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

NCT ID: NCT05136690

Last Updated: 2024-11-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 38 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-04-27
• Study Completion Date: 2022-11-04

Brief Summary

The primary purpose of this randomized, double-blind, placebo-controlled cross-over study was 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 was a 2-period study in which participants received either 21 mg nicotine patches and then placebo patches or vice versa, with each patch co-administered with placebo capsules, in a counterbalanced order. In Part 2, participants were randomized to receive either MK-4334 250 mg capsule or placebo capsule, each with placebo patches.

Conditions

Cognitive Impairment Associated With Schizophrenia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: TRIPLE

Study Groups

Panel A: Healthy Control Participants

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.

Group Type: EXPERIMENTAL

Nicotine patch

Intervention Type: DRUG

Nicotine 21 mg transdermal nicotine patch.

MK-4334

Intervention Type: DRUG

MK-4334 250 mg capsule taken by mouth.

Placebo patch

Intervention Type: DRUG

Placebo patch.

Placebo capsule

Intervention Type: DRUG

Placebo capsule taken by mouth.

Panel B: Participants with Mild-to-Moderate SZ

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.

Group Type: EXPERIMENTAL

Nicotine patch

Intervention Type: DRUG

Nicotine 21 mg transdermal nicotine patch.

MK-4334

Intervention Type: DRUG

MK-4334 250 mg capsule taken by mouth.

Placebo patch

Intervention Type: DRUG

Placebo patch.

Placebo capsule

Intervention Type: DRUG

Placebo capsule taken by mouth.

Interventions

Nicotine patch

Nicotine 21 mg transdermal nicotine patch.

Intervention Type: DRUG

MK-4334

MK-4334 250 mg capsule taken by mouth.

Intervention Type: DRUG

Placebo patch

Placebo patch.

Intervention Type: DRUG

Placebo capsule

Placebo capsule taken by mouth.

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Locations

Collaborative Neuroscience Research, LLC ( Site 0002)

Long Beach, California, United States

Hassman Research Institute Marlton Site ( Site 0001)

Marlton, New Jersey, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

http://www.merckclinicaltrials.com

Merck Clinical Trials Information

Other Identifiers

MK-4334-007

Identifier Type: OTHER

Identifier Source: secondary_id

4334-007

Identifier Type: -

Identifier Source: org_study_id