Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| MK-4334-007 | Other Identifier | Merck |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
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.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Nicotine patch | Drug | Nicotine 21 mg transdermal nicotine patch. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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) |
| Measure | Description | Time Frame |
|---|---|---|
| Duration Deviant Mismatch Negativity (DD-MMN) in HC and SZ Participants: MMN-A, N100-A, and P3A-A Tests | The mean MMN magnitude derived from baseline DD-MMN will be compared in HC and SZ participants. MMN is measured by subtracting the averaged response to a set of standard stimuli form the average response to deviant stimuli, and taking the amplitude of this difference in a given timepoint. Tests include amplitude of MMN (MMN-A), amplitude of negative peak at 100 msec (N100-A), and amplitude of P3A (P3A-A). |
Not provided
Inclusion Criteria:
HC Participants:
Participants with Mild-to-Moderate SZ:
All Participants:
Exclusion Criteria:
HC Participants:
Participants with Mild-to-Moderate SZ:
All Participants:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Merck Sharp & Dohme LLC | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Collaborative Neuroscience Research, LLC ( Site 0002) | Long Beach | California | 90806 | United States | ||
Not provided
| Label | URL |
|---|---|
| Merck Clinical Trials Information | View source |
Not provided
Not provided
Not provided
Not provided
Not provided
Participants with schizophrenia (SZ) and healthy control (HC) participants were enrolled at 2 study sites in the US.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | HC Participants | In Period 1, HC participants received both nicotine patches and placebo patches in a counterbalanced order. All patches were co-administered with placebo capsules. In Period 2, participants received MK-4334 250 mg capsule and placebo capsule in counterbalanced order. All capsules were co-administered with placebo patches. |
| FG001 | Mild-to-Moderate SZ Participants | In Period 1, SZ participants received both nicotine patches and placebo patches in a counterbalanced order. All patches were co-administered with placebo capsules. In Period 2, participants received MK-4334 250 mg capsule and placebo capsule in counterbalanced order. All capsules were co-administered with placebo patches. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Period 1 |
|
| ||||||||||||||||||
| Period 2 |
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Panel A: Healthy Control Participants | In Period 1, HC participants received both nicotine patches and placebo patches in a counterbalanced order. All patches were co-administered with placebo capsules. In Period 2, participants received MK-4334 250 mg capsule and placebo capsule in counterbalanced order. All capsules were co-administered with placebo patches. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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). | All participants who complied with the protocol sufficiently to ensure the the data are likely to exhibit the effects of treatment, according to the underlying scientific model. | Posted | Mean | Standard Deviation | ITC (40Hz*msec) | Day -1 (Baseline) |
|
Up to approximately 45 days
All treated participants are included. Events are reported according to actual treatment received.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Nicotine 21 mg | All participants who received nicotine 21 mg are included. | 0 |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Vertigo | Ear and labyrinth disorders | MedDRA 26.0 | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Senior Vice President, Global Clinical Development | Merck Sharp & Dohme LLC | 1-800-672-6372 | ClinicalTrialsDisclosure@merck.com |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Sep 21, 2022 | May 10, 2024 | Prot_SAP_000.pdf |
Not provided
| ID | Term |
|---|---|
| D061485 | Tobacco Use Cessation Devices |
| ID | Term |
|---|---|
| D013812 | Therapeutics |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| MK-4334 | Drug | MK-4334 250 mg capsule taken by mouth. |
|
| Placebo patch | Drug | Placebo patch. |
|
| Placebo capsule | Drug | Placebo capsule taken by mouth. |
|
| Day -1 (Baseline) |
| Duration Deviant Mismatch Negativity (DD-MMN) in HC and SZ Participants: MMN-L, N100-L, and P3A-L Tests | The mean MMN magnitude derived from baseline DD-MMN will be compared in HC and SZ participants. The mean MMN magnitude derived from baseline DD-MMN will be compared in HC and SZ participants. MMN is measured by subtracting the averaged response to a set of standard stimuli form the average response to deviant stimuli, and taking the amplitude of this difference in a given timepoint. Tests include latency of MMN (MMN-A), latency of negative peak at 100 msec (N100-A), and latency of P3A (P3A-A). | Day -1 (Baseline) |
| Effect of Nicotine on Mean ITC Magnitude of 40 Hz-derived ASSR in HC and SZ Participants Compared to Baseline | The effects of nicotine and placebo on in the change from baseline in 40-Hz-derived ASSR were determined in HC and SZ participants on Day 1 or Day 8 in a counterbalanced order, and compared to baseline ASSR. 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), Day 1, and Day 8 |
| Plasma Nicotine Concentration 2 Hours After Patch Application (C2h) Assessed During Event Related Potential (ERP) Recording Sessions | Plasma nicotine levels were determined 2 hours after patch application (C2h) during 21 mg nicotine patch test sessions. Participants received either a nicotine or placebo patch on Days 1 and 8 in a counterbalanced order. | 2 hours after patch application on Day 1 or Day 8 |
| Hassman Research Institute Marlton Site ( Site 0001) |
| Marlton |
| New Jersey |
| 08053 |
| United States |
| NOT COMPLETED |
|
|
| BG001 |
| Mild-to-Moderate SZ Participants |
In Period 1, SZ participants received both nicotine patches and placebo patches in a counterbalanced order. All patches were co-administered with placebo capsules. In Period 2, participants received MK-4334 250 mg capsule and placebo capsule in counterbalanced order. All capsules were co-administered with placebo patches. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| OG001 | Mild-to-Moderate SZ Participants | In Period 1, SZ participants received both nicotine patches and placebo patches in a counterbalanced order. All patches were co-administered with placebo capsules. In Period 2, participants received MK-4334 250 mg capsule and placebo capsule in counterbalanced order. All capsules were co-administered with placebo patches. |
|
|
| Secondary | Duration Deviant Mismatch Negativity (DD-MMN) in HC and SZ Participants: MMN-A, N100-A, and P3A-A Tests | The mean MMN magnitude derived from baseline DD-MMN will be compared in HC and SZ participants. MMN is measured by subtracting the averaged response to a set of standard stimuli form the average response to deviant stimuli, and taking the amplitude of this difference in a given timepoint. Tests include amplitude of MMN (MMN-A), amplitude of negative peak at 100 msec (N100-A), and amplitude of P3A (P3A-A). | All participants who complied with the protocol sufficiently to ensure the the data are likely to exhibit the effects of treatment, according to the underlying scientific model. | Posted | Mean | Standard Deviation | µV | Day -1 (Baseline) |
|
|
|
| Secondary | Duration Deviant Mismatch Negativity (DD-MMN) in HC and SZ Participants: MMN-L, N100-L, and P3A-L Tests | The mean MMN magnitude derived from baseline DD-MMN will be compared in HC and SZ participants. The mean MMN magnitude derived from baseline DD-MMN will be compared in HC and SZ participants. MMN is measured by subtracting the averaged response to a set of standard stimuli form the average response to deviant stimuli, and taking the amplitude of this difference in a given timepoint. Tests include latency of MMN (MMN-A), latency of negative peak at 100 msec (N100-A), and latency of P3A (P3A-A). | All participants who complied with the protocol sufficiently to ensure the the data are likely to exhibit the effects of treatment, according to the underlying scientific model. | Posted | Mean | Standard Deviation | msec | Day -1 (Baseline) |
|
|
|
| Secondary | Effect of Nicotine on Mean ITC Magnitude of 40 Hz-derived ASSR in HC and SZ Participants Compared to Baseline | The effects of nicotine and placebo on in the change from baseline in 40-Hz-derived ASSR were determined in HC and SZ participants on Day 1 or Day 8 in a counterbalanced order, and compared to baseline ASSR. 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). | All participants who complied with the protocol sufficiently to ensure the the data are likely to exhibit the effects of treatment, according to the underlying scientific model. | Posted | Mean | Standard Deviation | ITC (40Hz*msec) | Day -1 (baseline), Day 1, and Day 8 |
|
|
|
| Secondary | Plasma Nicotine Concentration 2 Hours After Patch Application (C2h) Assessed During Event Related Potential (ERP) Recording Sessions | Plasma nicotine levels were determined 2 hours after patch application (C2h) during 21 mg nicotine patch test sessions. Participants received either a nicotine or placebo patch on Days 1 and 8 in a counterbalanced order. | All participants who complied with the protocol sufficiently to ensure the the data are likely to exhibit the effects of treatment, according to the underlying scientific model. Participants received nicotine on either Day 1 or Day 8; results are shown according to actual day of nicotine patch application. | Posted | Geometric Mean | Geometric Coefficient of Variation | nM | 2 hours after patch application on Day 1 or Day 8 |
|
|
|
| 37 |
| 0 |
| 37 |
| 8 |
| 37 |
| EG001 | MK-4334 250 mg | All participants who received MK-4334 250 mg are included. | 0 | 27 | 0 | 27 | 0 | 27 |
| EG002 | Placebo | All participants who received placebo are included. | 0 | 38 | 0 | 38 | 4 | 38 |
| Diarrhoea | Gastrointestinal disorders | MedDRA 26.0 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 26.0 | Systematic Assessment |
|
| Application site pruritus | General disorders | MedDRA 26.0 | Systematic Assessment |
|
| COVID-19 | Infections and infestations | MedDRA 26.0 | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA 26.0 | Systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | MedDRA 26.0 | Systematic Assessment |
|
| White blood cell count decreased | Investigations | MedDRA 26.0 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 26.0 | Systematic Assessment |
|
| Somnolence | Nervous system disorders | MedDRA 26.0 | Systematic Assessment |
|
| Erythema | Skin and subcutaneous tissue disorders | MedDRA 26.0 | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA 26.0 | Systematic Assessment |
|
If publication activity is not directed by the Sponsor, the investigator agrees to submit all manuscripts or abstracts to the Sponsor before submission.
| P3A-A Test |
|
| P3A-A Test |
|
| ITC1500 Placebo |
|
|
| Nicotine on Day 8 |
|
|