Trial Outcomes & Findings for CVN058 Effect on Mismatch Negativity in Schizophrenics (NCT NCT03669250)
NCT ID: NCT03669250
Last Updated: 2024-10-04
Results Overview
MMN is a pre-attentive auditory component elicited by deviant stimuli in an auditory oddball task. Participants were repeatedly exposed to auditory tones and a small proportion of those tones (the "deviant" stimuli) differ from the others (the "standard" stimuli) in their frequency or duration. Typically, the tones are presented, and the evoked potentials are recorded while participants are engaged on a different task, such as reading. Normally, the occurrence of a deviant stimulus increases the amplitude of the negative component in the evoked potential occurring at around 200 msec. MMN is the difference in amplitude between deviant and standard stimuli responses and considered to represent an aspect of pre-attentive novelty detection.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
22 participants
Primary outcome timeframe
1.5 hours post-dose on Day 1
Results posted on
2024-10-04
Participant Flow
A total of 22 eligible participants with schizophrenia including schizoaffective disorder. Eligible participants were randomized to 6 treatment sequences.
Participant milestones
| Measure |
Treatment Sequence ABC
Participants were randomized to receive single oral dose of Placebo in treatment period 1 followed by CVN058 15 milligrams (mg) in treatment period 2 followed by CVN058 150 mg in treatment period 3. Each treatment period was followed by a washout-period of 7 days.
|
Treatment Sequence BAC
Participants were randomized to receive single oral dose of CVN058 15 mg in treatment period 1 followed by Placebo in treatment period 2 followed by CVN058 150 mg in treatment period 3. Each treatment period was followed by a washout-period of 7 days.
|
Treatment Sequence CAB
Participants were randomized to receive single oral dose of CVN058 150 mg in treatment period 1 followed by Placebo in treatment period 2 followed by CVN058 15 mg in treatment period 3. Each treatment period was followed by a washout-period of 7 days.
|
Treatment Sequence ACB
Participants were randomized to receive single oral dose of CVN058 15 mg in treatment period 1 followed by Placebo in treatment period 2 followed by CVN058 150 mg in treatment period 3. Each treatment period was followed by a washout-period of 7 days.
|
Treatment Sequence BCA
Participants were randomized to receive single oral dose of Placebo in treatment period 1 followed by CVN058 150 mg in treatment period 2 and CVN058 15 mg in treatment period 3. Each treatment period was followed by a washout-period of 7 days.
|
Treatment Sequence CBA
Participants were randomized to receive single oral dose of CVN058 150 mg in treatment period 1 followed by Placebo in treatment period 2 and CVN058 15 mg in treatment period 3. Each treatment period was followed by a washout-period of 7 days.
|
|---|---|---|---|---|---|---|
|
Overall Study
STARTED
|
3
|
3
|
4
|
4
|
4
|
4
|
|
Overall Study
COMPLETED
|
3
|
2
|
4
|
3
|
3
|
4
|
|
Overall Study
NOT COMPLETED
|
0
|
1
|
0
|
1
|
1
|
0
|
Reasons for withdrawal
| Measure |
Treatment Sequence ABC
Participants were randomized to receive single oral dose of Placebo in treatment period 1 followed by CVN058 15 milligrams (mg) in treatment period 2 followed by CVN058 150 mg in treatment period 3. Each treatment period was followed by a washout-period of 7 days.
|
Treatment Sequence BAC
Participants were randomized to receive single oral dose of CVN058 15 mg in treatment period 1 followed by Placebo in treatment period 2 followed by CVN058 150 mg in treatment period 3. Each treatment period was followed by a washout-period of 7 days.
|
Treatment Sequence CAB
Participants were randomized to receive single oral dose of CVN058 150 mg in treatment period 1 followed by Placebo in treatment period 2 followed by CVN058 15 mg in treatment period 3. Each treatment period was followed by a washout-period of 7 days.
|
Treatment Sequence ACB
Participants were randomized to receive single oral dose of CVN058 15 mg in treatment period 1 followed by Placebo in treatment period 2 followed by CVN058 150 mg in treatment period 3. Each treatment period was followed by a washout-period of 7 days.
|
Treatment Sequence BCA
Participants were randomized to receive single oral dose of Placebo in treatment period 1 followed by CVN058 150 mg in treatment period 2 and CVN058 15 mg in treatment period 3. Each treatment period was followed by a washout-period of 7 days.
|
Treatment Sequence CBA
Participants were randomized to receive single oral dose of CVN058 150 mg in treatment period 1 followed by Placebo in treatment period 2 and CVN058 15 mg in treatment period 3. Each treatment period was followed by a washout-period of 7 days.
|
|---|---|---|---|---|---|---|
|
Overall Study
Adverse Event
|
0
|
0
|
0
|
0
|
1
|
0
|
|
Overall Study
Withdrawal by Subject
|
0
|
1
|
0
|
1
|
0
|
0
|
Baseline Characteristics
analysis was divided between elderly (65 and over) and non elderly (18-65)
Baseline characteristics by cohort
| Measure |
Treatment Sequence ABC
n=3 Participants
Participants were randomized to receive single oral dose of Placebo in treatment period 1 followed by CVN058 15 milligrams (mg) in treatment period 2 followed by CVN058 150 mg in treatment period 3. Each treatment period was followed by a washout-period of 7 days.
|
Treatment Sequence BAC
n=3 Participants
Participants were randomized to receive single oral dose of CVN058 15 mg in treatment period 1 followed by Placebo in treatment period 2 followed by CVN058 150 mg in treatment period 3. Each treatment period was followed by a washout-period of 7 days.
|
Treatment Sequence CAB
n=4 Participants
Participants were randomized to receive single oral dose of CVN058 150 mg in treatment period 1 followed by Placebo in treatment period 2 followed by CVN058 15 mg in treatment period 3. Each treatment period was followed by a washout-period of 7 days.
|
Treatment Sequence ACB
n=4 Participants
Participants were randomized to receive single oral dose of CVN058 15 mg in treatment period 1 followed by Placebo in treatment period 2 followed by CVN058 150 mg in treatment period 3. Each treatment period was followed by a washout-period of 7 days.
|
Treatment Sequence BCA
n=4 Participants
Participants were randomized to receive single oral dose of Placebo in treatment period 1 followed by CVN058 150 mg in treatment period 2 and CVN058 15 mg in treatment period 3. Each treatment period was followed by a washout-period of 7 days.
|
Treatment Sequence CBA
n=4 Participants
Participants were randomized to receive single oral dose of CVN058 150 mg in treatment period 1 followed by Placebo in treatment period 2 and CVN058 15 mg in treatment period 3. Each treatment period was followed by a washout-period of 7 days.
|
Total
n=22 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|---|
|
Age, Continuous
|
36.0 Years
STANDARD_DEVIATION 4.00 • n=5 Participants
|
32.0 Years
STANDARD_DEVIATION 8.54 • n=7 Participants
|
35.0 Years
STANDARD_DEVIATION 6.06 • n=5 Participants
|
39.0 Years
STANDARD_DEVIATION 6.63 • n=4 Participants
|
32.5 Years
STANDARD_DEVIATION 14.15 • n=21 Participants
|
36.3 Years
STANDARD_DEVIATION 8.54 • n=10 Participants
|
35.2 Years
STANDARD_DEVIATION 8.06 • n=115 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=5 Participants • analysis was divided between elderly (65 and over) and non elderly (18-65)
|
0 Participants
n=7 Participants • analysis was divided between elderly (65 and over) and non elderly (18-65)
|
2 Participants
n=5 Participants • analysis was divided between elderly (65 and over) and non elderly (18-65)
|
2 Participants
n=4 Participants • analysis was divided between elderly (65 and over) and non elderly (18-65)
|
0 Participants
n=21 Participants • analysis was divided between elderly (65 and over) and non elderly (18-65)
|
0 Participants
n=10 Participants • analysis was divided between elderly (65 and over) and non elderly (18-65)
|
5 Participants
n=115 Participants • analysis was divided between elderly (65 and over) and non elderly (18-65)
|
|
Sex: Female, Male
Male
|
2 Participants
n=5 Participants • analysis was divided between elderly (65 and over) and non elderly (18-65)
|
3 Participants
n=7 Participants • analysis was divided between elderly (65 and over) and non elderly (18-65)
|
2 Participants
n=5 Participants • analysis was divided between elderly (65 and over) and non elderly (18-65)
|
2 Participants
n=4 Participants • analysis was divided between elderly (65 and over) and non elderly (18-65)
|
4 Participants
n=21 Participants • analysis was divided between elderly (65 and over) and non elderly (18-65)
|
4 Participants
n=10 Participants • analysis was divided between elderly (65 and over) and non elderly (18-65)
|
17 Participants
n=115 Participants • analysis was divided between elderly (65 and over) and non elderly (18-65)
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
1 Participants
n=10 Participants
|
9 Participants
n=115 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
3 Participants
n=21 Participants
|
3 Participants
n=10 Participants
|
13 Participants
n=115 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
|
Race/Ethnicity, Customized
Caucasian
|
0 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
5 Participants
n=115 Participants
|
|
Race/Ethnicity, Customized
Black/African American
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
1 Participants
n=10 Participants
|
9 Participants
n=115 Participants
|
|
Race/Ethnicity, Customized
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
1 Participants
n=10 Participants
|
1 Participants
n=115 Participants
|
|
Race/Ethnicity, Customized
Not Reported
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
3 Participants
n=115 Participants
|
|
Race/Ethnicity, Customized
Other
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
2 Participants
n=10 Participants
|
4 Participants
n=115 Participants
|
PRIMARY outcome
Timeframe: 1.5 hours post-dose on Day 1Population: Pharmacodynamic Population consisted of all participants who received study drug and had measurements in both the placebo-dosed period and at least one (1) CVN058-dosed period for at least one (1) electroencephalography (EEG)/evoked response endpoint. Only those participants with data available at specified time points has been presented.
MMN is a pre-attentive auditory component elicited by deviant stimuli in an auditory oddball task. Participants were repeatedly exposed to auditory tones and a small proportion of those tones (the "deviant" stimuli) differ from the others (the "standard" stimuli) in their frequency or duration. Typically, the tones are presented, and the evoked potentials are recorded while participants are engaged on a different task, such as reading. Normally, the occurrence of a deviant stimulus increases the amplitude of the negative component in the evoked potential occurring at around 200 msec. MMN is the difference in amplitude between deviant and standard stimuli responses and considered to represent an aspect of pre-attentive novelty detection.
Outcome measures
| Measure |
Placebo
n=19 Participants
Participants were randomized to receive Placebo in each treatment period.
|
15mg CVN058
n=13 Participants
Participants were randomized to receive CVN058 15 mg in each treatment period
|
75mg CVN058
n=6 Participants
Participants were randomized to receive CVN058 75 mg in each treatment period.
|
150 mg CVN058
n=19 Participants
Participants were randomized to receive CVN058 150 mg in each treatment period.
|
|---|---|---|---|---|
|
Mean Amplitude of Duration of Auditory Mismatch Negativity (MMN) by Dose Level
|
-0.551 microvolts
Standard Deviation 0.7303
|
-0.749 microvolts
Standard Deviation 0.7260
|
-0.386 microvolts
Standard Deviation 0.5682
|
-1.084 microvolts
Standard Deviation 0.7632
|
SECONDARY outcome
Timeframe: Screening through 30 days post-dose, up to 58 daysPopulation: Safety Population consisted of all participants who were randomized and received study drug.
An adverse event is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. A SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect, associated with liver injury and impaired liver function or any other situations as per medical or scientific judgement. TEAEs are defined as any event with onset during or after the first dose of study treatment (active or placebo)
Outcome measures
| Measure |
Placebo
n=20 Participants
Participants were randomized to receive Placebo in each treatment period.
|
15mg CVN058
n=13 Participants
Participants were randomized to receive CVN058 15 mg in each treatment period
|
75mg CVN058
n=8 Participants
Participants were randomized to receive CVN058 75 mg in each treatment period.
|
150 mg CVN058
n=19 Participants
Participants were randomized to receive CVN058 150 mg in each treatment period.
|
|---|---|---|---|---|
|
Number of Participants Reporting Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Any TEAE
|
1 Participants
|
1 Participants
|
1 Participants
|
4 Participants
|
|
Number of Participants Reporting Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Any SAE
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
Adverse Events
Placebo
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
15mg CVN058
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
75mg CVN058
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
150 mg CVN058
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 |
Placebo
n=20 participants at risk
Participants were randomized to receive placebo in each treatment period.
|
15mg CVN058
n=13 participants at risk
Participants were randomized to receive CVN058 15 mg in each treatment period.
|
75mg CVN058
n=8 participants at risk
Participants were randomized to receive CVN058 75 mg in each treatment period.
|
150 mg CVN058
n=19 participants at risk
Participants were randomized to receive CVN058 150 mg in each treatment period.
|
|---|---|---|---|---|
|
Nervous system disorders
Somnolence
|
5.0%
1/20 • Number of events 1 • 58 days from screen through study duration
TEAEs and SAEs has been presented for Safety Population. Safety Population consisted of all participants who were randomized and received study drug.
|
0.00%
0/13 • 58 days from screen through study duration
TEAEs and SAEs has been presented for Safety Population. Safety Population consisted of all participants who were randomized and received study drug.
|
12.5%
1/8 • Number of events 1 • 58 days from screen through study duration
TEAEs and SAEs has been presented for Safety Population. Safety Population consisted of all participants who were randomized and received study drug.
|
5.3%
1/19 • Number of events 1 • 58 days from screen through study duration
TEAEs and SAEs has been presented for Safety Population. Safety Population consisted of all participants who were randomized and received study drug.
|
|
Nervous system disorders
dizziness
|
0.00%
0/20 • 58 days from screen through study duration
TEAEs and SAEs has been presented for Safety Population. Safety Population consisted of all participants who were randomized and received study drug.
|
7.7%
1/13 • Number of events 1 • 58 days from screen through study duration
TEAEs and SAEs has been presented for Safety Population. Safety Population consisted of all participants who were randomized and received study drug.
|
0.00%
0/8 • 58 days from screen through study duration
TEAEs and SAEs has been presented for Safety Population. Safety Population consisted of all participants who were randomized and received study drug.
|
5.3%
1/19 • Number of events 1 • 58 days from screen through study duration
TEAEs and SAEs has been presented for Safety Population. Safety Population consisted of all participants who were randomized and received study drug.
|
|
Investigations
Blood glucose abnormal
|
0.00%
0/20 • 58 days from screen through study duration
TEAEs and SAEs has been presented for Safety Population. Safety Population consisted of all participants who were randomized and received study drug.
|
0.00%
0/13 • 58 days from screen through study duration
TEAEs and SAEs has been presented for Safety Population. Safety Population consisted of all participants who were randomized and received study drug.
|
0.00%
0/8 • 58 days from screen through study duration
TEAEs and SAEs has been presented for Safety Population. Safety Population consisted of all participants who were randomized and received study drug.
|
5.3%
1/19 • Number of events 1 • 58 days from screen through study duration
TEAEs and SAEs has been presented for Safety Population. Safety Population consisted of all participants who were randomized and received study drug.
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/20 • 58 days from screen through study duration
TEAEs and SAEs has been presented for Safety Population. Safety Population consisted of all participants who were randomized and received study drug.
|
7.7%
1/13 • Number of events 1 • 58 days from screen through study duration
TEAEs and SAEs has been presented for Safety Population. Safety Population consisted of all participants who were randomized and received study drug.
|
0.00%
0/8 • 58 days from screen through study duration
TEAEs and SAEs has been presented for Safety Population. Safety Population consisted of all participants who were randomized and received study drug.
|
5.3%
1/19 • Number of events 1 • 58 days from screen through study duration
TEAEs and SAEs has been presented for Safety Population. Safety Population consisted of all participants who were randomized and received study drug.
|
|
Investigations
Blood sodium abnormal
|
0.00%
0/20 • 58 days from screen through study duration
TEAEs and SAEs has been presented for Safety Population. Safety Population consisted of all participants who were randomized and received study drug.
|
0.00%
0/13 • 58 days from screen through study duration
TEAEs and SAEs has been presented for Safety Population. Safety Population consisted of all participants who were randomized and received study drug.
|
0.00%
0/8 • 58 days from screen through study duration
TEAEs and SAEs has been presented for Safety Population. Safety Population consisted of all participants who were randomized and received study drug.
|
5.3%
1/19 • 58 days from screen through study duration
TEAEs and SAEs has been presented for Safety Population. Safety Population consisted of all participants who were randomized and received study drug.
|
|
Respiratory, thoracic and mediastinal disorders
Throat irritation
|
0.00%
0/20 • 58 days from screen through study duration
TEAEs and SAEs has been presented for Safety Population. Safety Population consisted of all participants who were randomized and received study drug.
|
0.00%
0/13 • 58 days from screen through study duration
TEAEs and SAEs has been presented for Safety Population. Safety Population consisted of all participants who were randomized and received study drug.
|
0.00%
0/8 • 58 days from screen through study duration
TEAEs and SAEs has been presented for Safety Population. Safety Population consisted of all participants who were randomized and received study drug.
|
5.3%
1/19 • 58 days from screen through study duration
TEAEs and SAEs has been presented for Safety Population. Safety Population consisted of all participants who were randomized and received study drug.
|
|
Nervous system disorders
Headache
|
0.00%
0/20 • 58 days from screen through study duration
TEAEs and SAEs has been presented for Safety Population. Safety Population consisted of all participants who were randomized and received study drug.
|
0.00%
0/13 • 58 days from screen through study duration
TEAEs and SAEs has been presented for Safety Population. Safety Population consisted of all participants who were randomized and received study drug.
|
0.00%
0/8 • 58 days from screen through study duration
TEAEs and SAEs has been presented for Safety Population. Safety Population consisted of all participants who were randomized and received study drug.
|
5.3%
1/19 • 58 days from screen through study duration
TEAEs and SAEs has been presented for Safety Population. Safety Population consisted of all participants who were randomized and received study drug.
|
Additional Information
Michelle Charles, Executive Director Regulatory Affairs
Cerevance
Phone: (408) 220-5722
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place