Clinical Trials List
Protocol NumberMK-8189-008
NCT Number(ClinicalTrials.gov Identfier)NCT04624243
Completed
2020-12-01 - 2025-08-31
Phase II/III
Not yet recruiting1
Recruiting4
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
-
Trial Applicant
Merck Sharp & Dohme (I.A.) LLC
-
Sponsor
Merck Sharp & Dohme
-
Trial scale
Multi-Regional Multi-Center
-
Update
2026/02/01
Investigators and Locations
Co-Principal Investigator
- YI-LING CHIEN Division of Psychiatry
- Chen-Chung Liu Division of Psychiatry
- CHIH-MIN LIU Division of Psychiatry
- YI-TING LIN Division of Psychiatry
- 謝明憲 Division of Psychiatry
China Medical University Hospital
Taiwan National PI
藍先元
The Actual Total Number of Participants Enrolled
0 Recruiting
Audit
Sponsors
Co-Principal Investigator
- 胡力予 Division of Psychiatry
Co-Principal Investigator
- 林式穀 Division of Psychiatry
- 李宛臻醫師 Division of Psychiatry
- 陳易隆 Division of Psychiatry
- Po-Yu Chen 無
Co-Principal Investigator
- 楊緯聖 Division of Psychiatry
- 周亞欣 Division of Psychiatry
- Chia-Yi Liu Division of Psychiatry
- 林式穀 Division of Psychiatry
- 林皇利 Division of Psychiatry
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- 陳易隆 Division of Psychiatry
- 林式穀 Division of Psychiatry
- Po-Yu Chen Division of Psychiatry
- 李宛臻 Division of Psychiatry
The Actual Total Number of Participants Enrolled
0 Recruiting
Condition/Disease
Schizophrenia
Objectives
To realize the efficacy and safety of MK-8189 in participants experiencing an acute episode of schizophrenia
Test Drug
MK-8189
Active Ingredient
MK-8189
Dosage Form
Tablet
Dosage
8mg, 16mg, 24mg
Endpoints
The Efficacy and Safety of MK-8189
Inclution Criteria
1. Meet the diagnostic criteria for schizophrenia according to the DSM-5 ™.
2. Be currently experiencing active phase symptoms of schizophrenia (DSM-5 ™
Criterion A).
3. Have an illness duration for schizophrenia of at least 1 year and ≤15 years.
4. 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 ≤4 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
Note: this criterion will be reviewed and approved by the external SDE prior to
randomization.
5. Have a minimum PANSS total score of ≥80 at screening.
6. Have a score of ≥4 (moderate) in 2 or more of the following items in the positive
subscale of the PANSS at screening: delusions, hallucinations, conceptual
disorganization, suspiciousness; at least one must be hallucinations or delusions.
Note: these scores will be independently verified by the SDE prior to randomization.
7. Have a CGI-S score of ≥4 (moderately ill) at screening and baseline.
8. Be able to taper off psychotropic medications (including antipsychotics, antidepressants
and mood stabilizers) without significant destabilization or increased suicidality in the
opinion of the investigator (see Table 3) with the last dose taken no later than the evening
prior to the baseline visit (Visit 2/Day 1; the dosing cycle of depot neuroleptics must end
no later than the day prior to baseline), with the exception that the last dose of past MAO
inhibitors cannot be within 30 days of the screening visit.
9. Have had a positive response to antipsychotic medication (other than clozapine) during at
least 1 period of treatment for a prior psychotic episode.
10. Be male or female from 18 years to 50 years of age inclusive, at the time of signing the
informed consent.
11. A female participant is eligible to participate if she is not pregnant or breastfeeding, and
at least one of the following conditions applies:
Is not a WOCBP
OR
Is a WOCBP and using a contraceptive method that is highly effective (with a failure
rate of <1% per year), or be abstinent from heterosexual intercourse as their preferred
and usual lifestyle (abstinent on a long term and persistent basis), as described in
Appendix 5 during the intervention period and for at least 14 days after the last dose
of study intervention. The investigator should evaluate the potential for contraceptive
method failure (ie, noncompliance, recently initiated) in relationship to the first dose
of study intervention.
Additional requirements for pregnancy testing during and after study intervention are
located in Appendix 2.
The investigator is responsible for review of medical history, menstrual history, and
recent sexual activity to decrease the risk for inclusion of a woman with an early
undetected pregnancy.
12. Provide written informed consent for the study. The participant may also provide consent
for future biomedical research. However, the participant may participate in the main
study without participating in future biomedical research.
13. Have a level of decision-making capacity needed to make a meaningful choice about
whether to participate in the study.
14. Be willing and considered able by the investigator to participate in protocol assessments,
including recordings of interviews, adhere to dose and visit schedules, study procedures
and restrictions; this includes the ability to participate in all study procedures without the
use of a language interpreter.
15. Have an identified responsible person (eg, family member, social worker, case worker,
case manager, or nurse), referred to as the “external contact person” in the protocol, 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 with the participant, and with the expectation that this frequency of contact
would continue (either in person or via telephone) throughout duration of study,
including the follow-up period).
Note: if the participant does not have a reliable external contact person, then the site may
designate a site staff member who will take on the role of external contact person, with
the same responsibilities as described above.
2. Be currently experiencing active phase symptoms of schizophrenia (DSM-5 ™
Criterion A).
3. Have an illness duration for schizophrenia of at least 1 year and ≤15 years.
4. 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 ≤4 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
Note: this criterion will be reviewed and approved by the external SDE prior to
randomization.
5. Have a minimum PANSS total score of ≥80 at screening.
6. Have a score of ≥4 (moderate) in 2 or more of the following items in the positive
subscale of the PANSS at screening: delusions, hallucinations, conceptual
disorganization, suspiciousness; at least one must be hallucinations or delusions.
Note: these scores will be independently verified by the SDE prior to randomization.
7. Have a CGI-S score of ≥4 (moderately ill) at screening and baseline.
8. Be able to taper off psychotropic medications (including antipsychotics, antidepressants
and mood stabilizers) without significant destabilization or increased suicidality in the
opinion of the investigator (see Table 3) with the last dose taken no later than the evening
prior to the baseline visit (Visit 2/Day 1; the dosing cycle of depot neuroleptics must end
no later than the day prior to baseline), with the exception that the last dose of past MAO
inhibitors cannot be within 30 days of the screening visit.
9. Have had a positive response to antipsychotic medication (other than clozapine) during at
least 1 period of treatment for a prior psychotic episode.
10. Be male or female from 18 years to 50 years of age inclusive, at the time of signing the
informed consent.
11. A female participant is eligible to participate if she is not pregnant or breastfeeding, and
at least one of the following conditions applies:
Is not a WOCBP
OR
Is a WOCBP and using a contraceptive method that is highly effective (with a failure
rate of <1% per year), or be abstinent from heterosexual intercourse as their preferred
and usual lifestyle (abstinent on a long term and persistent basis), as described in
Appendix 5 during the intervention period and for at least 14 days after the last dose
of study intervention. The investigator should evaluate the potential for contraceptive
method failure (ie, noncompliance, recently initiated) in relationship to the first dose
of study intervention.
Additional requirements for pregnancy testing during and after study intervention are
located in Appendix 2.
The investigator is responsible for review of medical history, menstrual history, and
recent sexual activity to decrease the risk for inclusion of a woman with an early
undetected pregnancy.
12. Provide written informed consent for the study. The participant may also provide consent
for future biomedical research. However, the participant may participate in the main
study without participating in future biomedical research.
13. Have a level of decision-making capacity needed to make a meaningful choice about
whether to participate in the study.
14. Be willing and considered able by the investigator to participate in protocol assessments,
including recordings of interviews, adhere to dose and visit schedules, study procedures
and restrictions; this includes the ability to participate in all study procedures without the
use of a language interpreter.
15. Have an identified responsible person (eg, family member, social worker, case worker,
case manager, or nurse), referred to as the “external contact person” in the protocol, 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 with the participant, and with the expectation that this frequency of contact
would continue (either in person or via telephone) throughout duration of study,
including the follow-up period).
Note: if the participant does not have a reliable external contact person, then the site may
designate a site staff member who will take on the role of external contact person, with
the same responsibilities as described above.
Exclusion Criteria
no1. Has a primary current diagnosis other than schizophrenia or a comorbid diagnosis (for
example, major depression) that is primarily responsible for the current symptoms and
functional impairment.
2. Meets criteria for moderate to severe substance use disorder currently or within past 6
months prior to screening (excluding those related to caffeine or tobacco/nicotine).
3. Has a known history of the following:
a. Borderline personality disorder, antisocial 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 the ability of the participant to
participate in the study
4. Has a current diagnosis of a psychotic disorder (other than schizophrenia), or a behavioral
disturbance thought to be substance-induced or due to substance abuse.
5. Has moderate or severe tardive dyskinesia according to the investigator.
6. Is or was under involuntary commitment for the current acute episode, because the
participant is considered a danger to themselves or others.
7. Has committed an act of violence (assaultive behavior) ≤ 2 years prior to the screening
visit.
8. Has a body mass index (BMI) <18.5 kg/m2.
9. Has a risk factor for QTc prolongation as defined by:
a. A known history or current evidence of QTc interval >470 msec (men) or >480 msec
(women)
b. A known history of risk factors for Torsades de Pointes (eg, heart failure,
cardiomyopathy or family history of long QT syndrome)
10. Has known renal disease or is experiencing renal insufficiency as defined by:
eGFR of <60 mL/min/1.73m2 [as measured by CKD-EPI formula]
11. Has known history of chronic convulsive disorder (eg, epilepsy or seizure disorder)
except febrile seizures of childhood.
12. Has a history of neuroleptic malignant syndrome.
13. Has a history of malignancy ≤3 years prior to signing informed consent except for
adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer.
14. Is at imminent risk of self-harm or harm to others as assessed by the investigator, based
on clinical interview, MINI, or responses provided on the C-SSRS.
15. Has a history of 3 or more significant allergies (including latex allergy) to prescription or
nonprescription drugs or food, according to the investigator.
16. Has a known allergy or intolerance to risperidone or any of its active or inert ingredients.
17. Has hypothyroidism, diabetes, high blood pressure, cardiovascular condition, respiratory
condition or other chronic medical conditions unless the condition is stable according to
the investigator; the prescribed dose and regimen of medication are stable for ≥ 3 months
prior to screening; and there are no expected changes in comedication during the study.
Note: the prescribed dose and regimen of medication are considered stable if dose
adjustments reflect optimizing treatment rather than reacting to significant changes in the
treated conditions.
18. 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 (from at least 2 different chemical classes) at the maximally
tolerated dose. Participants who have responded to antipsychotics only when paired
with clozapine are considered treatment resistant
b. History of 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 5 years
19. Is currently taking and benefiting from a moderate or strong CYP3A and/or CYP2C9
inhibitors and inducers and/or CYP2B6 sensitive substrates.
20. Is currently taking and benefiting from strong CYP2D6 inhibitors.
21. Is currently participating in or has participated in an interventional clinical research study
within 12 months prior to the screening visit of this current study.
22. Has been previously participated in the MK-8189 program according to the following:
previous screen failure in this study; was previously randomized (regardless of treatment)
in any MK-8189 study.
23. Is unwilling to allow the recording of the MINI and PANSS interview at screening and
baseline.
24. Has laboratory or clinical evidence of clinically significant hepatic conditions such as one
or more of the following:
a. ALT or AST ˃2X ULN and total bilirubin ˃1.5X ULN.
b. ALT or AST ˃3X ULN
c. A history of hepatitis or liver disease that, in the opinion of the investigator, has been
active within the 6 months prior to screening
25. Has a prolactin laboratory value of ≥ 5X ULN at screening.
26. Has a positive urine alcohol/drug screen at the screening visit with the following
exceptions:
a. Participants with positive psychotropic medication results for drugs permitted at time
of screening may be included, provided the finding(s) can be accounted for by
documented prescription use, the participant is able and willing to comply with
protocol requirements regarding excluded medications, and eligibility criteria
pertaining to the use of concomitant medications and substance use disorder are met
b. Participants with positive alcohol or cannabis results on the urine alcohol/drug screen
may be included at the investigator’s discretion, provided the investigator does not
feel the participant is a compliance risk and the participant does not fulfill the criteria
for moderate or severe substance use disorder
27. Is unwilling or unable to remain hospitalized for the duration of screening and at least the
first 28 days of treatment period.
28. Has a severe, acute or chronic medical condition or laboratory abnormality that may
increase the risk associated with study participation or investigational product
administration or may interfere with the interpretation of study results and, in the
judgment of the investigator or Sponsor, would make the participant inappropriate for
entry into this study.
29. Has adverse events or clinically significant abnormal laboratory, vital sign, or physical
examination, or ECG finding during screening period indicative of emerging or unstable
medical conditions that potentially interfere with the ability to evaluate the safety,
tolerability and the efficacy of the study intervention, according to the judgment of the
investigator.
30. Is known to be repeatedly medically noncompliant in the management of their
schizophrenia as assessed by the investigator.
31. Is known to be noncompliant or who is assessed by the investigator to be potentially
noncompliant with the management of a current severe, acute or chronic medical
condition which requires strict adherence to treatment (eg, tuberculosis, HIV).
32. Is or has an immediate family member (eg, spouse, parent/legal guardian, sibling, or
child) who is investigational site or Sponsor staff directly involved with this study.
example, major depression) that is primarily responsible for the current symptoms and
functional impairment.
2. Meets criteria for moderate to severe substance use disorder currently or within past 6
months prior to screening (excluding those related to caffeine or tobacco/nicotine).
3. Has a known history of the following:
a. Borderline personality disorder, antisocial 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 the ability of the participant to
participate in the study
4. Has a current diagnosis of a psychotic disorder (other than schizophrenia), or a behavioral
disturbance thought to be substance-induced or due to substance abuse.
5. Has moderate or severe tardive dyskinesia according to the investigator.
6. Is or was under involuntary commitment for the current acute episode, because the
participant is considered a danger to themselves or others.
7. Has committed an act of violence (assaultive behavior) ≤ 2 years prior to the screening
visit.
8. Has a body mass index (BMI) <18.5 kg/m2.
9. Has a risk factor for QTc prolongation as defined by:
a. A known history or current evidence of QTc interval >470 msec (men) or >480 msec
(women)
b. A known history of risk factors for Torsades de Pointes (eg, heart failure,
cardiomyopathy or family history of long QT syndrome)
10. Has known renal disease or is experiencing renal insufficiency as defined by:
eGFR of <60 mL/min/1.73m2 [as measured by CKD-EPI formula]
11. Has known history of chronic convulsive disorder (eg, epilepsy or seizure disorder)
except febrile seizures of childhood.
12. Has a history of neuroleptic malignant syndrome.
13. Has a history of malignancy ≤3 years prior to signing informed consent except for
adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer.
14. Is at imminent risk of self-harm or harm to others as assessed by the investigator, based
on clinical interview, MINI, or responses provided on the C-SSRS.
15. Has a history of 3 or more significant allergies (including latex allergy) to prescription or
nonprescription drugs or food, according to the investigator.
16. Has a known allergy or intolerance to risperidone or any of its active or inert ingredients.
17. Has hypothyroidism, diabetes, high blood pressure, cardiovascular condition, respiratory
condition or other chronic medical conditions unless the condition is stable according to
the investigator; the prescribed dose and regimen of medication are stable for ≥ 3 months
prior to screening; and there are no expected changes in comedication during the study.
Note: the prescribed dose and regimen of medication are considered stable if dose
adjustments reflect optimizing treatment rather than reacting to significant changes in the
treated conditions.
18. 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 (from at least 2 different chemical classes) at the maximally
tolerated dose. Participants who have responded to antipsychotics only when paired
with clozapine are considered treatment resistant
b. History of 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 5 years
19. Is currently taking and benefiting from a moderate or strong CYP3A and/or CYP2C9
inhibitors and inducers and/or CYP2B6 sensitive substrates.
20. Is currently taking and benefiting from strong CYP2D6 inhibitors.
21. Is currently participating in or has participated in an interventional clinical research study
within 12 months prior to the screening visit of this current study.
22. Has been previously participated in the MK-8189 program according to the following:
previous screen failure in this study; was previously randomized (regardless of treatment)
in any MK-8189 study.
23. Is unwilling to allow the recording of the MINI and PANSS interview at screening and
baseline.
24. Has laboratory or clinical evidence of clinically significant hepatic conditions such as one
or more of the following:
a. ALT or AST ˃2X ULN and total bilirubin ˃1.5X ULN.
b. ALT or AST ˃3X ULN
c. A history of hepatitis or liver disease that, in the opinion of the investigator, has been
active within the 6 months prior to screening
25. Has a prolactin laboratory value of ≥ 5X ULN at screening.
26. Has a positive urine alcohol/drug screen at the screening visit with the following
exceptions:
a. Participants with positive psychotropic medication results for drugs permitted at time
of screening may be included, provided the finding(s) can be accounted for by
documented prescription use, the participant is able and willing to comply with
protocol requirements regarding excluded medications, and eligibility criteria
pertaining to the use of concomitant medications and substance use disorder are met
b. Participants with positive alcohol or cannabis results on the urine alcohol/drug screen
may be included at the investigator’s discretion, provided the investigator does not
feel the participant is a compliance risk and the participant does not fulfill the criteria
for moderate or severe substance use disorder
27. Is unwilling or unable to remain hospitalized for the duration of screening and at least the
first 28 days of treatment period.
28. Has a severe, acute or chronic medical condition or laboratory abnormality that may
increase the risk associated with study participation or investigational product
administration or may interfere with the interpretation of study results and, in the
judgment of the investigator or Sponsor, would make the participant inappropriate for
entry into this study.
29. Has adverse events or clinically significant abnormal laboratory, vital sign, or physical
examination, or ECG finding during screening period indicative of emerging or unstable
medical conditions that potentially interfere with the ability to evaluate the safety,
tolerability and the efficacy of the study intervention, according to the judgment of the
investigator.
30. Is known to be repeatedly medically noncompliant in the management of their
schizophrenia as assessed by the investigator.
31. Is known to be noncompliant or who is assessed by the investigator to be potentially
noncompliant with the management of a current severe, acute or chronic medical
condition which requires strict adherence to treatment (eg, tuberculosis, HIV).
32. Is or has an immediate family member (eg, spouse, parent/legal guardian, sibling, or
child) who is investigational site or Sponsor staff directly involved with this study.
The Estimated Number of Participants
-
Taiwan
30 participants
-
Global
500 participants
