Schizophrenia
Conditions
Brief summary
To evaluate the long-term safety and tolerability of pimavanserin after 52 weeks of adjunctive treatment in subjects with schizophrenia
Interventions
DRUGPimavanserin
Pimavanserin 10 mg, tablet, taken as one 10 mg tablets, once daily by mouth, OR Pimavanserin 20 mg, tablet, taken as two 10 mg tablets, once daily by mouth, OR Pimavanserin 34 mg, tablet, taken as two 17 mg tablets, once daily by mouth
Sponsors
ACADIA Pharmaceuticals Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patient is able to understand and provide signed informed consent 2. Has a caregiver or some other identified responsible person (e.g., family member, social worker, caseworker, or nurse) considered reliable by the Investigator in providing support to the subject to help ensure compliance with study treatment, study visits, and protocol procedures and who is also able to provide input helpful for completing study rating scale 3. Is completing the Week 6 visit in Study ACP-103-034 or the Week 26 visit in Study ACP-103-038 or 064 while continuing to take his/her assigned dose of blinded study drug and may, in the Investigator's opinion, benefit from continued adjunctive treatment with pimavanserin to a antipsychotic 4. If the subject is female, she must not be pregnant or breastfeeding. She must also be of non-childbearing potential (defined as either surgically sterilized or at least 1 year postmenopausal) or must agree to use two clinically acceptable methods of contraception 5. The main background antipsychotic with which the subject is being treated must continue to be on one of the antipsychotics listed below: * Aripiprazole * Aripiprazole long-acting injectables: * Abilify Maintena® * Aristada® * Asenapine * Risperidone * Risperidone long-acting injection * Olanzapine * Paliperidone extended release (ER) (≤9 mg) * Paliperidone palmitate * Invega Sustenna® (≤156 mg) * Invega Trinza® (≤546 mg) * Trevicta® (≤350 mg) * Xeplion® (≤100 mg) * Lurasidone * Cariprazine * Brexpiprazole * Asenapine
Exclusion criteria
1. Patient is judged by the Investigator or the Medical Monitor to be inappropriate for the study (e.g., significantly noncompliant in Studies ACP-103-034, -038, or -064) 2. A urine drug screen (UDS) result at Baseline that indicates the presence of any tested prohibited substance of potential abuse 1. Subjects from Studies 034 and 038 with a result indicating the presence of marijuana are permitted, if allowed by medical regulations, if they agree to abstain from marijuana use during the study and the medical monitor approves the subject's participation 2. Subjects from Study 064 with a result indicating the presence of marijuana are not permitted in the study 3. Is taking a medication or drug or other substance that is prohibited according to this protocol 4. Known family or personal history or symptoms of long QT syndrome or risk factors for torsade de pointes and/or sudden death, including symptomatic bradycardia, hypokalemia or hypomagnesemia, and the presence of congenital prolongation of the QT interval 5. 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 study. 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 |
|---|---|---|
| Treatment Emergent Adverse Events | Treatment period (52 weeks) and follow-up period (30 days): planned total of 56 weeks. Since the study was prematurely terminated, the reporting period was shortened; AEs were assessed to the end of treatment, at a mean duration of 319 days (or 46 weeks). | Number of patients with treatment emergent adverse events |
Countries
Argentina, Bulgaria, Canada, Croatia, Czechia, Hungary, Italy, Lithuania, Poland, Russia, Serbia, Spain, Ukraine, United States
Participant flow
Recruitment details
This was an open-label extension study for patients from studies ACP-103-034, 038, and 064. Patients who had completed any of those studies and had not shown significant worsening of symptoms, or who may have benefited, or were expected to benefit from continued pimavanserin treatment based on the investigator's judgment were eligible.
Participants by arm
| Arm | Count |
|---|---|
| Rollover From ACP-103-034 Starting dose of 20 mg at week 1. The dose could be continued, decreased to 10 mg, or increased to 34 mg at investigator discretion through Week 52. | 323 |
| Rollover From ACP-103-038 Starting dose of 20 mg at week 1. The dose could be continued, decreased to 10 mg, or increased to 34 mg at investigator discretion through Week 52. | 325 |
| Rollover From ACP-103-064 Pimavanserin dose of 34 mg throughout the study. | 347 |
| Total | 995 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 16 | 5 | 6 |
| Overall Study | Death | 2 | 0 | 0 |
| Overall Study | Lack of Efficacy | 3 | 3 | 1 |
| Overall Study | Lost to Follow-up | 4 | 2 | 0 |
| Overall Study | Noncompliance with study drug | 5 | 3 | 5 |
| Overall Study | Not further specified | 6 | 11 | 10 |
| Overall Study | Physician Decision | 2 | 2 | 0 |
| Overall Study | Protocol Violation | 0 | 5 | 0 |
| Overall Study | Study terminated by sponsor | 0 | 0 | 99 |
| Overall Study | Withdrawal by Subject | 37 | 14 | 9 |
Baseline characteristics
| Characteristic | Total | Rollover From ACP-103-034 | Rollover From ACP-103-038 | Rollover From ACP-103-064 |
|---|---|---|---|---|
| Age, Continuous | 37.7 years STANDARD_DEVIATION 9.36 | 37.2 years STANDARD_DEVIATION 9.3 | 37.8 years STANDARD_DEVIATION 9.32 | 38.0 years STANDARD_DEVIATION 9.47 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 0 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 38 Participants | 25 Participants | 13 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants | 2 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 950 Participants | 295 Participants | 309 Participants | 346 Participants |
| Region of Enrollment Europe | 858 participants | 278 participants | 296 participants | 284 participants |
| Region of Enrollment North America | 74 participants | 45 participants | 29 participants | 0 participants |
| Region of Enrollment South America | 63 participants | 0 participants | 0 participants | 63 participants |
| Sex: Female, Male Female | 625 Participants | 202 Participants | 215 Participants | 208 Participants |
| Sex: Female, Male Male | 370 Participants | 121 Participants | 110 Participants | 139 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 323 | 0 / 325 | 0 / 347 |
| other Total, other adverse events | 21 / 323 | 30 / 325 | 19 / 347 |
| serious Total, serious adverse events | 13 / 323 | 4 / 325 | 4 / 347 |
Outcome results
Primary
Treatment Emergent Adverse Events
Number of patients with treatment emergent adverse events
Time frame: Treatment period (52 weeks) and follow-up period (30 days): planned total of 56 weeks. Since the study was prematurely terminated, the reporting period was shortened; AEs were assessed to the end of treatment, at a mean duration of 319 days (or 46 weeks).
Population: Safety Analysis Set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Rollover From ACP-103-034 | Treatment Emergent Adverse Events | 128 Participants |
| Rollover From ACP-103-038 | Treatment Emergent Adverse Events | 111 Participants |
| Rollover From ACP-103-064 | Treatment Emergent Adverse Events | 110 Participants |