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

NCT04624243 | Completed Phase 2 Results DMC FDA Drug

• 4 other identifiers: 8189-008MK-8189-008jRCT20712000962020-000094-24
• Study Type: interventional
• Target: 499
• Locations: 12 countries
• Sites: 121

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

Outcome Measures

Primary Outcomes (3)

• Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 6

  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 was calculated as the sum of the rating assigned to each of the 30 PANSS items, and ranges from 30 (lowest total score) to 210 (highest total score). Higher and lower change scores reflect symptom worsening and improvement, respectively. Risperidone and placebo were active and inactive controls, respectively.

  Baseline and 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. Per protocol, events were assessed for the first 6 weeks of treatment.

  Up to Week 6

• Number of Participants Who Discontinued From Study Intervention Due to 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. Per protocol, events were assessed for the first 6 weeks of treatment.

  Up to Week 6

Secondary Outcomes (6)

• Change From Baseline in PANSS Positive Subscale (PSS) Score at Week 6

  Baseline and Week 6

• Change From Baseline in Clinical Global Impression-Severity of Illness (CGI-S) Score at Week 6

  Baseline and Week 6

• Change From Baseline in Body Weight at Week 12

  Baseline and Week 12

• Change From Baseline in Body Weight at Week 6

  Baseline and Week 6

• Change From Baseline in Body Weight at Week 12: Model-based Analysis

  Baseline and Week 12

Study Arms (5)

MK-8189 8 mg

EXPERIMENTAL

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

Drug: MK-8189; Drug: Placebo to risperidone

MK-8189 16 mg

EXPERIMENTAL

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

Drug: MK-8189; Drug: Placebo to risperidone

MK-8189 24 mg

EXPERIMENTAL

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

Drug: MK-8189; Drug: Placebo to risperidone

Risperidone 6 mg

ACTIVE COMPARATOR

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.

Drug: Risperidone; Drug: Placebo to MK-8189

Placebo and MK-8189 24 mg

EXPERIMENTAL

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.

Drug: MK-8189; Drug: Placebo to MK-8189; Drug: Placebo to risperidone

Interventions

MK-8189 DRUG

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

MK-8189 16 mg; MK-8189 24 mg; MK-8189 8 mg; Placebo and MK-8189 24 mg

Risperidone DRUG

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

Risperidone 6 mg

Placebo to MK-8189 DRUG

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

Placebo and MK-8189 24 mg; Risperidone 6 mg

Placebo to risperidone DRUG

Risperidone-matching placebo administered QD via oral capsule.

MK-8189 16 mg; MK-8189 24 mg; MK-8189 8 mg; Placebo and MK-8189 24 mg

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (121)

Pillar Clinical Research ( Site 1047)

Bentonville, Arkansas, 72712-3873, United States

Location

Woodland International Research Group, LLC ( Site 1002)

Little Rock, Arkansas, 72211, United States

Location

Woodland Research Northwest, LLC ( Site 1036)

Rogers, Arkansas, 72758, United States

Location

CITRIALS ( Site 1010)

Bellflower, California, 90706, United States

Location

ProScience Research Group ( Site 1046)

Culver City, California, 90230, United States

Location

Collaborative Neuroscience Research, LLC ( Site 1041)

Garden Grove, California, 92845, United States

Location

Behavioral Research Specialists, LLC ( Site 1032)

Glendale, California, 91206, United States

Location

CITRIALS ( Site 1016)

Riverside, California, 92506, United States

Location

Artemis Institute for Clinical Research ( Site 1019)

San Diego, California, 92103, United States

Location

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

San Diego, California, 92123, United States

Location

Schuster Medical Research Institute ( Site 1023)

Sherman Oaks, California, 91403, United States

Location

Behavioral Clinical Research ( Site 1058)

Hollywood, Florida, 33021, United States

Location

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

Hollywood, Florida, 33024, United States

Location

Premier Clinical Research Institute ( Site 1049)

Miami, Florida, 33122, United States

Location

Behavioral Clinical Research , Inc ( Site 1013)

Miami Lakes, Florida, 33016, United States

Location

Fort Lauderdale Behavioral Health Center ( Site 1028)

Oakland Park, Florida, 33334, United States

Location

Health Synergy Clinical Research ( Site 1051)

Stuart, Florida, 34997, United States

Location

Atlanta Center For Medical Research ( Site 1022)

Atlanta, Georgia, 30331, United States

Location

CenExel iResearch, LLC ( Site 1039)

Decatur, Georgia, 30030, United States

Location

Ascension Saint Elizabeth ( Site 1000)

Chicago, Illinois, 60622, United States

Location

Uptown Research Institute ( Site 1052)

Chicago, Illinois, 60640, United States

Location

Pillar Clinical Research, LLC ( Site 1038)

Chicago, Illinois, 60641, United States

Location

Benchmark Research ( Site 1054)

Shreveport, Louisiana, 71101, United States

Location

CBH Health ( Site 1044)

Gaithersburg, Maryland, 20877, United States

Location

Massachusetts General Hospital ( Site 1035)

Boston, Massachusetts, 02114, United States

Location

Arch Clinical Trials ( Site 1048)

St Louis, Missouri, 63141, United States

Location

Altea Research Institute ( Site 1012)

Las Vegas, Nevada, 89102, United States

Location

Hassman Research Institute Marlton Site ( Site 1040)

Marlton, New Jersey, 08053, United States

Location

Richmond Behavioral Associates ( Site 1064)

Staten Island, New York, 10314, United States

Location

New Hope Clinical Research ( Site 1050)

Charlotte, North Carolina, 28211, United States

Location

Midwest Clinical Research ( Site 1059)

Dayton, Ohio, 45417, United States

Location

Midwest Clinical Research Center ( Site 1033)

Dayton, Ohio, 45417, United States

Location

Neuro-Behavioral Clinical Research ( Site 1055)

North Canton, Ohio, 44720, United States

Location

Community Clinical Research ( Site 1057)

Austin, Texas, 78754, United States

Location

Pillar Clinical Research, LLC ( Site 1004)

Richardson, Texas, 75080, United States

Location

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

Novi Iskar, Sofia, 1282, Bulgaria

Location

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

Burgas, 8001, Bulgaria

Location

State Psychiatric Hospital - Kardzhali ( Site 3005)

Kardzhali, 6600, Bulgaria

Location

Mental Health Center - Ruse, EOOD ( Site 3003)

Rousse, 7000, Bulgaria

Location

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

Sofia, 1000, Bulgaria

Location

Mental Health Center - Veliko Tarnovo ( Site 3006)

Veliko Tarnovo, 5000, Bulgaria

Location

Klinika za psihijatriju Vrapce ( Site 4000)

Zagreb, City of Zagreb, 10090, Croatia

Location

Klinika za psihijatriju Vrapce ( Site 4001)

Zagreb, City of Zagreb, 10090, Croatia

Location

Klinicki bolnicki centar Rijeka ( Site 4005)

Rijeka, Primorje-Gorski Kotar County, 51000, Croatia

Location

Klinika za psihijatriju Sveti Ivan ( Site 4003)

Zagreb, Zagreb County, 10090, Croatia

Location

Seishinkai Okehazama Hospital Fujita Kokoro Care Center ( Site 2011)

Toyoake, Aichi-ken, 470-1168, Japan

Location

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

Ichikawa, Chiba, 272-8516, Japan

Location

Wakato Hospital ( Site 2031)

Kitakyushu, Fukuoka, 808-0139, Japan

Location

Shiranui Hospital ( Site 2043)

Omuta, Fukuoka, 8360004, Japan

Location

Seimou Hospital ( Site 2004)

Tomioka, Gunma, 3702455, Japan

Location

Soushu Hospital ( Site 2008)

Atsugi, Kanagawa, 243-0201, Japan

Location

Tanzawa Hospital ( Site 2037)

Hadano, Kanagawa, 259-1304, Japan

Location

Kanagawa Psychiatric Center ( Site 2035)

Yokohama, Kanagawa, 233-0006, Japan

Location

Komoro Kogen Hospital ( Site 2046)

Komoro, Nagano, 384-8540, Japan

Location

National Hospital Organization Ryukyu Hospital ( Site 2019)

Kunigamigun, Okinawa, 904-1201, Japan

Location

Amekudai Hospital ( Site 2020)

Naha, Okinawa, 900-0005, Japan

Location

National Hospital Organization Hizen Psychiatric Medical Center ( Site 2017)

Kanzaki-gun, Saga-ken, 8420192, Japan

Location

Rainbow and Sea Hospital ( Site 2016)

Karatsu, Saga-ken, 847-0031, Japan

Location

Ongata Hospital ( Site 2007)

Hachiōji, Tokyo, 192-0153, Japan

Location

Nishigahara Hospital ( Site 2042)

Kita-ku, Tokyo, 114-0024, Japan

Location

National Center of Neurology and Psychiatry ( Site 2023)

Kodaira, Tokyo, 187-8551, Japan

Location

Chiba University Hospital ( Site 2024)

Chiba, 260-8677, Japan

Location

Inokuchi Noma Hospital ( Site 2030)

Fukuoka, 815-0074, Japan

Location

Kuramitsu Hospital ( Site 2014)

Fukuoka, 819-0037, Japan

Location

Yuge Hospital ( Site 2018)

Kumamoto, 861-8002, Japan

Location

Seijin Hospital ( Site 2026)

Tokyo, 121-8515, Japan

Location

Narimasu Kosei Hospital ( Site 2006)

Tokyo, 175-0091, Japan

Location

Daugavpils Psihoneirologiska Slimnica ( Site 8005)

Daugavpils, 5417, Latvia

Location

Piejuras Slimnica Psihiatriska Klinika ( Site 8001)

Liepāja, 3401, Latvia

Location

Centrum Medyczne HCP ( Site 0913)

Poznan, Greater Poland Voivodeship, 61-485, Poland

Location

Klinika Psychiatryczna Wydzialu Nauki o Zdrowiu WUM ( Site 0900)

Pruszków, Masovian Voivodeship, 05-802, Poland

Location

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

Warsaw, Masovian Voivodeship, 00-665, Poland

Location

Uniwersyteckie Centrum Kliniczne ( Site 0902)

Gdansk, Pomeranian Voivodeship, 80-211, Poland

Location

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

Lodz, Łódź Voivodeship, 91-229, Poland

Location

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

Bucharest, București, 041914, Romania

Location

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

Bucharest, București, 041914, Romania

Location

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

Bucharest, București, 041914, Romania

Location

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

Bucharest, București, 041914, Romania

Location

Institutul de Psihiatrie Socola ( Site 0810)

Iași, Iaşi, 700282, Romania

Location

Institutul de Psihiatrie Socola ( Site 0814)

Iași, Iaşi, 700282, Romania

Location

Arkhangelsk Regional Psychiatric Clinical Hospital ( Site 6020)

Arkhangelsk, Arkhangelskaya oblast, 163530, Russia

Location

SGHI Leningrad Region Psyconeurology Dispensary ( Site 6017)

Leningrad Region, Leningradskaya Oblast', 188820, Russia

Location

Lipetsk Regional Psychoneurology Hospital ( Site 6021)

Lipetsk, Lipetsk Oblast, 399083, Russia

Location

Moscow Scientific Research Institute for Psychiatry ( Site 6013)

Moscow, Moscow, 107076, Russia

Location

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

Moscow, Moscow, 107076, Russia

Location

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

Moscow, Moscow, 107076, Russia

Location

Central Moscow Regional Clinical Psychiatric Hospital ( Site 6018)

Moscow, Moscow, 127083, Russia

Location

Bekhterev Research Institute for Psychoneurology ( Site 6008)

Saint Petersburg, Sankt-Peterburg, 192019, Russia

Location

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

Saint Petersburg, Sankt-Peterburg, 197341, Russia

Location

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

Saint Petersburg, Sankt-Peterburg, 197341, Russia

Location

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

Saint Petersburg, Sankt-Peterburg, 197341, Russia

Location

Stavropol Region Psychiatric Hospital #2 ( Site 6005)

Stavropol, Stavropol Kray, 357034, Russia

Location

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

Tomsk, Tomsk Oblast, 634014, Russia

Location

Yaroslavl Regional Clinical Psychiatry Hospital ( Site 6022)

Yaroslavl, Yaroslavl Oblast, 150003, Russia

Location

Clinical Center of Serbia ( Site 5101)

Belgrade, Beograd, 11000, Serbia

Location

Clinical Center of Serbia ( Site 5107)

Belgrade, Beograd, 11000, Serbia

Location

Institut za mentalno zdravlje ( Site 5105)

Belgrade, Beograd, 11000, Serbia

Location

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

Belgrade, Beograd, 11000, Serbia

Location

Clinical Center Kragujevac ( Site 5100)

Kragujevac, Sumadijski Okrug, 34000, Serbia

Location

Clinical Center Kragujevac ( Site 5102)

Kragujevac, Sumadijski Okrug, 34000, Serbia

Location

Clinical Center Kragujevac ( Site 5106)

Kragujevac, Sumadijski Okrug, 34000, Serbia

Location

Special Hospital for Psychiatric Diseases Kovin ( Site 5108)

Kovin, Vojvodina, 26220, Serbia

Location

Special Hospital for Psychiatric Diseases Kovin ( Site 5109)

Kovin, Vojvodina, 26220, Serbia

Location

Inje University Busan Paik Hospital ( Site 0604)

Busan, Pusan-Kwangyokshi, 47392, South Korea

Location

Kyungpook National University Hospital ( Site 0601)

Daegu, Taegu-Kwangyokshi, 41944, South Korea

Location

Seoul National University Hospital ( Site 0600)

Seoul, 03080, South Korea

Location

China Medical University Hospital ( Site 9006)

Taichung, 404, Taiwan

Location

National Taiwan University Hospital ( Site 9001)

Taipei, 100, Taiwan

Location

Taipei City Hospital, Songde Branch ( Site 9004)

Taipei, 110, Taiwan

Location

Taipei Veterans General Hospital ( Site 9000)

Taipei, 11217, Taiwan

Location

Chang Gung Memorial Hospital - Linkou Branch ( Site 9002)

Taoyuan District, 333, Taiwan

Location

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

Smila, Cherkasy Oblast, 20708, Ukraine

Location

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

Dnipro, Dnipropetrovsk Oblast, 49005, Ukraine

Location

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

Ivano-Frankivsk, Ivano-Frankivsk Oblast, 76014, Ukraine

Location

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

Kharkiv, Kharkivs’ka Oblast’, 61068, Ukraine

Location

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

Kharkiv, Kharkivs’ka Oblast’, 61068, Ukraine

Location

CNE. Kherson Regional Psychiatric Hospital ( Site 7004)

Kherson, Kherson Oblast, 73488, Ukraine

Location

Kyiv City Psychoneurological Hospital 2 ( Site 7008)

Kyiv, Kyivska Oblast, 02192, Ukraine

Location

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

Kyiv, Kyivska Oblast, 04080, Ukraine

Location

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

Kyiv, Kyivska Oblast, 08631, Ukraine

Location

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

Vinnytsia, Vinnytsia Oblast, 21037, Ukraine

Location

Related Links

• Merck Clinical Trials Information
• Plain Language Summary

MeSH Terms

Conditions

Schizophrenia

Interventions

MK-8189; Risperidone

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme LLC

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 5, 2020
• First Posted: November 10, 2020
• Study Start: December 15, 2020
• Primary Completion: June 21, 2024
• Study Completion: June 21, 2024
• Last Updated: February 5, 2026
• Results First Posted: August 22, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share

Locations

KR (3); RO (6); SE (9); UA (10); US (35); CR (4); JP (22); PL (5); BU (6); TW (5); RU (14); LA (2)