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

Cognitive Impairment Associated With Schizophrenia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05136690
• Other study ID #: 4334-007
• Secondary ID: MK-4334-007
• Status: Completed
• Phase: Phase 1
• Start date: April 27, 2022
• Est. completion date: November 4, 2022

Study information

• Verified date: November 2022
• Source: Merck Sharp & Dohme LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 38
• Est. completion date: November 4, 2022
• Est. primary completion date: September 23, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Cognitive Impairment Associated With Schizophrenia
• Schizophrenia

Intervention

Drug:
• Nicotine patch
Nicotine 21 mg transdermal nicotine patch.
• MK-4334
MK-4334 250 mg capsule taken by mouth.
• Placebo patch
Placebo patch.
• Placebo capsule
Placebo capsule taken by mouth.

Locations

Country	Name	City	State
United States	Collaborative Neuroscience Research, LLC ( Site 0002)	Long Beach	California
United States	Hassman Research Institute Marlton Site ( Site 0001)	Marlton	New Jersey

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Day -1
Secondary	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.	Day 1
Secondary	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.	Day 1 or Day 8
Secondary	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.	Day 1 or Day 8