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

NCT05136690 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 4334-007MK-4334-007
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 2

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.

Conditions

Cognitive Impairment Associated With Schizophrenia

Outcome Measures

Primary Outcomes (1)

• Mean Inter-trial Coherence (ITC) Magnitude of 40 Hz-derived Auditory Steady-state Response (ASSR) in HC and SZ Participants at Baseline

  The ITC magnitude derived from the 40Hz ASSR is presented. ASSR is measured following a short stream of click trains with a 500 msec inter-train interval (duration), at standard tone and at 40Hz tone. The magnitude of ITC represents the phase consistency of oscillatory activities, in response to EEG coherence at 40Hz stimulation. ITC as a unit of measure is expressed as frequency (40Hz) vs time (msec).

  Day -1 (Baseline)

Secondary Outcomes (4)

• Duration Deviant Mismatch Negativity (DD-MMN) in HC and SZ Participants: MMN-A, N100-A, and P3A-A Tests

  Day -1 (Baseline)

• Duration Deviant Mismatch Negativity (DD-MMN) in HC and SZ Participants: MMN-L, N100-L, and P3A-L Tests

  Day -1 (Baseline)

• Effect of Nicotine on Mean ITC Magnitude of 40 Hz-derived ASSR in HC and SZ Participants Compared to Baseline

  Day -1 (baseline), Day 1, and Day 8

• Plasma Nicotine Concentration 2 Hours After Patch Application (C2h) Assessed During Event Related Potential (ERP) Recording Sessions

  2 hours after patch application on Day 1 or Day 8

Study Arms (2)

Panel A: Healthy Control Participants

EXPERIMENTAL

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.

Drug: Nicotine patch; Drug: MK-4334; Drug: Placebo patch; Drug: Placebo capsule

Panel B: Participants with Mild-to-Moderate SZ

EXPERIMENTAL

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.

Drug: Nicotine patch; Drug: MK-4334; Drug: Placebo patch; Drug: Placebo capsule

Interventions

Nicotine patch DRUG

Nicotine 21 mg transdermal nicotine patch.

Panel A: Healthy Control Participants; Panel B: Participants with Mild-to-Moderate SZ

MK-4334 DRUG

MK-4334 250 mg capsule taken by mouth.

Panel A: Healthy Control Participants; Panel B: Participants with Mild-to-Moderate SZ

Placebo patch DRUG

Placebo patch.

Panel A: Healthy Control Participants; Panel B: Participants with Mild-to-Moderate SZ

Placebo capsule DRUG

Placebo capsule taken by mouth.

Panel A: Healthy Control Participants; Panel B: Participants with Mild-to-Moderate SZ

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (2)

Collaborative Neuroscience Research, LLC ( Site 0002)

Long Beach, California, 90806, United States

Location

Hassman Research Institute Marlton Site ( Site 0001)

Marlton, New Jersey, 08053, United States

Location

Related Links

• Merck Clinical Trials Information

MeSH Terms

Interventions

Tobacco Use Cessation Devices

Intervention Hierarchy (Ancestors)

Therapeutics

Results Point of Contact

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

ClinicalTrialsDisclosure@merck.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
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 19, 2021
• First Posted: November 29, 2021
• Study Start: April 27, 2022
• Primary Completion: September 23, 2022
• Study Completion: November 4, 2022
• Last Updated: November 29, 2024
• Results First Posted: November 29, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will share

Locations

US (2)