Clinical trial NCT05136690: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cognitive Impairment Associated With Schizophrenia
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2021-11-29
Enrollment: 38
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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.

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

Primary outcomes:
measure: Mean Inter-trial Coherence (ITC) Magnitude of 40 Hz-derived Auditory Steady-state Response (ASSR) in HC and SZ Participants at Baseline
timeFrame: Day -1 (Baseline)
Secondary outcomes:
measure: Duration Deviant Mismatch Negativity (DD-MMN) in HC and SZ Participants: MMN-A, N100-A, and P3A-A Tests
timeFrame: Day -1 (Baseline)
measure: Duration Deviant Mismatch Negativity (DD-MMN) in HC and SZ Participants: MMN-L, N100-L, and P3A-L Tests
timeFrame: Day -1 (Baseline)
measure: Effect of Nicotine on Mean ITC Magnitude of 40 Hz-derived ASSR in HC and SZ Participants Compared to Baseline
timeFrame: Day -1 (baseline), Day 1, and Day 8
measure: Plasma Nicotine Concentration 2 Hours After Patch Application (C2h) Assessed During Event Related Potential (ERP) Recording Sessions
timeFrame: 2 hours after patch application on Day 1 or Day 8
Other outcomes:
Locations:
city: Long Beach
country: United States
facility: Collaborative Neuroscience Research, LLC ( Site 0002)
state: California
city: Marlton
country: United States
facility: Hassman Research Institute Marlton Site ( Site 0001)
state: New Jersey
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: