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

• Sponsor: Merck Sharp & Dohme LLC (Industry)
• Overall Status: Not yet recruiting
• CT.gov ID: NCT05953740
• Collaborator: (none)
• Enrollment: 64
• Arms: 6
• Anticipated Duration (Months): 12.2

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics (PK) of MK-5720 in participants with schizophrenia. The primary study hypothesis is that the administration of MK-5720 is safe and well tolerated.

Condition or Disease	Intervention/Treatment	Phase
Schizophrenia	Drug: MK-5720; Drug: Placebo	Phase 1

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 64 participants
• Allocation: Randomized
• Intervention Model: Sequential Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Masking Description: Double blind
• Primary Purpose: Treatment
• 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
• Anticipated Study Start Date: Aug 14, 2023
• Anticipated Primary Completion Date: Aug 19, 2024
• Anticipated Study Completion Date: Aug 19, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Panel A Participants receive a single intramuscular (IM) injection of MK-5720 at a specified Dose 1 or a dose matched placebo	Drug: MK-5720; IM injection; Drug: Placebo; IM injection; Other Names: Normal saline Dextrose
Experimental: Panel B Participants receive a single IM injection of MK-5720 at a specified Dose 2 or a dose matched placebo	Drug: MK-5720; IM injection; Drug: Placebo; IM injection; Other Names: Normal saline Dextrose
Experimental: Panel C Participants receive a single IM injection of MK-5720 up to a specified Dose 3 or a dose matched placebo	Drug: MK-5720; IM injection; Drug: Placebo; IM injection; Other Names: Normal saline Dextrose
Experimental: Panel D Participants receive a single IM injection of MK-5720 up to a specified Dose 4 or a dose matched placebo	Drug: MK-5720; IM injection; Drug: Placebo; IM injection; Other Names: Normal saline Dextrose
Experimental: Panel E Participants receive a single IM injection of MK-5720 up to a specified Dose 5 or a dose matched placebo	Drug: MK-5720; IM injection; Drug: Placebo; IM injection; Other Names: Normal saline Dextrose
Experimental: Panel F Participants receive a single IM injection of MK-5720 up to a specified Dose 6 or a dose matched placebo	Drug: MK-5720; IM injection; Drug: Placebo; IM injection; Other Names: Normal saline Dextrose

Outcome Measures

Primary Outcome Measures

1. Number of Participants Who Experience One or More Adverse Event (AE) [Up to approximately 12 Months]

   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.

2. Number of Participants Who Discontinue Study Due to an AE [Up to approximately 12 Months]

   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.

3. 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]

   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.

4. 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]

   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.

5. 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]

   Blood samples will be collected at specified intervals for the determination of Cmax. Cmax is defined as the maximum concentration of MK-5720 reached.

6. 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]

   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.

7. 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]

   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.

8. 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]

   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.

9. 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]

   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.

10. 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]

    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).

11. 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]

    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).

12. 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]

    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.

13. 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]

    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).

14. 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]

    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).

15. 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]

    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.

16. 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]

    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).

17. 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]

    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.

Secondary Outcome Measures

1. 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]

   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.

2. 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 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.

3. 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 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.

4. 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 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.

5. Tmax of MK-8189 in Gluteal Muscle Versus Tmax of MK-8189 in Deltoid Muslce [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 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).

6. C28d of MK-8189 in Gluteal Muscle Versus C28d in Deltoid Muslce [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]

   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.

7. 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 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.

8. 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 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.

9. t1/2 of MK-8189 in Gluteal Muscle Versus t1/2 of MK-8189 in Deltoid Muslce [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 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.

10. 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 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.

11. 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 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.

12. 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 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.

13. 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 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.

14. 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 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.

15. 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 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.

16. 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 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts 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 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

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Merck Sharp & Dohme LLC

Investigators

• Study Director: Medical Director, Merck Sharp & Dohme LLC

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Merck Clinical Trials Information

Publications

None provided.

• Responsible Party: Merck Sharp & Dohme LLC
• ClinicalTrials.gov Identifier: NCT05953740
• Other Study ID Numbers: 5720-001; MK-5720-001
• First Posted: Jul 20, 2023
• Last Update Posted: Jul 27, 2023
• Last Verified: Jul 1, 2023

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Schizophrenia

Study Results

No Results Posted as of Jul 27, 2023