Trial Outcomes & Findings for Evoked Responses as Pharmacodynamic Biomarkers in Healthy and Schizophrenic Participants (MK-4334-007) (NCT NCT05136690)
NCT ID: NCT05136690
Last Updated: 2024-11-29
Results Overview
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).
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
38 participants
Primary outcome timeframe
Day -1 (Baseline)
Results posted on
2024-11-29
Participant Flow
Participants with schizophrenia (SZ) and healthy control (HC) participants were enrolled at 2 study sites in the US.
Participant milestones
| Measure |
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.
|
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.
|
|---|---|---|
|
Period 1
STARTED
|
13
|
25
|
|
Period 1
COMPLETED
|
13
|
24
|
|
Period 1
NOT COMPLETED
|
0
|
1
|
|
Period 2
STARTED
|
13
|
24
|
|
Period 2
COMPLETED
|
13
|
20
|
|
Period 2
NOT COMPLETED
|
0
|
4
|
Reasons for withdrawal
| Measure |
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.
|
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.
|
|---|---|---|
|
Period 1
Withdrawal by Subject
|
0
|
1
|
|
Period 2
Lost to Follow-up
|
0
|
3
|
|
Period 2
Withdrawal by Subject
|
0
|
1
|
Baseline Characteristics
Evoked Responses as Pharmacodynamic Biomarkers in Healthy and Schizophrenic Participants (MK-4334-007)
Baseline characteristics by cohort
| Measure |
Panel A: Healthy Control Participants
n=13 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.
|
Mild-to-Moderate SZ Participants
n=25 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.
|
Total
n=38 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
38.9 years
STANDARD_DEVIATION 8.4 • n=5 Participants
|
45.0 years
STANDARD_DEVIATION 7.8 • n=7 Participants
|
42.9 years
STANDARD_DEVIATION 8.4 • n=5 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
12 Participants
n=5 Participants
|
22 Participants
n=7 Participants
|
34 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
12 Participants
n=5 Participants
|
24 Participants
n=7 Participants
|
36 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
10 Participants
n=5 Participants
|
22 Participants
n=7 Participants
|
32 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Day -1 (Baseline)Population: 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.
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).
Outcome measures
| Measure |
Panel A: Healthy Control Participants
n=12 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.
|
Mild-to-Moderate SZ Participants
n=25 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.
|
|---|---|---|
|
Mean Inter-trial Coherence (ITC) Magnitude of 40 Hz-derived Auditory Steady-state Response (ASSR) in HC and SZ Participants at Baseline
|
0.432 ITC (40Hz*msec)
Standard Deviation 0.150
|
0.364 ITC (40Hz*msec)
Standard Deviation 0.160
|
SECONDARY outcome
Timeframe: Day -1 (Baseline)Population: 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.
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).
Outcome measures
| Measure |
Panel A: Healthy Control Participants
n=13 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.
|
Mild-to-Moderate SZ Participants
n=25 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.
|
|---|---|---|
|
Duration Deviant Mismatch Negativity (DD-MMN) in HC and SZ Participants: MMN-A, N100-A, and P3A-A Tests
MMN-A Test
|
-5.207 µV
Standard Deviation 2.558
|
-3.932 µV
Standard Deviation 2.031
|
|
Duration Deviant Mismatch Negativity (DD-MMN) in HC and SZ Participants: MMN-A, N100-A, and P3A-A Tests
N100-A Test
|
-1.616 µV
Standard Deviation 1.966
|
-1.117 µV
Standard Deviation 1.332
|
|
Duration Deviant Mismatch Negativity (DD-MMN) in HC and SZ Participants: MMN-A, N100-A, and P3A-A Tests
P3A-A Test
|
2.974 µV
Standard Deviation 0.774
|
3.121 µV
Standard Deviation 1.263
|
SECONDARY outcome
Timeframe: Day -1 (Baseline)Population: 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.
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).
Outcome measures
| Measure |
Panel A: Healthy Control Participants
n=13 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.
|
Mild-to-Moderate SZ Participants
n=25 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.
|
|---|---|---|
|
Duration Deviant Mismatch Negativity (DD-MMN) in HC and SZ Participants: MMN-L, N100-L, and P3A-L Tests
MMN-A Test
|
172.615 msec
Standard Deviation 27.122
|
178.880 msec
Standard Deviation 25.469
|
|
Duration Deviant Mismatch Negativity (DD-MMN) in HC and SZ Participants: MMN-L, N100-L, and P3A-L Tests
N100-A Test
|
90.462 msec
Standard Deviation 17.704
|
87.680 msec
Standard Deviation 14.739
|
|
Duration Deviant Mismatch Negativity (DD-MMN) in HC and SZ Participants: MMN-L, N100-L, and P3A-L Tests
P3A-A Test
|
284.308 msec
Standard Deviation 38.104
|
280.480 msec
Standard Deviation 26.691
|
SECONDARY outcome
Timeframe: Day -1 (baseline), Day 1, and Day 8Population: 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.
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).
Outcome measures
| Measure |
Panel A: Healthy Control Participants
n=11 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.
|
Mild-to-Moderate SZ Participants
n=23 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.
|
|---|---|---|
|
Effect of Nicotine on Mean ITC Magnitude of 40 Hz-derived ASSR in HC and SZ Participants Compared to Baseline
ITC1500 Nicotine
|
0.054 ITC (40Hz*msec)
Standard Deviation 0.109
|
0.040 ITC (40Hz*msec)
Standard Deviation 0.043
|
|
Effect of Nicotine on Mean ITC Magnitude of 40 Hz-derived ASSR in HC and SZ Participants Compared to Baseline
ITC1500 Placebo
|
0.000 ITC (40Hz*msec)
Standard Deviation 0.103
|
0.010 ITC (40Hz*msec)
Standard Deviation 0.093
|
SECONDARY outcome
Timeframe: 2 hours after patch application on Day 1 or Day 8Population: 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.
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.
Outcome measures
| Measure |
Panel A: Healthy Control Participants
n=2 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.
|
Mild-to-Moderate SZ Participants
n=17 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.
|
|---|---|---|
|
Plasma Nicotine Concentration 2 Hours After Patch Application (C2h) Assessed During Event Related Potential (ERP) Recording Sessions
Nicotine on Day 1
|
160.5 nM
Geometric Coefficient of Variation 24
|
163.3 nM
Geometric Coefficient of Variation 26
|
|
Plasma Nicotine Concentration 2 Hours After Patch Application (C2h) Assessed During Event Related Potential (ERP) Recording Sessions
Nicotine on Day 8
|
119.6 nM
Geometric Coefficient of Variation 52
|
159.3 nM
Geometric Coefficient of Variation 24
|
Adverse Events
Nicotine 21 mg
Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths
MK-4334 250 mg
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Placebo
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Nicotine 21 mg
n=37 participants at risk
All participants who received nicotine 21 mg are included.
|
MK-4334 250 mg
n=27 participants at risk
All participants who received MK-4334 250 mg are included.
|
Placebo
n=38 participants at risk
All participants who received placebo are included.
|
|---|---|---|---|
|
Ear and labyrinth disorders
Vertigo
|
2.7%
1/37 • Up to approximately 45 days
All treated participants are included. Events are reported according to actual treatment received.
|
0.00%
0/27 • Up to approximately 45 days
All treated participants are included. Events are reported according to actual treatment received.
|
0.00%
0/38 • Up to approximately 45 days
All treated participants are included. Events are reported according to actual treatment received.
|
|
Gastrointestinal disorders
Diarrhoea
|
2.7%
1/37 • Up to approximately 45 days
All treated participants are included. Events are reported according to actual treatment received.
|
0.00%
0/27 • Up to approximately 45 days
All treated participants are included. Events are reported according to actual treatment received.
|
0.00%
0/38 • Up to approximately 45 days
All treated participants are included. Events are reported according to actual treatment received.
|
|
Gastrointestinal disorders
Nausea
|
5.4%
2/37 • Up to approximately 45 days
All treated participants are included. Events are reported according to actual treatment received.
|
0.00%
0/27 • Up to approximately 45 days
All treated participants are included. Events are reported according to actual treatment received.
|
0.00%
0/38 • Up to approximately 45 days
All treated participants are included. Events are reported according to actual treatment received.
|
|
General disorders
Application site pruritus
|
8.1%
3/37 • Up to approximately 45 days
All treated participants are included. Events are reported according to actual treatment received.
|
0.00%
0/27 • Up to approximately 45 days
All treated participants are included. Events are reported according to actual treatment received.
|
0.00%
0/38 • Up to approximately 45 days
All treated participants are included. Events are reported according to actual treatment received.
|
|
Infections and infestations
COVID-19
|
0.00%
0/37 • Up to approximately 45 days
All treated participants are included. Events are reported according to actual treatment received.
|
0.00%
0/27 • Up to approximately 45 days
All treated participants are included. Events are reported according to actual treatment received.
|
2.6%
1/38 • Up to approximately 45 days
All treated participants are included. Events are reported according to actual treatment received.
|
|
Investigations
Alanine aminotransferase increased
|
0.00%
0/37 • Up to approximately 45 days
All treated participants are included. Events are reported according to actual treatment received.
|
0.00%
0/27 • Up to approximately 45 days
All treated participants are included. Events are reported according to actual treatment received.
|
2.6%
1/38 • Up to approximately 45 days
All treated participants are included. Events are reported according to actual treatment received.
|
|
Investigations
Aspartate aminotransferase increased
|
0.00%
0/37 • Up to approximately 45 days
All treated participants are included. Events are reported according to actual treatment received.
|
0.00%
0/27 • Up to approximately 45 days
All treated participants are included. Events are reported according to actual treatment received.
|
2.6%
1/38 • Up to approximately 45 days
All treated participants are included. Events are reported according to actual treatment received.
|
|
Investigations
White blood cell count decreased
|
0.00%
0/37 • Up to approximately 45 days
All treated participants are included. Events are reported according to actual treatment received.
|
0.00%
0/27 • Up to approximately 45 days
All treated participants are included. Events are reported according to actual treatment received.
|
2.6%
1/38 • Up to approximately 45 days
All treated participants are included. Events are reported according to actual treatment received.
|
|
Nervous system disorders
Dizziness
|
0.00%
0/37 • Up to approximately 45 days
All treated participants are included. Events are reported according to actual treatment received.
|
0.00%
0/27 • Up to approximately 45 days
All treated participants are included. Events are reported according to actual treatment received.
|
2.6%
1/38 • Up to approximately 45 days
All treated participants are included. Events are reported according to actual treatment received.
|
|
Nervous system disorders
Somnolence
|
2.7%
1/37 • Up to approximately 45 days
All treated participants are included. Events are reported according to actual treatment received.
|
0.00%
0/27 • Up to approximately 45 days
All treated participants are included. Events are reported according to actual treatment received.
|
0.00%
0/38 • Up to approximately 45 days
All treated participants are included. Events are reported according to actual treatment received.
|
|
Skin and subcutaneous tissue disorders
Erythema
|
5.4%
2/37 • Up to approximately 45 days
All treated participants are included. Events are reported according to actual treatment received.
|
0.00%
0/27 • Up to approximately 45 days
All treated participants are included. Events are reported according to actual treatment received.
|
0.00%
0/38 • Up to approximately 45 days
All treated participants are included. Events are reported according to actual treatment received.
|
|
Skin and subcutaneous tissue disorders
Rash
|
2.7%
1/37 • Up to approximately 45 days
All treated participants are included. Events are reported according to actual treatment received.
|
0.00%
0/27 • Up to approximately 45 days
All treated participants are included. Events are reported according to actual treatment received.
|
0.00%
0/38 • Up to approximately 45 days
All treated participants are included. Events are reported according to actual treatment received.
|
Additional Information
Senior Vice President, Global Clinical Development
Merck Sharp & Dohme LLC
Phone: 1-800-672-6372
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee If publication activity is not directed by the Sponsor, the investigator agrees to submit all manuscripts or abstracts to the Sponsor before submission.
- Publication restrictions are in place
Restriction type: OTHER