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

• ClinicalTrials.gov Identifier: NCT04624243
• Recruitment Status: Active, not recruiting
• First Posted: November 10, 2020
• Last Update Posted: March 19, 2024
• Sponsor: Merck Sharp & Dohme LLC
• Information provided by (Responsible Party): Merck Sharp & Dohme LLC

Tracking Information

• First Submitted Date: November 5, 2020
• First Posted Date: November 10, 2020
• Last Update Posted Date: March 19, 2024
• Actual Study Start Date: December 15, 2020
• Estimated Primary Completion Date: July 15, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 5, 2020)

• 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 [ Time Frame: 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) [ Time Frame: ~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 [ Time Frame: ~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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: December 8, 2022)

• Change from baseline in PANSS positive subscale (PSS) score at Week 6: MK-8189 24 mg, MK-8189 16 mg, or placebo [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Baseline, Week 12 ]
  Body weight will be measured using a standardized scale.
• Change from baseline in weight at Week 6: MK-8189 24 mg, MK-8189 16 mg, MK-8189 8 mg or placebo [ Time Frame: Baseline, Week 6 ]
  Body weight will be measured using a standardized scale.

Original Secondary Outcome Measures (submitted: November 5, 2020)

• Change from baseline in PANSS positive subscale (PSS) score at Week 6: MK-8189 24 mg, MK-8189 16 mg, or placebo [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Baseline, Week 6 ]
  Body weight will be measured using a standardized scale.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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

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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Schizophrenia

Intervention

• Drug: MK-8189
  MK-8189 administered QD at a dose of 8 mg, 16 mg, or 24 mg via oral tablet.
• 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.
• Drug: Placebo to risperidone
  Risperidone-matching placebo administered QD via oral capsule.

Study Arms

• 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. 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.
  Interventions:

  • Drug: MK-8189
  • Drug: Placebo to risperidone
• 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.
  Interventions:

  • Drug: MK-8189
  • Drug: Placebo to risperidone
• 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.
  Interventions:

  • Drug: MK-8189
  • Drug: Placebo to risperidone
• 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.
  Interventions:

  • Drug: Risperidone
  • Drug: Placebo to MK-8189
• 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.
  Interventions:

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

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: December 8, 2022): 500
• Original Estimated Enrollment (submitted: November 5, 2020): 576
• Estimated Study Completion Date: July 15, 2024
• Estimated Primary Completion Date: July 15, 2024 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 55 Years (Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Bulgaria, Croatia, Japan, Korea, Republic of, Latvia, Poland, Romania, Russian Federation, Serbia, Taiwan, Ukraine, United States

Administrative Information

• NCT Number: NCT04624243
• Other Study ID Numbers: 8189-008; MK-8189-008 ( Other Identifier: Merck Protocol Number ); jRCT2071200096 ( Registry Identifier: jRCT ); 2020-000094-24 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
• URL: http://engagezone.msd.com/ds_documentation.php

• Current Responsible Party: Merck Sharp & Dohme LLC
• Original Responsible Party: Same as current
• Current Study Sponsor: Merck Sharp & Dohme LLC
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Medical Director; Merck Sharp & Dohme LLC

• PRS Account: Merck Sharp & Dohme LLC
• Verification Date: March 2024