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

NCT05953740 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 5720-001MK-5720-001
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 4

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.

Conditions

Schizophrenia

Outcome Measures

Primary Outcomes (19)

• 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.

  Up to approximately 10 days

• 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.

  Up to approximately 72 days

• 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.

  Up to approximately 10 days

• 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.

  Up to approximately 72 days

• 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.

  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

  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.

  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

  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.

  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

  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.

  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

  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.

  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

  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.

  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

  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.

  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

  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.

  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

  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.

  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

  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.

  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

  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.

  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

  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."

  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

  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.

  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

  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.

  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

  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.

  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 Outcomes (16)

• 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

• 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

• 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

• 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

• 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

Study Arms (6)

Panel A

EXPERIMENTAL

Participants received 7 days of oral MK-8189 4 mg or matched placebo treatment (Period 1), followed by a single intramuscular (IM) injection of MK-5720 35 mg or a dose matched placebo (Period 2).

Drug: MK-5720; Drug: Placebo to MK-5720; Drug: MK-8189; Drug: Placebo to MK-8189

Panel B

EXPERIMENTAL

Participants received 7 days of oral MK-8189 8 mg or matched placebo treatment (Period 1), followed by a single IM injection of MK-5720 70 mg or a dose matched placebo (Period 2).

Drug: MK-5720; Drug: Placebo to MK-5720; Drug: MK-8189; Drug: Placebo to MK-8189

Panel C

EXPERIMENTAL

Participants received 7 days of oral MK-8189 up to 16 mg or matched placebo treatment (Period 1), followed by a single IM injection of MK-5720 up to 140 mg or a dose matched placebo (Period 2).

Drug: MK-5720; Drug: Placebo to MK-5720; Drug: MK-8189; Drug: Placebo to MK-8189

Panel D

EXPERIMENTAL

Participants received 7 days of oral MK-8189 up to 24 mg or matched placebo treatment (Period 1), followed by a single IM injection of MK-5720 up to 280 mg or a dose matched placebo (Period 2).

Drug: MK-5720; Drug: Placebo to MK-5720; Drug: MK-8189; Drug: Placebo to MK-8189

Panel E

EXPERIMENTAL

Participants received 7 days of oral MK-8189 up to 48 mg or matched placebo treatment (Period 1), followed by a single IM injection of MK-5720 up to 560 mg or a dose matched placebo (Period 2).

Drug: MK-5720; Drug: Placebo to MK-5720; Drug: MK-8189; Drug: Placebo to MK-8189

Panel F

EXPERIMENTAL

Participants received 7 days of oral MK-8189 up to 48 mg or matched placebo treatment (Period 1), followed by a single IM injection of MK-5720 up to 560 mg or a dose matched placebo (Period 2), after a Pharmacokinetic (PK) break following Panel E.

Drug: MK-5720; Drug: Placebo to MK-5720; Drug: MK-8189; Drug: Placebo to MK-8189

Interventions

MK-5720 DRUG

IM injection

Panel A; Panel B; Panel C; Panel D; Panel E; Panel F

Placebo to MK-5720 DRUG

Placebo IM Injection matched to MK-5720

Also known as: Normal saline, Dextrose

Panel A; Panel B; Panel C; Panel D; Panel E; Panel F

MK-8189 DRUG

Oral Tablet

Panel A; Panel B; Panel C; Panel D; Panel E; Panel F

Placebo to MK-8189 DRUG

Placebo oral tablet matched to MK-8189

Panel A; Panel B; Panel C; Panel D; Panel E; Panel F

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (4)

California Clinical Trials Medical Group managed by PAREXEL ( Site 0003)

Glendale, California, 91206, United States

Location

Velocity Clinical Research, Hallandale Beach ( Site 0002)

Hallandale, Florida, 33009, United States

Location

Research Centers of America ( Hollywood ) ( Site 0001)

Hollywood, Florida, 33024, United States

Location

Hassman Research Institute Marlton Site ( Site 0007)

Marlton, New Jersey, 08053, United States

Location

Related Links

• Merck Clinical Trials Information

MeSH Terms

Conditions

Schizophrenia

Interventions

Saline Solution; Glucose; MK-8189

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations; Hexoses; Monosaccharides; Sugars; Carbohydrates

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme LLC

ClinicalTrialsDisclosure@msd.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double blind
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 12, 2023
• First Posted: July 20, 2023
• Study Start: September 15, 2023
• Primary Completion: February 15, 2024
• Study Completion: February 15, 2024
• Last Updated: March 4, 2025
• Results First Posted: March 4, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will share

Locations

US (4)