Schizophrenia
Conditions
Brief summary
The objective of this study is to assess the safety and efficacy of 3 different doses of CTP-692 administered once daily (QD) for 12 weeks to adult participants with schizophrenia on stable dopaminergic antipsychotic medication.
Interventions
DRUGCTP-692
Administered as powder for oral solution.
DRUGPlacebo
Administered as powder for oral solution.
Sponsors
Cognitive Research Corporation
Concert Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
* Physician confirmed diagnostic and statistical manual-version 5 (DSM-V5) diagnosis of schizophrenia for the past 2 years * Patients with clinically stable schizophrenia with residual symptoms defined as positive and negative syndrome scale (PANSS) total score of 70-110 * Patients currently treated with one antipsychotic medication
Exclusion criteria
* Patients who, in the opinion of the Investigator, have a history of antipsychotic treatment resistance * Patients currently taking clozapine * History of meeting DSM-V5 criteria for moderate to severe alcohol or substance use disorder (other than nicotine or caffeine) within the 6 months before the first Screening Visit * Patients with positive blood screen for human immunodeficiency virus (HIV) antibody and/or hepatitis B virus surface antigen * Patients with history of renal disease or those taking medications to treat renal disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 12 | Baseline, Week 12 | PANSS measures symptom severity in participants with schizophrenia. PANSS includes 30 items (7 items for positive symptoms, 7 items for negative symptoms, and 16 items for general psychopathology symptoms), and each item is rated with 1 to 7 points. The PANSS is scored by summation of ratings across items such that the score ranges are 7 to 49 for each of the Positive and Negative Scales and 16 to 112 for the General Psychopathology Scale. The PANSS total score is a sum of scores from all the 30 items and the scores range from 30 to 210, where a higher score represents more severe symptoms, and lower scores represent a better quality of life in participants with schizophrenia. A negative change from baseline indicates low severity of symptoms. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Clinical Global Impression-Severity (CGI-S) Score at Week 12 | Baseline, Week 12 | The CGI-S rating scale is a commonly used measure of symptom severity and treatment response. CGI-S is a 7-point scale that requires the clinician to rate the severity of the patient's illness at the time of assessment and the score ranges from 1 to 7: 0 = not assessed; 1 = normal, not at all ill; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; 7 = among the most extremely ill participants. A higher score represents more severe symptoms. A negative change from baseline indicates low severity of symptoms. |
| Change From Baseline in Personal and Social Performance (PSP) Scale at Week 12 | Baseline, Week 12 | PSP scale is a measure of the personal and social functioning of participants with psychiatric disorders within four domains: socially useful activities, personal and social relationships, self-care, and disturbing and aggressive behavior. Each domain was assessed on a 6-point scale: 1 = absent, 2 = mild, 3 = manifest, 4 = marked, 5 = severe, and 6 = very severe. The final global score is defined according to a summary instruction table converting four domain scores into a single, overall rating from 1 to 100: 71 to 100 represent mild degree of difficulty; 31 to 70 represent varying degrees of disability, and 1 to 30 represent functioning so poorly as to require intensive supervision. Higher scores represent better personal and social function. A positive change from baseline indicates better personal and social function. |
Countries
United States
Participant flow
Recruitment details
Participants were enrolled at study centers in the United States from 26 November 2019 to 22 December 2020.
Pre-assignment details
521 participants were screened, out of which 326 participants with schizophrenia who were on a stable dopaminergic antipsychotic medication were enrolled and randomized.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received CTP-692 matched placebo powder for oral solution, QD for up to 12 weeks. | 81 |
| CTP-692 1 Gram QD Participants received CTP-692 1 gram powder for oral solution, QD for up to 12 weeks. | 81 |
| CTP-692 2 Grams QD Participants received CTP-692 2 grams powder for oral solution, QD for up to 12 weeks. | 85 |
| CTP-692 4 Grams QD Participants received CTP-692 4 grams powder for oral solution, QD for up to 12 weeks. | 78 |
| Total | 325 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 3 | 0 | 3 |
| Overall Study | Coronavirus Disease 2019 (COVID-19) Related Reasons | 2 | 3 | 2 | 0 |
| Overall Study | Investigator Decision | 0 | 0 | 2 | 0 |
| Overall Study | Lost to Follow-up | 5 | 12 | 4 | 5 |
| Overall Study | Non-Compliance with Study Medication | 2 | 2 | 3 | 0 |
| Overall Study | Protocol Violation | 0 | 2 | 1 | 0 |
| Overall Study | Reason not Specified | 3 | 2 | 4 | 4 |
| Overall Study | Withdrawal of Consent by Subject | 3 | 3 | 4 | 1 |
Baseline characteristics
| Characteristic | CTP-692 2 Grams QD | Total | CTP-692 4 Grams QD | Placebo | CTP-692 1 Gram QD |
|---|---|---|---|---|---|
| Age, Continuous | 42.7 years | 41.6 years | 40.9 years | 42.1 years | 40.8 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 9 Participants | 41 Participants | 15 Participants | 8 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 76 Participants | 283 Participants | 63 Participants | 72 Participants | 72 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Race American Indian or Alaska Native | 1 Participants | 4 Participants | 0 Participants | 2 Participants | 1 Participants |
| Race/Ethnicity, Customized Race Asian | 1 Participants | 9 Participants | 2 Participants | 2 Participants | 4 Participants |
| Race/Ethnicity, Customized Race Black or African American | 57 Participants | 210 Participants | 47 Participants | 49 Participants | 57 Participants |
| Race/Ethnicity, Customized Race Native Hawaiian or Other Pacific Islander | 0 Participants | 2 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Other | 3 Participants | 10 Participants | 2 Participants | 4 Participants | 1 Participants |
| Race/Ethnicity, Customized Race White | 23 Participants | 90 Participants | 26 Participants | 23 Participants | 18 Participants |
| Sex: Female, Male Female | 25 Participants | 94 Participants | 23 Participants | 21 Participants | 25 Participants |
| Sex: Female, Male Male | 60 Participants | 231 Participants | 55 Participants | 60 Participants | 56 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 81 | 0 / 81 | 0 / 85 | 0 / 79 |
| other Total, other adverse events | 3 / 81 | 5 / 81 | 6 / 85 | 7 / 78 |
| serious Total, serious adverse events | 0 / 81 | 1 / 81 | 0 / 85 | 1 / 78 |
Outcome results
Primary
Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 12
PANSS measures symptom severity in participants with schizophrenia. PANSS includes 30 items (7 items for positive symptoms, 7 items for negative symptoms, and 16 items for general psychopathology symptoms), and each item is rated with 1 to 7 points. The PANSS is scored by summation of ratings across items such that the score ranges are 7 to 49 for each of the Positive and Negative Scales and 16 to 112 for the General Psychopathology Scale. The PANSS total score is a sum of scores from all the 30 items and the scores range from 30 to 210, where a higher score represents more severe symptoms, and lower scores represent a better quality of life in participants with schizophrenia. A negative change from baseline indicates low severity of symptoms.
Time frame: Baseline, Week 12
Population: Efficacy population included all participants who received the study medication and had at least one available post-baseline PANSS assessment. 'Number of participants analyzed' indicates the number of participants with data available for analysis at the specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 12 | Baseline | 82.1 score on a scale | Standard Deviation 8.2 |
| Placebo | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 12 | Change From Baseline at Week 12 | -14.1 score on a scale | Standard Deviation 10.4 |
| CTP-692 1 Gram QD | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 12 | Change From Baseline at Week 12 | -15.9 score on a scale | Standard Deviation 10.3 |
| CTP-692 1 Gram QD | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 12 | Baseline | 81.2 score on a scale | Standard Deviation 8 |
| CTP-692 2 Grams QD | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 12 | Baseline | 81.6 score on a scale | Standard Deviation 7.8 |
| CTP-692 2 Grams QD | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 12 | Change From Baseline at Week 12 | -12.2 score on a scale | Standard Deviation 10.3 |
| CTP-692 4 Grams QD | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 12 | Baseline | 82.9 score on a scale | Standard Deviation 8.6 |
| CTP-692 4 Grams QD | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 12 | Change From Baseline at Week 12 | -11.0 score on a scale | Standard Deviation 10.6 |
p-value: 0.600395% CI: [-4.5, 2.6]Mixed model repeated measures (MMRM)
p-value: 0.39295% CI: [-2, 5]MMRM
p-value: 0.144495% CI: [-0.9, 6]MMRM
Secondary
Change From Baseline in Clinical Global Impression-Severity (CGI-S) Score at Week 12
The CGI-S rating scale is a commonly used measure of symptom severity and treatment response. CGI-S is a 7-point scale that requires the clinician to rate the severity of the patient's illness at the time of assessment and the score ranges from 1 to 7: 0 = not assessed; 1 = normal, not at all ill; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; 7 = among the most extremely ill participants. A higher score represents more severe symptoms. A negative change from baseline indicates low severity of symptoms.
Time frame: Baseline, Week 12
Population: Efficacy population included all participants who received the study medication and had at least one available post-baseline PANSS assessment. 'Number of participants analyzed' indicates the number of participants with data available for analysis at the specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Clinical Global Impression-Severity (CGI-S) Score at Week 12 | Baseline | 4.2 score on a scale | Standard Deviation 0.5 |
| Placebo | Change From Baseline in Clinical Global Impression-Severity (CGI-S) Score at Week 12 | Change From Baseline at Week 12 | -0.8 score on a scale | Standard Deviation 0.8 |
| CTP-692 1 Gram QD | Change From Baseline in Clinical Global Impression-Severity (CGI-S) Score at Week 12 | Change From Baseline at Week 12 | -0.8 score on a scale | Standard Deviation 0.9 |
| CTP-692 1 Gram QD | Change From Baseline in Clinical Global Impression-Severity (CGI-S) Score at Week 12 | Baseline | 4.1 score on a scale | Standard Deviation 0.5 |
| CTP-692 2 Grams QD | Change From Baseline in Clinical Global Impression-Severity (CGI-S) Score at Week 12 | Baseline | 4.1 score on a scale | Standard Deviation 0.5 |
| CTP-692 2 Grams QD | Change From Baseline in Clinical Global Impression-Severity (CGI-S) Score at Week 12 | Change From Baseline at Week 12 | -0.5 score on a scale | Standard Deviation 0.7 |
| CTP-692 4 Grams QD | Change From Baseline in Clinical Global Impression-Severity (CGI-S) Score at Week 12 | Baseline | 4.2 score on a scale | Standard Deviation 0.6 |
| CTP-692 4 Grams QD | Change From Baseline in Clinical Global Impression-Severity (CGI-S) Score at Week 12 | Change From Baseline at Week 12 | -0.5 score on a scale | Standard Deviation 0.7 |
p-value: 0.806595% CI: [-0.3, 0.2]MMRM
p-value: 0.212195% CI: [-0.1, 0.4]MMRM
p-value: 0.026495% CI: [0, 0.5]MMRM
Secondary
Change From Baseline in Personal and Social Performance (PSP) Scale at Week 12
PSP scale is a measure of the personal and social functioning of participants with psychiatric disorders within four domains: socially useful activities, personal and social relationships, self-care, and disturbing and aggressive behavior. Each domain was assessed on a 6-point scale: 1 = absent, 2 = mild, 3 = manifest, 4 = marked, 5 = severe, and 6 = very severe. The final global score is defined according to a summary instruction table converting four domain scores into a single, overall rating from 1 to 100: 71 to 100 represent mild degree of difficulty; 31 to 70 represent varying degrees of disability, and 1 to 30 represent functioning so poorly as to require intensive supervision. Higher scores represent better personal and social function. A positive change from baseline indicates better personal and social function.
Time frame: Baseline, Week 12
Population: Efficacy population included all participants who received the study medication and had at least one available post-baseline PANSS assessment. 'Number of participants analyzed' indicates the number of participants with data available for analysis at the specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Personal and Social Performance (PSP) Scale at Week 12 | Baseline | 57.5 score on a scale | Standard Deviation 10 |
| Placebo | Change From Baseline in Personal and Social Performance (PSP) Scale at Week 12 | Change From Baseline at Week 12 | 4.3 score on a scale | Standard Deviation 8.6 |
| CTP-692 1 Gram QD | Change From Baseline in Personal and Social Performance (PSP) Scale at Week 12 | Change From Baseline at Week 12 | 4.6 score on a scale | Standard Deviation 9.1 |
| CTP-692 1 Gram QD | Change From Baseline in Personal and Social Performance (PSP) Scale at Week 12 | Baseline | 58.7 score on a scale | Standard Deviation 8.9 |
| CTP-692 2 Grams QD | Change From Baseline in Personal and Social Performance (PSP) Scale at Week 12 | Baseline | 58.4 score on a scale | Standard Deviation 9.8 |
| CTP-692 2 Grams QD | Change From Baseline in Personal and Social Performance (PSP) Scale at Week 12 | Change From Baseline at Week 12 | 3.7 score on a scale | Standard Deviation 7.4 |
| CTP-692 4 Grams QD | Change From Baseline in Personal and Social Performance (PSP) Scale at Week 12 | Baseline | 58.0 score on a scale | Standard Deviation 9.2 |
| CTP-692 4 Grams QD | Change From Baseline in Personal and Social Performance (PSP) Scale at Week 12 | Change From Baseline at Week 12 | 2.3 score on a scale | Standard Deviation 8.3 |
p-value: 0.610195% CI: [-2.1, 3.5]MMRM
p-value: 0.623795% CI: [-3.4, 2.1]MMRM
p-value: 0.176495% CI: [-4.6, 0.8]MMRM