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Evoked Responses as Pharmacodynamic Biomarkers in Healthy and Schizophrenic Participants (MK-4334-007)

Primary Purpose

Cognitive Impairment Associated With Schizophrenia

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Nicotine patch

MK-4334

Placebo patch

Placebo capsule

About this trial

This is an interventional basic science trial for Cognitive Impairment Associated With Schizophrenia

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

HC Participants:

Is in generally good health
Has no history of clinically relevant neuropsychiatric illness
Is a mild-to-moderate tobacco user of ≥1-year duration, smoking the equivalent of ~10-15 cigarettes/day

Participants with Mild-to-Moderate SZ:

Has a current diagnosis of SZ with a duration ≥1 year
Is clinically stable and in the residual (non-acute) phase of illness for ≥12 weeks prior to the study
Is stably maintained on a regimen of up to 2 first- or second-generation antipsychotics with no dose changes >50% in combination with concomitant medication commonly prescribed to this population for ≥8 weeks prior to screening and during the study
Is a mild-to-moderate tobacco user of ≥1-year duration, smoking the equivalent of ~10-15 cigarettes/day

All Participants:

For males, agrees to be abstinent from heterosexual intercourse, or use an approved contraception method, during the study and for 90 days after the last dose of study drug
For females, is not of childbearing potential
Is willing to comply with restrictions on the use of nicotine or nicotine-containing products during the study

Exclusion Criteria:

HC Participants:

Has known biological family history of psychotic disorder in a first or second degree relative

Participants with Mild-to-Moderate SZ:

May be excluded from participation by the investigator based on treatment history and/or performance on various screening tests

All Participants:

Is positive for hepatitis B surface antigen, hepatitis C antibodies, or human immunodeficiency virus (HIV)
Is at imminent risk of self-harm
Has had major surgery or donated blood within 4 weeks prior to screening
Has evidence of cognitive impairment or significant mental disability
Has a history of clinically significant abnormality or disease
Has a history of cancer (malignancy)
Is unable to refrain, or anticipates use, of any non-prescription drugs or herbal remedies
Has participated in another clinical study within 6 weeks or 5 half-lives (whichever is greater) prior to screening

Sites / Locations

Collaborative Neuroscience Research, LLC ( Site 0002)
Hassman Research Institute Marlton Site ( Site 0001)

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Panel A: Healthy Control Participants

Panel B: Participants with Mild-to-Moderate SZ

Arm Description

In Part 1, HC participants receive nicotine patch + capsule placebo, and patch placebo + capsule placebo, under a cross-over design in Periods 1 and 2. In Part 2 (Period 3), HC participants are randomly assigned to receive either MK-4334 250 mg capsule + patch placebo or capsule placebo + patch placebo.

In Part 1, participants with mild-to-moderate SZ receive nicotine patch + capsule placebo, and patch placebo + capsule placebo, under a cross-over design in Periods 1 and 2. In Part 2 (Period 3), SZ participants are randomly assigned to receive either MK-4334 250 mg capsule + patch placebo or capsule placebo + patch placebo.

Outcomes

Primary Outcome Measures

Mean inter-trial coherence (ITC) magnitude of 40 Hz-derived auditory steady-state response (ASSR) in HC and SZ participants

The magnitude of ITC of 40 Hz-derived ASSR will be measured and recorded at baseline (Day -1) to determine if ITC differs between HC and SZ participants.

Secondary Outcome Measures

Duration deviant mismatch negativity (DD-MMN) in HC and SZ participants

The mean MMN magnitude derived from baseline DD-MMN will be compared in HC and SZ participants.

Effect of nicotine on mean ITC magnitude of 40 Hz-derived ASSR in HC and SZ participants

The effects of nicotine and placebo patches on 40 Hz-derived ASSR will be determined in HC and SZ participants on Day 1 or Day 8 in a counterbalanced order.

Plasma nicotine level during event related potential (ERP) recording

Plasma nicotine levels will be determined during nicotine patch test sessions occurring on Day 1 or Day 8 in a counterbalanced order.

Full Information

NCT ID

NCT05136690

First Posted

November 19, 2021

Last Updated

November 16, 2022

Sponsor

Merck Sharp & Dohme LLC

1. Study Identification

Unique Protocol Identification Number

NCT05136690

Brief Title

Evoked Responses as Pharmacodynamic Biomarkers in Healthy and Schizophrenic Participants (MK-4334-007)

Official Title

A Randomized, Double-Blind, Placebo-Controlled, Cross-over Evaluation of Evoked Responses as Pharmacodynamic Biomarkers in Healthy Adults and Schizophrenic Patients

Study Type

Interventional

2. Study Status

Record Verification Date

November 2022

Overall Recruitment Status

Completed

Study Start Date

April 27, 2022 (Actual)

Primary Completion Date

September 23, 2022 (Actual)

Study Completion Date

November 4, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Merck Sharp & Dohme LLC

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

The primary purpose of this randomized, double-blind, placebo-controlled cross-over study is to record and measure 40 Hz-auditory steady-state response (ASSR) in healthy controls (HC) and participants with mild-to-moderate schizophrenia (SZ) to determine if the mean inter-trial coherence (ITC) magnitude derived from the 40 Hz-ASSR is lower in SZ than in HC at baseline.

Detailed Description

This is a 2-part study. Part 1 is a 2-period study in which participants receive 21 mg nicotine patches or placebo patches, each with placebo capsules, in Period 1 and Period 2 under a cross-over design. In Part 2 (Period 3), participants are randomized to receive either MK-4334 250 mg capsule or placebo capsule, each with placebo patches.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Cognitive Impairment Associated With Schizophrenia

7. Study Design

Primary Purpose

Basic Science

Study Phase

Phase 1

Interventional Study Model

Crossover Assignment

Masking

ParticipantInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

38 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Panel A: Healthy Control Participants

Arm Type

Experimental

Arm Description

Arm Title

Panel B: Participants with Mild-to-Moderate SZ

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Nicotine patch

Intervention Description

Nicotine 21 mg transdermal nicotine patch.

Intervention Type

Drug

Intervention Name(s)

MK-4334

Intervention Description

MK-4334 250 mg capsule taken by mouth.

Intervention Type

Drug

Intervention Name(s)

Placebo patch

Intervention Description

Placebo patch.

Intervention Type

Drug

Intervention Name(s)

Placebo capsule

Intervention Description

Placebo capsule taken by mouth.

Primary Outcome Measure Information:

Title

Mean inter-trial coherence (ITC) magnitude of 40 Hz-derived auditory steady-state response (ASSR) in HC and SZ participants

Description

The magnitude of ITC of 40 Hz-derived ASSR will be measured and recorded at baseline (Day -1) to determine if ITC differs between HC and SZ participants.

Time Frame

Day -1

Secondary Outcome Measure Information:

Title

Duration deviant mismatch negativity (DD-MMN) in HC and SZ participants

Description

The mean MMN magnitude derived from baseline DD-MMN will be compared in HC and SZ participants.

Time Frame

Day 1

Title

Effect of nicotine on mean ITC magnitude of 40 Hz-derived ASSR in HC and SZ participants

Description

The effects of nicotine and placebo patches on 40 Hz-derived ASSR will be determined in HC and SZ participants on Day 1 or Day 8 in a counterbalanced order.

Time Frame

Day 1 or Day 8

Title

Plasma nicotine level during event related potential (ERP) recording

Description

Plasma nicotine levels will be determined during nicotine patch test sessions occurring on Day 1 or Day 8 in a counterbalanced order.

Time Frame

Day 1 or Day 8

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

55 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: HC Participants: Is in generally good health Has no history of clinically relevant neuropsychiatric illness Is a mild-to-moderate tobacco user of ≥1-year duration, smoking the equivalent of ~10-15 cigarettes/day Participants with Mild-to-Moderate SZ: Has a current diagnosis of SZ with a duration ≥1 year Is clinically stable and in the residual (non-acute) phase of illness for ≥12 weeks prior to the study Is stably maintained on a regimen of up to 2 first- or second-generation antipsychotics with no dose changes >50% in combination with concomitant medication commonly prescribed to this population for ≥8 weeks prior to screening and during the study Is a mild-to-moderate tobacco user of ≥1-year duration, smoking the equivalent of ~10-15 cigarettes/day All Participants: For males, agrees to be abstinent from heterosexual intercourse, or use an approved contraception method, during the study and for 90 days after the last dose of study drug For females, is not of childbearing potential Is willing to comply with restrictions on the use of nicotine or nicotine-containing products during the study Exclusion Criteria: HC Participants: Has known biological family history of psychotic disorder in a first or second degree relative Participants with Mild-to-Moderate SZ: May be excluded from participation by the investigator based on treatment history and/or performance on various screening tests All Participants: Is positive for hepatitis B surface antigen, hepatitis C antibodies, or human immunodeficiency virus (HIV) Is at imminent risk of self-harm Has had major surgery or donated blood within 4 weeks prior to screening Has evidence of cognitive impairment or significant mental disability Has a history of clinically significant abnormality or disease Has a history of cancer (malignancy) Is unable to refrain, or anticipates use, of any non-prescription drugs or herbal remedies Has participated in another clinical study within 6 weeks or 5 half-lives (whichever is greater) prior to screening

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Medical Director

Organizational Affiliation

Merck Sharp & Dohme LLC

Official's Role

Study Director

Facility Information:

Facility Name

Collaborative Neuroscience Research, LLC ( Site 0002)

City

Long Beach

State/Province

California

ZIP/Postal Code

90806

Country

United States

Facility Name

Hassman Research Institute Marlton Site ( Site 0001)

City

Marlton

State/Province

New Jersey

ZIP/Postal Code

08053

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

IPD Sharing URL

http://engagezone.msd.com/ds_documentation.php

Learn more about this trial

Evoked Responses as Pharmacodynamic Biomarkers in Healthy and Schizophrenic Participants (MK-4334-007)

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