Schizophrenia
Conditions
Brief summary
This 4-panel study will evaluate the safety, tolerability, pharmacokinetics (PK) and corrected QT interval (QTc) effect of MK-8189 versus placebo, as monotherapy in healthy participants (Panel A) including those of Japanese descent, as monotherapy in participants with schizophrenia (Panel B), as add-on therapy in participants with schizophrenia (Panel C), and under an alternative dosing regimen as monotherapy in participants with schizophrenia (Panel D). Analysis of QTc effect will be exploratory. There will be no hypothesis testing in this study.
Detailed description
As specified by Phase 1 protocol-flexible language in the protocol, modifications to the dose or dosing regimen can be made to achieve the scientific goals of the study objectives and/or to ensure appropriate safety of the study participants. The proposed doses for each Panel may be adjusted downward based on evaluation of observed safety, tolerability, and PK data.
Interventions
DRUGMK-8189
MK-8189 4 mg tablet(s) will be administered orally QD for a total daily dose of 4 mg, 8 mg, 12 mg, 16 mg, 20 mg, 24 mg, 36 mg or 48 mg.
DRUGPlacebo
MK-8189 dose-matching placebo tablets will be administered orally QD.
DRUGBackground AAP Therapy
Participants with schizophrenia in Panel C will be on background therapy with an AAP medication (e.g., olanzapine, quetiapine, paliperidone, asenapine, iloperidone, aripirprazole, lurasidone, risperidone \[not to exceed daily dose of 6 mg\], or ziprasidone) throughout the study. Participants should be on a stable and well tolerated treatment regimen for at least 2 months prior to screening. NOTE: clozapine is not allowed.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
Panel A (Healthy Participants) \- If participant is of Japanese descent, both biological parents and all biological grandparents must be born in Japan. Panels B and D (Participants with Schizophrenia; MK-8189 or Placebo Monotherapy / 15-Day Titration Monotherapy) - Is able to discontinue the use of all antipsychotic medication at least 5 days prior to the start of the treatment period and during the study period. Panels B, C, and D (Participants with Schizophrenia; MK-8189 or Placebo Monotherapy / Add-on Therapy / 15-Day Titration Monotherapy) * Meets diagnostic criteria for schizophrenia or schizoaffective disorder according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria with the onset of the first episode being no less than 2 years prior to screening and monotherapy with antipsychotics for treatment should be indicated. * Is in the non-acute phase of their illness and clinically stable for 3 months prior to screening as demonstrated by: a.) no clinically significant change in dose of prescribed antipsychotic medication, or clinically significant change in antipsychotic medication to treat symptoms of schizophrenia for 2 months prior to screening; b.) no increase in level of psychiatric care due to worsening of symptoms of schizophrenia for 3 months prior to screening. * Has a history of receiving and tolerating antipsychotic medication within the usual dose range employed for schizophrenia. * Has a stable living situation in which the participant or a contact person can be reached by the investigator if there is a need for follow up. * Participants with hypothyroidism, diabetes, high blood pressure, chronic respiratory conditions or other mild forms of these medical conditions could be considered as candidates for study enrollment if their condition is stable and the prescribed dose and regimen of medication is stable for at least 3 months prior to screening and there are no expected changes in co-medication during the study. * Has regular bowel movements. Panels A, B, C, and D \- 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 woman of childbearing potential (WOCBP) * Is a WOCBP and using a contraceptive method that is highly effective, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis), during the intervention period and for at least 14 days after the last dose of study intervention.
Exclusion criteria
Panel A (Healthy Participants) * Has a history of clinically diagnosed depression, anxiety disorder, or any history of psychiatric disorders having required drug treatment or hospitalization. Participants who have had situational depression more than 5 years before the start of the study may be enrolled in the study at the discretion of the investigator. * Has a history of stroke, chronic seizures, or major neurological disorder. * Has a history of dystonic reaction to antipsychotic, anti-emetic or related medication. * Is at imminent risk of self-harm, based on clinical interview and responses on the Columbia Suicide Severity Rating Scale (C-SSRS), or of harm to others in the opinion of the investigator. Participants must be excluded if they report suicidal ideation with intent, with or without a plan or method (e.g., positive response to item 4 or 5 in assessment of suicidal ideation on the C-SSRS) in the past 5 years or suicidal behavior in their lifetime. * Has a history of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary, or major neurological (including stroke and chronic seizures) abnormalities or diseases. Participants with a remote history of uncomplicated medical events may be enrolled in the study at the discretion of the investigator. * Is mentally or legally incapacitated, has a history of clinically significant psychiatric disorder of the last 5 years. Participants who have had situational depression may be enrolled in the study at the discretion of the investigator. * Is unable to refrain from or anticipates the use of any medication, including prescription and nonprescription drugs or herbal remedies, beginning approximately 2 weeks (or 5 half-lives) prior to administration of the initial dose of study drug, throughout the study (including washout intervals between treatment periods), until the poststudy visit. * Is a smoker and/or has used nicotine or nicotine-containing products (e.g., nicotine patch and electronic cigarette) within 3 months of screening. Panels B, C, and D (Participants with Schizophrenia; MK-8189 or Placebo Monotherapy / Add-on Therapy / 15-Day Titration Monotherapy) * Has evidence or history of a primary DSM-5 axis I psychiatric diagnosis other than schizophrenia or schizoaffective disorder per the allowed DSM-5 criteria within 1 month of screening. * Has evidence or history of mental retardation, borderline personality disorder, anxiety disorder, or organic brain syndrome. * Has a history of neuroleptic malignant syndrome or moderate to severe tardive dyskinesia (TD). * Has a substance-induced psychotic disorder or behavioral disturbance thought to be due to substance abuse. * Has a DSM-5 defined substance abuse or dependence disorder (excluding nicotine and caffeine) within three months of screening. * Has a history of seizure disorder beyond childhood or is receiving treatment with any anticonvulsant to prevent seizures. * Is at imminent risk of self-harm, based on clinical interview and responses on the C-SSRS, or of harm to others in the opinion of the investigator. Participants must be excluded if they report suicidal ideation with intent, with or without a plan or method (e.g., positive response to item 4 or 5 in assessment of suicidal ideation on the C-SSRS) in the past 2 months or suicidal behavior in the past 6 months. * Has received treatment with clozapine for schizophrenia or treatment with monoamine oxidase inhibitors within 3 months of screening. For Panel C participants, has received a total daily dose of risperidone \> 6 mg. * Is unable to refrain from the use of co-medication with a moderate or strong inhibiting or inducing effect on cytochrome P450 (CYP) 3A (CYP3A) and/or CYP2C9 beginning approximately 2 weeks or 5 half- lives, whichever is longer, prior to administration of the initial dose of trial drug and throughout the trial or is unable to refrain from the use of sensitive substrates of CYP2B6. Unable to refrain from cyclic hormone replacement therapy. There may be certain medications that are permitted * Has received a parenteral depot antipsychotic medication within 3 months of pre-trial (screening). Panels A, B, C, and D * Is a woman of childbearing potential (WOCBP) who has a positive serum pregnancy test at the screening visit or a positive urine pregnancy test within 48 hours before the first dose of study intervention. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. * Has a history of cancer (malignancy). Exceptions include: (1) Participants with adequately treated nonmelanomatous skin carcinoma or carcinoma in situ of the cervix may participate in the study; (2) Participants with other malignancies which have been successfully treated ≥10 years prior to the prestudy (screening) visit where, in the judgment of both the investigator and treating physician, appropriate follow-up has revealed no evidence of recurrence from the time of treatment through the time of the prestudy (screening) visit (except those cancers identified at the beginning of this
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Number of Participants Who Experienced One or More Adverse Events (AEs) | Up to ~32 days | An AE was defined as 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. Per protocol, safety was analyzed by panel and dose. The number of participants who experienced one or more AEs was reported. |
| The Number of Participants Who Discontinued Study Treatment Due to an AE | Up to ~18 days | An AE was defined as 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. Per protocol, safety was analyzed by panel and dose. The number of participants who discontinued study treatment due to an AE was reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Plasma Concentration at 24 Hours Post-dose (C24hr) of MK-8189 | 24 hours post-dose; Panel A, B: Days 7, 10, 13, 16, 18; Panel C: Days 9, 12, 15, 18; Panel D: Days 1, 4, 7, 10, 13, 15 | C24hr was the concentration of MK-8189 observed in plasma at the 24-hour nominal sampling time after administration of MK-8189, assessed using a linear mixed effects model. To estimate C24hr, per protocol blood samples were collected 24 hours post-dose on Days 7, 10, 13, 16, 18 for Panels A, B; Days 9, 12, 15, 18 for Panel C; Days 1, 4, 7, 10, 13, 15 for Panel D. Per protocol C24hr was analyzed by panel, dose, dosing regimen; due to differing dosing regimen some arms/doses weren't applicable to some timepoints, shown by 0 participants analyzed in the table. Per dosing regimen, the 4 mg, 8 mg (Panels A, B), 4 mg (Panel C) study arms weren't applicable to the protocol-specified timepoints/days of C24hr analysis and were excluded. GCV was reported as a percent. Per protocol placebo arms were excluded from C24hr analysis. |
| Time Post-dose to Maximum Observed Plasma Concentration (Tmax) of MK-8189 | Pre-dose, 2, 6, 8, 10, 12, 16, 24 hours post-dose; no pre-dose on Day 18 (Panel A, B, C), Day 15 (Panel D);additional 36, 48 hours post-dose on Days 18, 15; Panel A, B: Days 7, 10, 13, 16, 18; Panel C: Days 9, 12, 15, 18; Panel D:Days 1, 4, 7, 10, 13, 15 | Tmax was the actual sampling time at which maximum post-dose plasma concentration of MK-8189 was observed. To estimate Tmax, per protocol blood samples were collected pre-dose, 2, 6, 8, 10, 12, 16, 24 hours post-dose for Panels A, B, C, D; no pre-dose samples collected on Day 18 (Panels A, B, C), Day 15 (Panel D); additional post-dose samples collected at 36, 48 hours on Days 18 and 15. Samples were collected on Days 7, 10, 13, 16, 18 for Panels A, B; Days 9, 12, 15, 18 for Panel C; Days 1, 4, 7, 10, 13, 15 for Panel D. Per protocol Tmax was analyzed by panel, dose, dosing regimen; due to differing dosing regimen, some arms/doses weren't applicable to some timepoints, shown by 0 participants analyzed in the table. Per dosing regimen, the 4 mg, 8 mg (Panels A, B), 4 mg (Panel C) study arms weren't applicable to the protocol-specified timepoints/days of Tmax analysis and were excluded. Per protocol placebo arms were excluded from Tmax analysis. |
| Area Under the Plasma-concentration Curve at Zero to 24 Hours Post-dose (AUC0-24hr) of MK-8189 | Pre-dose, 2, 6, 8, 10, 12, 16, 24 hours post-dose; no pre-dose on Day 18 (Panel A, B, C), Day 15 (Panel D); Panel A, B: Days 7, 10, 13, 16, 18; Panel C: Days 9, 12, 15, 18; Panel D: Days 1, 4, 7, 10, 13, 15 | AUC was a measure of MK-8189 exposure assessed as a product of drug concentration and time, using a linear mixed effects model. To estimate AUC0-24hr per protocol blood samples were collected pre-dose, 2, 6, 8, 10, 12, 16, 24 hours post-dose for Panels A, B, C, D; no pre-dose samples collected on Day 18 (Panels A, B, C), Day 15 (Panel D). Samples were collected on Days 7, 10, 13, 16, 18 for Panels A, B; Days 9, 12, 15, 18 for Panel C; Days 1, 4, 7, 10, 13, 15 for Panel D. Per protocol AUC0-24hr was analyzed by panel, dose, dosing regimen; due to differing dosing regimen some arms/doses weren't applicable to some timepoints, shown by 0 participants analyzed in the table. Per dosing regimen the 4 mg, 8 mg (Panels A, B), 4 mg (Panel C) study arms weren't applicable to the protocol-specified timepoints/days of AUC0-24hr analysis and these arms were excluded. Geometric coefficient of variation (GCV) was reported as a percent. Per protocol placebo arms were excluded from AUC0-24hr analysis. |
| Apparent Volume of MK-8189 Distribution (Vd/F) on Day 18 (Panels A, B, C) and Day 15 (Panel D) | 2, 6, 8, 10, 12, 16, 24, 36, 48 hours post-dose on Day 18 (Panel A, B, C) and Day 15 (Panel D) | Vd/F was the apparent volume of distribution of MK-8189 between the plasma and the rest of the body, after dose, assessed as the total volume of MK-8189 that would need to be uniformly distributed to achieve the desired plasma drug concentration. To estimate Vd/F, per protocol blood samples were collected 2, 6, 8, 10, 12, 16, 24, 36, 48 hours post-dose on Day 18 for Panels A, B, C, and on Day 15 for Panel D. Per protocol Vd/F was analyzed by panel, dose and dosing regimen. Due to differing dosing regimen, some arms/doses weren't applicable to some timepoints, shown by 0 participants analyzed in the table. Per dosing regimen, the 4 mg, 8 mg, 12 mg, 16 mg, 20 mg (Panels A, B, C), 8 mg, 16 mg, 24 mg, 36 mg (Panel D) study arms weren't applicable to the protocol-specified timepoints/days of Vd/F analysis and were excluded. GCV was reported as a percent. Per protocol placebo arms were excluded from Vd/F analysis. |
| Time Required for Plasma Concentration of MK-8189 to Decrease by Half (Apparent Terminal Half-life [t1/2]) on Day 18 (Panels A, B, C) and Day 15 (Panel D) | 2, 6, 8, 10, 12, 16, 24, 36, 48 hours post-dose on Day 18 (Panel A, B, C) and Day 15 (Panel D) | t1/2 was the time required to divide the plasma concentration of MK-8189 by half after reaching pseudo-equilibrium. At least three quantifiable terminal phase concentrations collected were used to calculate t1/2. To estimate t1/2, per protocol blood samples were collected 2, 6, 8, 10, 12, 16, 24, 36, 48 hours post-dose on Day 18 for Panels A, B, C, and on Day 15 for Panel D. Per protocol t1/2 was analyzed by panel, dose and dosing regimen. Due to differing dosing regimen, some arms/doses weren't applicable to some timepoints, shown by 0 participants analyzed in the table. Per dosing regimen, the 4 mg, 8 mg, 12 mg, 16 mg, 20 mg (Panels A, B, C), 8 mg, 16 mg, 24 mg, 36 mg (Panel D) study arms weren't applicable to the protocol-specified timepoints/days of t1/2 analysis and were excluded. GCV was reported as a percent. Per protocol placebo arms were excluded from t1/2 analysis. |
| Apparent Total Plasma Clearance of MK-8189 (CL/F) on Day 18 (Panels A, B, C) and Day 15 (Panel D) | 2, 6, 8, 10, 12, 16, 24, 36, 48 hours post-dose on Day 18 (Panel A, B, C) and Day 15 (Panel D) | CL/F was the apparent total clearance of MK-8189 in plasma over time, assessed as the rate at which MK-8189 was removed from the plasma. To estimate CL/F, per protocol blood samples were collected 2, 6, 8, 10, 12, 16, 24, 36, 48 hours post-dose on Day 18 for Panels A, B, C, and on Day 15 for Panel D. Per protocol CL/F was analyzed by panel, dose and dosing regimen. Due to differing dosing regimen, some arms/doses weren't applicable to some timepoints, shown by 0 participants analyzed in the table. Per dosing regimen, the 4 mg, 8 mg, 12 mg, 16 mg, 20 mg (Panels A, B, C), 8 mg, 16 mg, 24 mg, 36 mg (Panel D) study arms weren't applicable to the protocol-specified timepoints/days of CL/F analysis and were excluded. GCV was reported as a percent. Per protocol placebo arms were excluded from CL/F analysis. |
| Maximum Observed Post-dose Plasma Concentration (Cmax) of MK-8189 | Pre-dose, 2, 6, 8, 10, 12, 16, 24 hours post-dose; no pre-dose on Day 18 (Panel A, B, C), Day 15 (Panel D);additional 36, 48 hours post-dose on Days 18, 15; Panel A, B: Days 7, 10, 13, 16, 18; Panel C: Days 9, 12, 15, 18; Panel D:Days 1, 4, 7, 10, 13, 15 | Cmax was the maximum concentration of MK-8189 observed in plasma, assessed using a linear mixed effects model. To estimate Cmax, per protocol blood samples were collected pre-dose, 2, 6, 8, 10, 12, 16, 24 hours post-dose for Panels A, B, C, D; no pre-dose samples collected on Day 18 (Panels A, B, C), Day 15 (Panel D); additional post-dose samples collected at 36, 48 hours on Days 18 and 15. Samples were collected on Days 7, 10, 13, 16, 18 for Panels A, B; Days 9, 12, 15, 18 for Panel C; Days 1, 4, 7, 10, 13, 15 for Panel D. Per protocol Cmax was analyzed by panel, dose, dosing regimen; due to differing dosing regimen some arms/doses weren't applicable to some timepoints, shown by 0 participants analyzed in the table. Per dosing regimen, the 4 mg, 8 mg (Panels A, B), 4 mg (Panel C) study arms weren't applicable to the protocol-specified timepoints/days of Cmax analysis and were excluded. GCV was reported as a percent. Per protocol placebo arms were excluded from Cmax analysis. |
Countries
United States
Participant flow
Pre-assignment details
Per protocol-specified dose modification, Panel C MK-8189 dose and schedule were modified, based on tolerability.
Participants by arm
| Arm | Count |
|---|---|
| Panel A (Healthy Participants): MK-8189 Monotherapy 4-24 mg Healthy participants received MK-8189 monotherapy orally once daily (QD) in escalating doses from 4 mg to 24 mg, as follows: Days 1-3: 4 mg, Days 4-6: 8 mg, Days 7-9: 12 mg, Days 10-12: 16 mg, Days 13-15: 20 mg, Days 16-18: 24 mg. | 12 |
| Panel A (Healthy Participants): Placebo Monotherapy Healthy participants received MK-8189 monotherapy matching placebo orally QD on Days 1-18. | 4 |
| Panel B (Schizophrenia Participants): MK-8189 Monotherapy 4-24 mg Participants with Schizophrenia received MK-8189 monotherapy orally QD in escalating doses from 4 mg to 24 mg, as follows: Days 1-3: 4 mg, Days 4-6: 8 mg, Days 7-9: 12 mg, Days 10-12: 16 mg, Days 13-15: 20 mg, Days 16-18: 24 mg. | 12 |
| Panel B (Schizophrenia Participants): Placebo Monotherapy Participants with Schizophrenia received MK-8189 monotherapy matching placebo orally QD on Days 1-18. | 4 |
| Panel C (Schizophrenia Participants): MK-8189 Add-on Therapy 4-24 mg In addition to background atypical antipsychotic (AAP) treatment, participants with Schizophrenia received MK-8189 add-on therapy orally QD in escalating doses from 4 mg to 24 mg, as follows: Days 1-3: 4 mg, Days 4-6: 8 mg, Days 7-9: 12 mg, Days 10-12: 16 mg, Days 13-15: 20 mg, Days 16-18: 24 mg. | 12 |
| Panel C (Schizophrenia Participants): MK-8189 Add-on Therapy 4-8 mg In addition to background AAP treatment, participant with Schizophrenia received modified regimen of MK-8189 add-on therapy orally QD in escalating doses from 4 mg to 8 mg, as follows: Days 1-3: 4 mg, Days 4-11: 8 mg. | 1 |
| Panel C (Schizophrenia Participants): Placebo Add-on Therapy In addition to background AAP treatment, participants with Schizophrenia received MK-8189 add-on therapy matching placebo orally QD on Days 1-18. | 4 |
| Panel D (Schizophrenia Participants): MK-8189 Monotherapy 8-48 mg Participants with Schizophrenia received MK-8189 monotherapy orally QD in escalating doses from 8 mg to 48 mg, as follows: Days 1-3: 8 mg, Days 4-6: 16 mg, Days 7-9: 24 mg, Days 10-12: 36 mg, Days 13-15: 48 mg. | 17 |
| Panel D (Schizophrenia Participants): Placebo Monotherapy Participants with Schizophrenia received MK-8189 monotherapy matching placebo orally QD on Days 1-15. | 9 |
| Total | 75 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 |
|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Physician Decision | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Protocol Violation | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 1 | 0 |
| Overall Study | Sponsor decision | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 | 0 | 2 | 0 | 1 | 5 | 1 |
Baseline characteristics
| Characteristic | Panel A (Healthy Participants): MK-8189 Monotherapy 4-24 mg | Panel D (Schizophrenia Participants): Placebo Monotherapy | Total | Panel C (Schizophrenia Participants): Placebo Add-on Therapy | Panel C (Schizophrenia Participants): MK-8189 Add-on Therapy 4-24 mg | Panel B (Schizophrenia Participants): MK-8189 Monotherapy 4-24 mg | Panel C (Schizophrenia Participants): MK-8189 Add-on Therapy 4-8 mg | Panel D (Schizophrenia Participants): MK-8189 Monotherapy 8-48 mg | Panel B (Schizophrenia Participants): Placebo Monotherapy | Panel A (Healthy Participants): Placebo Monotherapy |
|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 36.8 Years STANDARD_DEVIATION 8.2 | 41.7 Years STANDARD_DEVIATION 9.6 | 43.8 Years STANDARD_DEVIATION 9.6 | 47.8 Years STANDARD_DEVIATION 7.2 | 44.3 Years STANDARD_DEVIATION 7.1 | 49.3 Years STANDARD_DEVIATION 9.5 | 51.0 Years | 44.4 Years STANDARD_DEVIATION 10 | 44.0 Years STANDARD_DEVIATION 8.9 | 43.3 Years STANDARD_DEVIATION 15.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 6 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 2 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants | 9 Participants | 69 Participants | 4 Participants | 11 Participants | 11 Participants | 1 Participants | 15 Participants | 3 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 6 Participants | 0 Participants | 9 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 8 Participants | 54 Participants | 4 Participants | 10 Participants | 11 Participants | 1 Participants | 14 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 1 Participants | 10 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 3 Participants | 1 Participants | 1 Participants |
| Sex: Female, Male Female | 8 Participants | 4 Participants | 36 Participants | 2 Participants | 5 Participants | 6 Participants | 1 Participants | 8 Participants | 0 Participants | 2 Participants |
| Sex: Female, Male Male | 4 Participants | 5 Participants | 39 Participants | 2 Participants | 7 Participants | 6 Participants | 0 Participants | 9 Participants | 4 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk | EG014 affected / at risk | EG015 affected / at risk | EG016 affected / at risk | EG017 affected / at risk | EG018 affected / at risk | EG019 affected / at risk | EG020 affected / at risk | EG021 affected / at risk | EG022 affected / at risk | EG023 affected / at risk | EG024 affected / at risk | EG025 affected / at risk | EG026 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 12 | 0 / 11 | 0 / 11 | 0 / 10 | 0 / 10 | 0 / 4 | 0 / 12 | 0 / 11 | 0 / 11 | 0 / 11 | 0 / 10 | 0 / 10 | 0 / 4 | 0 / 13 | 0 / 11 | 0 / 10 | 0 / 8 | 0 / 7 | 0 / 7 | 0 / 4 | 0 / 17 | 0 / 16 | 0 / 15 | 0 / 13 | 0 / 11 | 0 / 9 |
| other Total, other adverse events | 5 / 12 | 3 / 12 | 4 / 11 | 5 / 11 | 2 / 10 | 5 / 10 | 3 / 4 | 4 / 12 | 3 / 11 | 4 / 11 | 8 / 11 | 5 / 10 | 7 / 10 | 4 / 4 | 6 / 13 | 8 / 11 | 5 / 10 | 5 / 8 | 4 / 7 | 4 / 7 | 1 / 4 | 8 / 17 | 8 / 16 | 5 / 15 | 4 / 13 | 8 / 11 | 9 / 9 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 | 0 / 11 | 0 / 11 | 0 / 10 | 0 / 10 | 0 / 4 | 0 / 12 | 0 / 11 | 0 / 11 | 0 / 11 | 0 / 10 | 0 / 10 | 0 / 4 | 0 / 13 | 0 / 11 | 0 / 10 | 0 / 8 | 0 / 7 | 0 / 7 | 0 / 4 | 0 / 17 | 0 / 16 | 0 / 15 | 1 / 13 | 0 / 11 | 0 / 9 |
Outcome results
Primary
The Number of Participants Who Discontinued Study Treatment Due to an AE
An AE was defined as 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. Per protocol, safety was analyzed by panel and dose. The number of participants who discontinued study treatment due to an AE was reported.
Time frame: Up to ~18 days
Population: All participants who got ≥1 dose of study drug. Per protocol, safety was analyzed by panel and dose.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Panel A (Healthy Participants): MK-8189 Monotherapy 4 mg | The Number of Participants Who Discontinued Study Treatment Due to an AE | 1 Participants |
| Panel A (Healthy Participants): MK-8189 Monotherapy 8 mg | The Number of Participants Who Discontinued Study Treatment Due to an AE | 0 Participants |
| Panel A (Healthy Participants): MK-8189 Monotherapy 12 mg | The Number of Participants Who Discontinued Study Treatment Due to an AE | 0 Participants |
| Panel A (Healthy Participants): MK-8189 Monotherapy 16 mg | The Number of Participants Who Discontinued Study Treatment Due to an AE | 1 Participants |
| Panel A (Healthy Participants): MK-8189 Monotherapy 20 mg | The Number of Participants Who Discontinued Study Treatment Due to an AE | 0 Participants |
| Panel A (Healthy Participants): MK-8189 Monotherapy 24 mg | The Number of Participants Who Discontinued Study Treatment Due to an AE | 0 Participants |
| Panel A (Healthy Participants): Placebo Monotherapy | The Number of Participants Who Discontinued Study Treatment Due to an AE | 0 Participants |
| Panel B (Schizophrenia Participants): MK-8189 Monotherapy 4 mg | The Number of Participants Who Discontinued Study Treatment Due to an AE | 1 Participants |
| Panel B (Schizophrenia Participants): MK-8189 Monotherapy 8 mg | The Number of Participants Who Discontinued Study Treatment Due to an AE | 0 Participants |
| Panel B (Schizophrenia Participants): MK-8189 Monotherapy 12 mg | The Number of Participants Who Discontinued Study Treatment Due to an AE | 0 Participants |
| Panel B (Schizophrenia Participants): MK-8189 Monotherapy 16 mg | The Number of Participants Who Discontinued Study Treatment Due to an AE | 1 Participants |
| Panel B (Schizophrenia Participants): MK-8189 Monotherapy 20 mg | The Number of Participants Who Discontinued Study Treatment Due to an AE | 0 Participants |
| Panel B (Schizophrenia Participants): MK-8189 Monotherapy 24 mg | The Number of Participants Who Discontinued Study Treatment Due to an AE | 0 Participants |
| Panel B (Schizophrenia Participants): Placebo Monotherapy | The Number of Participants Who Discontinued Study Treatment Due to an AE | 1 Participants |
| Panel C (Schizophrenia Participants): MK-8189 Add-on Therapy 4 mg | The Number of Participants Who Discontinued Study Treatment Due to an AE | 1 Participants |
| Panel C (Schizophrenia Participants): MK-8189 Add-on Therapy 8 mg | The Number of Participants Who Discontinued Study Treatment Due to an AE | 1 Participants |
| Panel C (Schizophrenia Participants): MK-8189 Add-on Therapy 12 mg | The Number of Participants Who Discontinued Study Treatment Due to an AE | 3 Participants |
| Panel C (Schizophrenia Participants): MK-8189 Add-on Therapy 16 mg | The Number of Participants Who Discontinued Study Treatment Due to an AE | 1 Participants |
| Panel C (Schizophrenia Participants): MK-8189 Add-on Therapy 20 mg | The Number of Participants Who Discontinued Study Treatment Due to an AE | 0 Participants |
| Panel C (Schizophrenia Participants): MK-8189 Add-on Therapy 24 mg | The Number of Participants Who Discontinued Study Treatment Due to an AE | 0 Participants |
| Panel C (Schizophrenia Participants): Placebo Add-on Therapy | The Number of Participants Who Discontinued Study Treatment Due to an AE | 0 Participants |
| Panel D (Schizophrenia Participants): MK-8189 Monotherapy 8 mg | The Number of Participants Who Discontinued Study Treatment Due to an AE | 1 Participants |
| Panel D (Schizophrenia Participants): MK-8189 Monotherapy 16 mg | The Number of Participants Who Discontinued Study Treatment Due to an AE | 3 Participants |
| Panel D (Schizophrenia Participants): MK-8189 Monotherapy 24 mg | The Number of Participants Who Discontinued Study Treatment Due to an AE | 0 Participants |
| Panel D (Schizophrenia Participants): MK-8189 Monotherapy 36 mg | The Number of Participants Who Discontinued Study Treatment Due to an AE | 1 Participants |
| Panel D (Schizophrenia Participants): MK-8189 Monotherapy 48 mg | The Number of Participants Who Discontinued Study Treatment Due to an AE | 0 Participants |
| Panel D (Schizophrenia Participants): Placebo Monotherapy | The Number of Participants Who Discontinued Study Treatment Due to an AE | 2 Participants |
Primary
The Number of Participants Who Experienced One or More Adverse Events (AEs)
An AE was defined as 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. Per protocol, safety was analyzed by panel and dose. The number of participants who experienced one or more AEs was reported.
Time frame: Up to ~32 days
Population: All participants who got ≥1 dose of study drug. Per protocol, safety was analyzed by panel and dose.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Panel A (Healthy Participants): MK-8189 Monotherapy 4 mg | The Number of Participants Who Experienced One or More Adverse Events (AEs) | 5 Participants |
| Panel A (Healthy Participants): MK-8189 Monotherapy 8 mg | The Number of Participants Who Experienced One or More Adverse Events (AEs) | 3 Participants |
| Panel A (Healthy Participants): MK-8189 Monotherapy 12 mg | The Number of Participants Who Experienced One or More Adverse Events (AEs) | 4 Participants |
| Panel A (Healthy Participants): MK-8189 Monotherapy 16 mg | The Number of Participants Who Experienced One or More Adverse Events (AEs) | 5 Participants |
| Panel A (Healthy Participants): MK-8189 Monotherapy 20 mg | The Number of Participants Who Experienced One or More Adverse Events (AEs) | 2 Participants |
| Panel A (Healthy Participants): MK-8189 Monotherapy 24 mg | The Number of Participants Who Experienced One or More Adverse Events (AEs) | 5 Participants |
| Panel A (Healthy Participants): Placebo Monotherapy | The Number of Participants Who Experienced One or More Adverse Events (AEs) | 3 Participants |
| Panel B (Schizophrenia Participants): MK-8189 Monotherapy 4 mg | The Number of Participants Who Experienced One or More Adverse Events (AEs) | 4 Participants |
| Panel B (Schizophrenia Participants): MK-8189 Monotherapy 8 mg | The Number of Participants Who Experienced One or More Adverse Events (AEs) | 3 Participants |
| Panel B (Schizophrenia Participants): MK-8189 Monotherapy 12 mg | The Number of Participants Who Experienced One or More Adverse Events (AEs) | 4 Participants |
| Panel B (Schizophrenia Participants): MK-8189 Monotherapy 16 mg | The Number of Participants Who Experienced One or More Adverse Events (AEs) | 8 Participants |
| Panel B (Schizophrenia Participants): MK-8189 Monotherapy 20 mg | The Number of Participants Who Experienced One or More Adverse Events (AEs) | 5 Participants |
| Panel B (Schizophrenia Participants): MK-8189 Monotherapy 24 mg | The Number of Participants Who Experienced One or More Adverse Events (AEs) | 7 Participants |
| Panel B (Schizophrenia Participants): Placebo Monotherapy | The Number of Participants Who Experienced One or More Adverse Events (AEs) | 4 Participants |
| Panel C (Schizophrenia Participants): MK-8189 Add-on Therapy 4 mg | The Number of Participants Who Experienced One or More Adverse Events (AEs) | 6 Participants |
| Panel C (Schizophrenia Participants): MK-8189 Add-on Therapy 8 mg | The Number of Participants Who Experienced One or More Adverse Events (AEs) | 8 Participants |
| Panel C (Schizophrenia Participants): MK-8189 Add-on Therapy 12 mg | The Number of Participants Who Experienced One or More Adverse Events (AEs) | 5 Participants |
| Panel C (Schizophrenia Participants): MK-8189 Add-on Therapy 16 mg | The Number of Participants Who Experienced One or More Adverse Events (AEs) | 5 Participants |
| Panel C (Schizophrenia Participants): MK-8189 Add-on Therapy 20 mg | The Number of Participants Who Experienced One or More Adverse Events (AEs) | 4 Participants |
| Panel C (Schizophrenia Participants): MK-8189 Add-on Therapy 24 mg | The Number of Participants Who Experienced One or More Adverse Events (AEs) | 4 Participants |
| Panel C (Schizophrenia Participants): Placebo Add-on Therapy | The Number of Participants Who Experienced One or More Adverse Events (AEs) | 1 Participants |
| Panel D (Schizophrenia Participants): MK-8189 Monotherapy 8 mg | The Number of Participants Who Experienced One or More Adverse Events (AEs) | 8 Participants |
| Panel D (Schizophrenia Participants): MK-8189 Monotherapy 16 mg | The Number of Participants Who Experienced One or More Adverse Events (AEs) | 8 Participants |
| Panel D (Schizophrenia Participants): MK-8189 Monotherapy 24 mg | The Number of Participants Who Experienced One or More Adverse Events (AEs) | 5 Participants |
| Panel D (Schizophrenia Participants): MK-8189 Monotherapy 36 mg | The Number of Participants Who Experienced One or More Adverse Events (AEs) | 5 Participants |
| Panel D (Schizophrenia Participants): MK-8189 Monotherapy 48 mg | The Number of Participants Who Experienced One or More Adverse Events (AEs) | 8 Participants |
| Panel D (Schizophrenia Participants): Placebo Monotherapy | The Number of Participants Who Experienced One or More Adverse Events (AEs) | 9 Participants |
Secondary
Apparent Total Plasma Clearance of MK-8189 (CL/F) on Day 18 (Panels A, B, C) and Day 15 (Panel D)
CL/F was the apparent total clearance of MK-8189 in plasma over time, assessed as the rate at which MK-8189 was removed from the plasma. To estimate CL/F, per protocol blood samples were collected 2, 6, 8, 10, 12, 16, 24, 36, 48 hours post-dose on Day 18 for Panels A, B, C, and on Day 15 for Panel D. Per protocol CL/F was analyzed by panel, dose and dosing regimen. Due to differing dosing regimen, some arms/doses weren't applicable to some timepoints, shown by 0 participants analyzed in the table. Per dosing regimen, the 4 mg, 8 mg, 12 mg, 16 mg, 20 mg (Panels A, B, C), 8 mg, 16 mg, 24 mg, 36 mg (Panel D) study arms weren't applicable to the protocol-specified timepoints/days of CL/F analysis and were excluded. GCV was reported as a percent. Per protocol placebo arms were excluded from CL/F analysis.
Time frame: 2, 6, 8, 10, 12, 16, 24, 36, 48 hours post-dose on Day 18 (Panel A, B, C) and Day 15 (Panel D)
Population: All participants who got ≥1 dose of MK-8189, had CL/F data for Day 18 (Panels A, B, C) or Day 15 (Panel D). Per protocol CL/F was analyzed by panel, dose, dosing regimen; based on dosing, some arms weren't applicable to some timepoints, shown by 0 participants analyzed. The 4 mg, 8 mg, 12 mg, 16 mg, 20 mg (Panels A, B, C), 8 mg, 16 mg, 24 mg, 36 mg (Panel D) arms weren't applicable to the CL/F timepoints; per protocol these arms and placebo arms were excluded.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Panel A (Healthy Participants): MK-8189 Monotherapy 24 mg | Apparent Total Plasma Clearance of MK-8189 (CL/F) on Day 18 (Panels A, B, C) and Day 15 (Panel D) | Day 18 | 4.63 Liter/hr | Geometric Coefficient of Variation 59.6 |
| Panel B (Schizophrenia Participants): MK-8189 Monotherapy 24 mg | Apparent Total Plasma Clearance of MK-8189 (CL/F) on Day 18 (Panels A, B, C) and Day 15 (Panel D) | Day 18 | 2.36 Liter/hr | Geometric Coefficient of Variation 38.3 |
| Panel C (Schizophrenia Participants): MK-8189 Add-on Therapy 24 mg | Apparent Total Plasma Clearance of MK-8189 (CL/F) on Day 18 (Panels A, B, C) and Day 15 (Panel D) | Day 18 | 3.32 Liter/hr | Geometric Coefficient of Variation 30.8 |
| Panel D (Schizophrenia Participants): MK-8189 Monotherapy 48 mg | Apparent Total Plasma Clearance of MK-8189 (CL/F) on Day 18 (Panels A, B, C) and Day 15 (Panel D) | Day 15 | 3.65 Liter/hr | Geometric Coefficient of Variation 66.5 |
Secondary
Apparent Volume of MK-8189 Distribution (Vd/F) on Day 18 (Panels A, B, C) and Day 15 (Panel D)
Vd/F was the apparent volume of distribution of MK-8189 between the plasma and the rest of the body, after dose, assessed as the total volume of MK-8189 that would need to be uniformly distributed to achieve the desired plasma drug concentration. To estimate Vd/F, per protocol blood samples were collected 2, 6, 8, 10, 12, 16, 24, 36, 48 hours post-dose on Day 18 for Panels A, B, C, and on Day 15 for Panel D. Per protocol Vd/F was analyzed by panel, dose and dosing regimen. Due to differing dosing regimen, some arms/doses weren't applicable to some timepoints, shown by 0 participants analyzed in the table. Per dosing regimen, the 4 mg, 8 mg, 12 mg, 16 mg, 20 mg (Panels A, B, C), 8 mg, 16 mg, 24 mg, 36 mg (Panel D) study arms weren't applicable to the protocol-specified timepoints/days of Vd/F analysis and were excluded. GCV was reported as a percent. Per protocol placebo arms were excluded from Vd/F analysis.
Time frame: 2, 6, 8, 10, 12, 16, 24, 36, 48 hours post-dose on Day 18 (Panel A, B, C) and Day 15 (Panel D)
Population: All participants who got ≥1 dose of MK-8189, had Vd/F data for Day 18 (Panels A, B, C) or Day 15 (Panel D). Per protocol Vd/F was analyzed by panel, dose, dosing regimen; based on dosing, some arms weren't applicable to some timepoints, shown by 0 participants analyzed. The 4 mg, 8 mg, 12 mg, 16 mg, 20 mg (Panels A, B, C), 8 mg, 16 mg, 24 mg, 36 mg (Panel D) arms weren't applicable to the Vd/F timepoints; per protocol these arms and placebo arms were excluded.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Panel A (Healthy Participants): MK-8189 Monotherapy 24 mg | Apparent Volume of MK-8189 Distribution (Vd/F) on Day 18 (Panels A, B, C) and Day 15 (Panel D) | Day 18 | 50.7 Liter | Geometric Coefficient of Variation 48.6 |
| Panel B (Schizophrenia Participants): MK-8189 Monotherapy 24 mg | Apparent Volume of MK-8189 Distribution (Vd/F) on Day 18 (Panels A, B, C) and Day 15 (Panel D) | Day 18 | 37.2 Liter | Geometric Coefficient of Variation 35.1 |
| Panel C (Schizophrenia Participants): MK-8189 Add-on Therapy 24 mg | Apparent Volume of MK-8189 Distribution (Vd/F) on Day 18 (Panels A, B, C) and Day 15 (Panel D) | Day 18 | 43.6 Liter | Geometric Coefficient of Variation 39.1 |
| Panel D (Schizophrenia Participants): MK-8189 Monotherapy 48 mg | Apparent Volume of MK-8189 Distribution (Vd/F) on Day 18 (Panels A, B, C) and Day 15 (Panel D) | Day 15 | 47.1 Liter | Geometric Coefficient of Variation 48 |
Secondary
Area Under the Plasma-concentration Curve at Zero to 24 Hours Post-dose (AUC0-24hr) of MK-8189
AUC was a measure of MK-8189 exposure assessed as a product of drug concentration and time, using a linear mixed effects model. To estimate AUC0-24hr per protocol blood samples were collected pre-dose, 2, 6, 8, 10, 12, 16, 24 hours post-dose for Panels A, B, C, D; no pre-dose samples collected on Day 18 (Panels A, B, C), Day 15 (Panel D). Samples were collected on Days 7, 10, 13, 16, 18 for Panels A, B; Days 9, 12, 15, 18 for Panel C; Days 1, 4, 7, 10, 13, 15 for Panel D. Per protocol AUC0-24hr was analyzed by panel, dose, dosing regimen; due to differing dosing regimen some arms/doses weren't applicable to some timepoints, shown by 0 participants analyzed in the table. Per dosing regimen the 4 mg, 8 mg (Panels A, B), 4 mg (Panel C) study arms weren't applicable to the protocol-specified timepoints/days of AUC0-24hr analysis and these arms were excluded. Geometric coefficient of variation (GCV) was reported as a percent. Per protocol placebo arms were excluded from AUC0-24hr analysis.
Time frame: Pre-dose, 2, 6, 8, 10, 12, 16, 24 hours post-dose; no pre-dose on Day 18 (Panel A, B, C), Day 15 (Panel D); Panel A, B: Days 7, 10, 13, 16, 18; Panel C: Days 9, 12, 15, 18; Panel D: Days 1, 4, 7, 10, 13, 15
Population: All participants who got ≥1 dose of MK-8189, had AUC0-24hr data for Days 7, 10, 13, 16 or 18 (Panels A, B); Days 9, 12, 15 or 18 (Panel C); Days 1, 4, 7, 10, 13 or 15 (Panel D). Per protocol AUC0-24hr was analyzed by panel, dose, dosing regimen; based on dosing, some arms weren't applicable to some timepoints shown by 0 participants analyzed. The 4 mg, 8 mg (Panels A, B), 4 mg (Panel C) arms weren't applicable to the AUC0-24hr timepoints; per protocol these arms and placebo arms were excluded.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Panel A (Healthy Participants): MK-8189 Monotherapy 12 mg | Area Under the Plasma-concentration Curve at Zero to 24 Hours Post-dose (AUC0-24hr) of MK-8189 | Day 7 | 8360 nM*hr | Geometric Coefficient of Variation 42.5 |
| Panel A (Healthy Participants): MK-8189 Monotherapy 16 mg | Area Under the Plasma-concentration Curve at Zero to 24 Hours Post-dose (AUC0-24hr) of MK-8189 | Day 10 | 10200 nM*hr | Geometric Coefficient of Variation 49 |
| Panel A (Healthy Participants): MK-8189 Monotherapy 20 mg | Area Under the Plasma-concentration Curve at Zero to 24 Hours Post-dose (AUC0-24hr) of MK-8189 | Day 13 | 12200 nM*hr | Geometric Coefficient of Variation 48.5 |
| Panel A (Healthy Participants): MK-8189 Monotherapy 24 mg | Area Under the Plasma-concentration Curve at Zero to 24 Hours Post-dose (AUC0-24hr) of MK-8189 | Day 16 | 15600 nM*hr | Geometric Coefficient of Variation 36.1 |
| Panel A (Healthy Participants): MK-8189 Monotherapy 24 mg | Area Under the Plasma-concentration Curve at Zero to 24 Hours Post-dose (AUC0-24hr) of MK-8189 | Day 18 | 13600 nM*hr | Geometric Coefficient of Variation 59.6 |
| Panel B (Schizophrenia Participants): MK-8189 Monotherapy 12 mg | Area Under the Plasma-concentration Curve at Zero to 24 Hours Post-dose (AUC0-24hr) of MK-8189 | Day 7 | 11700 nM*hr | Geometric Coefficient of Variation 32.9 |
| Panel B (Schizophrenia Participants): MK-8189 Monotherapy 16 mg | Area Under the Plasma-concentration Curve at Zero to 24 Hours Post-dose (AUC0-24hr) of MK-8189 | Day 10 | 17200 nM*hr | Geometric Coefficient of Variation 41.9 |
| Panel B (Schizophrenia Participants): MK-8189 Monotherapy 20 mg | Area Under the Plasma-concentration Curve at Zero to 24 Hours Post-dose (AUC0-24hr) of MK-8189 | Day 13 | 20200 nM*hr | Geometric Coefficient of Variation 44.7 |
| Panel B (Schizophrenia Participants): MK-8189 Monotherapy 24 mg | Area Under the Plasma-concentration Curve at Zero to 24 Hours Post-dose (AUC0-24hr) of MK-8189 | Day 18 | 26600 nM*hr | Geometric Coefficient of Variation 38.3 |
| Panel B (Schizophrenia Participants): MK-8189 Monotherapy 24 mg | Area Under the Plasma-concentration Curve at Zero to 24 Hours Post-dose (AUC0-24hr) of MK-8189 | Day 16 | 24600 nM*hr | Geometric Coefficient of Variation 36.6 |
| Panel C (Schizophrenia Participants): MK-8189 Add-on Therapy 8 mg | Area Under the Plasma-concentration Curve at Zero to 24 Hours Post-dose (AUC0-24hr) of MK-8189 | Day 9 | 11400 nM*hr | — |
| Panel C (Schizophrenia Participants): MK-8189 Add-on Therapy 12 mg | Area Under the Plasma-concentration Curve at Zero to 24 Hours Post-dose (AUC0-24hr) of MK-8189 | Day 9 | 11300 nM*hr | Geometric Coefficient of Variation 47.9 |
| Panel C (Schizophrenia Participants): MK-8189 Add-on Therapy 16 mg | Area Under the Plasma-concentration Curve at Zero to 24 Hours Post-dose (AUC0-24hr) of MK-8189 | Day 12 | 13800 nM*hr | Geometric Coefficient of Variation 28.2 |
| Panel C (Schizophrenia Participants): MK-8189 Add-on Therapy 20 mg | Area Under the Plasma-concentration Curve at Zero to 24 Hours Post-dose (AUC0-24hr) of MK-8189 | Day 15 | 15700 nM*hr | Geometric Coefficient of Variation 33.4 |
| Panel C (Schizophrenia Participants): MK-8189 Add-on Therapy 24 mg | Area Under the Plasma-concentration Curve at Zero to 24 Hours Post-dose (AUC0-24hr) of MK-8189 | Day 18 | 18900 nM*hr | Geometric Coefficient of Variation 30.8 |
| Panel D (Schizophrenia Participants): MK-8189 Monotherapy 8 mg | Area Under the Plasma-concentration Curve at Zero to 24 Hours Post-dose (AUC0-24hr) of MK-8189 | Day 1 | 4640 nM*hr | Geometric Coefficient of Variation 40.5 |
| Panel D (Schizophrenia Participants): MK-8189 Monotherapy 16 mg | Area Under the Plasma-concentration Curve at Zero to 24 Hours Post-dose (AUC0-24hr) of MK-8189 | Day 4 | 10900 nM*hr | Geometric Coefficient of Variation 72.1 |
| Panel D (Schizophrenia Participants): MK-8189 Monotherapy 24 mg | Area Under the Plasma-concentration Curve at Zero to 24 Hours Post-dose (AUC0-24hr) of MK-8189 | Day 7 | 14100 nM*hr | Geometric Coefficient of Variation 106.6 |
| Panel D (Schizophrenia Participants): MK-8189 Monotherapy 36 mg | Area Under the Plasma-concentration Curve at Zero to 24 Hours Post-dose (AUC0-24hr) of MK-8189 | Day 10 | 25100 nM*hr | Geometric Coefficient of Variation 54.6 |
| Panel D (Schizophrenia Participants): MK-8189 Monotherapy 48 mg | Area Under the Plasma-concentration Curve at Zero to 24 Hours Post-dose (AUC0-24hr) of MK-8189 | Day 15 | 34400 nM*hr | Geometric Coefficient of Variation 66.5 |
| Panel D (Schizophrenia Participants): MK-8189 Monotherapy 48 mg | Area Under the Plasma-concentration Curve at Zero to 24 Hours Post-dose (AUC0-24hr) of MK-8189 | Day 13 | 31800 nM*hr | Geometric Coefficient of Variation 54.5 |
Secondary
Maximum Observed Post-dose Plasma Concentration (Cmax) of MK-8189
Cmax was the maximum concentration of MK-8189 observed in plasma, assessed using a linear mixed effects model. To estimate Cmax, per protocol blood samples were collected pre-dose, 2, 6, 8, 10, 12, 16, 24 hours post-dose for Panels A, B, C, D; no pre-dose samples collected on Day 18 (Panels A, B, C), Day 15 (Panel D); additional post-dose samples collected at 36, 48 hours on Days 18 and 15. Samples were collected on Days 7, 10, 13, 16, 18 for Panels A, B; Days 9, 12, 15, 18 for Panel C; Days 1, 4, 7, 10, 13, 15 for Panel D. Per protocol Cmax was analyzed by panel, dose, dosing regimen; due to differing dosing regimen some arms/doses weren't applicable to some timepoints, shown by 0 participants analyzed in the table. Per dosing regimen, the 4 mg, 8 mg (Panels A, B), 4 mg (Panel C) study arms weren't applicable to the protocol-specified timepoints/days of Cmax analysis and were excluded. GCV was reported as a percent. Per protocol placebo arms were excluded from Cmax analysis.
Time frame: Pre-dose, 2, 6, 8, 10, 12, 16, 24 hours post-dose; no pre-dose on Day 18 (Panel A, B, C), Day 15 (Panel D);additional 36, 48 hours post-dose on Days 18, 15; Panel A, B: Days 7, 10, 13, 16, 18; Panel C: Days 9, 12, 15, 18; Panel D:Days 1, 4, 7, 10, 13, 15
Population: All participants who got ≥1 dose of MK-8189, had Cmax data for Days 7, 10, 13, 16 or 18 (Panels A, B); Days 9, 12, 15 or 18 (Panel C); Days 1, 4, 7, 10, 13 or 15 (Panel D). Per protocol Cmax was analyzed by panel, dose, dosing regimen; based on dosing, some arms weren't applicable to some timepoints shown by 0 participants analyzed. The 4 mg, 8 mg (Panels A, B), 4 mg (Panel C) arms weren't applicable to the Cmax timepoints; per protocol these arms and placebo arms were excluded.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Panel A (Healthy Participants): MK-8189 Monotherapy 12 mg | Maximum Observed Post-dose Plasma Concentration (Cmax) of MK-8189 | Day 7 | 481 nM | Geometric Coefficient of Variation 41.6 |
| Panel A (Healthy Participants): MK-8189 Monotherapy 16 mg | Maximum Observed Post-dose Plasma Concentration (Cmax) of MK-8189 | Day 10 | 613 nM | Geometric Coefficient of Variation 37.2 |
| Panel A (Healthy Participants): MK-8189 Monotherapy 20 mg | Maximum Observed Post-dose Plasma Concentration (Cmax) of MK-8189 | Day 13 | 709 nM | Geometric Coefficient of Variation 47.1 |
| Panel A (Healthy Participants): MK-8189 Monotherapy 24 mg | Maximum Observed Post-dose Plasma Concentration (Cmax) of MK-8189 | Day 16 | 807 nM | Geometric Coefficient of Variation 34 |
| Panel A (Healthy Participants): MK-8189 Monotherapy 24 mg | Maximum Observed Post-dose Plasma Concentration (Cmax) of MK-8189 | Day 18 | 741 nM | Geometric Coefficient of Variation 48 |
| Panel B (Schizophrenia Participants): MK-8189 Monotherapy 12 mg | Maximum Observed Post-dose Plasma Concentration (Cmax) of MK-8189 | Day 7 | 588 nM | Geometric Coefficient of Variation 33.7 |
| Panel B (Schizophrenia Participants): MK-8189 Monotherapy 16 mg | Maximum Observed Post-dose Plasma Concentration (Cmax) of MK-8189 | Day 10 | 868 nM | Geometric Coefficient of Variation 41.5 |
| Panel B (Schizophrenia Participants): MK-8189 Monotherapy 20 mg | Maximum Observed Post-dose Plasma Concentration (Cmax) of MK-8189 | Day 13 | 1010 nM | Geometric Coefficient of Variation 45 |
| Panel B (Schizophrenia Participants): MK-8189 Monotherapy 24 mg | Maximum Observed Post-dose Plasma Concentration (Cmax) of MK-8189 | Day 18 | 1300 nM | Geometric Coefficient of Variation 36.8 |
| Panel B (Schizophrenia Participants): MK-8189 Monotherapy 24 mg | Maximum Observed Post-dose Plasma Concentration (Cmax) of MK-8189 | Day 16 | 1250 nM | Geometric Coefficient of Variation 37.7 |
| Panel C (Schizophrenia Participants): MK-8189 Add-on Therapy 8 mg | Maximum Observed Post-dose Plasma Concentration (Cmax) of MK-8189 | Day 9 | 591 nM | — |
| Panel C (Schizophrenia Participants): MK-8189 Add-on Therapy 12 mg | Maximum Observed Post-dose Plasma Concentration (Cmax) of MK-8189 | Day 9 | 566 nM | Geometric Coefficient of Variation 46.3 |
| Panel C (Schizophrenia Participants): MK-8189 Add-on Therapy 16 mg | Maximum Observed Post-dose Plasma Concentration (Cmax) of MK-8189 | Day 12 | 693 nM | Geometric Coefficient of Variation 24.6 |
| Panel C (Schizophrenia Participants): MK-8189 Add-on Therapy 20 mg | Maximum Observed Post-dose Plasma Concentration (Cmax) of MK-8189 | Day 15 | 801 nM | Geometric Coefficient of Variation 27.3 |
| Panel C (Schizophrenia Participants): MK-8189 Add-on Therapy 24 mg | Maximum Observed Post-dose Plasma Concentration (Cmax) of MK-8189 | Day 18 | 972 nM | Geometric Coefficient of Variation 23.4 |
| Panel D (Schizophrenia Participants): MK-8189 Monotherapy 8 mg | Maximum Observed Post-dose Plasma Concentration (Cmax) of MK-8189 | Day 1 | 328 nM | Geometric Coefficient of Variation 42.8 |
| Panel D (Schizophrenia Participants): MK-8189 Monotherapy 16 mg | Maximum Observed Post-dose Plasma Concentration (Cmax) of MK-8189 | Day 4 | 619 nM | Geometric Coefficient of Variation 52.5 |
| Panel D (Schizophrenia Participants): MK-8189 Monotherapy 24 mg | Maximum Observed Post-dose Plasma Concentration (Cmax) of MK-8189 | Day 7 | 920 nM | Geometric Coefficient of Variation 54.5 |
| Panel D (Schizophrenia Participants): MK-8189 Monotherapy 36 mg | Maximum Observed Post-dose Plasma Concentration (Cmax) of MK-8189 | Day 10 | 1390 nM | Geometric Coefficient of Variation 46.1 |
| Panel D (Schizophrenia Participants): MK-8189 Monotherapy 48 mg | Maximum Observed Post-dose Plasma Concentration (Cmax) of MK-8189 | Day 15 | 1890 nM | Geometric Coefficient of Variation 52.9 |
| Panel D (Schizophrenia Participants): MK-8189 Monotherapy 48 mg | Maximum Observed Post-dose Plasma Concentration (Cmax) of MK-8189 | Day 13 | 1670 nM | Geometric Coefficient of Variation 51.9 |
Secondary
Plasma Concentration at 24 Hours Post-dose (C24hr) of MK-8189
C24hr was the concentration of MK-8189 observed in plasma at the 24-hour nominal sampling time after administration of MK-8189, assessed using a linear mixed effects model. To estimate C24hr, per protocol blood samples were collected 24 hours post-dose on Days 7, 10, 13, 16, 18 for Panels A, B; Days 9, 12, 15, 18 for Panel C; Days 1, 4, 7, 10, 13, 15 for Panel D. Per protocol C24hr was analyzed by panel, dose, dosing regimen; due to differing dosing regimen some arms/doses weren't applicable to some timepoints, shown by 0 participants analyzed in the table. Per dosing regimen, the 4 mg, 8 mg (Panels A, B), 4 mg (Panel C) study arms weren't applicable to the protocol-specified timepoints/days of C24hr analysis and were excluded. GCV was reported as a percent. Per protocol placebo arms were excluded from C24hr analysis.
Time frame: 24 hours post-dose; Panel A, B: Days 7, 10, 13, 16, 18; Panel C: Days 9, 12, 15, 18; Panel D: Days 1, 4, 7, 10, 13, 15
Population: All participants who got ≥1 dose of MK-8189, had C24hr data for Days 7, 10, 13, 16 or 18 (Panels A, B); Days 9, 12, 15 or 18 (Panel C); Days 1, 4, 7, 10, 13 or 15 (Panel D). Per protocol C24hr was analyzed by panel, dose, dosing regimen; based on dosing, some arms weren't applicable to some timepoints shown by 0 participants analyzed. The 4 mg, 8 mg (Panels A, B), 4 mg (Panel C) arms weren't applicable to the C24hr timepoints; per protocol these arms and placebo arms were excluded.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Panel A (Healthy Participants): MK-8189 Monotherapy 12 mg | Plasma Concentration at 24 Hours Post-dose (C24hr) of MK-8189 | Day 7 | 310 nM | Geometric Coefficient of Variation 47.2 |
| Panel A (Healthy Participants): MK-8189 Monotherapy 16 mg | Plasma Concentration at 24 Hours Post-dose (C24hr) of MK-8189 | Day 10 | 392 nM | Geometric Coefficient of Variation 61.4 |
| Panel A (Healthy Participants): MK-8189 Monotherapy 20 mg | Plasma Concentration at 24 Hours Post-dose (C24hr) of MK-8189 | Day 13 | 418 nM | Geometric Coefficient of Variation 65 |
| Panel A (Healthy Participants): MK-8189 Monotherapy 24 mg | Plasma Concentration at 24 Hours Post-dose (C24hr) of MK-8189 | Day 16 | 625 nM | Geometric Coefficient of Variation 39.7 |
| Panel A (Healthy Participants): MK-8189 Monotherapy 24 mg | Plasma Concentration at 24 Hours Post-dose (C24hr) of MK-8189 | Day 18 | 433 nM | Geometric Coefficient of Variation 111.3 |
| Panel B (Schizophrenia Participants): MK-8189 Monotherapy 12 mg | Plasma Concentration at 24 Hours Post-dose (C24hr) of MK-8189 | Day 7 | 501 nM | Geometric Coefficient of Variation 37.9 |
| Panel B (Schizophrenia Participants): MK-8189 Monotherapy 16 mg | Plasma Concentration at 24 Hours Post-dose (C24hr) of MK-8189 | Day 10 | 702 nM | Geometric Coefficient of Variation 46.9 |
| Panel B (Schizophrenia Participants): MK-8189 Monotherapy 20 mg | Plasma Concentration at 24 Hours Post-dose (C24hr) of MK-8189 | Day 13 | 836 nM | Geometric Coefficient of Variation 57 |
| Panel B (Schizophrenia Participants): MK-8189 Monotherapy 24 mg | Plasma Concentration at 24 Hours Post-dose (C24hr) of MK-8189 | Day 18 | 1010 nM | Geometric Coefficient of Variation 47.5 |
| Panel B (Schizophrenia Participants): MK-8189 Monotherapy 24 mg | Plasma Concentration at 24 Hours Post-dose (C24hr) of MK-8189 | Day 16 | 949 nM | Geometric Coefficient of Variation 45.7 |
| Panel C (Schizophrenia Participants): MK-8189 Add-on Therapy 8 mg | Plasma Concentration at 24 Hours Post-dose (C24hr) of MK-8189 | Day 9 | 416 nM | — |
| Panel C (Schizophrenia Participants): MK-8189 Add-on Therapy 12 mg | Plasma Concentration at 24 Hours Post-dose (C24hr) of MK-8189 | Day 9 | 490 nM | Geometric Coefficient of Variation 54 |
| Panel C (Schizophrenia Participants): MK-8189 Add-on Therapy 16 mg | Plasma Concentration at 24 Hours Post-dose (C24hr) of MK-8189 | Day 12 | 540 nM | Geometric Coefficient of Variation 39.1 |
| Panel C (Schizophrenia Participants): MK-8189 Add-on Therapy 20 mg | Plasma Concentration at 24 Hours Post-dose (C24hr) of MK-8189 | Day 15 | 651 nM | Geometric Coefficient of Variation 44.1 |
| Panel C (Schizophrenia Participants): MK-8189 Add-on Therapy 24 mg | Plasma Concentration at 24 Hours Post-dose (C24hr) of MK-8189 | Day 18 | 704 nM | Geometric Coefficient of Variation 39 |
| Panel D (Schizophrenia Participants): MK-8189 Monotherapy 8 mg | Plasma Concentration at 24 Hours Post-dose (C24hr) of MK-8189 | Day 1 | 287 nM | Geometric Coefficient of Variation 70.3 |
| Panel D (Schizophrenia Participants): MK-8189 Monotherapy 16 mg | Plasma Concentration at 24 Hours Post-dose (C24hr) of MK-8189 | Day 4 | 480 nM | Geometric Coefficient of Variation 101.8 |
| Panel D (Schizophrenia Participants): MK-8189 Monotherapy 24 mg | Plasma Concentration at 24 Hours Post-dose (C24hr) of MK-8189 | Day 7 | 567 nM | Geometric Coefficient of Variation 131.4 |
| Panel D (Schizophrenia Participants): MK-8189 Monotherapy 36 mg | Plasma Concentration at 24 Hours Post-dose (C24hr) of MK-8189 | Day 10 | 890 nM | Geometric Coefficient of Variation 80.3 |
| Panel D (Schizophrenia Participants): MK-8189 Monotherapy 48 mg | Plasma Concentration at 24 Hours Post-dose (C24hr) of MK-8189 | Day 15 | 1160 nM | Geometric Coefficient of Variation 97.8 |
| Panel D (Schizophrenia Participants): MK-8189 Monotherapy 48 mg | Plasma Concentration at 24 Hours Post-dose (C24hr) of MK-8189 | Day 13 | 1370 nM | Geometric Coefficient of Variation 47.5 |
Secondary
Time Post-dose to Maximum Observed Plasma Concentration (Tmax) of MK-8189
Tmax was the actual sampling time at which maximum post-dose plasma concentration of MK-8189 was observed. To estimate Tmax, per protocol blood samples were collected pre-dose, 2, 6, 8, 10, 12, 16, 24 hours post-dose for Panels A, B, C, D; no pre-dose samples collected on Day 18 (Panels A, B, C), Day 15 (Panel D); additional post-dose samples collected at 36, 48 hours on Days 18 and 15. Samples were collected on Days 7, 10, 13, 16, 18 for Panels A, B; Days 9, 12, 15, 18 for Panel C; Days 1, 4, 7, 10, 13, 15 for Panel D. Per protocol Tmax was analyzed by panel, dose, dosing regimen; due to differing dosing regimen, some arms/doses weren't applicable to some timepoints, shown by 0 participants analyzed in the table. Per dosing regimen, the 4 mg, 8 mg (Panels A, B), 4 mg (Panel C) study arms weren't applicable to the protocol-specified timepoints/days of Tmax analysis and were excluded. Per protocol placebo arms were excluded from Tmax analysis.
Time frame: Pre-dose, 2, 6, 8, 10, 12, 16, 24 hours post-dose; no pre-dose on Day 18 (Panel A, B, C), Day 15 (Panel D);additional 36, 48 hours post-dose on Days 18, 15; Panel A, B: Days 7, 10, 13, 16, 18; Panel C: Days 9, 12, 15, 18; Panel D:Days 1, 4, 7, 10, 13, 15
Population: All participants who got ≥1 dose of MK-8189, had Tmax data for Days 7, 10, 13, 16 or 18 (Panels A, B); Days 9, 12, 15 or 18 (Panel C); Days 1, 4, 7, 10, 13 or 15 (Panel D). Per protocol Tmax was analyzed by panel, dose, dosing regimen; based on dosing, some arms weren't applicable to some timepoints shown by 0 participants analyzed. The 4 mg, 8 mg (Panels A, B), 4 mg (Panel C) arms weren't applicable to the Tmax timepoints; per protocol these arms and placebo arms were excluded.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Panel A (Healthy Participants): MK-8189 Monotherapy 12 mg | Time Post-dose to Maximum Observed Plasma Concentration (Tmax) of MK-8189 | Day 7 | 12.02 hr |
| Panel A (Healthy Participants): MK-8189 Monotherapy 16 mg | Time Post-dose to Maximum Observed Plasma Concentration (Tmax) of MK-8189 | Day 10 | 16.02 hr |
| Panel A (Healthy Participants): MK-8189 Monotherapy 20 mg | Time Post-dose to Maximum Observed Plasma Concentration (Tmax) of MK-8189 | Day 13 | 14.04 hr |
| Panel A (Healthy Participants): MK-8189 Monotherapy 24 mg | Time Post-dose to Maximum Observed Plasma Concentration (Tmax) of MK-8189 | Day 16 | 13.99 hr |
| Panel A (Healthy Participants): MK-8189 Monotherapy 24 mg | Time Post-dose to Maximum Observed Plasma Concentration (Tmax) of MK-8189 | Day 18 | 11.99 hr |
| Panel B (Schizophrenia Participants): MK-8189 Monotherapy 12 mg | Time Post-dose to Maximum Observed Plasma Concentration (Tmax) of MK-8189 | Day 7 | 15.98 hr |
| Panel B (Schizophrenia Participants): MK-8189 Monotherapy 16 mg | Time Post-dose to Maximum Observed Plasma Concentration (Tmax) of MK-8189 | Day 10 | 16.07 hr |
| Panel B (Schizophrenia Participants): MK-8189 Monotherapy 20 mg | Time Post-dose to Maximum Observed Plasma Concentration (Tmax) of MK-8189 | Day 13 | 16.05 hr |
| Panel B (Schizophrenia Participants): MK-8189 Monotherapy 24 mg | Time Post-dose to Maximum Observed Plasma Concentration (Tmax) of MK-8189 | Day 16 | 10.09 hr |
| Panel B (Schizophrenia Participants): MK-8189 Monotherapy 24 mg | Time Post-dose to Maximum Observed Plasma Concentration (Tmax) of MK-8189 | Day 18 | 12.05 hr |
| Panel C (Schizophrenia Participants): MK-8189 Add-on Therapy 8 mg | Time Post-dose to Maximum Observed Plasma Concentration (Tmax) of MK-8189 | Day 9 | 12.00 hr |
| Panel C (Schizophrenia Participants): MK-8189 Add-on Therapy 12 mg | Time Post-dose to Maximum Observed Plasma Concentration (Tmax) of MK-8189 | Day 9 | 15.99 hr |
| Panel C (Schizophrenia Participants): MK-8189 Add-on Therapy 16 mg | Time Post-dose to Maximum Observed Plasma Concentration (Tmax) of MK-8189 | Day 12 | 11.09 hr |
| Panel C (Schizophrenia Participants): MK-8189 Add-on Therapy 20 mg | Time Post-dose to Maximum Observed Plasma Concentration (Tmax) of MK-8189 | Day 15 | 16.00 hr |
| Panel C (Schizophrenia Participants): MK-8189 Add-on Therapy 24 mg | Time Post-dose to Maximum Observed Plasma Concentration (Tmax) of MK-8189 | Day 18 | 12.00 hr |
| Panel D (Schizophrenia Participants): MK-8189 Monotherapy 8 mg | Time Post-dose to Maximum Observed Plasma Concentration (Tmax) of MK-8189 | Day 1 | 23.95 hr |
| Panel D (Schizophrenia Participants): MK-8189 Monotherapy 16 mg | Time Post-dose to Maximum Observed Plasma Concentration (Tmax) of MK-8189 | Day 4 | 12.04 hr |
| Panel D (Schizophrenia Participants): MK-8189 Monotherapy 24 mg | Time Post-dose to Maximum Observed Plasma Concentration (Tmax) of MK-8189 | Day 7 | 16.03 hr |
| Panel D (Schizophrenia Participants): MK-8189 Monotherapy 36 mg | Time Post-dose to Maximum Observed Plasma Concentration (Tmax) of MK-8189 | Day 10 | 12.00 hr |
| Panel D (Schizophrenia Participants): MK-8189 Monotherapy 48 mg | Time Post-dose to Maximum Observed Plasma Concentration (Tmax) of MK-8189 | Day 15 | 16.02 hr |
| Panel D (Schizophrenia Participants): MK-8189 Monotherapy 48 mg | Time Post-dose to Maximum Observed Plasma Concentration (Tmax) of MK-8189 | Day 13 | 16.02 hr |
Secondary
Time Required for Plasma Concentration of MK-8189 to Decrease by Half (Apparent Terminal Half-life [t1/2]) on Day 18 (Panels A, B, C) and Day 15 (Panel D)
t1/2 was the time required to divide the plasma concentration of MK-8189 by half after reaching pseudo-equilibrium. At least three quantifiable terminal phase concentrations collected were used to calculate t1/2. To estimate t1/2, per protocol blood samples were collected 2, 6, 8, 10, 12, 16, 24, 36, 48 hours post-dose on Day 18 for Panels A, B, C, and on Day 15 for Panel D. Per protocol t1/2 was analyzed by panel, dose and dosing regimen. Due to differing dosing regimen, some arms/doses weren't applicable to some timepoints, shown by 0 participants analyzed in the table. Per dosing regimen, the 4 mg, 8 mg, 12 mg, 16 mg, 20 mg (Panels A, B, C), 8 mg, 16 mg, 24 mg, 36 mg (Panel D) study arms weren't applicable to the protocol-specified timepoints/days of t1/2 analysis and were excluded. GCV was reported as a percent. Per protocol placebo arms were excluded from t1/2 analysis.
Time frame: 2, 6, 8, 10, 12, 16, 24, 36, 48 hours post-dose on Day 18 (Panel A, B, C) and Day 15 (Panel D)
Population: All participants who got ≥1 dose of MK-8189, had t1/2 data for Day 18 (Panels A, B, C) or Day 15 (Panel D). Per protocol t1/2 was analyzed by panel, dose, dosing regimen; based on dosing, some arms weren't applicable to some timepoints, shown by 0 participants analyzed. The 4 mg, 8 mg, 12 mg, 16 mg, 20 mg (Panels A, B, C), 8 mg, 16 mg, 24 mg, 36 mg (Panel D) arms weren't applicable to the t1/2 timepoints; per protocol these arms and placebo arms were excluded.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Panel A (Healthy Participants): MK-8189 Monotherapy 24 mg | Time Required for Plasma Concentration of MK-8189 to Decrease by Half (Apparent Terminal Half-life [t1/2]) on Day 18 (Panels A, B, C) and Day 15 (Panel D) | Day 18 | 7.60 hr | Geometric Coefficient of Variation 29.7 |
| Panel B (Schizophrenia Participants): MK-8189 Monotherapy 24 mg | Time Required for Plasma Concentration of MK-8189 to Decrease by Half (Apparent Terminal Half-life [t1/2]) on Day 18 (Panels A, B, C) and Day 15 (Panel D) | Day 18 | 10.9 hr | Geometric Coefficient of Variation 25.5 |
| Panel C (Schizophrenia Participants): MK-8189 Add-on Therapy 24 mg | Time Required for Plasma Concentration of MK-8189 to Decrease by Half (Apparent Terminal Half-life [t1/2]) on Day 18 (Panels A, B, C) and Day 15 (Panel D) | Day 18 | 9.10 hr | Geometric Coefficient of Variation 19.2 |
| Panel D (Schizophrenia Participants): MK-8189 Monotherapy 48 mg | Time Required for Plasma Concentration of MK-8189 to Decrease by Half (Apparent Terminal Half-life [t1/2]) on Day 18 (Panels A, B, C) and Day 15 (Panel D) | Day 15 | 8.25 hr | Geometric Coefficient of Variation 20 |