Efficacy and Safety of MK-8189 in Participants With an Acute Episode of Schizophrenia (MK-8189-008)
Study Details
Study Description
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
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Arms and Interventions
| 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. |
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 MK-8189
MK-8189-matching placebo administered QD via oral tablet.
Drug: Placebo to risperidone
Risperidone-matching placebo administered QD via oral capsule.
|
Outcome Measures
Primary Outcome Measures
- 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 [Baseline, 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 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.
- Number of participants who experience one or more adverse events (AEs) [~Up to Week 14]
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.
- Number of participants who discontinue study treatment due to an AE [~Up to Week 12]
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.
Secondary Outcome Measures
- Change from baseline in PANSS positive subscale (PSS) score at Week 6: MK-8189 24 mg, MK-8189 16 mg, or placebo [Baseline, Week 6]
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.
- 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 [Baseline, Week 6]
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.
- Change from baseline in weight at Week 12: MK-8189 24 mg, MK-8189 16 mg, or risperidone [Baseline, Week 12]
Body weight will be measured using a standardized scale.
- Change from baseline in PANSS total score at Week 6: MK-8189 8 mg or placebo [Baseline, 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 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.
- Change from baseline in weight at Week 6: MK-8189 24 mg, MK-8189 16 mg, MK-8189 8 mg or placebo [Baseline, Week 6]
Body weight will be measured using a standardized scale.
Eligibility Criteria
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 and ≤21 years
-
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 prior to 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
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Has a current diagnosis of a psychotic disorder other than schizophrenia or a behavioral disturbance thought to be due to substance abuse
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Is or was under involuntary commitment for the acute episode, because the participant is considered a danger to themselves or others
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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 5 years (c) past or current use of clozapine as single or adjunctive therapy for schizophrenia within the past 3 months
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Is currently participating in or has participated in an interventional clinical research study within 3 months prior to the screening visit of this current study and no more than 1 study in the past 2 years
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Woodland International Research Group, LLC ( Site 1002) | Little Rock | Arkansas | United States | 72211 |
| 2 | Woodland Research Northwest, LLC ( Site 1036) | Rogers | Arkansas | United States | 72758 |
| 3 | CITRIALS ( Site 1010) | Bellflower | California | United States | 90706 |
| 4 | Collaborative Neuroscience Research, LLC ( Site 1041) | Garden Grove | California | United States | 92845 |
| 5 | Behavioral Research Specialists, LLC ( Site 1032) | Glendale | California | United States | 91206 |
| 6 | CITRIALS ( Site 1016) | Riverside | California | United States | 92506 |
| 7 | CNRI - San Diego, LLC ( Site 1034) | San Diego | California | United States | 92102 |
| 8 | Artemis Institute for Clinical Research ( Site 1019) | San Diego | California | United States | 92103 |
| 9 | Schuster Medical Research Institute ( Site 1023) | Sherman Oaks | California | United States | 91403 |
| 10 | Behavioral Clinical Research , Inc ( Site 1013) | Miami Lakes | Florida | United States | 33016 |
| 11 | Fort Lauderdale Behavioral Health Center ( Site 1028) | Oakland Park | Florida | United States | 33334 |
| 12 | Atlanta Center For Medical Research ( Site 1022) | Atlanta | Georgia | United States | 30331 |
| 13 | AMITA Health - St. Elizabeth Campus ( Site 1000) | Chicago | Illinois | United States | 60622 |
| 14 | CBH Health ( Site 1044) | Gaithersburg | Maryland | United States | 20877 |
| 15 | Massachusetts General Hospital ( Site 1035) | Boston | Massachusetts | United States | 02114 |
| 16 | Arch Clinical Trials ( Site 1048) | Saint Louis | Missouri | United States | 63125 |
| 17 | Altea Research Institute ( Site 1012) | Las Vegas | Nevada | United States | 89102 |
| 18 | Hassman Research Institute Marlton Site ( Site 1040) | Marlton | New Jersey | United States | 08053 |
| 19 | New Hope Clinical Research ( Site 1050) | Charlotte | North Carolina | United States | 28211 |
| 20 | Midwest Clinical Research Center ( Site 1033) | Dayton | Ohio | United States | 45417 |
| 21 | Pillar Clinical Research, LLC ( Site 1004) | Richardson | Texas | United States | 75080 |
| 22 | Mental Health Center Prof. Dr. Ivan Temkov - Burgas EOOD ( Site 3002) | Burgas | Bulgaria | 8001 | |
| 23 | Center for Mental Health Prof. Nikola Shipkovenski Ltd ( Site 3000) | Sofia | Bulgaria | 1000 | |
| 24 | Klinika za psihijatriju Vrapce ( Site 4000) | Zagreb | Grad Zagreb | Croatia | 10090 |
| 25 | Klinika za psihijatriju Vrapce ( Site 4001) | Zagreb | Grad Zagreb | Croatia | 10090 |
| 26 | Klinicki bolnicki centar Rijeka ( Site 4005) | Rijeka | Primorsko-goranska Zupanija | Croatia | 51000 |
| 27 | Klinika za psihijatriju Sveti Ivan ( Site 4003) | Zagreb | Zagrebacka Zupanija | Croatia | 10090 |
| 28 | Seishinkai Okehazama Hospital Fujita Kokoro Care Center ( Site 2011) | Toyoake | Aichi | Japan | 470-1168 |
| 29 | Kohnodai Hospital, National Center for Global Health and Medicine ( Site 2005) | Ichikawa | Chiba | Japan | 272-8516 |
| 30 | Wakato Hospital ( Site 2031) | Kitakyushu | Fukuoka | Japan | 808-0139 |
| 31 | Shiranui Hospital ( Site 2043) | Omuta | Fukuoka | Japan | 8360004 |
| 32 | Seimou Hospital ( Site 2004) | Tomioka | Gunma | Japan | 3702455 |
| 33 | Soushu Hospital ( Site 2008) | Atsugi | Kanagawa | Japan | 243-0201 |
| 34 | Tanzawa Hospital ( Site 2037) | Hadano | Kanagawa | Japan | 259-1304 |
| 35 | Kanagawa Psychiatric Center ( Site 2035) | Yokohama-Shi | Kanagawa | Japan | 233-0006 |
| 36 | National Hospital Organization Ryukyu Hospital ( Site 2019) | Kunigamigun | Okinawa | Japan | 904-1201 |
| 37 | Amekudai Hospital ( Site 2020) | Naha | Okinawa | Japan | 900-0005 |
| 38 | National Hospital Organization Hizen Psychiatric Medical Center ( Site 2017) | Kanzaki-gun | Saga | Japan | 8420192 |
| 39 | Rainbow and Sea Hospital ( Site 2016) | Karatsu | Saga | Japan | 847-0031 |
| 40 | Ongata Hospital ( Site 2007) | Hachioji | Tokyo | Japan | 192-0153 |
| 41 | Nishigahara Hospital ( Site 2042) | Kita-ku | Tokyo | Japan | 114-0024 |
| 42 | National Center of Neurology and Psychiatry ( Site 2023) | Kodaira | Tokyo | Japan | 187-8551 |
| 43 | Chiba University Hospital ( Site 2024) | Chiba | Japan | 260-8677 | |
| 44 | Inokuchi Noma Hospital ( Site 2030) | Fukuoka | Japan | 815-0074 | |
| 45 | Kuramitsu Hospital ( Site 2014) | Fukuoka | Japan | 819-0037 | |
| 46 | Yuge Hospital ( Site 2018) | Kumamoto | Japan | 861-8002 | |
| 47 | Seijin Hospital ( Site 2026) | Tokyo | Japan | 121-8515 | |
| 48 | Narimasu Kosei Hospital ( Site 2006) | Tokyo | Japan | 175-0091 | |
| 49 | Inje University Busan Paik Hospital ( Site 0604) | Busan | Pusan-Kwangyokshi | Korea, Republic of | 47392 |
| 50 | Kyungpook National University Hospital ( Site 0601) | Daegu | Taegu-Kwangyokshi | Korea, Republic of | 41944 |
| 51 | Seoul National University Hospital ( Site 0600) | Seoul | Korea, Republic of | 03080 | |
| 52 | Daugavpils Psihoneirologiska Slimnica ( Site 8005) | Daugavpils | Latvia | 5417 | |
| 53 | Piejuras Slimnica Psihiatriska Klinika ( Site 8001) | Liepaja | Latvia | 3401 | |
| 54 | Specjal. Psychiatryczny ZOZ w Lodzi, Szpital im. Babinskiego ( Site 0905) | Lodz | Lodzkie | Poland | 91-229 |
| 55 | Klinika Psychiatryczna Wydzialu Nauki o Zdrowiu WUM ( Site 0900) | Pruszkow | Mazowieckie | Poland | 05-802 |
| 56 | Arkhangelsk Regional Psychiatric Clinical Hospital ( Site 6020) | Arkhangelsk | Arkhangel Skaya Oblast | Russian Federation | 163530 |
| 57 | SGHI Leningrad Region Psyconeurology Dispensary ( Site 6017) | Leningrad Region | Leningradskaya Oblast | Russian Federation | 188820 |
| 58 | Lipetsk Regional Psychoneurology Hospital ( Site 6021) | Lipetsk | Lipetskaya Oblast | Russian Federation | 399083 |
| 59 | Moscow Scientific Research Institute for Psychiatry ( Site 6013) | Moscow | Moskva | Russian Federation | 107076 |
| 60 | Psychiatric Clinical Hospital 4 named after PB Gannushkin ( Site 6016) | Moscow | Moskva | Russian Federation | 107076 |
| 61 | Psychiatric Clinical Hospital 4 named after PB Gannushkin-Psychiatric department 4 ( Site 6023) | Moscow | Moskva | Russian Federation | 107076 |
| 62 | Central Moscow Regional Clinical Psychiatric Hospital ( Site 6018) | Moscow | Moskva | Russian Federation | 127083 |
| 63 | Bekhterev Research Institute for Psychoneurology ( Site 6008) | Saint Petersburg | Sankt-Peterburg | Russian Federation | 192019 |
| 64 | SPb City Psychiatric Hospital #3 na II Skvortsov-Stepanov ( Site 6000) | St. Petersburg | Sankt-Peterburg | Russian Federation | |
| 65 | SPb City Psychiatric Hospital #3 na II Skvortsov-Stepanov ( Site 6001) | St. Petersburg | Sankt-Peterburg | Russian Federation | |
| 66 | SPb City Psychiatric Hospital #3 na II Skvortsov-Stepanov ( Site 6002) | St. Petersburg | Sankt-Peterburg | Russian Federation | |
| 67 | Stavropol Region Psychiatric Hospital #2 ( Site 6005) | Stavropol | Stavropol Skiy Kray | Russian Federation | 357034 |
| 68 | Federal State Scientific Institution Research Institute of Mental Health ( Site 6014) | Tomsk | Tomskaya Oblast | Russian Federation | 634014 |
| 69 | Yaroslavl Regional Clinical Psychiatry Hospital ( Site 6022) | Yaroslavl | Yaroslavskaya Oblast | Russian Federation | 150003 |
| 70 | China Medical University Hospital ( Site 9006) | Taichung | Taiwan | 40447 | |
| 71 | National Taiwan University Hospital ( Site 9001) | Taipei | Taiwan | 100 | |
| 72 | Taipei City Hospital, Songde Branch ( Site 9004) | Taipei | Taiwan | 110 | |
| 73 | Taipei Veterans General Hospital ( Site 9000) | Taipei | Taiwan | 11217 | |
| 74 | Chang Gung Memorial Hospital - Linkou Branch ( Site 9002) | Taoyuan | Taiwan | 333 | |
| 75 | CNE Cherkasy reg. psychiatric hospital of Cherkasy regional council ( Site 7009) | Smila | Cherkaska Oblast | Ukraine | 20708 |
| 76 | Dnepropetrovsk Regional Clinical Hospital Mechnikov-Regional Centre of Psychosomatic Disorders base | Dnipro | Dnipropetrovska Oblast | Ukraine | 49005 |
| 77 | CNE "Precarpathian Regional Clinical Center of Mental Health of Ivano-Frankivsk Regional Council"" ( | Ivano-Frankivsk | Ivano-Frankivska Oblast | Ukraine | 76014 |
| 78 | CNE of Kharkiv Reg. Council Reg. Clinical Psychiatric Hospital Nub 3 ( Site 7012) | Kharkiv | Kharkivska Oblast | Ukraine | 61068 |
| 79 | Institute of Neurology,Psychiatry and Narcology AMS Ukraine ( Site 7011) | Kharkiv | Kharkivska Oblast | Ukraine | 61068 |
| 80 | CNE. Kherson Regional Psychiatric Hospital ( Site 7004) | Kherson | Khersonska Oblast | Ukraine | 73488 |
| 81 | Kyiv City Psychoneurological Hospital 2 ( Site 7008) | Kyiv | Kyivska Oblast | Ukraine | 02192 |
| 82 | CNE Clinical Hospital PSYCHIATRY of executive body of Kyiv City Council -Kyiv City State Admin ( Sit | Kyiv | Kyivska Oblast | Ukraine | 04080 |
| 83 | MNE of KRC-Regional psychiatric and narcological medical association ( Site 7005) | Kyiv | Kyivska Oblast | Ukraine | 08631 |
| 84 | Reg. Psych. Hosp. n.a. O. Yuschenko, Dept #21, VNMU n.a. M.Pirogov ( Site 7001) | Vinnytsya | Vinnytska Oblast | Ukraine | 21037 |
Sponsors and Collaborators
- Merck Sharp & Dohme LLC
Investigators
- Study Director: Medical Director, Merck Sharp & Dohme LLC
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 8189-008
- MK-8189-008
- jRCT2071200096
- 2020-000094-24