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

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 1

Conditions: Cognitive Impairment Associated With Schizophrenia

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT05136690

MK-4334-007 (Other Identifier)

4334-007

Details and patient eligibility

About

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.

Full 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.

Enrollment: 38 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts 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

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Triple Blind

---

38 participants in 2 patient groups

Panel A: Healthy Control Participants

Experimental group

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.

Treatment:

Drug: Placebo patch

Drug: Placebo capsule

Drug: Nicotine patch

Drug: MK-4334

Panel B: Participants with Mild-to-Moderate SZ

Experimental group

Description:

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.

Treatment:

Drug: Placebo patch

Drug: Placebo capsule

Drug: Nicotine patch

Drug: MK-4334