Schizophrenia
Conditions
Brief summary
The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics (PK) of single ascending intramuscular doses of MK-5720, and the safety and tolerability of multiple once-daily oral doses of MK-8189, in participants with schizophrenia. The primary study hypothesis is that the administration of MK-5720 is safe and well tolerated.
Detailed description
In Period 1, participants receive once-daily MK-8189 for 7 days, followed by a 72-hour washout. In Period 2, participants receive a single dose of MK-5720.
Interventions
DRUGMK-5720
IM injection
DRUGPlacebo to MK-5720
Placebo IM Injection matched to MK-5720
DRUGMK-8189
Oral Tablet
Placebo oral tablet matched to MK-8189
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
Double blind
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
The main inclusion criteria include but are not limited to the following: * 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 * Has a history of receiving and tolerating antipsychotics medication within the usual dose range employed for schizophrenia * Can discontinue the use of all antipsychotic medication at least 5 days or 3 half-lives (which ever in longer) prior to the start of the treatment period and during the study
Exclusion criteria
The main
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| t1/2 of MK-8189 | Predose, 0.5, 1, 2, 4, 6, 24, 48, 96, 120, 144, 168, 192, 216, 264, 288, 312, 336, 360, 384, 432, 456, 504, 672, 840, 1008, 1176, and 1320 hours postdose | t1/2 is defined as the time required to divide plasma concentration of MK-8189 (a metabolite of MK-5720) by half after reaching pseudo-equilibrium. Blood samples were collected at specified intervals for the determination of Half-life (t1/2) for MK-8198 following a single dose administration of MK-5720 in Period 2. Per protocol, this outcome measure has been reported by panel and dose. |
| Number of Participants Who Discontinue Study Due to an AE in Period 1 | Up to approximately 10 days | An adverse event (AE) is 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. The number of participants who discontinued study treatment due to an AE is reported here for participants in Period 1. Per protocol, this outcome measure has been reported by panel and dose. As specified by the protocol, Period 2 has been analyzed separately and reported later in the record. |
| Number of Participants Who Discontinue Study Due to an AE in Period 2 | Up to approximately 72 days | An adverse event (AE) is 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. The number of participants who discontinued study treatment due to an AE is reported here for participants in Period 2. Per protocol, this outcome measure has been reported by panel and dose. As specified by the protocol, Period 1 has been analyzed separately and reported earlier in the record. |
| Area Under the Concentration-Time Curve From Time 0 to Last Quantifiable Concentration (AUC0-last) of MK-5720 | Predose, 0.5, 1, 2, 4, 6, 24, 48, 96, 120, 144, 168, 192, 216, 264, 288, 312, 336, 360, 384, 432, 456, 504, 672, 840, 1008, 1176, and 1320 hours postdose | AUC0-last was defined as the area under the concentration-time curve from time zero to time of last measurable concentration of MK-5720. Blood samples were collected at specified intervals were used to estimate AUC0-last following a single dose administration of MK-5720 in Period 2. Per protocol, this outcome measure has been reported by panel and dose. |
| Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC-inf) of MK-5720 | Predose, 0.5, 1, 2, 4, 6, 24, 48, 96, 120, 144, 168, 192, 216, 264, 288, 312, 336, 360, 384, 432, 456, 504, 672, 840, 1008, 1176, and 1320 hours postdose | AUC0-inf is defined as the area under concentration-time curve of MK-5720 from time zero to infinity. Blood samples were collected at specified intervals for the determination of AUC-inf following a single dose administration of MK-5720 in Period 2. Per protocol, this outcome measure has been reported by panel and dose. |
| Maximum Serum Concentration (Cmax) of MK-5720 | Predose, 0.5, 1, 2, 4, 6, 24, 48, 96, 120, 144, 168, 192, 216, 264, 288, 312, 336, 360, 384, 432, 456, 504, 672, 840, 1008, 1176, and 1320 hours postdose | Cmax is defined as the maximum concentration of MK-5720 reached. Blood samples were collected at specified intervals for the determination of Cmax following a single dose administration of MK-5720 in Period 2. Per protocol, this outcome measure has been reported by panel and dose. |
| Time to Maximum Concentration (Tmax) of MK-5720 | Predose, 0.5, 1, 2, 4, 6, 24, 48, 96, 120, 144, 168, 192, 216, 264, 288, 312, 336, 360, 384, 432, 456, 504, 672, 840, 1008, 1176, and 1320 hours postdose | Tmax is defined as the time to maximum concentration of MK-5720 reached. Blood samples were collected at specified intervals for the determination of Tmax following a single dose administration of MK-5720 in Period 2. Per protocol, this outcome measure has been reported by panel and dose. |
| Apparent Clearance (CL/F) of MK-5720 | Predose, 0.5, 1, 2, 4, 6, 24, 48, 96, 120, 144, 168, 192, 216, 264, 288, 312, 336, 360, 384, 432, 456, 504, 672, 840, 1008, 1176, and 1320 hours postdose | CL/F is the rate at which the MK-5720 is completely removed from plasma. Blood samples were collected at specified intervals for the determination of CL/F following a single dose administration of MK-5720 in Period 2. Per protocol, this outcome measure has been reported by panel and dose. |
| Apparent Volume of Distribution (Vz/F) of MK-5720 | Predose, 0.5, 1, 2, 4, 6, 24, 48, 96, 120, 144, 168, 192, 216, 264, 288, 312, 336, 360, 384, 432, 456, 504, 672, 840, 1008, 1176, and 1320 hours postdose | Vz/F is the apparent volume of distribution of MK-5720. Blood samples were collected at specified intervals for the determination of Vz/F following a single dose administration of MK-5720 in Period 2. Per protocol, this outcome measure has been reported by panel and dose. |
| Apparent Terminal Half-life (t1/2) of MK-5720 | Predose, 0.5, 1, 2, 4, 6, 24, 48, 96, 120, 144, 168, 192, 216, 264, 288, 312, 336, 360, 384, 432, 456, 504, 672, 840, 1008, 1176, and 1320 hours postdose | t1/2 is defined as the time required to divide plasma concentration of MK-5720 by half after reaching pseudo-equilibrium. Blood samples were collected at specified intervals for the determination t1/2 following a single dose administration of MK-5720 in Period 2. Per protocol, this outcome measure has been reported by panel and dose. |
| Area Under the Concentration-Time Curve From Time 0 to 28 Days (AUC0-28d) of MK-8189 | Predose, 0.5, 1, 2, 4, 6, 24, 48, 96, 120, 144, 168, 192, 216, 264, 288, 312, 336, 360, 384, 432, 456, 504, and 672 hours postdose | AUC0-28d is defined as the area under the concentration-time curve from time zero to 28 days of MK-8189 (a metabolite of MK-5720). Blood samples were collected at specified intervals for the determination of AUC0-28d for MK-8189 following a single dose administration of MK-5720 in Period 2. Per protocol, this outcome measure has been reported by panel and dose. |
| AUC0-inf of MK-8189 | Predose, 0.5, 1, 2, 4, 6, 24, 48, 96, 120, 144, 168, 192, 216, 264, 288, 312, 336, 360, 384, 432, 456, 504, 672, 840, 1008, 1176, and 1320 hours postdose | AUC0-inf is defined as the area under concentration-time curve from time zero to infinity of MK-8189 (a metabolite of MK-5720). Blood samples were collected at specified intervals for the determination of AUC0-inf for MK-8198 following a single dose administration of MK-5720 in Period 2. Per protocol, this outcome measure has been reported by panel and dose. |
| Cmax of MK-8189 | Predose, 0.5, 1, 2, 4, 6, 24, 48, 96, 120, 144, 168, 192, 216, 264, 288, 312, 336, 360, 384, 432, 456, 504, 672, 840, 1008, 1176, and 1320 hours postdose | Cmax is defined as the maximum concentration of MK-8189 (a metabolite of MK-5720) reached. Blood samples were collected at specified intervals for the determination of Cmax for MK-8198 following a single dose administration of MK-5720 in Period 2. Per protocol, this outcome measure has been reported by panel and dose. |
| Tmax of MK-8189 | Predose, 0.5, 1, 2, 4, 6, 24, 48, 96, 120, 144, 168, 192, 216, 264, 288, 312, 336, 360, 384, 432, 456, 504, 672, 840, 1008, 1176, and 1320 hours postdose | Tmax is defined as the time to maximum concentration of MK-8189 (a metabolite of MK-5720). Blood samples were collected at specified intervals for the determination of Tmax for MK-8198 following a single dose administration of MK-5720 in Period 2. Per protocol, this outcome measure has been reported by panel and dose. |
| Concentration at Day 28 (C28d) of MK-8189 | Predose, 0.5, 1, 2, 4, 6, 24, 48, 96, 120, 144, 168, 192, 216, 264, 288, 312, 336, 360, 384, 432, 456, 504, and 672 hours postdose | C28d is defined as the maximum concentration from time zero to 28 days of MK-8189 (a metabolite of MK-5720). Blood samples were collected at specified intervals for the determination of C28d for MK-8198 following a single dose administration of MK-5720 in Period 2. Per protocol, this outcome measure has been reported by panel and dose. In cases where C28d values were below the limit of quantitation, geometric mean was not calculable and indicated as NA. |
| CL/F of MK-8189 | Predose, 0.5, 1, 2, 4, 6, 24, 48, 96, 120, 144, 168, 192, 216, 264, 288, 312, 336, 360, 384, 432, 456, 504, 672, 840, 1008, 1176, and 1320 hours postdose | CL/F is the rate at which the MK-8189 (a metabolite of MK-5720) is completely removed from plasma. Blood samples were collected at specified intervals for the determination of CL/F for MK-8198 following a single dose administration of MK-5720 in Period 2. Per protocol, this outcome measure has been reported by panel and dose. |
| Vz/F of MK-8189 | Predose, 0.5, 1, 2, 4, 6, 24, 48, 96, 120, 144, 168, 192, 216, 264, 288, 312, 336, 360, 384, 432, 456, 504, 672, 840, 1008, 1176, and 1320 hours postdose | Vz/F is the apparent volume of distribution of MK-8189 (a metabolite of MK-5720). Blood samples were collected at specified intervals for the determination of Vz/F for MK-8198 following a single dose administration of MK-5720 in Period 2. Per protocol, this outcome measure has been reported by panel and dose. |
| Number of Participants Who Experience ≥1 Adverse Event (AE) in Period 1 | Up to approximately 10 days | An adverse event (AE) is 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. The number of participants who experienced one or more AEs is reported here for participants in Period 1. Per protocol, this outcome measure has been reported by panel and dose. As specified by the protocol, Period 2 has been analyzed separately and reported later in the record. |
| Number of Participants Who Experience ≥1 AE(s) in Period 2 | Up to approximately 72 days | An adverse event (AE) is 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. The number of participants who experienced one or more AEs is reported here for participants in Period 2. Per protocol, this outcome measure has been reported by panel and dose. As specified by the protocol, Period 1 has been analyzed separately and reported earlier in the record. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Panels C, D, E, and F: AUC0-28d of MK-8189 in Gluteal Muscle Versus AUC0-28 of MK-8189 in Deltoid Muscle | Predose, 0.5, 1, 2, 4, 6, 24, 48, 96, 120, 144, 168, 192, 216, 264, 288, 312, 336, 360, 384, 432, 456, 504, and 672 hours postdose | Blood samples were to be collected at specified intervals for the determination of AUC0-28 of MK-8189 (a metabolite of MK-5720) after administration of MK-5720 (Period 2) in the gluteal muscle and deltoid muscle. AUC0-28 is defined as the area under the plasma concentration-time curve from time zero to 28 days of MK-8189. Per protocol, this outcome measure is specific for Panels C, D, E, and F, and data was not planned or collected for Panels A or B. Panels C, D, E, and F were not enrolled, and no data was collected for this outcome measure. |
| Panels C, D, E, and F: AUC0-inf of MK-8189 in Gluteal Muscle Versus AUC0-inf of MK-8189 in Deltoid Muscle | Predose, 0.5, 1, 2, 4, 6, 24, 48, 96, 120, 144, 168, 192, 216, 264, 288, 312, 336, 360, 384, 432, 456, 504, 672, 840, 1008, 1176, and 1320 hours postdose | Blood samples were to be collected at specified intervals for the determination of AUC-inf of MK-8189 (a metabolite of MK-5720) after administration of MK-5720 (Period 2) in the gluteal muscle and deltoid muscle. AUC0-inf is defined as the area under concentration-time curve from time zero to infinity of MK-8189. Per protocol, this outcome measure is specific for Panels C, D, E, and F, and data was not planned or collected for Panels A or B. Panels C, D, E, and F were not enrolled, and no data was collected for this outcome measure. |
| Panels C, D, E, and F: Cmax of MK-8189 in Gluteal Muscle Versus Cmax of MK-8189 in Deltoid Muscle | Predose, 0.5, 1, 2, 4, 6, 24, 48, 96, 120, 144, 168, 192, 216, 264, 288, 312, 336, 360, 384, 432, 456, 504, 672, 840, 1008, 1176, and 1320 hours postdose | Blood samples were to be collected at specified intervals for the determination of Cmax of MK-8189 (a metabolite of MK-5720) after administration of MK-5720 (Period 2) in the gluteal muscle and deltoid muscle. Cmax is defined as the maximum concentration of MK-8189. Per protocol, this outcome measure is specific for Panels C, D, E, and F, and data was not planned or collected for Panels A or B. Panels C, D, E, and F were not enrolled, and no data was collected for this outcome measure. |
| Panels C, D, E, and F: Tmax of MK-8189 in Gluteal Muscle Versus Tmax of MK-8189 in Deltoid Muscle | Predose, 0.5, 1, 2, 4, 6, 24, 48, 96, 120, 144, 168, 192, 216, 264, 288, 312, 336, 360, 384, 432, 456, 504, 672, 840, 1008, 1176, 1320 hours postdose | Blood samples were to be collected at specified intervals for determination of Tmax of MK-8189 (a metabolite of MK-5720) after administration of MK-5720 (Period 2) in the gluteal muscle and deltoid muscle. Tmax is defined as the time to maximum concentration of MK-8189. Per protocol, this outcome measure is specific for Panels C, D, E, and F, and data was not planned or collected for Panels A or B. Panels C, D, E, and F were not enrolled, and no data was collected for this outcome measure. |
| Panels C, D, E, and F: C28d of MK-8189 in Gluteal Muscle Versus C28d in Deltoid Muscle | Predose, 0.5, 1, 2, 4, 6, 24, 48, 96, 120, 144, 168, 192, 216, 264, 288, 312, 336, 360, 384, 432, 456, 504, and 672 hours postdose | Blood samples were to be collected at specified intervals for the determination of C28d of MK-8189 (a metabolite of MK-5720) after administration of MK-5720 (Period 2) in the gluteal muscle and deltoid muscle. C28d is defined as the maximum concentration from time zero to 28 days of MK-8189. Per protocol, this outcome measure is specific for Panels C, D, E, and F, and data was not planned or collected for Panels A or B. Panels C, D, E, and F were not enrolled, and no data was collected for this outcome measure. |
| Panels C, D, E, and F: CL/F of MK-8189 in Gluteal Muscle Versus CL/F in Deltoid Muscle | Predose, 0.5, 1, 2, 4, 6, 24, 48, 96, 120, 144, 168, 192, 216, 264, 288, 312, 336, 360, 384, 432, 456, 504, 672, 840, 1008, 1176, and 1320 hours postdose | Blood samples were to be collected at specified intervals for the determination of CL/F of MK-8189 (a metabolite of MK-5720) after administration of MK-5720 (Period 2) in the gluteal muscle and deltoid muscle. CL/F is the rate at which the MK-8189 is completely removed from plasma. Per protocol, this outcome measure is specific for Panels C, D, E, and F, and data was not planned or collected for Panels A or B. Panels C, D, E, and F were not enrolled, and no data was collected for this outcome measure. |
| Panels C, D, E, and F: Vz/F of MK-8189 in Gluteal Muscle Versus Vz/F of MK-8189 in Deltoid Muscle | Predose, 0.5, 1, 2, 4, 6, 24, 48, 96, 120, 144, 168, 192, 216, 264, 288, 312, 336, 360, 384, 432, 456, 504, 672, 840, 1008, 1176, and 1320 hours postdose | Blood samples were to be collected at specified intervals for the determination of distribution of MK-8189 (metabolite of MK-5720) after administration of MK-5720 (Period 2) in the gluteal muscle versus deltoid muscle. Vz/F is the apparent volume of distribution of MK-8189. Per protocol, this outcome measure is specific for Panels C, D, E, and F, and data was not planned or collected for Panels A or B. Panels C, D, E, and F were not enrolled, and no data was collected for this outcome measure. |
| Panels C, D, E, and F: t1/2 of MK-8189 in Gluteal Muscle Versus t1/2 of MK-8189 in Deltoid Muscle | Predose, 0.5, 1, 2, 4, 6, 24, 48, 96, 120, 144, 168, 192, 216, 264, 288, 312, 336, 360, 384, 432, 456, 504, 672, 840, 1008, 1176, and 1320 hours postdose | Blood samples were to be collected at specified intervals for the determination of t1/2 of MK-8189 (metabolite of MK-5720) after administration of MK-5720 (Period 2) in the gluteal muscle and deltoid muscle. t1/2 is defined as the time required divide plasma concentration of MK-8189 (metabolite of MK-5720) by half after reaching pseudo-equilibrium. Per protocol, this outcome measure is specific for Panels C, D, E, and F, and data was not planned or collected for Panels A or B. Panels C, D, E, and F were not enrolled, and no data was collected for this outcome measure. |
| Panels C, D, E, and F: AUC0-last of MK 5720 in Gluteal Muscle Versus AUC0-last of MK-5720 in Deltoid Muscle | Predose, 0.5, 1, 2, 4, 6, 24, 48, 96, 120, 144, 168, 192, 216, 264, 288, 312, 336, 360, 384, 432, 456, 504, 672, 840, 1008, 1176, and 1320 hours postdose | Blood samples were to be collected at specified intervals for the determination of AUC0-last after administration of MK-5720 (Period 2) in the gluteal muscle and deltoid muscle. AUC0-last is defined as the area under the concentration-time curve from time zero to time of last measurable concentration of MK-5720. Per protocol, this outcome measure is specific for Panels C, D, E, and F, and data was not planned or collected for Panels A or B. Panels C, D, E, and F were not enrolled, and no data was collected for this outcome measure. |
| Panels C, D, E, and F: AUC0-inf of MK-5720 in Gluteal Muscle Versus AUC0-inf of MK-5720 in Deltoid Muscle | Predose, 0.5, 1, 2, 4, 6, 24, 48, 96, 120, 144, 168, 192, 216, 264, 288, 312, 336, 360, 384, 432, 456, 504, 672, 840, 1008, 1176, and 1320 hours postdose | Blood samples were to be collected at specified intervals for the determination of AUC-inf after administration of MK-5720 (Period 2) in the gluteal muscle and deltoid muscle. AUC0-inf is defined as the area under concentration-time curve from time zero to infinity. Per protocol, this outcome measure is specific for Panels C, D, E, and F, and data was not planned or collected for Panels A or B. Panels C, D, E, and F were not enrolled, and no data was collected for this outcome measure. |
| Panels C, D, E, and F: Cmax of MK-5720 in Gluteal Muscle Versus Cmax of MK-5720 in Deltoid Muscle | Predose, 0.5, 1, 2, 4, 6, 24, 48, 96, 120, 144, 168, 192, 216, 264, 288, 312, 336, 360, 384, 432, 456, 504, 672, 840, 1008, 1176, and 1320 hours postdose | Blood samples were to be collected at specified intervals for the determination of Cmax after administration of MK-5720 (Period 2) in the gluteal muscle and deltoid muscle. Cmax is defined as the maximum concentration of MK-5720 reached. Per protocol, this outcome measure is specific for Panels C, D, E, and F, and data was not planned or collected for Panels A or B. Panels C, D, E, and F were not enrolled, and no data was collected for this outcome measure. |
| Panels C, D, E, and F: Tmax of MK-5720 in Gluteal Muscle Versus Tmax of MK-5720 in Deltoid Muscle | Predose, 0.5, 1, 2, 4, 6, 24, 48, 96, 120, 144, 168, 192, 216, 264, 288, 312, 336, 360, 384, 432, 456, 504, 672, 840, 1008, 1176, and 1320 hours postdose | Blood samples were to be collected at specified intervals for the determination of Tmax after administration of MK-5720 (Period 2) in the gluteal muscle and deltoid muscle. Tmax is defined as the time to maximum concentration of MK-5720 reached. Per protocol, this outcome measure is specific for Panels C, D, E, and F, and data was not planned or collected for Panels A or B. Panels C, D, E, and F were not enrolled, and no data was collected for this outcome measure. |
| Panels C, D, E, and F: CL/F of MK-5720 in Gluteal Muscle Versus CL/F of MK-5720 in Deltoid Muscle | Predose, 0.5, 1, 2, 4, 6, 24, 48, 96, 120, 144, 168, 192, 216, 264, 288, 312, 336, 360, 384, 432, 456, 504, 672, 840, 1008, 1176, and 1320 hours postdose | Blood samples were to be collected at specified intervals for the determination of CL/F after administration of MK-5720 (Period 2) in the gluteal muscle and deltoid muscle. CL/F is the rate at which the MK-5720 is completely removed from plasma. Per protocol, this outcome measure is specific for Panels C, D, E, and F, and data was not planned or collected for Panels A or B. Panels C, D, E, and F were not enrolled, and no data was collected for this outcome measure. |
| Panels C, D, E, and F: Vz/F of MK-5720 in Gluteal Muscle Versus Vz/F of MK-5720 in Deltoid Muscle | Predose, 0.5, 1, 2, 4, 6, 24, 48, 96, 120, 144, 168, 192, 216, 264, 288, 312, 336, 360, 384, 432, 456, 504, 672, 840, 1008, 1176, and 1320 hours postdose | Blood samples were to be collected at specified intervals for the determination Vz/F after administration of MK-5720 (Period 2) in the gluteal muscle and deltoid muscle. Vz/F is the apparent volume of distribution of MK-5720. Per protocol, this outcome measure is specific for Panels C, D, E, and F, and data was not planned or collected for Panels A or B. Panels C, D, E, and F were not enrolled, and no data was collected for this outcome measure. |
| Panels C, D, E, and F: t1/2 of MK-5720 in Gluteal Muscle Versus t1/2 of MK-5720 in Deltoid Muscle | Predose, 0.5, 1, 2, 4, 6, 24, 48, 96, 120, 144, 168, 192, 216, 264, 288, 312, 336, 360, 384, 432, 456, 504, 672, 840, 1008, 1176, and 1320 hours postdose | Blood samples were to be collected at specified intervals for the determination t1/2 after administration of MK-5720 (Period 2) in the gluteal muscle and deltoid muscle. t1/2 is defined as the time required to divide plasma concentration of MK-5720 by half after reaching pseudo-equilibrium. Per protocol, this outcome measure is specific for Panels C, D, E, and F, and data was not planned or collected for Panels A or B. Panels C, D, E, and F were not enrolled, and no data was collected for this outcome measure. |
| Panels D, E, and F: C28d Tied to Specific Exposures of MK-8189 | Predose, 0.5, 1, 2, 4, 6, 24, 48, 96, 120, 144, 168, 192, 216, 264, 288, 312, 336, 360, 384, 432, 456, 504, and 672 postdose | C28d tied to specific exposures of MK-8189 is defined as the maximum concentration from time zero to 28 days of MK-8189 tied to specific exposures. Blood samples were collected at specified intervals for the determination of C28d tied to specific exposures of MK-8189 (metabolite of MK-5720) following a single dose administration of MK-5720 in Period 2. Per protocol, this outcome measure is specific for Panels D, E, and F only. Panels C, D, E and F were not enrolled, and no data was collected for this outcome measure. |
Countries
United States
Participant flow
Pre-assignment details
Participants with schizophrenia were enrolled. Only participants in Panel A, Panel B, and dose-matched placebo were enrolled. Participants were not enrolled in Panels C, D, E, and F and no data was collected.
Participants by arm
| Arm | Count |
|---|---|
| Panel A: Period 1 MK-8189 4 mg → Period 2 MK-5720 35mg Participants received 7 days of oral MK-8189 4 mg (Period 1), followed by a single intramuscular (IM) injection of MK-5720 35 mg (Period 2). | 6 |
| Panel B: Period 1 MK-8189 8 mg → Period 2 MK-5720 70 mg Participants received 7 days of oral MK-8189 8 mg (Period 1), followed by a single IM injection of MK-5720 70 mg (Period 2). | 7 |
| Placebo Period 1 → Placebo Period 2 Participants received 7 days of oral MK-8189 dose-matched placebo treatment (Period 1), followed by a single intramuscular (IM) injection of MK-5720 dose-matched placebo treatment (Period 2). | 4 |
| Total | 17 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Period 1 | Physician Decision | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Period 2 | Withdrawal by Subject | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Panel A: Period 1 MK-8189 4 mg → Period 2 MK-5720 35mg | Panel B: Period 1 MK-8189 8 mg → Period 2 MK-5720 70 mg | Placebo Period 1 → Placebo Period 2 | Total |
|---|---|---|---|---|
| Age, Continuous | 45.8 Years STANDARD_DEVIATION 9.4 | 46.3 Years STANDARD_DEVIATION 11.3 | 51.5 Years STANDARD_DEVIATION 5.8 | 47.4 Years STANDARD_DEVIATION 9.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 4 Participants | 0 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 3 Participants | 4 Participants | 13 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 3 Participants | 3 Participants | 12 Participants |
| Race (NIH/OMB) More than one race | 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 |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 4 Participants | 1 Participants | 5 Participants |
| Sex: Female, Male Female | 0 Participants | 2 Participants | 1 Participants | 3 Participants |
| Sex: Female, Male Male | 6 Participants | 5 Participants | 3 Participants | 14 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 / 6 | 0 / 7 | 0 / 4 | 0 / 6 | 0 / 6 | 0 / 4 |
| other Total, other adverse events | 1 / 6 | 4 / 7 | 2 / 4 | 1 / 6 | 2 / 6 | 1 / 4 |
| serious Total, serious adverse events | 0 / 6 | 0 / 7 | 0 / 4 | 0 / 6 | 0 / 6 | 0 / 4 |
Outcome results
Primary
Apparent Clearance (CL/F) of MK-5720
CL/F is the rate at which the MK-5720 is completely removed from plasma. Blood samples were collected at specified intervals for the determination of CL/F following a single dose administration of MK-5720 in Period 2. Per protocol, this outcome measure has been reported by panel and dose.
Time frame: Predose, 0.5, 1, 2, 4, 6, 24, 48, 96, 120, 144, 168, 192, 216, 264, 288, 312, 336, 360, 384, 432, 456, 504, 672, 840, 1008, 1176, and 1320 hours postdose
Population: Per protocol population includes all participants who complied with the protocol, had received MK-8189 treatment in Period 1 and MK-5720 treatment in Period 2, and had data available. Per protocol, placebo arms were not included in any PK outcome analyses. Panels C, D, E, and F were not enrolled, and no data was collected for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Panel A: Period 1 MK-8189 4 mg | Apparent Clearance (CL/F) of MK-5720 | 892 Liters/hr | Geometric Coefficient of Variation 61.6 |
| Panel B: Period 1 MK-8189 8 mg | Apparent Clearance (CL/F) of MK-5720 | 933 Liters/hr | Geometric Coefficient of Variation 61.6 |
Primary
Apparent Terminal Half-life (t1/2) of MK-5720
t1/2 is defined as the time required to divide plasma concentration of MK-5720 by half after reaching pseudo-equilibrium. Blood samples were collected at specified intervals for the determination t1/2 following a single dose administration of MK-5720 in Period 2. Per protocol, this outcome measure has been reported by panel and dose.
Time frame: Predose, 0.5, 1, 2, 4, 6, 24, 48, 96, 120, 144, 168, 192, 216, 264, 288, 312, 336, 360, 384, 432, 456, 504, 672, 840, 1008, 1176, and 1320 hours postdose
Population: Per protocol population includes all participants who complied with the protocol, had received MK-8189 treatment in Period 1 and MK-5720 treatment in Period 2, and had data available. Per protocol, placebo arms were not included in any PK outcome analyses. Panels C, D, E, and F were not enrolled, and no data was collected for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Panel A: Period 1 MK-8189 4 mg | Apparent Terminal Half-life (t1/2) of MK-5720 | 43.0 hr | Geometric Coefficient of Variation 15.9 |
| Panel B: Period 1 MK-8189 8 mg | Apparent Terminal Half-life (t1/2) of MK-5720 | 162 hr | Geometric Coefficient of Variation 271.2 |
Primary
Apparent Volume of Distribution (Vz/F) of MK-5720
Vz/F is the apparent volume of distribution of MK-5720. Blood samples were collected at specified intervals for the determination of Vz/F following a single dose administration of MK-5720 in Period 2. Per protocol, this outcome measure has been reported by panel and dose.
Time frame: Predose, 0.5, 1, 2, 4, 6, 24, 48, 96, 120, 144, 168, 192, 216, 264, 288, 312, 336, 360, 384, 432, 456, 504, 672, 840, 1008, 1176, and 1320 hours postdose
Population: Per protocol population includes all participants who complied with the protocol, had received MK-8189 treatment in Period 1 and MK-5720 treatment in Period 2, and had data available. Per protocol, placebo arms were not included in any PK outcome analyses. Panels C, D, E, and F were not enrolled, and no data was collected for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Panel A: Period 1 MK-8189 4 mg | Apparent Volume of Distribution (Vz/F) of MK-5720 | 55400 Liters | Geometric Coefficient of Variation 83.2 |
| Panel B: Period 1 MK-8189 8 mg | Apparent Volume of Distribution (Vz/F) of MK-5720 | 218000 Liters | Geometric Coefficient of Variation 243.8 |
Primary
Area Under the Concentration-Time Curve From Time 0 to 28 Days (AUC0-28d) of MK-8189
AUC0-28d is defined as the area under the concentration-time curve from time zero to 28 days of MK-8189 (a metabolite of MK-5720). Blood samples were collected at specified intervals for the determination of AUC0-28d for MK-8189 following a single dose administration of MK-5720 in Period 2. Per protocol, this outcome measure has been reported by panel and dose.
Time frame: Predose, 0.5, 1, 2, 4, 6, 24, 48, 96, 120, 144, 168, 192, 216, 264, 288, 312, 336, 360, 384, 432, 456, 504, and 672 hours postdose
Population: Per protocol population includes all participants who complied with the protocol, had received MK-8189 treatment in Period 1 and MK-5720 treatment in Period 2, and had data available. Per protocol, placebo arms were not included in any PK outcome analyses. Panels C, D, E, and F were not enrolled, and no data was collected for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Panel A: Period 1 MK-8189 4 mg | Area Under the Concentration-Time Curve From Time 0 to 28 Days (AUC0-28d) of MK-8189 | 2850 hr*nM | Geometric Coefficient of Variation 4121.1 |
| Panel B: Period 1 MK-8189 8 mg | Area Under the Concentration-Time Curve From Time 0 to 28 Days (AUC0-28d) of MK-8189 | 29800 hr*nM | Geometric Coefficient of Variation 89.3 |
Primary
Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC-inf) of MK-5720
AUC0-inf is defined as the area under concentration-time curve of MK-5720 from time zero to infinity. Blood samples were collected at specified intervals for the determination of AUC-inf following a single dose administration of MK-5720 in Period 2. Per protocol, this outcome measure has been reported by panel and dose.
Time frame: Predose, 0.5, 1, 2, 4, 6, 24, 48, 96, 120, 144, 168, 192, 216, 264, 288, 312, 336, 360, 384, 432, 456, 504, 672, 840, 1008, 1176, and 1320 hours postdose
Population: Per protocol population includes all participants who complied with the protocol, had received MK-8189 treatment in Period 1 and MK-5720 treatment in Period 2, and had data available. Per protocol, placebo arms were not included in any PK outcome analyses. Panels C, D, E, and F were not enrolled, and no data was collected for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Panel A: Period 1 MK-8189 4 mg | Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC-inf) of MK-5720 | 70.0 hr*nM | Geometric Coefficient of Variation 61.6 |
| Panel B: Period 1 MK-8189 8 mg | Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC-inf) of MK-5720 | 134 hr*nM | Geometric Coefficient of Variation 61.6 |
Primary
Area Under the Concentration-Time Curve From Time 0 to Last Quantifiable Concentration (AUC0-last) of MK-5720
AUC0-last was defined as the area under the concentration-time curve from time zero to time of last measurable concentration of MK-5720. Blood samples were collected at specified intervals were used to estimate AUC0-last following a single dose administration of MK-5720 in Period 2. Per protocol, this outcome measure has been reported by panel and dose.
Time frame: Predose, 0.5, 1, 2, 4, 6, 24, 48, 96, 120, 144, 168, 192, 216, 264, 288, 312, 336, 360, 384, 432, 456, 504, 672, 840, 1008, 1176, and 1320 hours postdose
Population: Per protocol population includes all participants who complied with the protocol, had received MK-8189 treatment in Period 1 and MK-5720 treatment in Period 2, and had data available. Per protocol, placebo arms were not included in any PK outcome analyses. Panels C, D, E, and F were not enrolled, and no data was collected for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Panel A: Period 1 MK-8189 4 mg | Area Under the Concentration-Time Curve From Time 0 to Last Quantifiable Concentration (AUC0-last) of MK-5720 | 34.3 hr*nM | Geometric Coefficient of Variation 128.3 |
| Panel B: Period 1 MK-8189 8 mg | Area Under the Concentration-Time Curve From Time 0 to Last Quantifiable Concentration (AUC0-last) of MK-5720 | 73.3 hr*nM | Geometric Coefficient of Variation 96.2 |
Primary
AUC0-inf of MK-8189
AUC0-inf is defined as the area under concentration-time curve from time zero to infinity of MK-8189 (a metabolite of MK-5720). Blood samples were collected at specified intervals for the determination of AUC0-inf for MK-8198 following a single dose administration of MK-5720 in Period 2. Per protocol, this outcome measure has been reported by panel and dose.
Time frame: Predose, 0.5, 1, 2, 4, 6, 24, 48, 96, 120, 144, 168, 192, 216, 264, 288, 312, 336, 360, 384, 432, 456, 504, 672, 840, 1008, 1176, and 1320 hours postdose
Population: Per protocol population includes all participants who complied with the protocol, had received MK-8189 treatment in Period 1 and MK-5720 treatment in Period 2, and had data available. Per protocol, placebo arms were not included in any PK outcome analyses. Panels C, D, E, and F were not enrolled, and no data was collected for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Panel A: Period 1 MK-8189 4 mg | AUC0-inf of MK-8189 | 8400 hr*nM | Geometric Coefficient of Variation 75.3 |
| Panel B: Period 1 MK-8189 8 mg | AUC0-inf of MK-8189 | 31900 hr*nM | Geometric Coefficient of Variation 93.9 |
Primary
CL/F of MK-8189
CL/F is the rate at which the MK-8189 (a metabolite of MK-5720) is completely removed from plasma. Blood samples were collected at specified intervals for the determination of CL/F for MK-8198 following a single dose administration of MK-5720 in Period 2. Per protocol, this outcome measure has been reported by panel and dose.
Time frame: Predose, 0.5, 1, 2, 4, 6, 24, 48, 96, 120, 144, 168, 192, 216, 264, 288, 312, 336, 360, 384, 432, 456, 504, 672, 840, 1008, 1176, and 1320 hours postdose
Population: Per protocol population includes all participants who complied with the protocol, had received MK-8189 treatment in Period 1 and MK-5720 treatment in Period 2, and had data available. Per protocol, placebo arms were not included in any PK outcome analyses. Panels C, D, E, and F were not enrolled, and no data was collected for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Panel A: Period 1 MK-8189 4 mg | CL/F of MK-8189 | 7.43 Liters/hr | Geometric Coefficient of Variation 75.3 |
| Panel B: Period 1 MK-8189 8 mg | CL/F of MK-8189 | 3.92 Liters/hr | Geometric Coefficient of Variation 93.9 |
Primary
Cmax of MK-8189
Cmax is defined as the maximum concentration of MK-8189 (a metabolite of MK-5720) reached. Blood samples were collected at specified intervals for the determination of Cmax for MK-8198 following a single dose administration of MK-5720 in Period 2. Per protocol, this outcome measure has been reported by panel and dose.
Time frame: Predose, 0.5, 1, 2, 4, 6, 24, 48, 96, 120, 144, 168, 192, 216, 264, 288, 312, 336, 360, 384, 432, 456, 504, 672, 840, 1008, 1176, and 1320 hours postdose
Population: Per protocol population includes all participants who complied with the protocol, had received MK-8189 treatment in Period 1 and MK-5720 treatment in Period 2, and had data available. Per protocol, placebo arms were not included in any PK outcome analyses. Panels C, D, E, and F were not enrolled, and no data was collected for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Panel A: Period 1 MK-8189 4 mg | Cmax of MK-8189 | 18.8 nM | Geometric Coefficient of Variation 569.7 |
| Panel B: Period 1 MK-8189 8 mg | Cmax of MK-8189 | 104 nM | Geometric Coefficient of Variation 90.1 |
Primary
Concentration at Day 28 (C28d) of MK-8189
C28d is defined as the maximum concentration from time zero to 28 days of MK-8189 (a metabolite of MK-5720). Blood samples were collected at specified intervals for the determination of C28d for MK-8198 following a single dose administration of MK-5720 in Period 2. Per protocol, this outcome measure has been reported by panel and dose. In cases where C28d values were below the limit of quantitation, geometric mean was not calculable and indicated as NA.
Time frame: Predose, 0.5, 1, 2, 4, 6, 24, 48, 96, 120, 144, 168, 192, 216, 264, 288, 312, 336, 360, 384, 432, 456, 504, and 672 hours postdose
Population: Per protocol population includes all participants who complied with the protocol, had received MK-8189 treatment in Period 1 and MK-5720 treatment in Period 2, and had data available. Per protocol, placebo arms were not included in any PK outcome analyses. Panels C, D, E, and F were not enrolled, and no data was collected for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Panel A: Period 1 MK-8189 4 mg | Concentration at Day 28 (C28d) of MK-8189 | NA nM | — |
| Panel B: Period 1 MK-8189 8 mg | Concentration at Day 28 (C28d) of MK-8189 | 2.96 nM | Geometric Coefficient of Variation 693.7 |
Primary
Maximum Serum Concentration (Cmax) of MK-5720
Cmax is defined as the maximum concentration of MK-5720 reached. Blood samples were collected at specified intervals for the determination of Cmax following a single dose administration of MK-5720 in Period 2. Per protocol, this outcome measure has been reported by panel and dose.
Time frame: Predose, 0.5, 1, 2, 4, 6, 24, 48, 96, 120, 144, 168, 192, 216, 264, 288, 312, 336, 360, 384, 432, 456, 504, 672, 840, 1008, 1176, and 1320 hours postdose
Population: Per protocol population includes all participants who complied with the protocol, had received MK-8189 treatment in Period 1 and MK-5720 treatment in Period 2, and had data available. Per protocol, placebo arms were not included in any PK outcome analyses. Panels C, D, E, and F were not enrolled, and no data was collected for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Panel A: Period 1 MK-8189 4 mg | Maximum Serum Concentration (Cmax) of MK-5720 | 0.165 nM | Geometric Coefficient of Variation 156.2 |
| Panel B: Period 1 MK-8189 8 mg | Maximum Serum Concentration (Cmax) of MK-5720 | 0.473 nM | Geometric Coefficient of Variation 105.1 |
Primary
Number of Participants Who Discontinue Study Due to an AE in Period 1
An adverse event (AE) is 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. The number of participants who discontinued study treatment due to an AE is reported here for participants in Period 1. Per protocol, this outcome measure has been reported by panel and dose. As specified by the protocol, Period 2 has been analyzed separately and reported later in the record.
Time frame: Up to approximately 10 days
Population: All participants in Period 1 who received at least one dose of study treatment and had data available for Period 1. Panels C, D, E, and F were not enrolled, and no data was collected for this outcome measure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Panel A: Period 1 MK-8189 4 mg | Number of Participants Who Discontinue Study Due to an AE in Period 1 | 0 Participants |
| Panel B: Period 1 MK-8189 8 mg | Number of Participants Who Discontinue Study Due to an AE in Period 1 | 1 Participants |
| Placebo Period 1 | Number of Participants Who Discontinue Study Due to an AE in Period 1 | 0 Participants |
Primary
Number of Participants Who Discontinue Study Due to an AE in Period 2
An adverse event (AE) is 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. The number of participants who discontinued study treatment due to an AE is reported here for participants in Period 2. Per protocol, this outcome measure has been reported by panel and dose. As specified by the protocol, Period 1 has been analyzed separately and reported earlier in the record.
Time frame: Up to approximately 72 days
Population: All participants in Period 2 who received at least one dose of study treatment and had data available for Period 2. In Panel B 1 participant discontinued treatment between Period 1 and Period 2. Panels C, D, E, and F were not enrolled, and no data was collected for this outcome measure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Panel A: Period 1 MK-8189 4 mg | Number of Participants Who Discontinue Study Due to an AE in Period 2 | 0 Participants |
| Panel B: Period 1 MK-8189 8 mg | Number of Participants Who Discontinue Study Due to an AE in Period 2 | 0 Participants |
| Placebo Period 1 | Number of Participants Who Discontinue Study Due to an AE in Period 2 | 0 Participants |
Primary
Number of Participants Who Experience ≥1 Adverse Event (AE) in Period 1
An adverse event (AE) is 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. The number of participants who experienced one or more AEs is reported here for participants in Period 1. Per protocol, this outcome measure has been reported by panel and dose. As specified by the protocol, Period 2 has been analyzed separately and reported later in the record.
Time frame: Up to approximately 10 days
Population: All participants in Period 1 who received at least one dose of study treatment and had data available for Period 1. Panels C, D, E, and F were not enrolled, and no data was collected for this outcome measure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Panel A: Period 1 MK-8189 4 mg | Number of Participants Who Experience ≥1 Adverse Event (AE) in Period 1 | 1 Participants |
| Panel B: Period 1 MK-8189 8 mg | Number of Participants Who Experience ≥1 Adverse Event (AE) in Period 1 | 4 Participants |
| Placebo Period 1 | Number of Participants Who Experience ≥1 Adverse Event (AE) in Period 1 | 2 Participants |
Primary
Number of Participants Who Experience ≥1 AE(s) in Period 2
An adverse event (AE) is 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. The number of participants who experienced one or more AEs is reported here for participants in Period 2. Per protocol, this outcome measure has been reported by panel and dose. As specified by the protocol, Period 1 has been analyzed separately and reported earlier in the record.
Time frame: Up to approximately 72 days
Population: All participants in Period 2 who received at least one dose of study treatment and had data available for Period 2. In Panel B 1 participant discontinued treatment between Period 1 and Period 2. Panels C, D, E, and F were not enrolled, and no data was collected for this outcome measure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Panel A: Period 1 MK-8189 4 mg | Number of Participants Who Experience ≥1 AE(s) in Period 2 | 1 Participants |
| Panel B: Period 1 MK-8189 8 mg | Number of Participants Who Experience ≥1 AE(s) in Period 2 | 2 Participants |
| Placebo Period 1 | Number of Participants Who Experience ≥1 AE(s) in Period 2 | 1 Participants |
Primary
t1/2 of MK-8189
t1/2 is defined as the time required to divide plasma concentration of MK-8189 (a metabolite of MK-5720) by half after reaching pseudo-equilibrium. Blood samples were collected at specified intervals for the determination of Half-life (t1/2) for MK-8198 following a single dose administration of MK-5720 in Period 2. Per protocol, this outcome measure has been reported by panel and dose.
Time frame: Predose, 0.5, 1, 2, 4, 6, 24, 48, 96, 120, 144, 168, 192, 216, 264, 288, 312, 336, 360, 384, 432, 456, 504, 672, 840, 1008, 1176, and 1320 hours postdose
Population: Per protocol population includes all participants who complied with the protocol, had received MK-8189 treatment in Period 1 and MK-5720 treatment in Period 2, and had data available. Per protocol, placebo arms were not included in any PK outcome analyses. Panels C, D, E, and F were not enrolled, and no data was collected for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Panel A: Period 1 MK-8189 4 mg | t1/2 of MK-8189 | 65.0 hr | Geometric Coefficient of Variation 62.5 |
| Panel B: Period 1 MK-8189 8 mg | t1/2 of MK-8189 | 105 hr | Geometric Coefficient of Variation 71.3 |
Primary
Time to Maximum Concentration (Tmax) of MK-5720
Tmax is defined as the time to maximum concentration of MK-5720 reached. Blood samples were collected at specified intervals for the determination of Tmax following a single dose administration of MK-5720 in Period 2. Per protocol, this outcome measure has been reported by panel and dose.
Time frame: Predose, 0.5, 1, 2, 4, 6, 24, 48, 96, 120, 144, 168, 192, 216, 264, 288, 312, 336, 360, 384, 432, 456, 504, 672, 840, 1008, 1176, and 1320 hours postdose
Population: Per protocol population includes all participants who complied with the protocol, had received MK-8189 treatment in Period 1 and MK-5720 treatment in Period 2, and had data available. Per protocol, placebo arms were not included in any PK outcome analyses. Panels C, D, E, and F were not enrolled, and no data was collected for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Panel A: Period 1 MK-8189 4 mg | Time to Maximum Concentration (Tmax) of MK-5720 | 48.00 hr |
| Panel B: Period 1 MK-8189 8 mg | Time to Maximum Concentration (Tmax) of MK-5720 | 108.00 hr |
Primary
Tmax of MK-8189
Tmax is defined as the time to maximum concentration of MK-8189 (a metabolite of MK-5720). Blood samples were collected at specified intervals for the determination of Tmax for MK-8198 following a single dose administration of MK-5720 in Period 2. Per protocol, this outcome measure has been reported by panel and dose.
Time frame: Predose, 0.5, 1, 2, 4, 6, 24, 48, 96, 120, 144, 168, 192, 216, 264, 288, 312, 336, 360, 384, 432, 456, 504, 672, 840, 1008, 1176, and 1320 hours postdose
Population: Per protocol population includes all participants who complied with the protocol, had received MK-8189 treatment in Period 1 and MK-5720 treatment in Period 2, and had data available. Per protocol, placebo arms were not included in any PK outcome analyses. Panels C, D, E, and F were not enrolled, and no data was collected for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Panel A: Period 1 MK-8189 4 mg | Tmax of MK-8189 | 96.00 hr |
| Panel B: Period 1 MK-8189 8 mg | Tmax of MK-8189 | 120.00 hr |
Primary
Vz/F of MK-8189
Vz/F is the apparent volume of distribution of MK-8189 (a metabolite of MK-5720). Blood samples were collected at specified intervals for the determination of Vz/F for MK-8198 following a single dose administration of MK-5720 in Period 2. Per protocol, this outcome measure has been reported by panel and dose.
Time frame: Predose, 0.5, 1, 2, 4, 6, 24, 48, 96, 120, 144, 168, 192, 216, 264, 288, 312, 336, 360, 384, 432, 456, 504, 672, 840, 1008, 1176, and 1320 hours postdose
Population: Per protocol population includes all participants who complied with the protocol, had received MK-8189 treatment in Period 1 and MK-5720 treatment in Period 2, and had data available. Per protocol, placebo arms were not included in any PK outcome analyses. Panels C, D, E, and F were not enrolled, and no data was collected for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Panel A: Period 1 MK-8189 4 mg | Vz/F of MK-8189 | 697 Liters | Geometric Coefficient of Variation 97 |
| Panel B: Period 1 MK-8189 8 mg | Vz/F of MK-8189 | 593 Liters | Geometric Coefficient of Variation 126.7 |
Secondary
Panels C, D, E, and F: AUC0-28d of MK-8189 in Gluteal Muscle Versus AUC0-28 of MK-8189 in Deltoid Muscle
Blood samples were to be collected at specified intervals for the determination of AUC0-28 of MK-8189 (a metabolite of MK-5720) after administration of MK-5720 (Period 2) in the gluteal muscle and deltoid muscle. AUC0-28 is defined as the area under the plasma concentration-time curve from time zero to 28 days of MK-8189. Per protocol, this outcome measure is specific for Panels C, D, E, and F, and data was not planned or collected for Panels A or B. Panels C, D, E, and F were not enrolled, and no data was collected for this outcome measure.
Time frame: Predose, 0.5, 1, 2, 4, 6, 24, 48, 96, 120, 144, 168, 192, 216, 264, 288, 312, 336, 360, 384, 432, 456, 504, and 672 hours postdose
Population: Per protocol, this outcome measure is specific for Panels C, D, E, and F, and data was not planned or collected for Panels A and B. Per protocol, placebo arms were not included in any PK outcome analyses. Panels C, D, E, and F were not enrolled, and no data was collected for this outcome measure.
Secondary
Panels C, D, E, and F: AUC0-inf of MK-5720 in Gluteal Muscle Versus AUC0-inf of MK-5720 in Deltoid Muscle
Blood samples were to be collected at specified intervals for the determination of AUC-inf after administration of MK-5720 (Period 2) in the gluteal muscle and deltoid muscle. AUC0-inf is defined as the area under concentration-time curve from time zero to infinity. Per protocol, this outcome measure is specific for Panels C, D, E, and F, and data was not planned or collected for Panels A or B. Panels C, D, E, and F were not enrolled, and no data was collected for this outcome measure.
Time frame: Predose, 0.5, 1, 2, 4, 6, 24, 48, 96, 120, 144, 168, 192, 216, 264, 288, 312, 336, 360, 384, 432, 456, 504, 672, 840, 1008, 1176, and 1320 hours postdose
Population: Per protocol, this outcome measure is specific for Panels C, D, E, and F, and data was not planned or collected for Panels A and B. Per protocol, placebo arms were not included in any PK outcome analyses. Panels C, D, E, and F were not enrolled, and no data was collected for this outcome measure.
Secondary
Panels C, D, E, and F: AUC0-inf of MK-8189 in Gluteal Muscle Versus AUC0-inf of MK-8189 in Deltoid Muscle
Blood samples were to be collected at specified intervals for the determination of AUC-inf of MK-8189 (a metabolite of MK-5720) after administration of MK-5720 (Period 2) in the gluteal muscle and deltoid muscle. AUC0-inf is defined as the area under concentration-time curve from time zero to infinity of MK-8189. Per protocol, this outcome measure is specific for Panels C, D, E, and F, and data was not planned or collected for Panels A or B. Panels C, D, E, and F were not enrolled, and no data was collected for this outcome measure.
Time frame: Predose, 0.5, 1, 2, 4, 6, 24, 48, 96, 120, 144, 168, 192, 216, 264, 288, 312, 336, 360, 384, 432, 456, 504, 672, 840, 1008, 1176, and 1320 hours postdose
Population: Per protocol, this outcome measure is specific for Panels C, D, E, and F, and data was not planned or collected for Panels A and B. Per protocol, placebo arms were not included in any PK outcome analyses. Panels C, D, E, and F were not enrolled, and no data was collected for this outcome measure.
Secondary
Panels C, D, E, and F: AUC0-last of MK 5720 in Gluteal Muscle Versus AUC0-last of MK-5720 in Deltoid Muscle
Blood samples were to be collected at specified intervals for the determination of AUC0-last after administration of MK-5720 (Period 2) in the gluteal muscle and deltoid muscle. AUC0-last is defined as the area under the concentration-time curve from time zero to time of last measurable concentration of MK-5720. Per protocol, this outcome measure is specific for Panels C, D, E, and F, and data was not planned or collected for Panels A or B. Panels C, D, E, and F were not enrolled, and no data was collected for this outcome measure.
Time frame: Predose, 0.5, 1, 2, 4, 6, 24, 48, 96, 120, 144, 168, 192, 216, 264, 288, 312, 336, 360, 384, 432, 456, 504, 672, 840, 1008, 1176, and 1320 hours postdose
Population: Per protocol, this outcome measure is specific for Panels C, D, E, and F, and data was not planned or collected for Panels A and B. Per protocol, placebo arms were not included in any PK outcome analyses. Panels C, D, E, and F were not enrolled, and no data was collected for this outcome measure.
Secondary
Panels C, D, E, and F: C28d of MK-8189 in Gluteal Muscle Versus C28d in Deltoid Muscle
Blood samples were to be collected at specified intervals for the determination of C28d of MK-8189 (a metabolite of MK-5720) after administration of MK-5720 (Period 2) in the gluteal muscle and deltoid muscle. C28d is defined as the maximum concentration from time zero to 28 days of MK-8189. Per protocol, this outcome measure is specific for Panels C, D, E, and F, and data was not planned or collected for Panels A or B. Panels C, D, E, and F were not enrolled, and no data was collected for this outcome measure.
Time frame: Predose, 0.5, 1, 2, 4, 6, 24, 48, 96, 120, 144, 168, 192, 216, 264, 288, 312, 336, 360, 384, 432, 456, 504, and 672 hours postdose
Population: Per protocol, this outcome measure is specific for Panels C, D, E, and F, and data was not planned or collected for Panels A and B. Per protocol, placebo arms were not included in any PK outcome analyses. Panels C, D, E, and F were not enrolled, and no data was collected for this outcome measure.
Secondary
Panels C, D, E, and F: CL/F of MK-5720 in Gluteal Muscle Versus CL/F of MK-5720 in Deltoid Muscle
Blood samples were to be collected at specified intervals for the determination of CL/F after administration of MK-5720 (Period 2) in the gluteal muscle and deltoid muscle. CL/F is the rate at which the MK-5720 is completely removed from plasma. Per protocol, this outcome measure is specific for Panels C, D, E, and F, and data was not planned or collected for Panels A or B. Panels C, D, E, and F were not enrolled, and no data was collected for this outcome measure.
Time frame: Predose, 0.5, 1, 2, 4, 6, 24, 48, 96, 120, 144, 168, 192, 216, 264, 288, 312, 336, 360, 384, 432, 456, 504, 672, 840, 1008, 1176, and 1320 hours postdose
Population: Per protocol, this outcome measure is specific for Panels C, D, E, and F, and data was not planned or collected for Panels A and B. Per protocol, placebo arms were not included in any PK outcome analyses. Panels C, D, E, and F were not enrolled, and no data was collected for this outcome measure.
Secondary
Panels C, D, E, and F: CL/F of MK-8189 in Gluteal Muscle Versus CL/F in Deltoid Muscle
Blood samples were to be collected at specified intervals for the determination of CL/F of MK-8189 (a metabolite of MK-5720) after administration of MK-5720 (Period 2) in the gluteal muscle and deltoid muscle. CL/F is the rate at which the MK-8189 is completely removed from plasma. Per protocol, this outcome measure is specific for Panels C, D, E, and F, and data was not planned or collected for Panels A or B. Panels C, D, E, and F were not enrolled, and no data was collected for this outcome measure.
Time frame: Predose, 0.5, 1, 2, 4, 6, 24, 48, 96, 120, 144, 168, 192, 216, 264, 288, 312, 336, 360, 384, 432, 456, 504, 672, 840, 1008, 1176, and 1320 hours postdose
Population: Per protocol, this outcome measure is specific for Panels C, D, E, and F, and data was not planned or collected for Panels A and B. Per protocol, placebo arms were not included in any PK outcome analyses. Panels C, D, E, and F were not enrolled, and no data was collected for this outcome measure.
Secondary
Panels C, D, E, and F: Cmax of MK-5720 in Gluteal Muscle Versus Cmax of MK-5720 in Deltoid Muscle
Blood samples were to be collected at specified intervals for the determination of Cmax after administration of MK-5720 (Period 2) in the gluteal muscle and deltoid muscle. Cmax is defined as the maximum concentration of MK-5720 reached. Per protocol, this outcome measure is specific for Panels C, D, E, and F, and data was not planned or collected for Panels A or B. Panels C, D, E, and F were not enrolled, and no data was collected for this outcome measure.
Time frame: Predose, 0.5, 1, 2, 4, 6, 24, 48, 96, 120, 144, 168, 192, 216, 264, 288, 312, 336, 360, 384, 432, 456, 504, 672, 840, 1008, 1176, and 1320 hours postdose
Population: Per protocol, this outcome measure is specific for Panels C, D, E, and F, and data was not planned or collected for Panels A and B. Per protocol, placebo arms were not included in any PK outcome analyses. Panels C, D, E, and F were not enrolled, and no data was collected for this outcome measure.
Secondary
Panels C, D, E, and F: Cmax of MK-8189 in Gluteal Muscle Versus Cmax of MK-8189 in Deltoid Muscle
Blood samples were to be collected at specified intervals for the determination of Cmax of MK-8189 (a metabolite of MK-5720) after administration of MK-5720 (Period 2) in the gluteal muscle and deltoid muscle. Cmax is defined as the maximum concentration of MK-8189. Per protocol, this outcome measure is specific for Panels C, D, E, and F, and data was not planned or collected for Panels A or B. Panels C, D, E, and F were not enrolled, and no data was collected for this outcome measure.
Time frame: Predose, 0.5, 1, 2, 4, 6, 24, 48, 96, 120, 144, 168, 192, 216, 264, 288, 312, 336, 360, 384, 432, 456, 504, 672, 840, 1008, 1176, and 1320 hours postdose
Population: Per protocol, this outcome measure is specific for Panels C, D, E, and F, and data was not planned or collected for Panels A and B. Per protocol, placebo arms were not included in any PK outcome analyses. Panels C, D, E, and F were not enrolled, and no data was collected for this outcome measure.
Secondary
Panels C, D, E, and F: t1/2 of MK-5720 in Gluteal Muscle Versus t1/2 of MK-5720 in Deltoid Muscle
Blood samples were to be collected at specified intervals for the determination t1/2 after administration of MK-5720 (Period 2) in the gluteal muscle and deltoid muscle. t1/2 is defined as the time required to divide plasma concentration of MK-5720 by half after reaching pseudo-equilibrium. Per protocol, this outcome measure is specific for Panels C, D, E, and F, and data was not planned or collected for Panels A or B. Panels C, D, E, and F were not enrolled, and no data was collected for this outcome measure.
Time frame: Predose, 0.5, 1, 2, 4, 6, 24, 48, 96, 120, 144, 168, 192, 216, 264, 288, 312, 336, 360, 384, 432, 456, 504, 672, 840, 1008, 1176, and 1320 hours postdose
Population: Per protocol, this outcome measure is specific for Panels C, D, E, and F, and data was not planned or collected for Panels A and B. Per protocol, placebo arms were not included in any PK outcome analyses. Panels C, D, E, and F were not enrolled, and no data was collected for this outcome measure.
Secondary
Panels C, D, E, and F: t1/2 of MK-8189 in Gluteal Muscle Versus t1/2 of MK-8189 in Deltoid Muscle
Blood samples were to be collected at specified intervals for the determination of t1/2 of MK-8189 (metabolite of MK-5720) after administration of MK-5720 (Period 2) in the gluteal muscle and deltoid muscle. t1/2 is defined as the time required divide plasma concentration of MK-8189 (metabolite of MK-5720) by half after reaching pseudo-equilibrium. Per protocol, this outcome measure is specific for Panels C, D, E, and F, and data was not planned or collected for Panels A or B. Panels C, D, E, and F were not enrolled, and no data was collected for this outcome measure.
Time frame: Predose, 0.5, 1, 2, 4, 6, 24, 48, 96, 120, 144, 168, 192, 216, 264, 288, 312, 336, 360, 384, 432, 456, 504, 672, 840, 1008, 1176, and 1320 hours postdose
Population: Per protocol, this outcome measure is specific for Panels C, D, E, and F, and data was not planned or collected for Panels A and B. Per protocol, placebo arms were not included in any PK outcome analyses. Panels C, D, E, and F were not enrolled, and no data was collected for this outcome measure.
Secondary
Panels C, D, E, and F: Tmax of MK-5720 in Gluteal Muscle Versus Tmax of MK-5720 in Deltoid Muscle
Blood samples were to be collected at specified intervals for the determination of Tmax after administration of MK-5720 (Period 2) in the gluteal muscle and deltoid muscle. Tmax is defined as the time to maximum concentration of MK-5720 reached. Per protocol, this outcome measure is specific for Panels C, D, E, and F, and data was not planned or collected for Panels A or B. Panels C, D, E, and F were not enrolled, and no data was collected for this outcome measure.
Time frame: Predose, 0.5, 1, 2, 4, 6, 24, 48, 96, 120, 144, 168, 192, 216, 264, 288, 312, 336, 360, 384, 432, 456, 504, 672, 840, 1008, 1176, and 1320 hours postdose
Population: Per protocol, this outcome measure is specific for Panels C, D, E, and F, and data was not planned or collected for Panels A and B. Per protocol, placebo arms were not included in any PK outcome analyses. Panels C, D, E, and F were not enrolled, and no data was collected for this outcome measure.
Secondary
Panels C, D, E, and F: Tmax of MK-8189 in Gluteal Muscle Versus Tmax of MK-8189 in Deltoid Muscle
Blood samples were to be collected at specified intervals for determination of Tmax of MK-8189 (a metabolite of MK-5720) after administration of MK-5720 (Period 2) in the gluteal muscle and deltoid muscle. Tmax is defined as the time to maximum concentration of MK-8189. Per protocol, this outcome measure is specific for Panels C, D, E, and F, and data was not planned or collected for Panels A or B. Panels C, D, E, and F were not enrolled, and no data was collected for this outcome measure.
Time frame: Predose, 0.5, 1, 2, 4, 6, 24, 48, 96, 120, 144, 168, 192, 216, 264, 288, 312, 336, 360, 384, 432, 456, 504, 672, 840, 1008, 1176, 1320 hours postdose
Population: Per protocol, this outcome measure is specific for Panels C, D, E, and F, and data was not planned or collected for Panels A and B. Per protocol, placebo arms were not included in any PK outcome analyses. Panels C, D, E, and F were not enrolled, and no data was collected for this outcome measure.
Secondary
Panels C, D, E, and F: Vz/F of MK-5720 in Gluteal Muscle Versus Vz/F of MK-5720 in Deltoid Muscle
Blood samples were to be collected at specified intervals for the determination Vz/F after administration of MK-5720 (Period 2) in the gluteal muscle and deltoid muscle. Vz/F is the apparent volume of distribution of MK-5720. Per protocol, this outcome measure is specific for Panels C, D, E, and F, and data was not planned or collected for Panels A or B. Panels C, D, E, and F were not enrolled, and no data was collected for this outcome measure.
Time frame: Predose, 0.5, 1, 2, 4, 6, 24, 48, 96, 120, 144, 168, 192, 216, 264, 288, 312, 336, 360, 384, 432, 456, 504, 672, 840, 1008, 1176, and 1320 hours postdose
Population: Per protocol, this outcome measure is specific for Panels C, D, E, and F, and data was not planned or collected for Panels A and B. Per protocol, placebo arms were not included in any PK outcome analyses. Panels C, D, E, and F were not enrolled, and no data was collected for this outcome measure.
Secondary
Panels C, D, E, and F: Vz/F of MK-8189 in Gluteal Muscle Versus Vz/F of MK-8189 in Deltoid Muscle
Blood samples were to be collected at specified intervals for the determination of distribution of MK-8189 (metabolite of MK-5720) after administration of MK-5720 (Period 2) in the gluteal muscle versus deltoid muscle. Vz/F is the apparent volume of distribution of MK-8189. Per protocol, this outcome measure is specific for Panels C, D, E, and F, and data was not planned or collected for Panels A or B. Panels C, D, E, and F were not enrolled, and no data was collected for this outcome measure.
Time frame: Predose, 0.5, 1, 2, 4, 6, 24, 48, 96, 120, 144, 168, 192, 216, 264, 288, 312, 336, 360, 384, 432, 456, 504, 672, 840, 1008, 1176, and 1320 hours postdose
Population: Per protocol, this outcome measure is specific for Panels C, D, E, and F, and data was not planned or collected for Panels A and B. Per protocol, placebo arms were not included in any PK outcome analyses. Panels C, D, E, and F were not enrolled, and no data was collected for this outcome measure.
Secondary
Panels D, E, and F: C28d Tied to Specific Exposures of MK-8189
C28d tied to specific exposures of MK-8189 is defined as the maximum concentration from time zero to 28 days of MK-8189 tied to specific exposures. Blood samples were collected at specified intervals for the determination of C28d tied to specific exposures of MK-8189 (metabolite of MK-5720) following a single dose administration of MK-5720 in Period 2. Per protocol, this outcome measure is specific for Panels D, E, and F only. Panels C, D, E and F were not enrolled, and no data was collected for this outcome measure.
Time frame: Predose, 0.5, 1, 2, 4, 6, 24, 48, 96, 120, 144, 168, 192, 216, 264, 288, 312, 336, 360, 384, 432, 456, 504, and 672 postdose
Population: Per protocol, this outcome measure is specific for Panels D, E, and F only. Panels C, D, E and F were not enrolled, and no data was collected for this outcome measure. Per protocol, placebo arms were not included in any PK outcome analyses.