<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04506905</url>
  </required_header>
  <id_info>
    <org_study_id>8189-011</org_study_id>
    <secondary_id>Merck Protocol Number</secondary_id>
    <nct_id>NCT04506905</nct_id>
  </id_info>
  <brief_title>Safety, Tolerability, and Pharmacokinetics Study of MK-8189 in Participants With Schizophrenia and Healthy Participants (MK-8189-011)</brief_title>
  <official_title>A 2-Part Randomized Clinical Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Alternate MK-8189 Titration Regimens in Young Adult Participants With Schizophrenia and to Evaluate the Safety, Tolerability and Pharmacokinetics of MK-8189 in Elderly Participants With Schizophrenia and Healthy Elderly</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Merck Sharp &amp; Dohme LLC</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Merck Sharp &amp; Dohme LLC</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This 2-Part Randomized Clinical Study will evaluate the safety, tolerability and&#xD;
      pharmacokinetics of alternate MK-8189 titration regimens. Part 1 will assess multiple dose&#xD;
      once-daily titration regimens of MK-8189 in young adult participants with schizophrenia. Part&#xD;
      2 will assess multiple once-daily doses of MK-8189 in elderly participants with schizophrenia&#xD;
      and healthy elderly participants.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 28, 2020</start_date>
  <completion_date type="Actual">March 22, 2022</completion_date>
  <primary_completion_date type="Actual">March 22, 2022</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
    <masking_description>Double blind</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Part 1 &amp; 2: Number of Participants Who Experienced an Adverse Event (AE)</measure>
    <time_frame>Up to approximately 27 days</time_frame>
    <description>The number of participants experiencing an AE will be assessed. An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 1 &amp; 2: Number of Participants Discontinuing Study Treatment Due to an AE</measure>
    <time_frame>Up to approximately 27 days</time_frame>
    <description>The number of participants discontinuing study treatment due to an AE will be assessed. An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Part 1: Area Under the Concentration Time-curve From Hour 0 to 24 Hours (AUC0-24hr) of MK-8189</measure>
    <time_frame>Panels A, B, C: Predose and selected time points postdose on Days 1 and 7. Additional collections for Panel A on Day 4 and Panel C on Days 2 and 3</time_frame>
    <description>AUC0-24hr is defined as the area under concentration-time curve from 0 to 24 hours. Blood samples taken at predose and up to 24 hours postdose to determine the AUC0-24hr of MK-8189.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 1: Maximum Concentration (Cmax) of MK-8189</measure>
    <time_frame>Panels A, B, C: Predose and selected time points postdose on Days 1 and 7. Additional collections for Panel A on Day 4 and Panel C on Days 2 and 3</time_frame>
    <description>Cmax is defined as the maximum concentration of MK-8189 observed in plasma. Blood samples taken at predose and at specified times postdose to determine the Cmax of MK-8189.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 1: Concentration of MK-8189 at 24 Hours (C24hr) postdose</measure>
    <time_frame>Panels A, B, C: Predose and up to 24 hours postdose on Days 1 and 7. Additional collections for Panel A on Day 4 and Panel C on Days 2 and 3</time_frame>
    <description>C24hr is defined as the concentration of MK-8189 observed in plasma at 24 hours. Blood samples taken at predose and up to 24 hours postdose to determine the C24hr of MK-8189.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 1: Time to Cmax (Tmax) of MK-8189</measure>
    <time_frame>Panels A, B, C: Predose and selected time points postdose on Days 1 and 7. Additional collections for Panel A on Day 4 and Panel C on Days 2 and 3</time_frame>
    <description>Tmax is defined as the time of maximum concentration of MK-8189 observed in plasma. Blood samples taken at predose and at specified times postdose to determine the Tmax of MK-8189.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 1: Clearance (CL) of MK-8189</measure>
    <time_frame>Panels A, B, C: Predose and selected time points postdose on Day 7</time_frame>
    <description>Blood samples taken at predose and at specified times postdose to determine the CL of MK-8189.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 1: Volume of Distribution (Vd) of MK-8189</measure>
    <time_frame>Panels A, B, C: Predose and selected time points postdose on Day 7</time_frame>
    <description>Blood samples taken at predose and at specified times postdose to determine the Vd of MK-8189.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 1: Apparent Terminal Half-life (t1/2) of MK-8189</measure>
    <time_frame>Panels A, B, C: Predose and selected time points postdose on Day 7</time_frame>
    <description>Blood samples taken at predose and at specified times postdose to determine the t1/2 of MK-8189.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 2: Area Under the Concentration Time-curve From Hour 0 to 24 Hours (AUC0-24hr) of MK-8189</measure>
    <time_frame>Panels D, F: Predose and selected time points postdose on Days 1, 4, 7 and 13; Panels E, G: Predose and selected time points postdose on Days 1, 4, and 10</time_frame>
    <description>AUC0-24hr is defined as the area under concentration-time curve from 0 to 24 hours. Blood samples taken at predose and up to 24 hours postdose to determine the AUC0-24hr of MK-8189.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 2: Maximum Concentration (Cmax) of MK-8189</measure>
    <time_frame>Panels D, F: Predose and selected time points postdose on Days 1, 4, 7 and 13; Panels E, G: Predose and selected time points postdose on Days 1, 4, and 10</time_frame>
    <description>Cmax is defined as the maximum concentration of MK-8189 observed in plasma. Blood samples taken at predose and at specified times postdose to determine the Cmax of MK-8189.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 2: Concentration of MK-8189 at 24 Hours (C24hr) postdose</measure>
    <time_frame>Panels D, F: Predose and up to 24 hours postdose on Days 1, 4, 7 and 13; Panels E, G: Predose and up to 24 hours postdose on Days 1, 4, and 10</time_frame>
    <description>C24hr is defined as the concentration of MK-8189 observed in plasma at 24 hours. Blood samples taken at predose and up to 24 hours postdose to determine the C24hr of MK-8189.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 2: Time to Cmax (Tmax) of MK-8189</measure>
    <time_frame>Panels D, F: Predose and selected time points postdose on Days 1, 4, 7 and 13; Panels E, G: Predose and selected time points postdose on Days 1, 4, and 10</time_frame>
    <description>Tmax is defined as the time of maximum concentration of MK-8189 observed in plasma. Blood samples taken at predose and at specified times postdose to determine the Tmax of MK-8189.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 2: Clearance (CL) of MK-8189</measure>
    <time_frame>Panels D, F: Predose and selected time points postdose on Day 13; Panels E, G: Predose and selected time points postdose on Day 10</time_frame>
    <description>Blood samples taken at predose and at specified times postdose to determine the CL of MK-8189.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 2: Volume of Distribution (Vd) of MK-8189</measure>
    <time_frame>Panels D, F: Predose and selected time points postdose on Day 13; Panels E, G: Predose and selected time points postdose on Day 10</time_frame>
    <description>Blood samples taken at predose and at specified times postdose to determine the Vd of MK-8189.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 2: Apparent Terminal Half-life (t1/2) of MK-8189</measure>
    <time_frame>Panels D, F: Predose and selected time points postdose on Day 13; Panels E, G: Predose and selected time points postdose on Day 10</time_frame>
    <description>Blood samples taken at predose and at specified times postdose to determine the t1/2 of MK-8189.</description>
  </secondary_outcome>
  <number_of_arms>9</number_of_arms>
  <enrollment type="Actual">63</enrollment>
  <condition>Schizophrenia</condition>
  <arm_group>
    <arm_group_label>Part 1 (Panel A) MK-8189</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Young adult participants with schizophrenia receive MK-8189 titrated from 16 mg to 24 mg once daily (QD), orally, over a course of 7-day treatment.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 1 (Panel B) MK-8189</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Young adult participants with schizophrenia receive MK-8189 titrated up to 24 mg QD, orally, over a course of 7-day treatment period with starting doses based on safety and tolerability of previous starting dose in previous panel.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 1 (Panel C) MK-8189</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Young adult participants with schizophrenia receive MK-8189 titrated from 8 mg to 24 mg QD, orally, over a course of 7-day treatment period with starting doses based on safety and tolerability of previous starting dose in previous panels.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 2 (Panel D) MK-8189</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Elderly adult participants with schizophrenia receive MK-8189 titrated from 8 mg to 24 mg QD, orally, over the course of a 13-day treatment period with starting doses based on safety and tolerability of previous starting dose in previous panels.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 2 (Panel E) MK-8189</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Elderly adult participants with schizophrenia receive MK-8189 titrated from 16 mg to 24 mg QD, orally, over the course of 10-day treatment period with starting doses based on safety and tolerability of previous starting dose in previous panels.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 2 (Panel F) MK-8189</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Healthy elderly adult participants receive MK-8189 titrated from 8 mg to 24 mg QD, orally, over the course of a 13-day treatment period with starting doses based on safety and tolerability of previous starting dose in previous panels.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 2 (Panel G) MK-8189</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Healthy elderly adult participants receive MK-8189 titrated from 16 mg to 24 mg QD, orally, over the course of 10-day treatment period with starting doses based on safety and tolerability of previous starting dose in previous panels.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 1 (Panels A, B, C) Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Oral tablets of dose-matched placebo to total daily dose of MK-8189.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 2 (Panels D, E, F, G) Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Oral tablets of dose-matched placebo to total daily dose of MK-8189.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>MK-8189</intervention_name>
    <description>MK-8189, oral, 4 mg and/or 12 mg tablets for a total daily dose of 8, 16 or 24 mg QD according to randomization</description>
    <arm_group_label>Part 1 (Panel A) MK-8189</arm_group_label>
    <arm_group_label>Part 1 (Panel B) MK-8189</arm_group_label>
    <arm_group_label>Part 1 (Panel C) MK-8189</arm_group_label>
    <arm_group_label>Part 2 (Panel D) MK-8189</arm_group_label>
    <arm_group_label>Part 2 (Panel E) MK-8189</arm_group_label>
    <arm_group_label>Part 2 (Panel F) MK-8189</arm_group_label>
    <arm_group_label>Part 2 (Panel G) MK-8189</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Oral tablets of dose-matched placebo to MK-8189 according to randomization</description>
    <arm_group_label>Part 1 (Panels A, B, C) Placebo</arm_group_label>
    <arm_group_label>Part 2 (Panels D, E, F, G) Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Has a body mass index (BMI) ≤40 kg/m2&#xD;
&#xD;
          -  Has no clinically significant abnormality on 12-lead safety electrocardiogram (ECG)&#xD;
             performed at the prestudy (screening) visit and/or prior to randomization&#xD;
&#xD;
          -  Has a normal resting blood pressure (BP: systolic BP is ≥90 millimeter of mercury&#xD;
             [mmHg] and ≤140 mmHg; diastolic BP is ≥60 mmHg and ≤90 mmHg) and normal resting heart&#xD;
             rate (≥45 beats per minute [bpm] and ≤100 bpm) in the semirecumbent position at the&#xD;
             prestudy (screening) visit and/or prior to randomization. Repeat evaluations may be&#xD;
             done if the values for a participant are, per investigator discretion, minimally&#xD;
             outside the designated range. Participants may be included if values are outside the&#xD;
             normal range but considered not clinically significant per investigator discretion&#xD;
&#xD;
          -  Participants with schizophrenia only: Meets diagnostic criteria for schizophrenia or&#xD;
             schizoaffective disorder according to the Diagnostic and Statistical Manual of Mental&#xD;
             Disorders, 5th Edition (DSM-5) criteria with the onset of the first episode being no&#xD;
             less than 2 years prior to screening and monotherapy with antipsychotics for treatment&#xD;
             should be indicated&#xD;
&#xD;
          -  Participants with schizophrenia only: Has a total Brief Psychiatric Rating Scale&#xD;
             (BPRS) score of &lt;48 with a BPRS score &lt;4 for #10 (hostility) and #14&#xD;
             (uncooperativeness) at the screening visit&#xD;
&#xD;
          -  Participants with schizophrenia only: Is in the nonacute phase of their illness and&#xD;
             clinically stable for 3 months prior to screening as demonstrated by the following: 1)&#xD;
             no clinically significant change in dose of prescribed antipsychotic medication, or&#xD;
             clinically significant change in antipsychotic medication to treat symptoms of&#xD;
             schizophrenia for 2 months prior to screening 2) no increase in level of psychiatric&#xD;
             care due to worsening of symptoms of schizophrenia for 3 months prior to screening&#xD;
&#xD;
          -  Participants with schizophrenia only: Has a history of receiving and tolerating&#xD;
             antipsychotic medication within the usual dose range employed for schizophrenia&#xD;
&#xD;
          -  Participants with schizophrenia only: Has a stable living situation&#xD;
&#xD;
          -  Participants with hypothyroidism, diabetes, high BP, chronic respiratory conditions or&#xD;
             other mild forms of these medical conditions could be considered as candidates for&#xD;
             study enrollment if their condition is stable&#xD;
&#xD;
          -  Has regular bowel movements&#xD;
&#xD;
          -  Participants with schizophrenia only: Is able to discontinue the use of all&#xD;
             antipsychotic medication at least 5 days prior to the start of the treatment period&#xD;
             and during the study period&#xD;
&#xD;
          -  Female participants are not pregnant and not breastfeeding, and are not a woman of&#xD;
             childbearing potential (WOCBP) or are a WOCBP who agrees to follow contraceptive&#xD;
             guidance during the treatment period and for at least 14 days after the last dose of&#xD;
             study intervention&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Is a WOCBP who has a positive urine pregnancy test within 48 hours before the first&#xD;
             dose of study intervention&#xD;
&#xD;
          -  Participants with schizophrenia only: Has evidence or history of a primary DSM-5 axis&#xD;
             I psychiatric diagnosis other than schizophrenia or schizoaffective disorder per the&#xD;
             allowed DSM-5 criteria within 1 month of screening&#xD;
&#xD;
          -  Has evidence or history of a primary DSM-5 axis I psychiatric diagnosis other than&#xD;
             schizophrenia or schizoaffective disorder per the allowed DSM-5 criteria within 1&#xD;
             month of screening&#xD;
&#xD;
          -  Has evidence or history of mental retardation, borderline personality disorder,&#xD;
             anxiety disorder, or organic brain syndrome&#xD;
&#xD;
          -  Has a history of neuroleptic malignant syndrome or moderate to severe tardive&#xD;
             dyskinesia&#xD;
&#xD;
          -  Has a substance-induced psychotic disorder or behavioral disturbance thought to be due&#xD;
             to substance abuse&#xD;
&#xD;
          -  Has a DSM-5 defined substance use disorder within 3 months of screening&#xD;
&#xD;
          -  Has a history of seizure disorder beyond childhood or is receiving treatment with any&#xD;
             anticonvulsant to prevent seizures&#xD;
&#xD;
          -  Has an untreated or uncompensated clinically significant renal, endocrine, hepatic,&#xD;
             respiratory, gastrointestinal, psychiatric, neurologic, cardiovascular, hematological,&#xD;
             immunological or cerebrovascular disease, malignancy, allergic disease or other&#xD;
             chronic and/or degenerative process at screening&#xD;
&#xD;
          -  Has any clinically significant abnormal laboratory, vital sign (VS), physical&#xD;
             examination, or 12-lead safety ECG findings at screening or changes from baseline&#xD;
             parameters or, in the opinion of the investigator, would make the participant&#xD;
             inappropriate for entry into this study&#xD;
&#xD;
          -  Has a history of cancer with following exceptions: 1) Adequately treated&#xD;
             nonmelanomatous skin carcinoma or carcinoma in situ of the cervix or; 2) Other&#xD;
             malignancies which have been successfully treated with appropriate follow up and&#xD;
             therefore unlikely to recur for the duration of the study, in the opinion of the&#xD;
             investigator and with agreement of the Sponsor&#xD;
&#xD;
          -  Has a clinically significant history or presence of sick sinus syndrome, first,&#xD;
             second, or third-degree AV block, myocardial infarction, pulmonary congestion, cardiac&#xD;
             arrhythmia, prolonged corrected QT (QTc) interval, or conduction abnormalities&#xD;
&#xD;
          -  Has history of repeated or frequent syncope, vasovagal episodes, or epileptic seizures&#xD;
&#xD;
          -  Has a family history of sudden death&#xD;
&#xD;
          -  Has a history of any illness that, in the opinion of the study investigator, might&#xD;
             confound the results of the study or poses an additional risk to the participant by&#xD;
             their participation in the study&#xD;
&#xD;
          -  For Part 2 participants only: Participant has an estimated glomerular filtration rate&#xD;
             (eGFR) &lt;60 mL/min/1.73 m2 based on the modification of diet in renal disease (MDRD).&#xD;
             Participants who have an eGFR or measured creatinine clearance of up to10% below of&#xD;
             either 60 milliliter/minute [mL/min] (for creatinine clearance) or 60 mL/min/1.73m2&#xD;
             (for eGFR) may be enrolled in the study at the discretion of the investigator&#xD;
&#xD;
          -  Has a history of significant multiple and/or severe allergies or has had an&#xD;
             anaphylactic reaction or significant intolerability to prescription or&#xD;
             non-prescription drugs or food&#xD;
&#xD;
          -  Is positive for Hepatitis B surface antigen, Hepatitis C antibodies or HIV&#xD;
&#xD;
          -  Had major surgery, donated or lost 1 unit of blood within 4 weeks prior to the&#xD;
             prestudy (screening) visit&#xD;
&#xD;
          -  Healthy participants only: Is mentally or legally incapacitated, has significant&#xD;
             emotional problems at the time of prestudy (screening) visit or expected during the&#xD;
             conduct of the study or has a history of clinically significant psychiatric disorder&#xD;
             of the last 5 years (participants who have had situational depression may be enrolled&#xD;
             in the study at investigator's discretion)&#xD;
&#xD;
          -  Participants with schizophrenia only: Is at imminent risk of self-harm, based on&#xD;
             clinical interview and responses on the Columbia-Suicide Severity Rating Scale&#xD;
             (C-SSRS), or of harm to others in the opinion of the investigator&#xD;
&#xD;
          -  Healthy participants only: Is at imminent risk of self-harm, based on clinical&#xD;
             interview and responses on the CSSRS, or of harm to others in the opinion of the&#xD;
             investigator. Participants must be excluded if they report suicidal ideation with&#xD;
             intent, with or without a plan or in the past 5 years or suicidal behavior in their&#xD;
             lifetime&#xD;
&#xD;
          -  Has received treatment with clozapine for schizophrenia or treatment with monoamine&#xD;
             oxidase inhibitors within 3 months of screening or cariprazine within 2 months of&#xD;
             screening&#xD;
&#xD;
          -  Has received a parenteral depot antipsychotic medication within 3 months of screening&#xD;
&#xD;
          -  Is unable to refrain from the use of co-medication with a moderate or strong&#xD;
             inhibiting or inducing effect on cytochrome (CYP3A) and/or cytochrome (CYP2C9)&#xD;
             beginning approximately 2 weeks or 5 half-lives, whichever is longer, prior to&#xD;
             administration of the initial dose of trial drug and throughout the trial or is unable&#xD;
             to refrain from the use of sensitive substrates of cytochrome (CYP2B6)&#xD;
&#xD;
          -  Has participated in another investigational study within 4 weeks (or 5 half-lives,&#xD;
             whichever is greater) prior to the prestudy (screening) visit&#xD;
&#xD;
          -  Has been in incarceration or imprisonment within three months prior to screening&#xD;
&#xD;
          -  Is a current smoker (healthy participants only) or is a smoker (participants with&#xD;
             schizophrenia only) that does not agree to follow the smoking restrictions as defined&#xD;
             by the clinical research unit (CRU)&#xD;
&#xD;
          -  Consumes greater than 3 glasses of alcoholic beverages per day. Participants who&#xD;
             consume 4 glasses of alcoholic beverages per day may be enrolled at the discretion of&#xD;
             the investigator&#xD;
&#xD;
          -  Consumes excessive amounts, defined as greater than 6 servings of caffeinated&#xD;
             beverages per day&#xD;
&#xD;
          -  Is a regular user of cannabis, any illicit drugs or has a history of drug abuse within&#xD;
             approximately 3 years&#xD;
&#xD;
          -  Presents any concern by the investigator regarding safe participation in the study or&#xD;
             for any other reason the investigator considers the participant inappropriate for&#xD;
             participation in the study&#xD;
&#xD;
          -  Is or has an immediate family member who is investigational site or Sponsor staff&#xD;
             directly involved with this study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Medical Director</last_name>
    <role>Study Director</role>
    <affiliation>Merck Sharp &amp; Dohme LLC</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Woodland Research Northwest, LLC ( Site 0002)</name>
      <address>
        <city>Rogers</city>
        <state>Arkansas</state>
        <zip>72758-6442</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Parexel ( Site 0004)</name>
      <address>
        <city>Glendale</city>
        <state>California</state>
        <zip>91206</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Collaborative NeuroScience Network ( Site 0008)</name>
      <address>
        <city>Long Beach</city>
        <state>California</state>
        <zip>90806</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Velocity Clinical Research, Hallandale Beach ( Site 0001)</name>
      <address>
        <city>Hallandale Beach</city>
        <state>Florida</state>
        <zip>33009</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>RCA at Fort Lauderdale Behavioral Health Center ( Site 0006)</name>
      <address>
        <city>Oakland Park</city>
        <state>Florida</state>
        <zip>33334</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hassman Research Institute ( Site 0007)</name>
      <address>
        <city>Berlin</city>
        <state>New Jersey</state>
        <zip>08009</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2022</verification_date>
  <study_first_submitted>August 6, 2020</study_first_submitted>
  <study_first_submitted_qc>August 6, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 10, 2020</study_first_posted>
  <last_update_submitted>April 7, 2022</last_update_submitted>
  <last_update_submitted_qc>April 7, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">April 8, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Schizophrenia</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf</ipd_description>
    <ipd_url>http://engagezone.msd.com/ds_documentation.php</ipd_url>
  </patient_data>
  <pending_results>
    <submitted>March 7, 2023</submitted>
  </pending_results>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04506905
org study id: 8189-011
secondary id: Merck Protocol Number
nct id: NCT04506905
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This 2-Part Randomized Clinical Study will evaluate the safety, tolerability and
      pharmacokinetics of alternate MK-8189 titration regimens. Part 1 will assess multiple dose
      once-daily titration regimens of MK-8189 in young adult participants with schizophrenia. Part
      2 will assess multiple once-daily doses of MK-8189 in elderly participants with schizophrenia
      and healthy elderly participants.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
masking description: Double blind
measure: Part 1 & 2: Number of Participants Who Experienced an Adverse Event (AE)
time frame: Up to approximately 27 days
description: The number of participants experiencing an AE will be assessed. An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
measure: Part 1 & 2: Number of Participants Discontinuing Study Treatment Due to an AE
time frame: Up to approximately 27 days
description: The number of participants discontinuing study treatment due to an AE will be assessed. An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
measure: Part 1: Area Under the Concentration Time-curve From Hour 0 to 24 Hours (AUC0-24hr) of MK-8189
time frame: Panels A, B, C: Predose and selected time points postdose on Days 1 and 7. Additional collections for Panel A on Day 4 and Panel C on Days 2 and 3
description: AUC0-24hr is defined as the area under concentration-time curve from 0 to 24 hours. Blood samples taken at predose and up to 24 hours postdose to determine the AUC0-24hr of MK-8189.
measure: Part 1: Maximum Concentration (Cmax) of MK-8189
time frame: Panels A, B, C: Predose and selected time points postdose on Days 1 and 7. Additional collections for Panel A on Day 4 and Panel C on Days 2 and 3
description: Cmax is defined as the maximum concentration of MK-8189 observed in plasma. Blood samples taken at predose and at specified times postdose to determine the Cmax of MK-8189.
measure: Part 1: Concentration of MK-8189 at 24 Hours (C24hr) postdose
time frame: Panels A, B, C: Predose and up to 24 hours postdose on Days 1 and 7. Additional collections for Panel A on Day 4 and Panel C on Days 2 and 3
description: C24hr is defined as the concentration of MK-8189 observed in plasma at 24 hours. Blood samples taken at predose and up to 24 hours postdose to determine the C24hr of MK-8189.
measure: Part 1: Time to Cmax (Tmax) of MK-8189
time frame: Panels A, B, C: Predose and selected time points postdose on Days 1 and 7. Additional collections for Panel A on Day 4 and Panel C on Days 2 and 3
description: Tmax is defined as the time of maximum concentration of MK-8189 observed in plasma. Blood samples taken at predose and at specified times postdose to determine the Tmax of MK-8189.
measure: Part 1: Clearance (CL) of MK-8189
time frame: Panels A, B, C: Predose and selected time points postdose on Day 7
description: Blood samples taken at predose and at specified times postdose to determine the CL of MK-8189.
measure: Part 1: Volume of Distribution (Vd) of MK-8189
time frame: Panels A, B, C: Predose and selected time points postdose on Day 7
description: Blood samples taken at predose and at specified times postdose to determine the Vd of MK-8189.
measure: Part 1: Apparent Terminal Half-life (t1/2) of MK-8189
time frame: Panels A, B, C: Predose and selected time points postdose on Day 7
description: Blood samples taken at predose and at specified times postdose to determine the t1/2 of MK-8189.
measure: Part 2: Area Under the Concentration Time-curve From Hour 0 to 24 Hours (AUC0-24hr) of MK-8189
time frame: Panels D, F: Predose and selected time points postdose on Days 1, 4, 7 and 13; Panels E, G: Predose and selected time points postdose on Days 1, 4, and 10
description: AUC0-24hr is defined as the area under concentration-time curve from 0 to 24 hours. Blood samples taken at predose and up to 24 hours postdose to determine the AUC0-24hr of MK-8189.
measure: Part 2: Maximum Concentration (Cmax) of MK-8189
time frame: Panels D, F: Predose and selected time points postdose on Days 1, 4, 7 and 13; Panels E, G: Predose and selected time points postdose on Days 1, 4, and 10
description: Cmax is defined as the maximum concentration of MK-8189 observed in plasma. Blood samples taken at predose and at specified times postdose to determine the Cmax of MK-8189.
measure: Part 2: Concentration of MK-8189 at 24 Hours (C24hr) postdose
time frame: Panels D, F: Predose and up to 24 hours postdose on Days 1, 4, 7 and 13; Panels E, G: Predose and up to 24 hours postdose on Days 1, 4, and 10
description: C24hr is defined as the concentration of MK-8189 observed in plasma at 24 hours. Blood samples taken at predose and up to 24 hours postdose to determine the C24hr of MK-8189.
measure: Part 2: Time to Cmax (Tmax) of MK-8189
time frame: Panels D, F: Predose and selected time points postdose on Days 1, 4, 7 and 13; Panels E, G: Predose and selected time points postdose on Days 1, 4, and 10
description: Tmax is defined as the time of maximum concentration of MK-8189 observed in plasma. Blood samples taken at predose and at specified times postdose to determine the Tmax of MK-8189.
measure: Part 2: Clearance (CL) of MK-8189
time frame: Panels D, F: Predose and selected time points postdose on Day 13; Panels E, G: Predose and selected time points postdose on Day 10
description: Blood samples taken at predose and at specified times postdose to determine the CL of MK-8189.
measure: Part 2: Volume of Distribution (Vd) of MK-8189
time frame: Panels D, F: Predose and selected time points postdose on Day 13; Panels E, G: Predose and selected time points postdose on Day 10
description: Blood samples taken at predose and at specified times postdose to determine the Vd of MK-8189.
measure: Part 2: Apparent Terminal Half-life (t1/2) of MK-8189
time frame: Panels D, F: Predose and selected time points postdose on Day 13; Panels E, G: Predose and selected time points postdose on Day 10
description: Blood samples taken at predose and at specified times postdose to determine the t1/2 of MK-8189.
arm group label: Part 1 (Panel A) MK-8189
arm group type: Experimental
description: Young adult participants with schizophrenia receive MK-8189 titrated from 16 mg to 24 mg once daily (QD), orally, over a course of 7-day treatment.
arm group label: Part 1 (Panel B) MK-8189
arm group type: Experimental
description: Young adult participants with schizophrenia receive MK-8189 titrated up to 24 mg QD, orally, over a course of 7-day treatment period with starting doses based on safety and tolerability of previous starting dose in previous panel.
arm group label: Part 1 (Panel C) MK-8189
arm group type: Experimental
description: Young adult participants with schizophrenia receive MK-8189 titrated from 8 mg to 24 mg QD, orally, over a course of 7-day treatment period with starting doses based on safety and tolerability of previous starting dose in previous panels.
arm group label: Part 2 (Panel D) MK-8189
arm group type: Experimental
description: Elderly adult participants with schizophrenia receive MK-8189 titrated from 8 mg to 24 mg QD, orally, over the course of a 13-day treatment period with starting doses based on safety and tolerability of previous starting dose in previous panels.
arm group label: Part 2 (Panel E) MK-8189
arm group type: Experimental
description: Elderly adult participants with schizophrenia receive MK-8189 titrated from 16 mg to 24 mg QD, orally, over the course of 10-day treatment period with starting doses based on safety and tolerability of previous starting dose in previous panels.
arm group label: Part 2 (Panel F) MK-8189
arm group type: Experimental
description: Healthy elderly adult participants receive MK-8189 titrated from 8 mg to 24 mg QD, orally, over the course of a 13-day treatment period with starting doses based on safety and tolerability of previous starting dose in previous panels.
arm group label: Part 2 (Panel G) MK-8189
arm group type: Experimental
description: Healthy elderly adult participants receive MK-8189 titrated from 16 mg to 24 mg QD, orally, over the course of 10-day treatment period with starting doses based on safety and tolerability of previous starting dose in previous panels.
arm group label: Part 1 (Panels A, B, C) Placebo
arm group type: Placebo Comparator
description: Oral tablets of dose-matched placebo to total daily dose of MK-8189.
arm group label: Part 2 (Panels D, E, F, G) Placebo
arm group type: Placebo Comparator
description: Oral tablets of dose-matched placebo to total daily dose of MK-8189.
intervention type: Drug
intervention name: MK-8189
description: MK-8189, oral, 4 mg and/or 12 mg tablets for a total daily dose of 8, 16 or 24 mg QD according to randomization
arm group label: Part 1 (Panel A) MK-8189
arm group label: Part 1 (Panel B) MK-8189
arm group label: Part 1 (Panel C) MK-8189
arm group label: Part 2 (Panel D) MK-8189
arm group label: Part 2 (Panel E) MK-8189
arm group label: Part 2 (Panel F) MK-8189
arm group label: Part 2 (Panel G) MK-8189
intervention type: Drug
intervention name: Placebo
description: Oral tablets of dose-matched placebo to MK-8189 according to randomization
arm group label: Part 1 (Panels A, B, C) Placebo
arm group label: Part 2 (Panels D, E, F, G) Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Medical Director
role: Study Director
affiliation: Merck Sharp & Dohme LLC
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Schizophrenia
sharing ipd: Yes
ipd description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
ipd url: http://engagezone.msd.com/ds_documentation.php
submitted: March 7, 2023