Clinical trial NCT04624243: Efficacy and Safety of MK-8189 in Participants With an Acute Episode of Schizophrenia (MK-8189-008)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Schizophrenia
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2020-11-10
Enrollment: 500
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: Baseline, Week 6
measure: Number of participants who experience one or more adverse events (AEs)
timeFrame: ~Up to Week 14
measure: Number of participants who discontinue study treatment due to an AE
timeFrame: ~Up to Week 12
Secondary outcomes:
measure: Change from baseline in PANSS positive subscale (PSS) score at Week 6: MK-8189 24 mg, MK-8189 16 mg, or placebo
timeFrame: Baseline, Week 6
measure: 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
timeFrame: Baseline, Week 6
measure: Change from baseline in weight at Week 12: MK-8189 24 mg, MK-8189 16 mg, or risperidone
timeFrame: Baseline, Week 12
measure: Change from baseline in weight at Week 6: MK-8189 24 mg, MK-8189 16 mg, MK-8189 8 mg or placebo
timeFrame: Baseline, Week 6
Other outcomes:
Locations:
city: Bentonville
country: United States
facility: Pillar Clinical Research ( Site 1047)
state: Arkansas
city: Little Rock
country: United States
facility: Woodland International Research Group, LLC ( Site 1002)
state: Arkansas
city: Rogers
country: United States
facility: Woodland Research Northwest, LLC ( Site 1036)
state: Arkansas
city: Bellflower
country: United States
facility: CITRIALS ( Site 1010)
state: California
city: Culver City
country: United States
facility: ProScience Research Group ( Site 1046)
state: California
city: Garden Grove
country: United States
facility: Collaborative Neuroscience Research, LLC ( Site 1041)
state: California
city: Glendale
country: United States
facility: Behavioral Research Specialists, LLC ( Site 1032)
state: California
city: Riverside
country: United States
facility: CITRIALS ( Site 1016)
state: California
city: San Diego
country: United States
facility: Artemis Institute for Clinical Research ( Site 1019)
state: California
city: San Diego
country: United States
facility: California Neuropsychopharmacology Clinical Research Institute, LLC (CNRI-San Diego, LLC) ( Site 103
state: California
city: Sherman Oaks
country: United States
facility: Schuster Medical Research Institute ( Site 1023)
state: California
city: Hollywood
country: United States
facility: Behavioral Clinical Research ( Site 1058)
state: Florida
city: Hollywood
country: United States
facility: Research Centers of America ( Hollywood )-Central Nervous System (CNS) ( Site 1065)
state: Florida
city: Miami Lakes
country: United States
facility: Behavioral Clinical Research , Inc ( Site 1013)
state: Florida
city: Miami
country: United States
facility: Premier Clinical Research Institute ( Site 1049)
state: Florida
city: Oakland Park
country: United States
facility: Fort Lauderdale Behavioral Health Center ( Site 1028)
state: Florida
city: Stuart
country: United States
facility: Health Synergy Clinical Research ( Site 1051)
state: Florida
city: Atlanta
country: United States
facility: Atlanta Center For Medical Research ( Site 1022)
state: Georgia
city: Decatur
country: United States
facility: CenExel iResearch, LLC ( Site 1039)
state: Georgia
city: Chicago
country: United States
facility: Ascension Saint Elizabeth ( Site 1000)
state: Illinois
city: Chicago
country: United States
facility: Uptown Research Institute ( Site 1052)
state: Illinois
city: Chicago
country: United States
facility: Pillar Clinical Research, LLC ( Site 1038)
state: Illinois
city: Shreveport
country: United States
facility: Benchmark Research ( Site 1054)
state: Louisiana
city: Gaithersburg
country: United States
facility: CBH Health ( Site 1044)
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital ( Site 1035)
state: Massachusetts
city: Saint Louis
country: United States
facility: Arch Clinical Trials ( Site 1048)
state: Missouri
city: Las Vegas
country: United States
facility: Altea Research Institute ( Site 1012)
state: Nevada
city: Marlton
country: United States
facility: Hassman Research Institute Marlton Site ( Site 1040)
state: New Jersey
city: Staten Island
country: United States
facility: Richmond Behavioral Associates ( Site 1064)
state: New York
city: Charlotte
country: United States
facility: New Hope Clinical Research ( Site 1050)
state: North Carolina
city: Dayton
country: United States
facility: Midwest Clinical Research ( Site 1059)
state: Ohio
city: Dayton
country: United States
facility: Midwest Clinical Research Center ( Site 1033)
state: Ohio
city: North Canton
country: United States
facility: Neuro-Behavioral Clinical Research ( Site 1055)
state: Ohio
city: Austin
country: United States
facility: Community Clinical Research ( Site 1057)
state: Texas
city: Richardson
country: United States
facility: Pillar Clinical Research, LLC ( Site 1004)
state: Texas
city: Novi Iskar
country: Bulgaria
facility: State Psychiatric Hospital "Sv. Ivan Rilski", Novi Iskar ( Site 3001)
state: Sofia
city: Burgas
country: Bulgaria
facility: Mental Health Center Prof. Dr. Ivan Temkov - Burgas EOOD ( Site 3002)
city: Kardzhali
country: Bulgaria
facility: State Psychiatric Hospital - Kardzhali ( Site 3005)
city: Ruse
country: Bulgaria
facility: Mental Health Center - Ruse, EOOD ( Site 3003)
city: Sofia
country: Bulgaria
facility: Center for Mental Health Prof. Nikola Shipkovenski Ltd ( Site 3000)
city: Veliko Tarnovo
country: Bulgaria
facility: Mental Health Center - Veliko Tarnovo ( Site 3006)
city: Zagreb
country: Croatia
facility: Klinika za psihijatriju Vrapce ( Site 4000)
state: Grad Zagreb
city: Zagreb
country: Croatia
facility: Klinika za psihijatriju Vrapce ( Site 4001)
state: Grad Zagreb
city: Rijeka
country: Croatia
facility: Klinicki bolnicki centar Rijeka ( Site 4005)
state: Primorsko-goranska Zupanija
city: Zagreb
country: Croatia
facility: Klinika za psihijatriju Sveti Ivan ( Site 4003)
state: Zagrebacka Zupanija
city: Toyoake
country: Japan
facility: Seishinkai Okehazama Hospital Fujita Kokoro Care Center ( Site 2011)
state: Aichi
city: Ichikawa
country: Japan
facility: Kohnodai Hospital, National Center for Global Health and Medicine ( Site 2005)
state: Chiba
city: Kitakyushu
country: Japan
facility: Wakato Hospital ( Site 2031)
state: Fukuoka
city: Omuta
country: Japan
facility: Shiranui Hospital ( Site 2043)
state: Fukuoka
city: Tomioka
country: Japan
facility: Seimou Hospital ( Site 2004)
state: Gunma
city: Atsugi
country: Japan
facility: Soushu Hospital ( Site 2008)
state: Kanagawa
city: Hadano
country: Japan
facility: Tanzawa Hospital ( Site 2037)
state: Kanagawa
city: Yokohama-Shi
country: Japan
facility: Kanagawa Psychiatric Center ( Site 2035)
state: Kanagawa
city: Komoro
country: Japan
facility: Komoro Kogen Hospital ( Site 2046)
state: Nagano
city: Kunigamigun
country: Japan
facility: National Hospital Organization Ryukyu Hospital ( Site 2019)
state: Okinawa
city: Naha
country: Japan
facility: Amekudai Hospital ( Site 2020)
state: Okinawa
city: Kanzaki-gun
country: Japan
facility: National Hospital Organization Hizen Psychiatric Medical Center ( Site 2017)
state: Saga
city: Karatsu
country: Japan
facility: Rainbow and Sea Hospital ( Site 2016)
state: Saga
city: Hachioji
country: Japan
facility: Ongata Hospital ( Site 2007)
state: Tokyo
city: Kita-ku
country: Japan
facility: Nishigahara Hospital ( Site 2042)
state: Tokyo
city: Kodaira
country: Japan
facility: National Center of Neurology and Psychiatry ( Site 2023)
state: Tokyo
city: Chiba
country: Japan
facility: Chiba University Hospital ( Site 2024)
city: Fukuoka
country: Japan
facility: Inokuchi Noma Hospital ( Site 2030)
city: Fukuoka
country: Japan
facility: Kuramitsu Hospital ( Site 2014)
city: Kumamoto
country: Japan
facility: Yuge Hospital ( Site 2018)
city: Tokyo
country: Japan
facility: Seijin Hospital ( Site 2026)
city: Tokyo
country: Japan
facility: Narimasu Kosei Hospital ( Site 2006)
city: Busan
country: Korea, Republic of
facility: Inje University Busan Paik Hospital ( Site 0604)
state: Pusan-Kwangyokshi
city: Daegu
country: Korea, Republic of
facility: Kyungpook National University Hospital ( Site 0601)
state: Taegu-Kwangyokshi
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital ( Site 0600)
city: Daugavpils
country: Latvia
facility: Daugavpils Psihoneirologiska Slimnica ( Site 8005)
city: Liepaja
country: Latvia
facility: Piejuras Slimnica Psihiatriska Klinika ( Site 8001)
city: Lodz
country: Poland
facility: Specjal. Psychiatryczny ZOZ w Lodzi, Szpital im. Babinskiego ( Site 0905)
state: Lodzkie
city: Pruszkow
country: Poland
facility: Klinika Psychiatryczna Wydzialu Nauki o Zdrowiu WUM ( Site 0900)
state: Mazowieckie
city: Warsaw
country: Poland
facility: Samodzielny Wojewódzki Zespół Publicznych Zakładów Psychiatrycznej Opieki Zdrowotnej w Warszawie ( S
state: Mazowieckie
city: Gdansk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne ( Site 0902)
state: Pomorskie
city: Poznań
country: Poland
facility: Centrum Medyczne HCP ( Site 0913)
state: Wielkopolskie
city: Bucharest
country: Romania
facility: Prof. Dr. Alexandru Obregia Psychiatry Hospital ( Site 0815)
state: Bucuresti
city: Bucharest
country: Romania
facility: Prof. Dr. Alexandru Obregia Psychiatry Hospital ( Site 0816)
state: Bucuresti
city: Bucharest
country: Romania
facility: Prof. Dr. Alexandru Obregia Psychiatry Hospital ( Site 0817)
state: Bucuresti
city: Bucharest
country: Romania
facility: Prof. Dr. Alexandru Obregia Psychiatry Hospital ( Site 0818)
state: Bucuresti
city: Iași
country: Romania
facility: Institutul de Psihiatrie Socola ( Site 0810)
state: Iasi
city: Iași
country: Romania
facility: Institutul de Psihiatrie Socola ( Site 0814)
state: Iasi
city: Arkhangelsk
country: Russian Federation
facility: Arkhangelsk Regional Psychiatric Clinical Hospital ( Site 6020)
state: Arkhangel Skaya Oblast
city: Leningrad Region
country: Russian Federation
facility: SGHI Leningrad Region Psyconeurology Dispensary ( Site 6017)
state: Leningradskaya Oblast
city: Lipetsk
country: Russian Federation
facility: Lipetsk Regional Psychoneurology Hospital ( Site 6021)
state: Lipetskaya Oblast
city: Moscow
country: Russian Federation
facility: Moscow Scientific Research Institute for Psychiatry ( Site 6013)
state: Moskva
city: Moscow
country: Russian Federation
facility: Psychiatric Clinical Hospital 4 named after PB Gannushkin ( Site 6016)
state: Moskva
city: Moscow
country: Russian Federation
facility: Psychiatric Clinical Hospital 4 named after PB Gannushkin-Psychiatric department 4 ( Site 6023)
state: Moskva
city: Moscow
country: Russian Federation
facility: Central Moscow Regional Clinical Psychiatric Hospital ( Site 6018)
state: Moskva
city: Saint Petersburg
country: Russian Federation
facility: Bekhterev Research Institute for Psychoneurology ( Site 6008)
state: Sankt-Peterburg
city: St. Petersburg
country: Russian Federation
facility: SPb City Psychiatric Hospital #3 na II Skvortsov-Stepanov ( Site 6000)
state: Sankt-Peterburg
city: St. Petersburg
country: Russian Federation
facility: SPb City Psychiatric Hospital #3 na II Skvortsov-Stepanov ( Site 6001)
state: Sankt-Peterburg
city: St. Petersburg
country: Russian Federation
facility: SPb City Psychiatric Hospital #3 na II Skvortsov-Stepanov ( Site 6002)
state: Sankt-Peterburg
city: Stavropol
country: Russian Federation
facility: Stavropol Region Psychiatric Hospital #2 ( Site 6005)
state: Stavropol Skiy Kray
city: Tomsk
country: Russian Federation
facility: Federal State Scientific Institution Research Institute of Mental Health ( Site 6014)
state: Tomskaya Oblast
city: Yaroslavl
country: Russian Federation
facility: Yaroslavl Regional Clinical Psychiatry Hospital ( Site 6022)
state: Yaroslavskaya Oblast
city: Belgrade
country: Serbia
facility: Clinical Center of Serbia ( Site 5101)
state: Beograd
city: Belgrade
country: Serbia
facility: Clinical Center of Serbia ( Site 5107)
state: Beograd
city: Belgrade
country: Serbia
facility: Institut za mentalno zdravlje ( Site 5105)
state: Beograd
city: Belgrade
country: Serbia
facility: University Clinical Hospital Center "Dr. Dragisa Misovic - Dedinje" ( Site 5104)
state: Beograd
city: Kragujevac
country: Serbia
facility: Clinical Center Kragujevac ( Site 5100)
state: Sumadijski Okrug
city: Kragujevac
country: Serbia
facility: Clinical Center Kragujevac ( Site 5102)
state: Sumadijski Okrug
city: Kragujevac
country: Serbia
facility: Clinical Center Kragujevac ( Site 5106)
state: Sumadijski Okrug
city: Kovin
country: Serbia
facility: Special Hospital for Psychiatric Diseases Kovin ( Site 5108)
state: Vojvodina
city: Kovin
country: Serbia
facility: Special Hospital for Psychiatric Diseases Kovin ( Site 5109)
state: Vojvodina
city: Taichung
country: Taiwan
facility: China Medical University Hospital ( Site 9006)
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital ( Site 9001)
city: Taipei
country: Taiwan
facility: Taipei City Hospital, Songde Branch ( Site 9004)
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital ( Site 9000)
city: Taoyuan
country: Taiwan
facility: Chang Gung Memorial Hospital - Linkou Branch ( Site 9002)
city: Smila
country: Ukraine
facility: CNE Cherkasy reg. psychiatric hospital of Cherkasy regional council ( Site 7009)
state: Cherkaska Oblast
city: Dnipro
country: Ukraine
facility: Dnepropetrovsk Regional Clinical Hospital Mechnikov-Regional Centre of Psychosomatic Disorders base
state: Dnipropetrovska Oblast
city: Ivano-Frankivsk
country: Ukraine
facility: CNE "Precarpathian Regional Clinical Center of Mental Health of Ivano-Frankivsk Regional Council"" (
state: Ivano-Frankivska Oblast
city: Kharkiv
country: Ukraine
facility: CNE of Kharkiv Reg. Council Reg. Clinical Psychiatric Hospital Nub 3 ( Site 7012)
state: Kharkivska Oblast
city: Kharkiv
country: Ukraine
facility: Institute of Neurology,Psychiatry and Narcology AMS Ukraine ( Site 7011)
state: Kharkivska Oblast
city: Kherson
country: Ukraine
facility: CNE. Kherson Regional Psychiatric Hospital ( Site 7004)
state: Khersonska Oblast
city: Kyiv
country: Ukraine
facility: Kyiv City Psychoneurological Hospital 2 ( Site 7008)
state: Kyivska Oblast
city: Kyiv
country: Ukraine
facility: CNE Clinical Hospital PSYCHIATRY of executive body of Kyiv City Council -Kyiv City State Admin ( Sit
state: Kyivska Oblast
city: Kyiv
country: Ukraine
facility: MNE of KRC-Regional psychiatric and narcological medical association ( Site 7005)
state: Kyivska Oblast
city: Vinnytsya
country: Ukraine
facility: CNE "Vinnytsia Regional Clinical Psycho-neurological hospita-Mixed (men and women) department #2 ( S
state: Vinnytska Oblast
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: