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

Schizophrenia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05953740
• Other study ID #: 5720-001
• Secondary ID: MK-5720-001
• Status: Completed
• Phase: Phase 1
• Start date: September 15, 2023
• Est. completion date: February 15, 2024

Study information

• Verified date: March 2024
• Source: Merck Sharp & Dohme LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 17
• Est. completion date: February 15, 2024
• Est. primary completion date: February 15, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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

Related Conditions & MeSH terms

• Schizophrenia

Intervention

Drug:
• MK-5720
MK-5720 IM injection
• Placebo to MK-5720
Placebo matched to MK-5720 IM injection
• MK-8189
MK-8189 tablet taken by mouth
• Placebo to MK-8189
Placebo tablet matched to MK-8189

Locations

Country	Name	City	State
United States	California Clinical Trials Medical Group managed by PAREXEL ( Site 0003)	Glendale	California
United States	Velocity Clinical Research, Hallandale Beach ( Site 0002)	Hallandale Beach	Florida
United States	Research Centers of America ( Hollywood ) ( Site 0001)	Hollywood	Florida
United States	Hassman Research Institute Marlton Site ( Site 0007)	Marlton	New Jersey

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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

External Links

•   Merck Clinical Trials Information