Schizophrenia
Conditions
Brief summary
To evaluate the efficacy and safety of adjunctive pimavanserin compared with adjunctive placebo in the treatment of schizophrenia
Interventions
DRUGPimavanserin
Pimavanserin 34 mg, 20 mg, or 10 mg , taken as two tablets once daily by mouth
DRUGPlacebo
Placebo, taken as two tablets, once daily by mouth
Sponsors
ACADIA Pharmaceuticals Inc.
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
1. Adults patients, between 18 and 55 years of age 2. A clinical diagnosis of schizophrenia with a minimum duration of 1 year 3. The main background antipsychotic with which the subject is being treated must be one of the antipsychotics listed below: * Aripiprazole * Aripiprazole long-acting injectables: * Abilify Maintena® * Aristada® * Risperidone * Risperidone long-acting injection * Olanzapine * Lurasidone * Cariprazine * Brexpiprazole * Asenapine 4. Has had a partial but inadequate response to antipsychotic treatment 5. Has a history of response to antipsychotic treatment other than clozapine
Exclusion criteria
1. Patient has a psychiatric disorder other than schizophrenia 2. Patient has a history of resistance to antipsychotic treatment 3. A urine drug screen (UDS) result at Baseline that indicates the presence of any tested prohibited substance of potential abuse, except marijuana a. Patients with a result indicating the presence of marijuana are permitted if they agree to abstain from marijuana use during the study and the medical monitor approves the subject's participation 4. Patient has current evidence of a serious and/or unstable psychiatric, neurologic, cardiovascular, respiratory, gastrointestinal, renal, hepatic, hematologic, or other medical disorder, including cancer or malignancies, which would affect the patient's ability to participate in the program 5. Patient has had a myocardial infarction in the last six months 6. Patient is taking a medication or drug that prolongs the QT interval or has a family or personal history or symptoms of long QT syndrome Patients will be evaluated at screening to ensure that all criteria for study participation are met. Patients may be excluded from the study based on these assessments (and specifically if it is determined that their baseline health and psychiatric condition do not meet all pre-specified entry criteria).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 6 in the Positive and Negative Syndrome Scale (PANSS) Total Score | From baseline to Week 6 | The PANSS is a 30-item scale used to evaluate the presence, absence, and severity of schizophrenia symptoms. The 30 items are arranged as 7 positive symptom items (P1 to P7), 7 negative symptom items (N1 to N7), and 16 general psychopathology symptom items (G1 to G16). Items are scored over the past week (7 days) on a 7-point scale ranging from 1 (absent) to 7 (extreme). The PANSS total score can range from a minimum of 30 to a maximum of 210, where a higher score signifies greater severity of schizophrenia symptoms. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline (CFBL) to Week 6 in PANSS Subscale Scores, i.e. PANSS Positive Subscale Score, PANSS Negative Subscale Score and PANSS General Psychopathological Scale Score | From baseline to Week 6 | The PANSS is a 30-item scale used to evaluate the presence, absence, and severity of schizophrenia symptoms. The 30 items are arranged as 7 positive symptom items (P1 to P7), 7 negative symptom items (N1 to N7), and 16 general psychopathology symptom items (G1 to G16). Items are scored over the past week (7 days) on a 7-point scale ranging from 1 (absent) to 7 (extreme). The PANSS positive subscale score can range from 7 to 49; the PANSS negative subscale score can range from 7 to 49; the PANSS general psychopathology scale score can range from 16 to 112. For each of the subscale scores, a higher score signifies greater severity of schizophrenia symptoms. |
| PANSS Responders | From baseline to Week 6 | Porportion of patients showing a PANSS response of \>=20% or \>=30% reduction in PANSS total score PANSS total score reduction signifies improvement. |
| Clinical Global Impression-Improvement (CGI-I) Response | From baseline to Week 6 | The CGI-I is a 1-item scale, used to rate the improvement from 1 (very much improved) to 7 (very much worse). Higher scores denote less improvement. A CGI-I score of 1 or 2 was counted as response. The Analysis was performed twice; once including missing values as non-responders (MN) and once including only observed cases (OC). |
| Change From Baseline to Week 6 in the Clinical Global Impression-Severity (CGI-S) Score | From baseline to Week 6 | The CGI-S is a 1-item scale, used to rate the severity of the disorder from 0 (not assessed) to 7 (among the most extremely ill patients). A higher CGI-S score denotes greater severity of the disorder. |
| Change From Baseline to Week 6 in Personal and Social Performance (PSP) Scale Score | From baseline to Week 6 | The PSP is a validated 100-point (1 to100) single-item rating scale to assess the psychosocial functioning of patients with schizophrenia. The maximum score is 100. Higher scores denote better psychosocial functioning. |
| Drug Attitude Inventory (DAI-10) | From baseline to Week 6 | The DAI-10 contains 6 items (1, 3, 4, 7, 9, and 10) that a patient who is fully adherent to study medication would answer as True and 4 items (2, 5, 6, and 8) that a patient who is fully adherent to study medication would answer as False. A correct answer is scored +1 and an incorrect answer is scored -1; the total score is derived as overall sum. The score can range from -10 to 10. Positive total scores indicate adherence and negative total scores indicate non-adherence. Higher scores denote better adherence. |
| Change From Baseline to Week 6 in Karolinska Sleepiness Scale (KSS) Score | From baseline to Week 6 | The KSS is a self-reported measure of a patient's level of drowsiness. In this study, drowsiness was to be rated during the last week (7 days). Scoring is based on a 9-point verbally anchored scale ranging from 1 (extremely alert) to 9 (very sleepy, great effort to keep awake, fighting sleep). The maximum score is 9. Higher scores denote more drowsiness. |
| Clinical Global Impression-Improvement (CGI-I) Score at Week 6 | From baseline to Week 6 | The CGI-I is a 1-item scale, used to rate the improvement from 1 (very much improved) to 7 (very much worse). Higher scores denote less improvement. |
Countries
Bulgaria, Canada, Czechia, Hungary, Lithuania, Poland, Russia, Serbia, Ukraine, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Pimavanserin Patients started treatment with pimavanserin 20 mg once daily (QD). At the Week 1, Week 2 and Week 3 visit, the dose could be increased to 34 mg QD or decreased to 10 mg QD at the investigator's discretion (to improve symptom reliev or tolerability, respectively). Thereafter, the daily dose was to remain the same for the remainder of the study.
Patients were to continue their background antipsychotic treatment. | 198 |
| Placebo Pimavanserin-matching Placebo.
Patients were to continue their background antipsychotic treatment. | 198 |
| Total | 396 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 5 | 0 |
| Overall Study | Lack of Efficacy | 1 | 0 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Noncompliance with study drug | 2 | 2 |
| Overall Study | Other | 1 | 0 |
| Overall Study | Physician Decision | 1 | 1 |
| Overall Study | Protocol Violation | 2 | 0 |
| Overall Study | Withdrawal by Subject | 11 | 5 |
Baseline characteristics
| Characteristic | Pimavanserin | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 36.8 years STANDARD_DEVIATION 9.42 | 37.1 years STANDARD_DEVIATION 9.43 | 37.4 years STANDARD_DEVIATION 9.45 |
| BMI | 26.74 kg/m2 STANDARD_DEVIATION 4.177 | 26.83 kg/m2 STANDARD_DEVIATION 4.099 | 26.92 kg/m2 STANDARD_DEVIATION 4.029 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 22 Participants | 44 Participants | 22 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 3 Participants | 3 Participants |
| Race (NIH/OMB) White | 176 Participants | 348 Participants | 172 Participants |
| Region of Enrollment Bulgaria | 43 participants | 93 participants | 50 participants |
| Region of Enrollment Canada | 0 participants | 2 participants | 2 participants |
| Region of Enrollment Czechia | 1 participants | 2 participants | 1 participants |
| Region of Enrollment Hungary | 3 participants | 6 participants | 3 participants |
| Region of Enrollment Lithuania | 3 participants | 9 participants | 6 participants |
| Region of Enrollment Poland | 3 participants | 6 participants | 3 participants |
| Region of Enrollment Russia | 48 participants | 90 participants | 42 participants |
| Region of Enrollment Serbia | 44 participants | 77 participants | 33 participants |
| Region of Enrollment Ukraine | 16 participants | 40 participants | 24 participants |
| Region of Enrollment United States | 37 participants | 71 participants | 34 participants |
| Sex: Female, Male Female | 72 Participants | 150 Participants | 78 Participants |
| Sex: Female, Male Male | 126 Participants | 246 Participants | 120 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 198 | 0 / 198 |
| other Total, other adverse events | 31 / 198 | 31 / 198 |
| serious Total, serious adverse events | 2 / 198 | 2 / 198 |
Outcome results
Primary
Change From Baseline to Week 6 in the Positive and Negative Syndrome Scale (PANSS) Total Score
The PANSS is a 30-item scale used to evaluate the presence, absence, and severity of schizophrenia symptoms. The 30 items are arranged as 7 positive symptom items (P1 to P7), 7 negative symptom items (N1 to N7), and 16 general psychopathology symptom items (G1 to G16). Items are scored over the past week (7 days) on a 7-point scale ranging from 1 (absent) to 7 (extreme). The PANSS total score can range from a minimum of 30 to a maximum of 210, where a higher score signifies greater severity of schizophrenia symptoms.
Time frame: From baseline to Week 6
Population: Patients randomised and treated (at least 1 dose of study medication) who had both a baseline value and at least 1 post-baseline value for the PANSS total score.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pimavanserin | Change From Baseline to Week 6 in the Positive and Negative Syndrome Scale (PANSS) Total Score | Baseline | 88.3 score on a scale | Standard Error 0.68 |
| Pimavanserin | Change From Baseline to Week 6 in the Positive and Negative Syndrome Scale (PANSS) Total Score | Change from baseline to Week 6 | -15.3 score on a scale | Standard Error 0.93 |
| Placebo | Change From Baseline to Week 6 in the Positive and Negative Syndrome Scale (PANSS) Total Score | Baseline | 88.1 score on a scale | Standard Error 0.61 |
| Placebo | Change From Baseline to Week 6 in the Positive and Negative Syndrome Scale (PANSS) Total Score | Change from baseline to Week 6 | -13.4 score on a scale | Standard Error 0.83 |
p-value: 0.09495% CI: [-4.5, 0.4]mixed-effects model for repeated measure
Secondary
Change From Baseline (CFBL) to Week 6 in PANSS Subscale Scores, i.e. PANSS Positive Subscale Score, PANSS Negative Subscale Score and PANSS General Psychopathological Scale Score
The PANSS is a 30-item scale used to evaluate the presence, absence, and severity of schizophrenia symptoms. The 30 items are arranged as 7 positive symptom items (P1 to P7), 7 negative symptom items (N1 to N7), and 16 general psychopathology symptom items (G1 to G16). Items are scored over the past week (7 days) on a 7-point scale ranging from 1 (absent) to 7 (extreme). The PANSS positive subscale score can range from 7 to 49; the PANSS negative subscale score can range from 7 to 49; the PANSS general psychopathology scale score can range from 16 to 112. For each of the subscale scores, a higher score signifies greater severity of schizophrenia symptoms.
Time frame: From baseline to Week 6
Population: Patients randomised and treated (at least 1 dose of study medication) who had both a baseline value and at least 1 post-baseline value for the PANSS total score.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pimavanserin | Change From Baseline (CFBL) to Week 6 in PANSS Subscale Scores, i.e. PANSS Positive Subscale Score, PANSS Negative Subscale Score and PANSS General Psychopathological Scale Score | PANSS positive scale BL | 23.0 score on a scale | Standard Error 0.25 |
| Pimavanserin | Change From Baseline (CFBL) to Week 6 in PANSS Subscale Scores, i.e. PANSS Positive Subscale Score, PANSS Negative Subscale Score and PANSS General Psychopathological Scale Score | PANSS general psychopatholigy scale BL | 42.4 score on a scale | Standard Error 0.45 |
| Pimavanserin | Change From Baseline (CFBL) to Week 6 in PANSS Subscale Scores, i.e. PANSS Positive Subscale Score, PANSS Negative Subscale Score and PANSS General Psychopathological Scale Score | PANSS positive scale CFBL to 6 weeks | -5.4 score on a scale | Standard Error 0.34 |
| Pimavanserin | Change From Baseline (CFBL) to Week 6 in PANSS Subscale Scores, i.e. PANSS Positive Subscale Score, PANSS Negative Subscale Score and PANSS General Psychopathological Scale Score | PANSS gen. psychopath. scale CFBL to 6 w | -7.2 score on a scale | Standard Error 0.47 |
| Pimavanserin | Change From Baseline (CFBL) to Week 6 in PANSS Subscale Scores, i.e. PANSS Positive Subscale Score, PANSS Negative Subscale Score and PANSS General Psychopathological Scale Score | PANSS negative scale BL | 23.0 score on a scale | Standard Error 0.29 |
| Pimavanserin | Change From Baseline (CFBL) to Week 6 in PANSS Subscale Scores, i.e. PANSS Positive Subscale Score, PANSS Negative Subscale Score and PANSS General Psychopathological Scale Score | PANSS negative scale CFBL to 6 weeks | -2.8 score on a scale | Standard Error 0.28 |
| Placebo | Change From Baseline (CFBL) to Week 6 in PANSS Subscale Scores, i.e. PANSS Positive Subscale Score, PANSS Negative Subscale Score and PANSS General Psychopathological Scale Score | PANSS general psychopatholigy scale BL | 42.2 score on a scale | Standard Error 0.45 |
| Placebo | Change From Baseline (CFBL) to Week 6 in PANSS Subscale Scores, i.e. PANSS Positive Subscale Score, PANSS Negative Subscale Score and PANSS General Psychopathological Scale Score | PANSS negative scale CFBL to 6 weeks | -2.1 score on a scale | Standard Error 0.28 |
| Placebo | Change From Baseline (CFBL) to Week 6 in PANSS Subscale Scores, i.e. PANSS Positive Subscale Score, PANSS Negative Subscale Score and PANSS General Psychopathological Scale Score | PANSS gen. psychopath. scale CFBL to 6 w | -6.4 score on a scale | Standard Error 0.47 |
| Placebo | Change From Baseline (CFBL) to Week 6 in PANSS Subscale Scores, i.e. PANSS Positive Subscale Score, PANSS Negative Subscale Score and PANSS General Psychopathological Scale Score | PANSS positive scale BL | 22.8 score on a scale | Standard Error 0.23 |
| Placebo | Change From Baseline (CFBL) to Week 6 in PANSS Subscale Scores, i.e. PANSS Positive Subscale Score, PANSS Negative Subscale Score and PANSS General Psychopathological Scale Score | PANSS positive scale CFBL to 6 weeks | -4.9 score on a scale | Standard Error 0.3 |
| Placebo | Change From Baseline (CFBL) to Week 6 in PANSS Subscale Scores, i.e. PANSS Positive Subscale Score, PANSS Negative Subscale Score and PANSS General Psychopathological Scale Score | PANSS negative scale BL | 23.1 score on a scale | Standard Error 0.29 |
Secondary
Change From Baseline to Week 6 in Karolinska Sleepiness Scale (KSS) Score
The KSS is a self-reported measure of a patient's level of drowsiness. In this study, drowsiness was to be rated during the last week (7 days). Scoring is based on a 9-point verbally anchored scale ranging from 1 (extremely alert) to 9 (very sleepy, great effort to keep awake, fighting sleep). The maximum score is 9. Higher scores denote more drowsiness.
Time frame: From baseline to Week 6
Population: Patients randomised and treated (at least 1 dose of study medication) who had both a baseline value and at least 1 post-baseline value for the PANSS total score.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pimavanserin | Change From Baseline to Week 6 in Karolinska Sleepiness Scale (KSS) Score | Baseline | 4.6 score on a scale | Standard Error 0.11 |
| Pimavanserin | Change From Baseline to Week 6 in Karolinska Sleepiness Scale (KSS) Score | Change from baseline to Week 6 | -0.5 score on a scale | Standard Error 0.12 |
| Placebo | Change From Baseline to Week 6 in Karolinska Sleepiness Scale (KSS) Score | Baseline | 4.7 score on a scale | Standard Error 0.12 |
| Placebo | Change From Baseline to Week 6 in Karolinska Sleepiness Scale (KSS) Score | Change from baseline to Week 6 | -0.2 score on a scale | Standard Error 0.12 |
Secondary
Change From Baseline to Week 6 in Personal and Social Performance (PSP) Scale Score
The PSP is a validated 100-point (1 to100) single-item rating scale to assess the psychosocial functioning of patients with schizophrenia. The maximum score is 100. Higher scores denote better psychosocial functioning.
Time frame: From baseline to Week 6
Population: Patients randomised and treated (at least 1 dose of study medication) who had both a baseline value and at least 1 post-baseline value for the PANSS total score.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pimavanserin | Change From Baseline to Week 6 in Personal and Social Performance (PSP) Scale Score | Baseline | 51.8 score on a scale | Standard Error 0.79 |
| Pimavanserin | Change From Baseline to Week 6 in Personal and Social Performance (PSP) Scale Score | Change from baseline to Week 6 | 6.8 score on a scale | Standard Error 0.71 |
| Placebo | Change From Baseline to Week 6 in Personal and Social Performance (PSP) Scale Score | Baseline | 51.6 score on a scale | Standard Error 0.78 |
| Placebo | Change From Baseline to Week 6 in Personal and Social Performance (PSP) Scale Score | Change from baseline to Week 6 | 5.7 score on a scale | Standard Error 0.64 |
Secondary
Change From Baseline to Week 6 in the Clinical Global Impression-Severity (CGI-S) Score
The CGI-S is a 1-item scale, used to rate the severity of the disorder from 0 (not assessed) to 7 (among the most extremely ill patients). A higher CGI-S score denotes greater severity of the disorder.
Time frame: From baseline to Week 6
Population: Patients randomised and treated (at least 1 dose of study medication) who had both a baseline value and at least 1 post-baseline value for the PANSS total score.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pimavanserin | Change From Baseline to Week 6 in the Clinical Global Impression-Severity (CGI-S) Score | Baseline | 4.6 score on a scale | Standard Error 0.04 |
| Pimavanserin | Change From Baseline to Week 6 in the Clinical Global Impression-Severity (CGI-S) Score | Change from baseline to Week 6 | -0.8 score on a scale | Standard Error 0.06 |
| Placebo | Change From Baseline to Week 6 in the Clinical Global Impression-Severity (CGI-S) Score | Baseline | 4.6 score on a scale | Standard Error 0.04 |
| Placebo | Change From Baseline to Week 6 in the Clinical Global Impression-Severity (CGI-S) Score | Change from baseline to Week 6 | -0.7 score on a scale | Standard Error 0.05 |
Secondary
Clinical Global Impression-Improvement (CGI-I) Response
The CGI-I is a 1-item scale, used to rate the improvement from 1 (very much improved) to 7 (very much worse). Higher scores denote less improvement. A CGI-I score of 1 or 2 was counted as response. The Analysis was performed twice; once including missing values as non-responders (MN) and once including only observed cases (OC).
Time frame: From baseline to Week 6
Population: Patients randomised and treated (at least 1 dose of study medication) who had both a baseline value and at least 1 post-baseline value for the PANSS total score.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Pimavanserin | Clinical Global Impression-Improvement (CGI-I) Response | CGI-I response (MN) | 68 Participants |
| Pimavanserin | Clinical Global Impression-Improvement (CGI-I) Response | CGI-I response (OC) | 68 Participants |
| Placebo | Clinical Global Impression-Improvement (CGI-I) Response | CGI-I response (MN) | 65 Participants |
| Placebo | Clinical Global Impression-Improvement (CGI-I) Response | CGI-I response (OC) | 65 Participants |
Secondary
Clinical Global Impression-Improvement (CGI-I) Score at Week 6
The CGI-I is a 1-item scale, used to rate the improvement from 1 (very much improved) to 7 (very much worse). Higher scores denote less improvement.
Time frame: From baseline to Week 6
Population: Patients randomised and treated (at least 1 dose of study medication) who had both a baseline value and at least 1 post-baseline value for the PANSS total score.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pimavanserin | Clinical Global Impression-Improvement (CGI-I) Score at Week 6 | 2.8 score on a scale | Standard Error 0.07 |
| Placebo | Clinical Global Impression-Improvement (CGI-I) Score at Week 6 | 3.0 score on a scale | Standard Error 0.07 |
Secondary
Drug Attitude Inventory (DAI-10)
The DAI-10 contains 6 items (1, 3, 4, 7, 9, and 10) that a patient who is fully adherent to study medication would answer as True and 4 items (2, 5, 6, and 8) that a patient who is fully adherent to study medication would answer as False. A correct answer is scored +1 and an incorrect answer is scored -1; the total score is derived as overall sum. The score can range from -10 to 10. Positive total scores indicate adherence and negative total scores indicate non-adherence. Higher scores denote better adherence.
Time frame: From baseline to Week 6
Population: Patients randomised and treated (at least 1 dose of study medication) who had both a baseline value and at least 1 post-baseline value for the PANSS total score.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pimavanserin | Drug Attitude Inventory (DAI-10) | Change from baseline to Week 6 | 0.4 score on a scale | Standard Error 0.2 |
| Pimavanserin | Drug Attitude Inventory (DAI-10) | Baseline | 5.6 score on a scale | Standard Error 0.24 |
| Placebo | Drug Attitude Inventory (DAI-10) | Baseline | 5.8 score on a scale | Standard Error 0.23 |
| Placebo | Drug Attitude Inventory (DAI-10) | Change from baseline to Week 6 | 0.4 score on a scale | Standard Error 0.2 |
Secondary
PANSS Responders
Porportion of patients showing a PANSS response of \>=20% or \>=30% reduction in PANSS total score PANSS total score reduction signifies improvement.
Time frame: From baseline to Week 6
Population: Patients randomised and treated (at least 1 dose of study medication) who had both a baseline value and at least 1 post-baseline value for the PANSS total score.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Pimavanserin | PANSS Responders | PANSS total score reduction >=20% | 109 Participants |
| Pimavanserin | PANSS Responders | PANSS total score reduction >=30% | 71 Participants |
| Placebo | PANSS Responders | PANSS total score reduction >=20% | 99 Participants |
| Placebo | PANSS Responders | PANSS total score reduction >=30% | 67 Participants |