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

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 2

Conditions: Schizophrenia

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT04624243

jRCT2071200096 (Registry Identifier)

2020-000094-24 (EudraCT Number)

MK-8189-008 (Other Identifier)

8189-008

Details and patient eligibility

About

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.

Enrollment: 500 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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500 participants in 5 patient groups

MK-8189 8 mg (Acute) - MK-8189 8 mg (Extension)

Experimental group

Description:

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.

Treatment:

Drug: MK-8189

Drug: Placebo to risperidone

MK-8189 16 mg (Acute) - MK-8189 16 mg (Extension)

Experimental group

Description:

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.

Treatment:

Drug: MK-8189

Drug: Placebo to risperidone

MK-8189 24 mg (Acute) - MK-8189 24 mg (Extension)

Experimental group

Description:

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.

Treatment:

Drug: MK-8189

Drug: Placebo to risperidone

Risperidone 6 mg (Acute) - Risperidone 6 mg (Extension)

Active Comparator group

Description:

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.

Treatment:

Drug: Placebo to MK-8189

Drug: Risperidone

Placebo to MK-8189 (Acute) - MK-8189 24 mg (Extension)

Experimental group

Description:

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.

Treatment:

Drug: Placebo to MK-8189

Drug: MK-8189

Drug: Placebo to risperidone