnytska Oblast
    • Vinnytsya, Vinnytska Oblast, Ukraine, 21037
      • CNE "Vinnytsia Regional Clinical Psycho-neurological hospita-Mixed (men and women) department #2 ( S
• United States
  • Arkansas
    • Bentonville, Arkansas, United States, 72712-3873
      • Pillar Clinical Research ( Site 1047)
    • Little Rock, Arkansas, United States, 72211
      • Woodland International Research Group, LLC ( Site 1002)
    • Rogers, Arkansas, United States, 72758
      • Woodland Research Northwest, LLC ( Site 1036)
  • California
    • Bellflower, California, United States, 90706
      • CITRIALS ( Site 1010)
    • Culver City, California, United States, 90230
      • ProScience Research Group ( Site 1046)
    • Garden Grove, California, United States, 92845
      • Collaborative Neuroscience Research, LLC ( Site 1041)
    • Glendale, California, United States, 91206
      • Behavioral Research Specialists, LLC ( Site 1032)
    • Riverside, California, United States, 92506
      • CITRIALS ( Site 1016)
    • San Diego, California, United States, 92103
      • Artemis Institute for Clinical Research ( Site 1019)
    • San Diego, California, United States, 92123
      • California Neuropsychopharmacology Clinical Research Institute, LLC (CNRI-San Diego, LLC) ( Site 103
    • Sherman Oaks, California, United States, 91403
      • Schuster Medical Research Institute ( Site 1023)
  • Florida
    • Hollywood, Florida, United States, 33021
      • Behavioral Clinical Research ( Site 1058)
    • Hollywood, Florida, United States, 33024
      • Research Centers of America ( Hollywood )-Central Nervous System (CNS) ( Site 1065)
    • Miami, Florida, United States, 33122
      • Premier Clinical Research Institute ( Site 1049)
    • Miami Lakes, Florida, United States, 33016
      • Behavioral Clinical Research , Inc ( Site 1013)
    • Oakland Park, Florida, United States, 33334
      • Fort Lauderdale Behavioral Health Center ( Site 1028)
    • Stuart, Florida, United States, 34997
      • Health Synergy Clinical Research ( Site 1051)
  • Georgia
    • Atlanta, Georgia, United States, 30331
      • Atlanta Center For Medical Research ( Site 1022)
    • Decatur, Georgia, United States, 30030
      • CenExel iResearch, LLC ( Site 1039)
  • Illinois
    • Chicago, Illinois, United States, 60622
      • Ascension Saint Elizabeth ( Site 1000)
    • Chicago, Illinois, United States, 60640
      • Uptown Research Institute ( Site 1052)
    • Chicago, Illinois, United States, 60641
      • Pillar Clinical Research, LLC ( Site 1038)
  • Louisiana
    • Shreveport, Louisiana, United States, 71101
      • Benchmark Research ( Site 1054)
  • Maryland
    • Gaithersburg, Maryland, United States, 20877
      • CBH Health ( Site 1044)
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital ( Site 1035)
  • Missouri
    • Saint Louis, Missouri, United States, 63141
      • Arch Clinical Trials ( Site 1048)
  • Nevada
    • Las Vegas, Nevada, United States, 89102
      • Altea Research Institute ( Site 1012)
  • New Jersey
    • Marlton, New Jersey, United States, 08053
      • Hassman Research Institute Marlton Site ( Site 1040)
  • New York
    • Staten Island, New York, United States, 10314
      • Richmond Behavioral Associates ( Site 1064)
  • North Carolina
    • Charlotte, North Carolina, United States, 28211
      • New Hope Clinical Research ( Site 1050)
  • Ohio
    • Dayton, Ohio, United States, 45417
      • Midwest Clinical Research ( Site 1059)
    • Dayton, Ohio, United States, 45417
      • Midwest Clinical Research Center ( Site 1033)
    • North Canton, Ohio, United States, 44720
      • Neuro-Behavioral Clinical Research ( Site 1055)
  • Texas
    • Austin, Texas, United States, 78754
      • Community Clinical Research ( Site 1057)
    • Richardson, Texas, United States, 75080
      • Pillar Clinical Research, LLC ( Site 1004)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

The main inclusion criteria include, but are not limited to the following:

• Meet the diagnostic criteria for schizophrenia according to the DSM-5
• Have an illness duration for schizophrenia of at least 1 year
• Be confirmed to be experiencing an acute episode of schizophrenia as evidenced by ALL of the following: (a) onset of the current acute episode is ≤6 weeks before screening (b) current symptoms represent a marked and substantial worsening compared with the participant's usual symptomatic state prior to the current acute episode, and are associated with diminished functional ability (c) in need of increased psychiatric attention to treat worsening acute episode symptoms
• Have a CGI-S score of ≥4 (moderately ill) at screening and baseline
• Have an identified responsible person referred to as the "external contact person" who has agreed to provide information about the participant's location if needed during outpatient portion of the study. The site personnel must consider this identified responsible person a reliable contact person, and the contact person must have regular contact with the participant (defined at screening as direct contact no fewer than 3 times per week), and with the expectation that this frequency of contact would continue (either in person or via other contact method), throughout duration of the study, including the follow-up period)

Exclusion Criteria:

The main exclusion criteria include, but are not limited to the following:

• Has a primary current diagnosis other than schizophrenia or a comorbid diagnosis that is primarily responsible for the current symptoms and functional impairment
• Meets criteria for moderate to severe substance use disorder within past 6 months prior to screening (excluding those related to caffeine or nicotine)
• Has a known history of the following: (a) borderline personality disorder, anti-social personality disorder, or bipolar disorder (b) traumatic brain injury causing ongoing cognitive difficulties, Alzheimer's Disease, or another form of dementia, or any chronic organic disease of the central nervous system (c) intellectual disability of a severity that would impact ability to participate in the study
• Has a current diagnosis of a psychotic disorder other than schizophrenia or a behavioral disturbance thought to be due to substance abuse
• Is or was under involuntary commitment for the acute episode, because the participant is considered a danger to themselves or others
• Has a history of treatment resistance exhibited by any of the following: (a) no or minimal response to at least 2 periods of treatment lasting 6 weeks or longer, with antipsychotic agents at the maximally tolerated dose. Participants who have responded to antipsychotics only when paired with clozapine are considered treatment-resistant (b) history of electroconvulsive therapy (ECT) treatment for treatment-resistant schizophrenia within the past 6 months (c) past or current use of clozapine as single or adjunctive therapy for schizophrenia within the past 3 months
• Is currently participating in or has participated in another clinical study and received an experimental or investigational drug agent within 3 months prior to screening visit of this current study and has participated in no more than 2 studies in the past 2 years

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MK-8189 8 mg (Acute) - MK-8189 8 mg (Extension); Participants will be treated for a total of 12 weeks. Participants will receive MK-8189 8 mg once daily (QD) in the acute treatment period from Week 1-6 followed by MK-8189 8 mg QD in the extension treatment period from Week 7-12 and participants will simultaneously receive risperidone-matching placebo QD from Week 1-12. Enrollment of participants in the MK-8189 8 mg arm was closed with Amendment 4. Participants enrolled before Amendment 4 that have been assigned to 8 mg MK-8189 will remain on 8 mg MK-8189 per protocol.	Drug: MK-8189; MK-8189 administered QD at a dose of 8 mg, 16 mg, or 24 mg via oral tablet.; Drug: Placebo to risperidone; Risperidone-matching placebo administered QD via oral capsule.
Experimental: MK-8189 16 mg (Acute) - MK-8189 16 mg (Extension); Participants will be treated for a total of 12 weeks. Participants will receive MK-8189 16 mg QD in the acute treatment period from Week 1-6 followed by MK-8189 16 mg QD in the extension treatment period from Week 7-12 and participants will simultaneously receive risperidone-matching placebo QD from Week 1-12.	Drug: MK-8189; MK-8189 administered QD at a dose of 8 mg, 16 mg, or 24 mg via oral tablet.; Drug: Placebo to risperidone; Risperidone-matching placebo administered QD via oral capsule.
Experimental: MK-8189 24 mg (Acute) - MK-8189 24 mg (Extension); Participants will be treated for a total of 12 weeks. Participants will receive MK-8189 24 mg QD in the acute treatment period from Week 1-6 followed by MK-8189 24 mg QD in the extension treatment period from Week 7-12 and participants will simultaneously receive risperidone-matching placebo QD from Week 1-12.	Drug: MK-8189; MK-8189 administered QD at a dose of 8 mg, 16 mg, or 24 mg via oral tablet.; Drug: Placebo to risperidone; Risperidone-matching placebo administered QD via oral capsule.
Active Comparator: Risperidone 6 mg (Acute) - Risperidone 6 mg (Extension); Participants will be treated for a total of 12 weeks. Participants will receive risperidone 6 mg QD in the acute treatment period from Week 1-6 followed by risperidone 6 mg QD in the extension treatment period from Week 7-12 and participants will simultaneously receive MK-8189-matching placebo QD from Week 1-12.	Drug: Risperidone; Risperidone administered QD at a dose of 6 mg via oral capsule.; Drug: Placebo to MK-8189; MK-8189-matching placebo administered QD via oral tablet.
Experimental: Placebo to MK-8189 (Acute) - MK-8189 24 mg (Extension); Participants will be treated for a total of 12 weeks. Participants will receive MK-8189-matching placebo QD in the acute treatment period from Week 1-6 followed by MK-8189 24 mg QD in the extension treatment period from Week 7-12 and participants will simultaneously receive risperidone-matching placebo QD from Week 1-12.	Drug: MK-8189; MK-8189 administered QD at a dose of 8 mg, 16 mg, or 24 mg via oral tablet.; Drug: Placebo to risperidone; Risperidone-matching placebo administered QD via oral capsule.; Drug: Placebo to MK-8189; MK-8189-matching placebo administered QD via oral tablet.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in Positive and Negative Syndrome Scale (PANSS) total score at Week 6: MK-8189 24 mg, MK-8189 16 mg, or placebo	The PANSS assesses the severity of schizophrenia symptoms through a 30-item clinician-rated inventory organized into a positive subscale (7 items), a negative subscale (7 items) and a general psychopathology subscale (16 items). For each item, symptoms are rated on a 7-point scale from 1 (absent) to 7 (extreme). The PANSS total score for each participant will be calculated as the sum of the rating assigned to each of the 30 PANSS items and will range from 30 (lowest total score) to 210 (highest total score). Higher scores reflect more severe symptoms of schizophrenia.	Baseline, Week 6
Number of participants who experience one or more adverse events (AEs)	An AE is any untoward medical occurrence in a clinical study participant, temporarily associated with the use of study intervention, whether or not considered related to the study intervention.	~Up to Week 14
Number of participants who discontinue study treatment due to an AE	An AE is any untoward medical occurrence in a clinical study participant, temporarily associated with the use of study intervention, whether or not considered related to the study intervention.	~Up to Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in PANSS positive subscale (PSS) score at Week 6: MK-8189 24 mg, MK-8189 16 mg, or placebo	The PANSS Positive Subscale (PSS) assesses the severity of schizophrenia symptoms and the PANSS PSS score for each participant will be calculated as the sum of the rating assigned to each of the 7 PSS items and will range from 7 (lowest total score) to 49 (highest total score). Higher scores reflect more severe symptoms of schizophrenia.	Baseline, Week 6
Change from baseline in Clinical Global Impression-Severity of Illness (CGI-S) score at Week 6: MK-8189 24 mg, MK-8189 16 mg, or placebo	The CGI-S is a single item 7-point clinician rated scale for assessing the global severity of the participant's illness. CGI-S scores range from 1 (participant normal, not ill) to 7 (participant extremely ill). A decrease in the CGI-S score indicates reduced severity of the participant's illness.	Baseline, Week 6
Change from baseline in weight at Week 12: MK-8189 24 mg, MK-8189 16 mg, or risperidone	Body weight will be measured using a standardized scale.	Baseline, Week 12
Change from baseline in weight at Week 6: MK-8189 24 mg, MK-8189 16 mg, MK-8189 8 mg or placebo	Body weight will be measured using a standardized scale.	Baseline, Week 6

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC
• Investigators: Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

Helpful Links

• Merck Clinical Trials Information

Study record dates

Study Major Dates

• Study Start (Actual): December 15, 2020
• Primary Completion (Estimated): July 15, 2024
• Study Completion (Estimated): July 15, 2024

Study Registration Dates

• First Submitted: November 5, 2020
• First Submitted That Met QC Criteria: November 5, 2020
• First Posted (Actual): November 10, 2020

Study Record Updates

• Last Update Posted (Actual): March 19, 2024
• Last Update Submitted That Met QC Criteria: March 18, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Agents; Dopamine Agents; Serotonin Antagonists; Dopamine Antagonists; Risperidone
• Other Study ID Numbers: 8189-008; MK-8189-008 (Other Identifier: Merck Protocol Number); jRCT2071200096 (Registry Identifier: jRCT); 2020-000094-24 (EudraCT Number)

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: Yes
• Studies a U.S. FDA-regulated device product: No