A Study of MK-5720 in Participants With Schizophrenia (MK-5720-001)

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Single Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of the Long-Acting Injectable of MK-5720 in Participants With Schizophrenia

Conditions
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Schizophrenia

Intervention / Treatment
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* Drug: MK-5720
* Drug: Placebo to MK-5720
* Drug: MK-8189
* Drug: Placebo to MK-8189


Participation Criteria
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Eligibility Criteria
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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 exclusion criteria include but are not limited to the following: 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 Has history of mental retardation, borderline personality 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 history of seizure disorder beyond childhood or is receiving treatment with any anticonvulsant to prevent seizures Has a family history of sudden death Has claustrophobia to a degree that prevents tolerance of magnetic resonance imaging (MRI) scanning procedure Has a metallic implant of any sort that prevents MRI examination, or any other contraindication to MRI examination 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 History of significant multiple and/or severe allergies or has had an anaphylactic reaction or significant intolerability to prescription or nonprescription drugs or food Positive test(s) for hepatitis B surface antigen (HBsAg), hepatitis C antibodies or human immunodeficiency virus (HIV) Has received or is currently receiving treatment with clozapine for any length of time Has received any live vaccines within 30 days prior to the first dose of study intervention or is scheduled to receive any live vaccine through 60 days following study intervention

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Panel A<br>Participants receive 7 days of oral MK-8189 or matched placebo treatment (Period 1), followed by a single intramuscular (IM) injection of MK-5720 at a specified Dose 1 or a dose matched placebo (Period 2). | Drug: MK-5720<br>* MK-5720 IM injection<br>Drug: Placebo to MK-5720<br>* Placebo matched to MK-5720 IM injection<br>* Other names: Dextrose;Drug: MK-8189<br>* MK-8189 tablet taken by mouth<br>Drug: Placebo to MK-8189<br>* Placebo tablet matched to MK-8189<br>|
| Experimental: Panel B<br>Participants receive 7 days of oral MK-8189 or matched placebo treatment (Period 1), followed by a single IM injection of MK-5720 at a specified Dose 2 or a dose matched placebo (Period 2). | Drug: MK-5720<br>* MK-5720 IM injection<br>Drug: Placebo to MK-5720<br>* Placebo matched to MK-5720 IM injection<br>* Other names: Dextrose;Drug: MK-8189<br>* MK-8189 tablet taken by mouth<br>Drug: Placebo to MK-8189<br>* Placebo tablet matched to MK-8189<br>|
| Experimental: Panel C<br>Participants receive 7 days of oral MK-8189 or matched placebo treatment (Period 1), followed by a single IM injection of MK-5720 at a specified Dose 3 or a dose matched placebo (Period 2). | Drug: MK-5720<br>* MK-5720 IM injection<br>Drug: Placebo to MK-5720<br>* Placebo matched to MK-5720 IM injection<br>* Other names: Dextrose;Drug: MK-8189<br>* MK-8189 tablet taken by mouth<br>Drug: Placebo to MK-8189<br>* Placebo tablet matched to MK-8189<br>|
| Experimental: Panel D<br>Participants receive 7 days of oral MK-8189 or matched placebo treatment (Period 1), followed by a single IM injection of MK-5720 at a specified Dose 4 or a dose matched placebo (Period 2). | Drug: MK-5720<br>* MK-5720 IM injection<br>Drug: Placebo to MK-5720<br>* Placebo matched to MK-5720 IM injection<br>* Other names: Dextrose;Drug: MK-8189<br>* MK-8189 tablet taken by mouth<br>Drug: Placebo to MK-8189<br>* Placebo tablet matched to MK-8189<br>|
| Experimental: Panel E<br>Participants receive 7 days of oral MK-8189 or matched placebo treatment (Period 1), followed by a single IM injection of MK-5720 at a specified Dose 5 or a dose matched placebo (Period 2). | Drug: MK-5720<br>* MK-5720 IM injection<br>Drug: Placebo to MK-5720<br>* Placebo matched to MK-5720 IM injection<br>* Other names: Dextrose;Drug: MK-8189<br>* MK-8189 tablet taken by mouth<br>Drug: Placebo to MK-8189<br>* Placebo tablet matched to MK-8189<br>|
| Experimental: Panel F<br>Participants receive 7 days of oral MK-8189 or matched placebo treatment (Period 1), followed by a single IM injection of MK-5720 at a specified Dose 6 or a dose matched placebo (Period 2). | Drug: MK-5720<br>* MK-5720 IM injection<br>Drug: Placebo to MK-5720<br>* Placebo matched to MK-5720 IM injection<br>* Other names: Dextrose;Drug: MK-8189<br>* MK-8189 tablet taken by mouth<br>Drug: Placebo to MK-8189<br>* Placebo tablet matched to MK-8189<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Experience ≥1 Adverse Event (AE) in Period 1 | An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. The number of participants who experience one or more AE will be reported. | Up to approximately 12 Months | 
| Number of Participants Who Experience ≥1 AE(s) in Period 2 | An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. The number of participants who experience one or more AE will be reported. | Up to approximately 12 Months | 
| Number of Participants Who Discontinue Study Due to an AE in Period 1 | An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. The number of participants who discontinue study due to an AE will be reported. | Up to approximately 12 Months | 
| Number of Participants Who Discontinue Study Due to an AE in Period 2 | An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. The number of participants who discontinue study due to an AE will be reported. | Up to approximately 12 Months | 
| Area Under the Concentration-Time Curve from Time 0 to Last Quantifiable Concentration (AUC0-last) of MK 5720 | Blood samples will be collected at specified intervals for the determination of AUC0-last. AUC0-last is defined as the area under the concentration-time curve from time zero to time of last measurable concentration 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 | 
| Area Under the Concentration-Time Curve from Time 0 to Infinity (AUC-inf) of MK-5720 | Blood samples will be collected at specified intervals for the determination of AUC-inf. AUC0-inf is defined as the area under concentration-time curve of MK-5720 from time zero to infinity. | 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 | 
| Maximum Serum Concentration (Cmax) of MK-5720 | Blood samples will be collected at specified intervals for the determination of Cmax. Cmax is defined as the maximum concentration of MK-5720 reached. | 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 | 
| Time to Maximum Concentration (Tmax) of MK-5720 | Blood samples will be collected at specified intervals for the determination of Tmax. Tmax is defined as the time to maximum concentration of MK-5720 reached. | 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 | 
| Apparent Clearance (CL/F) of MK-5720 | Blood samples will be collected at specified intervals for the determination of CL/F. CL/F is the rate at which the MK-5720 is completely removed from plasma. | 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 | 
| Apparent Volume of Distribution (Vz/F) of MK-5720 | Blood samples will be collected at specified intervals for the determination of Vz/F. Vz/F is the apparent volume of distribution 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 | 
| Apparent Terminal Half-life (t1/2) of MK-5720 | Blood samples will be collected at specified intervals for the determination t1/2. t1/2 is defined as the time required to divide plasma concentration of MK-5720 by half after reaching pseudo-equilibrium. | 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 | 
| Area Under the concentration-Time Curve from Time 0 to 28 Days (AUC0-28d) of MK-8189 | Blood samples will be collected at specified intervals for the determination of AUC0-28d. 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). | 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-inf of MK-8189 | Blood samples will be collected at specified intervals for the determination of AUC-inf. AUC0-inf is defined as the area under concentration-time curve from time zero to infinity of MK-8189 (a metabolite 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 of MK-8189 | Blood samples will be collected at specified intervals for the determination of Cmax. Cmax is defined as the maximum concentration of MK-8189 (a metabolite of MK-5720) reached. | 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 of MK-8189 | Blood samples will be collected at specified intervals for the determination of Tmax. Tmax is defined as the time to maximum concentration of MK-8189 (a metabolite 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 | 
| Concentration at Day 28 (C28d) of MK-8189 | Blood samples will be collected at specified intervals for the determination of C28d. C28d is defined as the maximum concentration from time zero to 28 days of MK-8189 (a metabolite 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, and 672 hours postdose | 
| CL/F of MK-8189 | Blood samples will be collected at specified intervals for the determination of CL/F. CL/F is the rate at which the MK-8189 (a metabolite of MK-5720) is completely removed from plasma. | 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 of MK-8189 | Blood samples will be collected at specified intervals for the determination of Vz/F. Vz/F is the apparent volume of distribution of MK-8189 (a metabolite 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 of MK-8189 | Blood samples will be collected at specified intervals for the determination of Half-life (t1/2). 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. | 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 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| C28d Tied to Specific Exposures of MK-8189 | Blood samples will be collected at specified intervals for the determination of C28d tied to specific exposures of MK-8189 (metabolite of MK-5720). 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. | 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 | 
| AUC0-28d of MK-8189 in Gluteal Muscle Versus AUC0-28 of MK-8189 in Deltoid Muscle | Blood samples will be collected at specified intervals for the determination of AUC0-28 of MK-8189 (a metabolite of MK-5720) after administration of MK-5720 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. | 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-inf of MK-8189 in Gluteal Muscle Versus AUC0-inf of MK-8189 in Deltoid Muscle | Blood samples will be collected at specified intervals for the determination of AUC-inf of MK-8189 (a metabolite of MK-5720) after administration of MK-5720 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. | 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 of MK-8189 in Gluteal Muscle Versus Cmax of MK-8189 in Deltoid Muscle | Blood samples will be collected at specified intervals for the determination of Cmax of MK-8189 (a metabolite of MK-5720) after administration of MK-5720 in the gluteal muscle and deltoid muscle. Cmax is defined as the maximum concentration 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 of MK-8189 in Gluteal Muscle Versus Tmax of MK-8189 in Deltoid Muslce | Blood samples will be collected at specified intervals for determination of Tmax of MK-8189 (a metabolite of MK-5720) after administration of MK-5720 in the gluteal muscle and deltoid muscle. Tmax is defined as the time to maximum concentration of MK-8189 (metabolite 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, 1320 hours postdose | 
| C28d of MK-8189 in Gluteal Muscle Versus C28d in Deltoid Muslce | Blood samples will be collected at specified intervals for the determination of C28d of MK-8189 (a metabolite of MK-5720) after administration of MK-5720 in the gluteal muscle and deltoid muscle. C28d is defined as the maximum concentration from time zero to 28 days of MK-8189. | Predose, 0.5, 1, 2, 4, 6, 24, 48, 96, 120, 144, 168, 192, 216, 264, 288, 312, 336, 360, 432, 456, 504, and 672 hours postdose | 
| CL/F of MK-8189 in Gluteal Muscle Versus CL/F in Deltoid Muscle | Blood samples will be collected at specified intervals for the determination of CL/F of MK-8189 (a metabolite of MK-5720) after administration of MK-5720 in the gluteal muscle and deltoid muscle. CL/F is the rate at which the MK-8189 is completely removed from plasma. | 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 of MK-8189 in Gluteal Muscle Versus Vz/F of MK-8189 in Deltoid Muscle | Blood samples will be collected at specified intervals for the determination of distribution of MK-8189 (metabolite of MK-5720) after administration of MK-5720 in the gluteal muscle versus deltoid muscle. Vz/F is the apparent volume of distribution 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 of MK-8189 in Gluteal Muscle Versus t1/2 of MK-8189 in Deltoid Muslce | Blood samples will be collected at specified intervals for the determination of t1/2 of MK-8189 (metabolite of MK-5720) after administration of MK-5720 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. | 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 of MK 5720 in Gluteal Muscle Versus AUC0-last of MK-5720 in Deltoid Muscle | Blood samples will be collected at specified intervals for the determination of AUC0-last after administration of MK-5720 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. | 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 of MK-5720 in Gluteal Muscle Versus AUC0-inf of MK-5720 in Deltoid Muscle | Blood samples will be collected at specified intervals for the determination of AUC-inf after administration of MK-5720 in the gluteal muscle and deltoid muscle. AUC0-inf is defined as the area under concentration-time curve from time zero to infinity. | 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 of MK-5720 in Gluteal Muscle Versus Cmax of MK-5720 in Deltoid Muscle | Blood samples will be collected at specified intervals for the determination of Cmax after administration of MK-5720 in the gluteal muscle and deltoid muscle. Cmax is defined as the maximum concentration of MK-5720 reached. | 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 of MK-5720 in Gluteal Muscle Versus Tmax of MK-5720 in Deltoid Muscle | Blood samples will be collected at specified intervals for the determination of Tmax after administration of MK-5720 in the gluteal muscle and deltoid muscle. Tmax is defined as the time to maximum concentration of MK-5720 reached. | 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 of MK-5720 in Gluteal Muscle Versus CL/F of MK-5720 in Deltoid Muscle | Blood samples will be collected at specified intervals for the determination of CL/F after administration of MK-5720 in the gluteal muscle and deltoid muscle. CL/F is the rate at which the MK-5720 is completely removed from plasma. | 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 of MK-5720 in Gluteal Muscle Versus Vz/F of MK-5720 in Deltoid Muscle | Blood samples will be collected at specified intervals for the determination Vz/F after administration of MK-5720 in the gluteal muscle and deltoid muscle. Vz/F is the apparent volume of distribution 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 of MK-5720 in Gluteal Muscle Versus t1/2 of MK-5720 in Deltoid Muscle | Blood samples will be collected at specified intervals for the determination t1/2 after administration of MK-5720 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. | 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 |