E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
E.1.1.1 | Medical condition in easily understood language |
Chronic, debilitating mental illness characterized by disturbances in
thinking, emotional reaction, and behavior |
|
E.1.1.2 | Therapeutic area | Psychiatry and Psychology [F] - Mental Disorders [F03] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10039626 |
E.1.2 | Term | Schizophrenia |
E.1.2 | System Organ Class | 10037175 - Psychiatric disorders |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the long-term safety and tolerability of pimavanserin after 52 weeks of adjunctive treatment in subjects with schizophrenia |
|
E.2.2 | Secondary objectives of the trial |
Clinical global assessment of overall severity of symptoms
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Procedures:
1.Able to understand and provide signed informed consent, and must be
able to sign and date a request for medical records and/or subject
privacy form, if applicable, according to local regulations
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
scales
3.Is completing the Week 6 visit in Study ACP-103-034 or the Week 26
visit in Studies 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 an antipsychotic
Medical Status:
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 or be abstinent
duringg the study and for 41 days following completion of the study.
Abstinence as a method of contraception is defined as refraining from
heterosexual intercourse during the entire period of risk associated with
the study treatments. This option is usually made for specific moral,
religious, legal, or health reason. If heterosexual intercourse does occur,
two acceptable methods of birth control are required. Acceptable method
of contraception include the following:
a. A barrier method (condom, diaphragm, or cervical cap) with
spermicide
b. Hormonal contraception, including oral, injectable, transdermal, or
implantable methods
c. Intrauterine device (IUD)
Only one of the two clinically acceptable methods can be a hormonal
method.
•All female subjects of childbearing potential must have a negative urine
human chorionic gonadotropin (hCG) pregnancy test at Baseline and at
Weeks 2, 6, 12, 20, 28, 36, 44, and 52.
Note: Specific contraceptive methods are not required for male subjects
with partners of childbearing potential, but may be used as a general
precaution.
5.Continue to be medically stable at enrollment, in the opinion of the
Investigator
Medications:
6.Continues to take a stable dose of an antipsychotic within the dose
range recommended according to the local Prescribing Information
7.The main antipsychotic with which the subject is being treated must
continue to be one of the antipsychotics listed below:
•Aripiprazole
•Aripiprazole long-acting injectables
–Abilify Maintena®
–Aristada®
•Asenapine
•Brexpiprazole
•Cariprazine
•Lurasidone
•Olanzapine
• Paliperidone extended release (ER) (≤9 mg)
• Paliperidone palmitate
o Invega Sustenna® (≤156 mg)
o Invega Trinza® (≤546 mg)
o Trevicta® (≤350 mg)
o Xeplion® (≤100 mg)
•Risperidone
•Risperidone long-acting injection |
|
E.4 | Principal exclusion criteria |
Procedures:
1.Subject 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)
Medical Status:
2.A urine drug screen (UDS) result at Baseline that indicates the
presence of any tested prohibited substance of potential abuse
• Subjects from studies 034 and 038 with a result indicating the
presence of marijuana are permitted, if allowed by local regulations, if
they agree to abstain from marijuana use during the study and the
medical monitor approves the subject's participation
• 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, including medications that prolong the QT
interval, strong cytochrome P450 (CYP) 3A4 enzyme (CYP3A4) inhibitors
and inducers
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.Has a QRS interval <120 ms and QTcF ≥460 ms OR
has a QRS interval ≥120 ms and QTcF ≥480 ms at Baseline
6.Has developed a serious and/or unstable psychiatric, neurologic,
cardiovascular, respiratory, gastrointestinal, renal, hepatic, hematologic,
or other medical disorder, including cancer or malignancies that, in the
judgment of the Investigator, would jeopardize the safe participation of
the subject in the study
7.Is breastfeeding or lactating
8.Has a significant sensitivity or allergic reaction to pimavanserin or its
excipients
9.Subject and/or caregiver has any condition that, in the opinion of the
Investigator, would interfere with the ability to comply with study
instructions, might confound the interpretation of the study results, or
put the subject at undue risk
10.Presence of any change in medical or treatment status which may
increase the risk associated with taking study medication, would
interfere with safety assessments, or would confound the interpretation
of the study results, based on Investigator's judgment
Neuropsychiatric:
11.Is at a significant risk of suicide, (e.g., answers "Yes" to suicidal
ideation question 4 or 5 [current or over last 6 months] or answers
"Yes" to suicidal behavior questions on the C-SSRS [over last 6
months)], in the opinion of the Investigator
12.Has a significant risk of violent behavior in the opinion of the
Investigator
Other:
13.Is an employee of ACADIA, or has a family member who is an
employee of ACADIA |
|
E.5 End points |
E.5.1 | Primary end point(s) |
•Incidence and severity of treatment-emergent adverse events (TEAEs),
serious adverse events (SAEs), and withdrawals due to TEAEs
•Vital sign measurements, weight, clinical laboratory assessments,
physical examination findings, electrocardiogram (ECG) parameters, the
Abnormal Involuntary Movement Scale (AIMS) score, the Barnes
Akathisia Rating Scale (BARS) score, and the Simpson-Angus
Extrapyramidal Side Effects Scale (SAS) score
•Changes from Baseline in vital sign measurements, weight, clinical
laboratory and ECG parameters, the AIMS score, the BARS score, and the
SAS score
•Suicidality: the incidence of subjects with suicidal ideation or suicidal
behavior during the study as assessed by the Columbia-Suicide Severity
Rating Scale (C SSRS) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
•Change from Baseline in the Clinical Global Impression – Severity scale
(CGI-S)
•Change from Baseline in the Clinical Global Impression of Schizophrenia
Scale – Severity (CGI-SCH-S); (for subjects from Studies ACP-103-038
and 064 only) |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Tolerability after 52 weeks of adjunctive treatment |
|
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 40 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Argentina |
Russian Federation |
Serbia |
Ukraine |
Croatia |
Czechia |
Hungary |
Italy |
Lithuania |
Poland |
Bulgaria |
Spain |
|
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 4 |
E.8.9.2 | In all countries concerned by the trial days | 0 |