Phase 1
N=38
Evoked Responses as Pharmacodynamic Biomarkers in Healthy and Schizophrenic Participants (MK-4334-007)
Cognitive Impairment Associated With Schizophrenia
Bottom Line
View on ClinicalTrials.gov: NCT05136690 ↗Enrolled (actual)
38
Serious AEs
0.0%
Results posted
Nov 2024
Primary outcome: Primary: Mean Inter-trial Coherence (ITC) Magnitude of 40 Hz-derived Auditory Steady-state Response (ASSR) in HC and SZ Participants at Baseline — 0.432; 0.364 ITC (40Hz*msec)
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- Nicotine patch (Drug); MK-4334 (Drug); Placebo patch (Drug); Placebo capsule (Drug)
- Age
- Adult · 18+ yrs
- Sex
- All
- Sponsor
- Merck Sharp & Dohme LLC
- Primary completion
- Sep 2022
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Mean Inter-trial Coherence (ITC) Magnitude of 40 Hz-derived Auditory Steady-state Response (ASSR) in HC and SZ Participants at Baseline |
0.432; 0.364 | — |
| SECONDARY Duration Deviant Mismatch Negativity (DD-MMN) in HC and SZ Participants: MMN-A, N100-A, and P3A-A Tests |
-5.207; -3.932; -1.616; -1.117; 2.974; 3.121 | — |
| SECONDARY Duration Deviant Mismatch Negativity (DD-MMN) in HC and SZ Participants: MMN-L, N100-L, and P3A-L Tests |
172.615; 178.880; 90.462; 87.680; 284.308; 280.480 | — |
| SECONDARY Effect of Nicotine on Mean ITC Magnitude of 40 Hz-derived ASSR in HC and SZ Participants Compared to Baseline |
0.054; 0.040; 0.000; 0.010 | — |
| SECONDARY Plasma Nicotine Concentration 2 Hours After Patch Application (C2h) Assessed During Event Related Potential (ERP) Recording Sessions |
160.5; 163.3; 119.6; 159.3 | — |
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.
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
Data sourced from ClinicalTrials.gov (NCT05136690). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.