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

NCT ID: NCT04624243

Last Updated: 2025-08-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 499 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-12-15
• Study Completion Date: 2024-06-21

Brief Summary

The purpose of this study was to evaluate the efficacy and safety of MK-8189 at a range of doses (8 mg, 16 mg, and 24 mg once daily [QD]) 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 were the following: (1) that 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, and (2) that 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 who were assigned to MK-8189 8 mg QD remained on that dose regimen per protocol.

Conditions

Schizophrenia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

MK-8189 8 mg

Participants received MK-8189 8 mg QD from Weeks 1 to 12, with 2 weeks of follow-up

Group Type: EXPERIMENTAL

MK-8189

Intervention Type: DRUG

MK-8189 administered QD at a dose of 8 mg, 16 mg, or 24 mg via oral tablet.

Placebo to risperidone

Intervention Type: DRUG

Risperidone-matching placebo administered QD via oral capsule.

MK-8189 16 mg

Participants received MK-8189 16 mg QD from Weeks 1 to 12, with 2 weeks of follow-up.

Group Type: EXPERIMENTAL

MK-8189

Intervention Type: DRUG

MK-8189 administered QD at a dose of 8 mg, 16 mg, or 24 mg via oral tablet.

Placebo to risperidone

Intervention Type: DRUG

Risperidone-matching placebo administered QD via oral capsule.

MK-8189 24 mg

Participants received MK-8189 24 mg QD from Weeks 1 to 12, with 2 weeks of follow-up.

Group Type: EXPERIMENTAL

MK-8189

Intervention Type: DRUG

MK-8189 administered QD at a dose of 8 mg, 16 mg, or 24 mg via oral tablet.

Placebo to risperidone

Intervention Type: DRUG

Risperidone-matching placebo administered QD via oral capsule.

Risperidone 6 mg

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.

Group Type: ACTIVE_COMPARATOR

Risperidone

Intervention Type: DRUG

Risperidone administered QD at a dose of 6 mg via oral capsule.

Placebo to MK-8189

Intervention Type: DRUG

MK-8189-matching placebo administered QD via oral tablet.

Placebo and MK-8189 24 mg

Participants received placebo QD from Weeks 1 to 6 and MK-8189 24 mg from Weeks 7 to 12, with 2 weeks of follow-up.

Group Type: EXPERIMENTAL

MK-8189

Intervention Type: DRUG

MK-8189 administered QD at a dose of 8 mg, 16 mg, or 24 mg via oral tablet.

Placebo to MK-8189

Intervention Type: DRUG

MK-8189-matching placebo administered QD via oral tablet.

Placebo to risperidone

Intervention Type: DRUG

Risperidone-matching placebo administered QD via oral capsule.

Interventions

MK-8189

MK-8189 administered QD at a dose of 8 mg, 16 mg, or 24 mg via oral tablet.

Intervention Type: DRUG

Risperidone

Risperidone administered QD at a dose of 6 mg via oral capsule.

Intervention Type: DRUG

Placebo to MK-8189

MK-8189-matching placebo administered QD via oral tablet.

Intervention Type: DRUG

Placebo to risperidone

Risperidone-matching placebo administered QD via oral capsule.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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

• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Locations

Pillar Clinical Research ( Site 1047)

Bentonville, Arkansas, United States

Woodland International Research Group, LLC ( Site 1002)

Little Rock, Arkansas, United States

Woodland Research Northwest, LLC ( Site 1036)

Rogers, Arkansas, United States

CITRIALS ( Site 1010)

Bellflower, California, United States

ProScience Research Group ( Site 1046)

Culver City, California, United States

Collaborative Neuroscience Research, LLC ( Site 1041)

Garden Grove, California, United States

Behavioral Research Specialists, LLC ( Site 1032)

Glendale, California, United States

CITRIALS ( Site 1016)

Riverside, California, United States

Artemis Institute for Clinical Research ( Site 1019)

San Diego, California, United States

California Neuropsychopharmacology Clinical Research Institute, LLC (CNRI-San Diego, LLC) ( Site 103

San Diego, California, United States

Schuster Medical Research Institute ( Site 1023)

Sherman Oaks, California, United States

Behavioral Clinical Research ( Site 1058)

Hollywood, Florida, United States

Research Centers of America ( Hollywood )-Central Nervous System (CNS) ( Site 1065)

Hollywood, Florida, United States

Premier Clinical Research Institute ( Site 1049)

Miami, Florida, United States

Behavioral Clinical Research , Inc ( Site 1013)

Miami Lakes, Florida, United States

Fort Lauderdale Behavioral Health Center ( Site 1028)

Oakland Park, Florida, United States

Health Synergy Clinical Research ( Site 1051)

Stuart, Florida, United States

Atlanta Center For Medical Research ( Site 1022)

Atlanta, Georgia, United States

CenExel iResearch, LLC ( Site 1039)

Decatur, Georgia, United States

Ascension Saint Elizabeth ( Site 1000)

Chicago, Illinois, United States

Uptown Research Institute ( Site 1052)

Chicago, Illinois, United States

Pillar Clinical Research, LLC ( Site 1038)

Chicago, Illinois, United States

Benchmark Research ( Site 1054)

Shreveport, Louisiana, United States

CBH Health ( Site 1044)

Gaithersburg, Maryland, United States

Massachusetts General Hospital ( Site 1035)

Boston, Massachusetts, United States

Arch Clinical Trials ( Site 1048)

St Louis, Missouri, United States

Altea Research Institute ( Site 1012)

Las Vegas, Nevada, United States

Hassman Research Institute Marlton Site ( Site 1040)

Marlton, New Jersey, United States

Richmond Behavioral Associates ( Site 1064)

Staten Island, New York, United States

New Hope Clinical Research ( Site 1050)

Charlotte, North Carolina, United States

Midwest Clinical Research ( Site 1059)

Dayton, Ohio, United States

Midwest Clinical Research Center ( Site 1033)

Dayton, Ohio, United States

Neuro-Behavioral Clinical Research ( Site 1055)

North Canton, Ohio, United States

Community Clinical Research ( Site 1057)

Austin, Texas, United States

Pillar Clinical Research, LLC ( Site 1004)

Richardson, Texas, United States

State Psychiatric Hospital "Sv. Ivan Rilski", Novi Iskar ( Site 3001)

Novi Iskar, Sofia, Bulgaria

Mental Health Center Prof. Dr. Ivan Temkov - Burgas EOOD ( Site 3002)

Burgas, , Bulgaria

State Psychiatric Hospital - Kardzhali ( Site 3005)

Kardzhali, , Bulgaria

Mental Health Center - Ruse, EOOD ( Site 3003)

Rousse, , Bulgaria

Center for Mental Health Prof. Nikola Shipkovenski Ltd ( Site 3000)

Sofia, , Bulgaria

Mental Health Center - Veliko Tarnovo ( Site 3006)

Veliko Tarnovo, , Bulgaria

Klinika za psihijatriju Vrapce ( Site 4000)

Zagreb, City of Zagreb, Croatia

Klinika za psihijatriju Vrapce ( Site 4001)

Zagreb, City of Zagreb, Croatia

Klinicki bolnicki centar Rijeka ( Site 4005)

Rijeka, Primorje-Gorski Kotar County, Croatia

Klinika za psihijatriju Sveti Ivan ( Site 4003)

Zagreb, Zagreb County, Croatia

Seishinkai Okehazama Hospital Fujita Kokoro Care Center ( Site 2011)

Toyoake, Aichi-ken, Japan

Kohnodai Hospital, National Center for Global Health and Medicine ( Site 2005)

Ichikawa, Chiba, Japan

Wakato Hospital ( Site 2031)

Kitakyushu, Fukuoka, Japan

Shiranui Hospital ( Site 2043)

Omuta, Fukuoka, Japan

Seimou Hospital ( Site 2004)

Tomioka, Gunma, Japan

Soushu Hospital ( Site 2008)

Atsugi, Kanagawa, Japan

Tanzawa Hospital ( Site 2037)

Hadano, Kanagawa, Japan

Kanagawa Psychiatric Center ( Site 2035)

Yokohama, Kanagawa, Japan

Komoro Kogen Hospital ( Site 2046)

Komoro, Nagano, Japan

National Hospital Organization Ryukyu Hospital ( Site 2019)

Kunigamigun, Okinawa, Japan

Amekudai Hospital ( Site 2020)

Naha, Okinawa, Japan

National Hospital Organization Hizen Psychiatric Medical Center ( Site 2017)

Kanzaki-gun, Saga-ken, Japan

Rainbow and Sea Hospital ( Site 2016)

Karatsu, Saga-ken, Japan

Ongata Hospital ( Site 2007)

Hachiōji, Tokyo, Japan

Nishigahara Hospital ( Site 2042)

Kita-ku, Tokyo, Japan

National Center of Neurology and Psychiatry ( Site 2023)

Kodaira, Tokyo, Japan

Chiba University Hospital ( Site 2024)

Chiba, , Japan

Inokuchi Noma Hospital ( Site 2030)

Fukuoka, , Japan

Kuramitsu Hospital ( Site 2014)

Fukuoka, , Japan

Yuge Hospital ( Site 2018)

Kumamoto, , Japan

Seijin Hospital ( Site 2026)

Tokyo, , Japan

Narimasu Kosei Hospital ( Site 2006)

Tokyo, , Japan

Daugavpils Psihoneirologiska Slimnica ( Site 8005)

Daugavpils, , Latvia

Piejuras Slimnica Psihiatriska Klinika ( Site 8001)

Liepāja, , Latvia

Centrum Medyczne HCP ( Site 0913)

Poznan, Greater Poland Voivodeship, Poland

Klinika Psychiatryczna Wydzialu Nauki o Zdrowiu WUM ( Site 0900)

Pruszków, Masovian Voivodeship, Poland

Samodzielny Wojewódzki Zespół Publicznych Zakładów Psychiatrycznej Opieki Zdrowotnej w Warszawie ( S

Warsaw, Masovian Voivodeship, Poland

Uniwersyteckie Centrum Kliniczne ( Site 0902)

Gdansk, Pomeranian Voivodeship, Poland

Specjal. Psychiatryczny ZOZ w Lodzi, Szpital im. Babinskiego ( Site 0905)

Lodz, Łódź Voivodeship, Poland

Prof. Dr. Alexandru Obregia Psychiatry Hospital ( Site 0815)

Bucharest, București, Romania

Prof. Dr. Alexandru Obregia Psychiatry Hospital ( Site 0816)

Bucharest, București, Romania

Prof. Dr. Alexandru Obregia Psychiatry Hospital ( Site 0817)

Bucharest, București, Romania

Prof. Dr. Alexandru Obregia Psychiatry Hospital ( Site 0818)

Bucharest, București, Romania

Institutul de Psihiatrie Socola ( Site 0810)

Iași, Iaşi, Romania

Institutul de Psihiatrie Socola ( Site 0814)

Iași, Iaşi, Romania

Arkhangelsk Regional Psychiatric Clinical Hospital ( Site 6020)

Arkhangelsk, Arkhangelskaya oblast, Russia

SGHI Leningrad Region Psyconeurology Dispensary ( Site 6017)

Leningrad Region, Leningradskaya Oblast', Russia

Lipetsk Regional Psychoneurology Hospital ( Site 6021)

Lipetsk, Lipetsk Oblast, Russia

Moscow Scientific Research Institute for Psychiatry ( Site 6013)

Moscow, Moscow, Russia

Psychiatric Clinical Hospital 4 named after PB Gannushkin ( Site 6016)

Moscow, Moscow, Russia

Psychiatric Clinical Hospital 4 named after PB Gannushkin-Psychiatric department 4 ( Site 6023)

Moscow, Moscow, Russia

Central Moscow Regional Clinical Psychiatric Hospital ( Site 6018)

Moscow, Moscow, Russia

Bekhterev Research Institute for Psychoneurology ( Site 6008)

Saint Petersburg, Sankt-Peterburg, Russia

SPb City Psychiatric Hospital #3 na II Skvortsov-Stepanov ( Site 6000)

Saint Petersburg, Sankt-Peterburg, Russia

SPb City Psychiatric Hospital #3 na II Skvortsov-Stepanov ( Site 6001)

Saint Petersburg, Sankt-Peterburg, Russia

SPb City Psychiatric Hospital #3 na II Skvortsov-Stepanov ( Site 6002)

Saint Petersburg, Sankt-Peterburg, Russia

Stavropol Region Psychiatric Hospital #2 ( Site 6005)

Stavropol, Stavropol Kray, Russia

Federal State Scientific Institution Research Institute of Mental Health ( Site 6014)

Tomsk, Tomsk Oblast, Russia

Yaroslavl Regional Clinical Psychiatry Hospital ( Site 6022)

Yaroslavl, Yaroslavl Oblast, Russia

Clinical Center of Serbia ( Site 5101)

Belgrade, Beograd, Serbia

Clinical Center of Serbia ( Site 5107)

Belgrade, Beograd, Serbia

Institut za mentalno zdravlje ( Site 5105)

Belgrade, Beograd, Serbia

University Clinical Hospital Center "Dr. Dragisa Misovic - Dedinje" ( Site 5104)

Belgrade, Beograd, Serbia

Clinical Center Kragujevac ( Site 5100)

Kragujevac, Sumadijski Okrug, Serbia

Clinical Center Kragujevac ( Site 5102)

Kragujevac, Sumadijski Okrug, Serbia

Clinical Center Kragujevac ( Site 5106)

Kragujevac, Sumadijski Okrug, Serbia

Special Hospital for Psychiatric Diseases Kovin ( Site 5108)

Kovin, Vojvodina, Serbia

Special Hospital for Psychiatric Diseases Kovin ( Site 5109)

Kovin, Vojvodina, Serbia

Inje University Busan Paik Hospital ( Site 0604)

Busan, Pusan-Kwangyokshi, South Korea

Kyungpook National University Hospital ( Site 0601)

Daegu, Taegu-Kwangyokshi, South Korea

Seoul National University Hospital ( Site 0600)

Seoul, , South Korea

China Medical University Hospital ( Site 9006)

Taichung, , Taiwan

National Taiwan University Hospital ( Site 9001)

Taipei, , Taiwan

Taipei City Hospital, Songde Branch ( Site 9004)

Taipei, , Taiwan

Taipei Veterans General Hospital ( Site 9000)

Taipei, , Taiwan

Chang Gung Memorial Hospital - Linkou Branch ( Site 9002)

Taoyuan District, , Taiwan

CNE Cherkasy reg. psychiatric hospital of Cherkasy regional council ( Site 7009)

Smila, Cherkasy Oblast, Ukraine

Dnepropetrovsk Regional Clinical Hospital Mechnikov-Regional Centre of Psychosomatic Disorders base

Dnipro, Dnipropetrovsk Oblast, Ukraine

CNE "Precarpathian Regional Clinical Center of Mental Health of Ivano-Frankivsk Regional Council"" (

Ivano-Frankivsk, Ivano-Frankivsk Oblast, Ukraine

CNE of Kharkiv Reg. Council Reg. Clinical Psychiatric Hospital Nub 3 ( Site 7012)

Kharkiv, Kharkivs’ka Oblast’, Ukraine

Institute of Neurology,Psychiatry and Narcology AMS Ukraine ( Site 7011)

Kharkiv, Kharkivs’ka Oblast’, Ukraine

CNE. Kherson Regional Psychiatric Hospital ( Site 7004)

Kherson, Kherson Oblast, Ukraine

Kyiv City Psychoneurological Hospital 2 ( Site 7008)

Kyiv, Kyivska Oblast, Ukraine

CNE Clinical Hospital PSYCHIATRY of executive body of Kyiv City Council -Kyiv City State Admin ( Sit

Kyiv, Kyivska Oblast, Ukraine

MNE of KRC-Regional psychiatric and narcological medical association ( Site 7005)

Kyiv, Kyivska Oblast, Ukraine

CNE "Vinnytsia Regional Clinical Psycho-neurological hospita-Mixed (men and women) department #2 ( S

Vinnytsia, Vinnytsia Oblast, Ukraine

Countries

United States; Bulgaria; Croatia; Japan; Latvia; Poland; Romania; Russia; Serbia; South Korea; Taiwan; Ukraine

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

https://www.merckclinicaltrials.com/

Merck Clinical Trials Information

Other Identifiers

MK-8189-008

Identifier Type: OTHER

Identifier Source: secondary_id

jRCT2071200096

Identifier Type: REGISTRY

Identifier Source: secondary_id

2020-000094-24

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

8189-008

Identifier Type: -

Identifier Source: org_study_id