Schizophrenia
Conditions
Brief summary
This is a randomized, double-blind, 2-part clinical study of the safety, tolerability and pharmacokinetics of alternate elpipodect titration regimens. Part 1 assessed multiple dose once-daily titration regimens of elpipodect in young adult participants with schizophrenia. Part 2 assessed multiple once-daily doses of elpipodect in elderly participants with schizophrenia and healthy elderly participants.
Interventions
DRUGElpipodect
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
DRUGPlacebo
Oral tablets of dose-matched placebo to MK-8189 according to randomization
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Double blind
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
Yes
Inclusion criteria
* Has a body mass index (BMI) ≤40 kg/m2 * Has no clinically significant abnormality on 12-lead safety electrocardiogram (ECG) performed at the prestudy (screening) visit and/or prior to randomization * Has a normal resting blood pressure (BP: systolic BP is ≥90 millimeter of mercury \[mmHg\] and ≤140 mmHg; diastolic BP is ≥60 mmHg and ≤90 mmHg) and normal resting heart rate (≥45 beats per minute \[bpm\] and ≤100 bpm) in the semirecumbent position at the prestudy (screening) visit and/or prior to randomization. Repeat evaluations may be done if the values for a participant are, per investigator discretion, minimally outside the designated range. Participants may be included if values are outside the normal range but considered not clinically significant per investigator discretion * Participants with schizophrenia only: Meets diagnostic criteria for schizophrenia or schizoaffective disorder according to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (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 * Participants with schizophrenia only: Has a total Brief Psychiatric Rating Scale (BPRS) score of \<48 with a BPRS score \<4 for #10 (hostility) and #14 (uncooperativeness) at the screening visit * Participants with schizophrenia only: Is in the nonacute phase of their illness and clinically stable for 3 months prior to screening as demonstrated by the following: 1) 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 2) no increase in level of psychiatric care due to worsening of symptoms of schizophrenia for 3 months prior to screening * Participants with schizophrenia only: Has a history of receiving and tolerating antipsychotic medication within the usual dose range employed for schizophrenia * Participants with schizophrenia only: Has a stable living situation * Participants with hypothyroidism, diabetes, high BP, chronic respiratory conditions or other mild forms of these medical conditions could be considered as candidates for study enrollment if their condition is stable * Has regular bowel movements * Participants with schizophrenia only: 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 * Female participants are not pregnant and not breastfeeding, and are not a woman of childbearing potential (WOCBP) or are a WOCBP who agrees to follow contraceptive guidance during the treatment period and for at least 14 days after the last dose of study intervention
Exclusion criteria
* Is a WOCBP who has a positive urine pregnancy test within 48 hours before the first dose of study intervention * Participants with schizophrenia only: 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 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 * Has a substance-induced psychotic disorder or behavioral disturbance thought to be due to substance abuse * Has a DSM-5 defined substance use disorder within 3 months of screening * Has a history of seizure disorder beyond childhood or is receiving treatment with any anticonvulsant to prevent seizures * Has an untreated or uncompensated clinically significant renal, endocrine, hepatic, respiratory, gastrointestinal, psychiatric, neurologic, cardiovascular, hematological, immunological or cerebrovascular disease, malignancy, allergic disease or other chronic and/or degenerative process at screening * Has any clinically significant abnormal laboratory, vital sign (VS), physical examination, or 12-lead safety ECG findings at screening or changes from baseline parameters or, in the opinion of the investigator, would make the participant inappropriate for entry into this study * Has a history of cancer with following exceptions: 1) Adequately treated nonmelanomatous skin carcinoma or carcinoma in situ of the cervix or; 2) Other malignancies which have been successfully treated with appropriate follow up and therefore unlikely to recur for the duration of the study, in the opinion of the investigator and with agreement of the Sponsor * Has a clinically significant history or presence of sick sinus syndrome, first, second, or third-degree AV block, myocardial infarction, pulmonary congestion, cardiac arrhythmia, prolonged corrected QT (QTc) interval, or conduction abnormalities * Has history of repeated or frequent syncope, vasovagal episodes, or epileptic seizures * Has a family history of sudden death * Has a history of any illness that, in the opinion of the study investigator, might confound the results of the study or poses an additional risk to the participant by their participation in the study * For Part 2 participants only: Participant has an estimated glomerular filtration rate (eGFR) \<60 mL/min/1.73 m2 based on the modification of diet in renal disease (MDRD). Participants who have an eGFR or measured creatinine clearance of up to10% below of either 60 milliliter/minute \[mL/min\] (for creatinine clearance) or 60 mL/min/1.73m2 (for eGFR) may be enrolled in the study at the discretion of the investigator * Has a history of significant multiple and/or severe allergies or has had an anaphylactic reaction or significant intolerability to prescription or non-prescription drugs or food * Is positive for Hepatitis B surface antigen, Hepatitis C antibodies or HIV * Had major surgery, donated or lost 1 unit of blood within 4 weeks prior to the prestudy (screening) visit * Healthy participants only: Is mentally or legally incapacitated, has significant emotional problems at the time of prestudy (screening) visit or expected during the conduct of the study or 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 investigator's discretion) * Participants with schizophrenia only: 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 * Healthy participants only: Is at imminent risk of self-harm, based on clinical interview and responses on the CSSRS, 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 in the past 5 years or suicidal behavior in their lifetime * Has received treatment with clozapine for schizophrenia or treatment with monoamine oxidase inhibitors within 3 months of screening or cariprazine within 2 months of screening * Has received a parenteral depot antipsychotic medication within 3 months of screening * Is unable to refrain from the use of co-medication with a moderate or strong inhibiting or inducing effect on cytochrome (CYP3A) and/or cytochrome (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 cytochrome (CYP2B6) * Has participated in another investigational study within 4 weeks (or 5 half-lives, whichever is greater) prior to the prestudy (screening) visit * Has been in incarceration or imprisonment within three months prior to screening * Is a current smoker (healthy participants only) or is a smoker (participants with schizophrenia only) that does not agree to follow the smoking restrictions as defined by the clinical research unit (CRU) * Consumes greater than 3 glasses of alcoholic beverages per day. Participants who consume 4 glasses of alcoholic beverages per day may be enrolled at the discretion of the investigator * Consumes excessive amounts, defined as greater than 6 servings of caffeinated beverages per day * Is a regular user of cannabis, any illicit drugs or has a history of drug abuse within approximately 3 years * Presents any concern by the investigator regarding safe participation in the study or for any other reason the investigator considers the participant inappropriate for participation in the study * Is or has an immediate family member who is investigational site or Sponsor staff directly involved with this study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1 & 2: Number of Participants Who Experienced an Adverse Event (AE) | Up to approximately 27 days | The number of participants with ≥1 AE is reported. 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. |
| Part 1 & 2: Number of Participants Discontinuing Study Treatment Due to an AE | Up to approximately 27 days | The number of participants discontinuing from study treatment due to ≥1 AE is reported. 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Area Under the Concentration Time-curve From Hour 0 to 24 Hours Postdose (AUC0-24) of MK-8189 | Days 1, 2, 4, and Day 7: Predose and 2, 6, 8, 10, 12, 16, and 24 hours postdose | AUC0-24 was determined for participants in Part 1 panels who received MK-8189. |
| Part 1: Concentration 24 Hours Postdose (C24) of MK-8189 | Days 1, 2, 4, and Day 7: Predose and 2, 6, 8, 10, 12, 16, and 24 hours postdose | C24 was determined for participants in Part 1 panels who received MK-8189. |
| Part 1: Maximum Plasma Concentration (Cmax) of MK-8189 | Days 1, 2, 3, 4, and Day 7: Predose and 2, 6, 8, 10, 12, 16, and 24 hours postdose | Cmax was determined for participants in Part 1 panels who received MK-8189. |
| Part 1: Time to Maximum Concentration (Tmax) of MK-8189 | Days 1, 2, 3, 4, and Day 7: Predose and 2, 6, 8, 10, 12, 16, and 24 hours postdose | Tmax was determined for participants in Part 1 panels who received MK-8189. |
| Part 1: Clearance (CL/F) of MK-8189 | Day 7: Predose and 2, 6, 8, 10, 12, 16, and 24 hours postdose | CL/F was determined for participants in Part 1 panels who received MK-8189. |
| Part 1: Apparent Terminal Half-life (t½) of MK-8189 | Day 7: Predose and 2, 6, 8, 10, 12, 16, and 24 hours postdose | t½ was determined for participants in Part 1 panels who received MK-8189. |
| Part 1: Volume of Distribution (Vd/F) of MK-8189 | Day 7: Predose and 2, 6, 8, 10, 12, 16, and 24 hours postdose | Vd/F was determined for participants in Part 1 panels who received MK-8189. |
| Part 2: AUC0-24 of MK-8189 | Days 1, 4, 7, 10, and 13: Predose and 2, 6, 8, 10, 12, 16, and 24 hours postdose | AUC0-24 was determined for participants in Part 2 panels who received MK-8189. |
| Part 2: C24 of MK-8189 | Days 1, 4, 7, 10, and 13: Predose and 2, 6, 8, 10, 12, 16, and 24 hours postdose | C24 was determined for participants in Part 2 panels who received MK-8189. |
| Part 2: Cmax of MK-8189 | Days 1, 4, 7, 10, and 13: Predose and 2, 6, 8, 10, 12, 16, and 24 hours postdose | Cmax was determined for participants in Part 2 panels who received MK-8189. |
| Part 2: Tmax of MK-8189 | Days 1, 4, 7, 10, and 13: Predose and 2, 6, 8, 10, 12, 16, and 24 hours postdose | Tmax was determined for participants in Part 2 panels who received MK-8189. |
| Part 2: CL/F of MK-8189 | Days 10 and 13: Predose and 2, 6, 8, 10, 12, 16, and 24 hours postdose | CL/F was determined for participants in Part 2 panels who received MK-8189. |
| Part 2: t½ of MK-8189 | Days 10 and 13: Predose and 2, 6, 8, 10, 12, 16, and 24 hours postdose | t½ was determined for participants in Part 2 panels who received MK-8189. |
| Part 2: Vd/F of MK-8189 | Days 10 and 13: Predose and 2, 6, 8, 10, 12, 16, and 24 hours postdose | Vd/F was determined for participants in Part 2 panels who received MK-8189. |
Countries
United States
Contacts
STUDY_DIRECTORMedical Director
Merck Sharp & Dohme LLC
Participant flow
Recruitment details
Participants were enrolled at 6 study centers in USA.
Participants by arm
| Arm | Count |
|---|---|
| Part 1, Panel A: MK-8189 16 mg to 24 mg Young adult participants with schizophrenia receive MK-8189 titrated from 16 mg (Days 1 to 3) to 24 mg (Days 4 to 7) QD for 7 days. | 6 |
| Part 1, Panel B: MK-8189 24 mg Young adult participants with schizophrenia receive MK-8189 24 mg QD from Day 1 to Day 7. | 14 |
| Part 1, Panel C: MK-8189 8 mg t0 24 mg Young adult participants with schizophrenia were planned to receive MK-8189 titrated from 8 mg to 24 mg QD over 7 days. | 0 |
| Part 2, Panel D: MK-8189 8 mg to 24 mg Elderly adult participants with schizophrenia receive MK-8189 titrated from 8 mg (Days 1 to 3), to 16 mg (Days 4 to 7), to 24 mg (Days 7 to 13) QD over 13 days. | 12 |
| Part 2, Panel E: MK-8189 16 mg to 24 mg Elderly adult participants with schizophrenia were intended to receive MK-8189 titrated from 16 mg to 24 mg QD, over 10 days. | 0 |
| Part 2, Panel F: MK-8189 8 mg to 24 mg Healthy elderly adult participants receive receive MK-8189 titrated from 8 mg (Days 1 to 3), to 16 mg (Days 4 to 7), to 24 mg (Days 7 to 13) QD over 13 days. | 5 |
| Part 2, Panel G: MK-8189 16 mg to 24 mg Healthy elderly adult participants receive MK-8189 titrated from 16 mg (Days 1 to 3), to 24 mg (Days 4 to 10) QD over 10 days. | 13 |
| Part 1: Placebo Young adult participants with schizophrenia receive placebo matched to MK-8189 QD for 7 days. | 6 |
| Part 2: Placebo Elderly participants with schizophrenia and heathy elderly participants receive placebo matched to MK-8189 for up to 13 days. | 7 |
| Total | 63 |
Baseline characteristics
| Characteristic | Part 1: Placebo | Total | Part 2: Placebo | Part 1, Panel A: MK-8189 16 mg to 24 mg | Part 1, Panel B: MK-8189 24 mg | Part 2, Panel D: MK-8189 8 mg to 24 mg | Part 2, Panel F: MK-8189 8 mg to 24 mg | Part 2, Panel G: MK-8189 16 mg to 24 mg | Part 1, Panel C: MK-8189 8 mg t0 24 mg | Part 2, Panel E: MK-8189 16 mg to 24 mg |
|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 43.3 years STANDARD_DEVIATION 8.6 | 57.4 years STANDARD_DEVIATION 13.1 | 66.3 years STANDARD_DEVIATION 4.7 | 43.5 years STANDARD_DEVIATION 8.8 | 44.9 years STANDARD_DEVIATION 10.8 | 64.2 years STANDARD_DEVIATION 2 | 69.4 years STANDARD_DEVIATION 2.3 | 68.4 years STANDARD_DEVIATION 3.6 | — | — |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 18 Participants | 3 Participants | 2 Participants | 1 Participants | 0 Participants | 3 Participants | 9 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 44 Participants | 4 Participants | 4 Participants | 13 Participants | 11 Participants | 2 Participants | 4 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 34 Participants | 4 Participants | 3 Participants | 11 Participants | 9 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 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 | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 1 Participants | 27 Participants | 3 Participants | 3 Participants | 2 Participants | 2 Participants | 5 Participants | 11 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 1 Participants | 25 Participants | 5 Participants | 1 Participants | 2 Participants | 5 Participants | 1 Participants | 10 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 5 Participants | 38 Participants | 2 Participants | 5 Participants | 12 Participants | 7 Participants | 4 Participants | 3 Participants | 0 Participants | 0 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 |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 17 | 0 / 36 | 0 / 45 | 0 / 13 | 0 / 50 | 0 / 63 |
| other Total, other adverse events | 5 / 17 | 19 / 36 | 26 / 45 | 6 / 13 | 36 / 50 | 42 / 63 |
| serious Total, serious adverse events | 0 / 17 | 0 / 36 | 0 / 45 | 0 / 13 | 0 / 50 | 0 / 63 |
Outcome results
Primary
Part 1 & 2: Number of Participants Discontinuing Study Treatment Due to an AE
The number of participants discontinuing from study treatment due to ≥1 AE is reported. 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.
Time frame: Up to approximately 27 days
Population: All randomized and treated participants are included.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1, Panel A: MK-8189 16 mg to 24 mg | Part 1 & 2: Number of Participants Discontinuing Study Treatment Due to an AE | 0 Participants |
| Part 1, Panel B: MK-8189 24 mg | Part 1 & 2: Number of Participants Discontinuing Study Treatment Due to an AE | 1 Participants |
| Part 2, Panel D: MK-8189 8 mg to 24 mg | Part 1 & 2: Number of Participants Discontinuing Study Treatment Due to an AE | 2 Participants |
| Part 2, Panel F: MK-8189 8 mg to 24 mg | Part 1 & 2: Number of Participants Discontinuing Study Treatment Due to an AE | 1 Participants |
| Part 2, Panel G: MK-8189 16 mg to 24 mg | Part 1 & 2: Number of Participants Discontinuing Study Treatment Due to an AE | 3 Participants |
| Part 1: Placebo | Part 1 & 2: Number of Participants Discontinuing Study Treatment Due to an AE | 0 Participants |
| Part 2: Placebo | Part 1 & 2: Number of Participants Discontinuing Study Treatment Due to an AE | 1 Participants |
Primary
Part 1 & 2: Number of Participants Who Experienced an Adverse Event (AE)
The number of participants with ≥1 AE is reported. 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.
Time frame: Up to approximately 27 days
Population: All randomized and treated participants are included.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1, Panel A: MK-8189 16 mg to 24 mg | Part 1 & 2: Number of Participants Who Experienced an Adverse Event (AE) | 4 Participants |
| Part 1, Panel B: MK-8189 24 mg | Part 1 & 2: Number of Participants Who Experienced an Adverse Event (AE) | 9 Participants |
| Part 2, Panel D: MK-8189 8 mg to 24 mg | Part 1 & 2: Number of Participants Who Experienced an Adverse Event (AE) | 3 Participants |
| Part 2, Panel F: MK-8189 8 mg to 24 mg | Part 1 & 2: Number of Participants Who Experienced an Adverse Event (AE) | 2 Participants |
| Part 2, Panel G: MK-8189 16 mg to 24 mg | Part 1 & 2: Number of Participants Who Experienced an Adverse Event (AE) | 8 Participants |
| Part 1: Placebo | Part 1 & 2: Number of Participants Who Experienced an Adverse Event (AE) | 2 Participants |
| Part 2: Placebo | Part 1 & 2: Number of Participants Who Experienced an Adverse Event (AE) | 4 Participants |
Secondary
Part 1: Apparent Terminal Half-life (t½) of MK-8189
t½ was determined for participants in Part 1 panels who received MK-8189.
Time frame: Day 7: Predose and 2, 6, 8, 10, 12, 16, and 24 hours postdose
Population: Part 1 participants who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1, Panel A: MK-8189 16 mg to 24 mg | Part 1: Apparent Terminal Half-life (t½) of MK-8189 | 7.99 Hours | Geometric Coefficient of Variation 15.6 |
| Part 1, Panel B: MK-8189 24 mg | Part 1: Apparent Terminal Half-life (t½) of MK-8189 | 8.68 Hours | Geometric Coefficient of Variation 26.8 |
Secondary
Part 1: Area Under the Concentration Time-curve From Hour 0 to 24 Hours Postdose (AUC0-24) of MK-8189
AUC0-24 was determined for participants in Part 1 panels who received MK-8189.
Time frame: Days 1, 2, 4, and Day 7: Predose and 2, 6, 8, 10, 12, 16, and 24 hours postdose
Population: Part 1 participants who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Part 1, Panel A: MK-8189 16 mg to 24 mg | Part 1: Area Under the Concentration Time-curve From Hour 0 to 24 Hours Postdose (AUC0-24) of MK-8189 | 10500 hr*nmol/L |
| Part 1, Panel B: MK-8189 24 mg | Part 1: Area Under the Concentration Time-curve From Hour 0 to 24 Hours Postdose (AUC0-24) of MK-8189 | 21200 hr*nmol/L |
| Part 1, Panel C: MK-8189 8 mg t0 24 mg | Part 1: Area Under the Concentration Time-curve From Hour 0 to 24 Hours Postdose (AUC0-24) of MK-8189 | 22700 hr*nmol/L |
| Part 2, Panel D: MK-8189 8 mg to 24 mg | Part 1: Area Under the Concentration Time-curve From Hour 0 to 24 Hours Postdose (AUC0-24) of MK-8189 | 12500 hr*nmol/L |
| Part 2, Panel E: MK-8189 16 mg to 24 mg | Part 1: Area Under the Concentration Time-curve From Hour 0 to 24 Hours Postdose (AUC0-24) of MK-8189 | 17600 hr*nmol/L |
| Part 2, Panel F: MK-8189 8 mg to 24 mg | Part 1: Area Under the Concentration Time-curve From Hour 0 to 24 Hours Postdose (AUC0-24) of MK-8189 | 20500 hr*nmol/L |
Secondary
Part 1: Clearance (CL/F) of MK-8189
CL/F was determined for participants in Part 1 panels who received MK-8189.
Time frame: Day 7: Predose and 2, 6, 8, 10, 12, 16, and 24 hours postdose
Population: Part 1 participants who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1, Panel A: MK-8189 16 mg to 24 mg | Part 1: Clearance (CL/F) of MK-8189 | 3.21 L/hr | Geometric Coefficient of Variation 36.5 |
| Part 1, Panel B: MK-8189 24 mg | Part 1: Clearance (CL/F) of MK-8189 | 3.22 L/hr | Geometric Coefficient of Variation 48.1 |
Secondary
Part 1: Concentration 24 Hours Postdose (C24) of MK-8189
C24 was determined for participants in Part 1 panels who received MK-8189.
Time frame: Days 1, 2, 4, and Day 7: Predose and 2, 6, 8, 10, 12, 16, and 24 hours postdose
Population: Part 1 participants who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Part 1, Panel A: MK-8189 16 mg to 24 mg | Part 1: Concentration 24 Hours Postdose (C24) of MK-8189 | 615 nmol/L |
| Part 1, Panel B: MK-8189 24 mg | Part 1: Concentration 24 Hours Postdose (C24) of MK-8189 | 322 nmol/L |
| Part 1, Panel C: MK-8189 8 mg t0 24 mg | Part 1: Concentration 24 Hours Postdose (C24) of MK-8189 | 669 nmol/L |
| Part 2, Panel D: MK-8189 8 mg to 24 mg | Part 1: Concentration 24 Hours Postdose (C24) of MK-8189 | 565 nmol/L |
| Part 2, Panel E: MK-8189 16 mg to 24 mg | Part 1: Concentration 24 Hours Postdose (C24) of MK-8189 | 567 nmol/L |
| Part 2, Panel F: MK-8189 8 mg to 24 mg | Part 1: Concentration 24 Hours Postdose (C24) of MK-8189 | 666 nmol/L |
Secondary
Part 1: Maximum Plasma Concentration (Cmax) of MK-8189
Cmax was determined for participants in Part 1 panels who received MK-8189.
Time frame: Days 1, 2, 3, 4, and Day 7: Predose and 2, 6, 8, 10, 12, 16, and 24 hours postdose
Population: Part 1 participants who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Part 1, Panel A: MK-8189 16 mg to 24 mg | Part 1: Maximum Plasma Concentration (Cmax) of MK-8189 | 700 nmol/L |
| Part 1, Panel B: MK-8189 24 mg | Part 1: Maximum Plasma Concentration (Cmax) of MK-8189 | 1220 nmol/L |
| Part 1, Panel C: MK-8189 8 mg t0 24 mg | Part 1: Maximum Plasma Concentration (Cmax) of MK-8189 | 1270 nmol/L |
| Part 2, Panel D: MK-8189 8 mg to 24 mg | Part 1: Maximum Plasma Concentration (Cmax) of MK-8189 | 941 nmol/L |
| Part 2, Panel E: MK-8189 16 mg to 24 mg | Part 1: Maximum Plasma Concentration (Cmax) of MK-8189 | 996 nmol/L |
| Part 2, Panel F: MK-8189 8 mg to 24 mg | Part 1: Maximum Plasma Concentration (Cmax) of MK-8189 | 956 nmol/L |
| Part 2, Panel G: MK-8189 16 mg to 24 mg | Part 1: Maximum Plasma Concentration (Cmax) of MK-8189 | 1200 nmol/L |
Secondary
Part 1: Time to Maximum Concentration (Tmax) of MK-8189
Tmax was determined for participants in Part 1 panels who received MK-8189.
Time frame: Days 1, 2, 3, 4, and Day 7: Predose and 2, 6, 8, 10, 12, 16, and 24 hours postdose
Population: Part 1 participants who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1, Panel A: MK-8189 16 mg to 24 mg | Part 1: Time to Maximum Concentration (Tmax) of MK-8189 | 19.97 Hours |
| Part 1, Panel B: MK-8189 24 mg | Part 1: Time to Maximum Concentration (Tmax) of MK-8189 | 16.00 Hours |
| Part 1, Panel C: MK-8189 8 mg t0 24 mg | Part 1: Time to Maximum Concentration (Tmax) of MK-8189 | 16.00 Hours |
| Part 2, Panel D: MK-8189 8 mg to 24 mg | Part 1: Time to Maximum Concentration (Tmax) of MK-8189 | 16.00 Hours |
| Part 2, Panel E: MK-8189 16 mg to 24 mg | Part 1: Time to Maximum Concentration (Tmax) of MK-8189 | 8.00 Hours |
| Part 2, Panel F: MK-8189 8 mg to 24 mg | Part 1: Time to Maximum Concentration (Tmax) of MK-8189 | 8.00 Hours |
| Part 2, Panel G: MK-8189 16 mg to 24 mg | Part 1: Time to Maximum Concentration (Tmax) of MK-8189 | 11.03 Hours |
Secondary
Part 1: Volume of Distribution (Vd/F) of MK-8189
Vd/F was determined for participants in Part 1 panels who received MK-8189.
Time frame: Day 7: Predose and 2, 6, 8, 10, 12, 16, and 24 hours postdose
Population: Part 1 participants who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1, Panel A: MK-8189 16 mg to 24 mg | Part 1: Volume of Distribution (Vd/F) of MK-8189 | 37.03 Liters | Geometric Coefficient of Variation 28.5 |
| Part 1, Panel B: MK-8189 24 mg | Part 1: Volume of Distribution (Vd/F) of MK-8189 | 40.31 Liters | Geometric Coefficient of Variation 40.4 |
Secondary
Part 2: AUC0-24 of MK-8189
AUC0-24 was determined for participants in Part 2 panels who received MK-8189.
Time frame: Days 1, 4, 7, 10, and 13: Predose and 2, 6, 8, 10, 12, 16, and 24 hours postdose
Population: Part 2 participants who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Part 1, Panel A: MK-8189 16 mg to 24 mg | Part 2: AUC0-24 of MK-8189 | 4600 hr*nmol/L |
| Part 1, Panel B: MK-8189 24 mg | Part 2: AUC0-24 of MK-8189 | 12400 hr*nmol/L |
| Part 1, Panel C: MK-8189 8 mg t0 24 mg | Part 2: AUC0-24 of MK-8189 | 17100 hr*nmol/L |
| Part 2, Panel D: MK-8189 8 mg to 24 mg | Part 2: AUC0-24 of MK-8189 | 24000 hr*nmol/L |
| Part 2, Panel E: MK-8189 16 mg to 24 mg | Part 2: AUC0-24 of MK-8189 | 5930 hr*nmol/L |
| Part 2, Panel F: MK-8189 8 mg to 24 mg | Part 2: AUC0-24 of MK-8189 | 13800 hr*nmol/L |
| Part 2, Panel G: MK-8189 16 mg to 24 mg | Part 2: AUC0-24 of MK-8189 | 23600 hr*nmol/L |
| Part 1: Placebo | Part 2: AUC0-24 of MK-8189 | 27800 hr*nmol/L |
| Part 2: Placebo | Part 2: AUC0-24 of MK-8189 | 9860 hr*nmol/L |
| Part 2, Panel G: MK-8189 24 mg | Part 2: AUC0-24 of MK-8189 | 23500 hr*nmol/L |
| Part 2, Panel G: MK-8189 24 mg Day 10 | Part 2: AUC0-24 of MK-8189 | 26800 hr*nmol/L |
Secondary
Part 2: C24 of MK-8189
C24 was determined for participants in Part 2 panels who received MK-8189.
Time frame: Days 1, 4, 7, 10, and 13: Predose and 2, 6, 8, 10, 12, 16, and 24 hours postdose
Population: Part 2 participants who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Part 1, Panel A: MK-8189 16 mg to 24 mg | Part 2: C24 of MK-8189 | 302 nmol/L |
| Part 1, Panel B: MK-8189 24 mg | Part 2: C24 of MK-8189 | 508 nmol/L |
| Part 1, Panel C: MK-8189 8 mg t0 24 mg | Part 2: C24 of MK-8189 | 637 nmol/L |
| Part 2, Panel D: MK-8189 8 mg to 24 mg | Part 2: C24 of MK-8189 | 926 nmol/L |
| Part 2, Panel E: MK-8189 16 mg to 24 mg | Part 2: C24 of MK-8189 | 349 nmol/L |
| Part 2, Panel F: MK-8189 8 mg to 24 mg | Part 2: C24 of MK-8189 | 612 nmol/L |
| Part 2, Panel G: MK-8189 16 mg to 24 mg | Part 2: C24 of MK-8189 | 927 nmol/L |
| Part 1: Placebo | Part 2: C24 of MK-8189 | 1260 nmol/L |
| Part 2: Placebo | Part 2: C24 of MK-8189 | 569 nmol/L |
| Part 2, Panel G: MK-8189 24 mg | Part 2: C24 of MK-8189 | 885 nmol/L |
| Part 2, Panel G: MK-8189 24 mg Day 10 | Part 2: C24 of MK-8189 | 1090 nmol/L |
Secondary
Part 2: CL/F of MK-8189
CL/F was determined for participants in Part 2 panels who received MK-8189.
Time frame: Days 10 and 13: Predose and 2, 6, 8, 10, 12, 16, and 24 hours postdose
Population: Part 2 participants who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1, Panel A: MK-8189 16 mg to 24 mg | Part 2: CL/F of MK-8189 | 2.67 L/hr | Geometric Coefficient of Variation 28.5 |
| Part 1, Panel B: MK-8189 24 mg | Part 2: CL/F of MK-8189 | 2.18 L/hr | Geometric Coefficient of Variation 57.3 |
| Part 1, Panel C: MK-8189 8 mg t0 24 mg | Part 2: CL/F of MK-8189 | 2.34 L/hr | Geometric Coefficient of Variation 29.8 |
Secondary
Part 2: Cmax of MK-8189
Cmax was determined for participants in Part 2 panels who received MK-8189.
Time frame: Days 1, 4, 7, 10, and 13: Predose and 2, 6, 8, 10, 12, 16, and 24 hours postdose
Population: Part 2 participants who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Part 1, Panel A: MK-8189 16 mg to 24 mg | Part 2: Cmax of MK-8189 | 326 nmol/L |
| Part 1, Panel B: MK-8189 24 mg | Part 2: Cmax of MK-8189 | 680 nmol/L |
| Part 1, Panel C: MK-8189 8 mg t0 24 mg | Part 2: Cmax of MK-8189 | 918 nmol/L |
| Part 2, Panel D: MK-8189 8 mg to 24 mg | Part 2: Cmax of MK-8189 | 1250 nmol/L |
| Part 2, Panel E: MK-8189 16 mg to 24 mg | Part 2: Cmax of MK-8189 | 373 nmol/L |
| Part 2, Panel F: MK-8189 8 mg to 24 mg | Part 2: Cmax of MK-8189 | 817 nmol/L |
| Part 2, Panel G: MK-8189 16 mg to 24 mg | Part 2: Cmax of MK-8189 | 1300 nmol/L |
| Part 1: Placebo | Part 2: Cmax of MK-8189 | 1330 nmol/L |
| Part 2: Placebo | Part 2: Cmax of MK-8189 | 644 nmol/L |
| Part 2, Panel G: MK-8189 24 mg | Part 2: Cmax of MK-8189 | 1280 nmol/L |
| Part 2, Panel G: MK-8189 24 mg Day 10 | Part 2: Cmax of MK-8189 | 1290 nmol/L |
Secondary
Part 2: t½ of MK-8189
t½ was determined for participants in Part 2 panels who received MK-8189.
Time frame: Days 10 and 13: Predose and 2, 6, 8, 10, 12, 16, and 24 hours postdose
Population: Part 2 participants who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1, Panel A: MK-8189 16 mg to 24 mg | Part 2: t½ of MK-8189 | 13.98 Hours | Geometric Coefficient of Variation 51 |
| Part 1, Panel B: MK-8189 24 mg | Part 2: t½ of MK-8189 | 8.90 Hours | Geometric Coefficient of Variation 33.4 |
| Part 1, Panel C: MK-8189 8 mg t0 24 mg | Part 2: t½ of MK-8189 | 9.99 Hours | Geometric Coefficient of Variation 27.4 |
Secondary
Part 2: Tmax of MK-8189
Tmax was determined for participants in Part 2 panels who received MK-8189.
Time frame: Days 1, 4, 7, 10, and 13: Predose and 2, 6, 8, 10, 12, 16, and 24 hours postdose
Population: Part 2 participants who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1, Panel A: MK-8189 16 mg to 24 mg | Part 2: Tmax of MK-8189 | 23.90 Hours |
| Part 1, Panel B: MK-8189 24 mg | Part 2: Tmax of MK-8189 | 14.00 Hours |
| Part 1, Panel C: MK-8189 8 mg t0 24 mg | Part 2: Tmax of MK-8189 | 16.02 Hours |
| Part 2, Panel D: MK-8189 8 mg to 24 mg | Part 2: Tmax of MK-8189 | 10.08 Hours |
| Part 2, Panel E: MK-8189 16 mg to 24 mg | Part 2: Tmax of MK-8189 | 16.10 Hours |
| Part 2, Panel F: MK-8189 8 mg to 24 mg | Part 2: Tmax of MK-8189 | 16.07 Hours |
| Part 2, Panel G: MK-8189 16 mg to 24 mg | Part 2: Tmax of MK-8189 | 15.97 Hours |
| Part 1: Placebo | Part 2: Tmax of MK-8189 | 16.00 Hours |
| Part 2: Placebo | Part 2: Tmax of MK-8189 | 16.17 Hours |
| Part 2, Panel G: MK-8189 24 mg | Part 2: Tmax of MK-8189 | 11.99 Hours |
| Part 2, Panel G: MK-8189 24 mg Day 10 | Part 2: Tmax of MK-8189 | 15.88 Hours |
Secondary
Part 2: Vd/F of MK-8189
Vd/F was determined for participants in Part 2 panels who received MK-8189.
Time frame: Days 10 and 13: Predose and 2, 6, 8, 10, 12, 16, and 24 hours postdose
Population: Part 2 participants who comply with the protocol sufficiently to ensure that generated data will be likely to exhibit the effects of treatment, according to the underlying scientific model.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1, Panel A: MK-8189 16 mg to 24 mg | Part 2: Vd/F of MK-8189 | 55.23 Liters | Geometric Coefficient of Variation 52.3 |
| Part 1, Panel B: MK-8189 24 mg | Part 2: Vd/F of MK-8189 | 27.94 Liters | Geometric Coefficient of Variation 57.2 |
| Part 1, Panel C: MK-8189 8 mg t0 24 mg | Part 2: Vd/F of MK-8189 | 32.91 Liters | Geometric Coefficient of Variation 26.8 |