E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Major Depressive Disorder |
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E.1.1.1 | Medical condition in easily understood language |
Major Depressive Disorder |
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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 | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10025454 |
E.1.2 | Term | Major depressive disorder, recurrent episode |
E.1.2 | System Organ Class | 100000004873 |
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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 assess the safety and tolerability of long-term pimavanserin treatment in subjects with major depressive disorder and inadequate response to antidepressant treatment |
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E.2.2 | Secondary objectives of the trial |
Exploratory Objectives •To explore the safety and tolerability of long-term pimavanserin treatment in subjects with major depressive disorder and inadequate response to antidepressant treatment on the following: - suicidality - extrapyramidal symptoms - general health assessments
•To explore the benefits of long-term pimavanserin treatment in subjects with major depressive disorder and inadequate response to antidepressant treatment on the following: improvement of depression symptoms clinical global impression of severity of depressive symptoms general health assessments
•To explore the benefits of long-term pimavanserin treatment in subjects with major depressive disorder and inadequate response to antidepressant treatment on the following: improvement of depression symptoms clinical global impression of severity of depressive symptoms functional impairment sexual functioning
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Completed the antecedent study, Study ACP 103 054 or Study ACP-103-059 2.May benefit from longer term therapy with open-label pimavanserin treatment in the judgment of the Investigator 3.Is willing and able to provide informed consent. Consent for the present study must be obtained prior to the procedures being performed at the Week 6/EOT visit of Study ACP 103 054 or Study ACP-103-059 4.Is capable of communicating with the site personnel, able to complete subject-reported outcome measures and can be reliably rated on assessment scales (in the opinion of the Investigator) 5.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 during the study and 1 month following completion of the study. Acceptable methods 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.
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E.4 | Principal exclusion criteria |
1.Is judged by the Investigator or the Medical Monitor to be inappropriate for the study, due to adverse events, medical condition, or noncompliance with investigational product or study procedures in Study ACP-103-054 or Study ACP-103-059, or is judged to be a danger to self or others 2.Has any of the following electrocardiogram (ECG) results at Baseline (i.e.: Week 6/EOT visit of Study ACP-103-054 or Study ACP-103-059): a.If the subject is not on citalopram, escitalopram, or venlafaxine (immediate or extended release): i.QTcF >450 ms, if QRS duration <120 ms ii.QTcF >470 ms, if QRS duration ≥120 ms b.If the subject is on citalopram, escitalopram, or venlafaxine (immediate or extended release): i.QTcF >425 ms, if QRS duration <120 ms ii.QTcF >450 ms, if QRS duration ≥120 ms 3.Has a heart rate (as measured by peripheral pulse rate) <50 beats per minute at Baseline (i.e., the Week 6/EOT visit of Study ACP 103 054 or Study ACP-103-059) not explained by regular exercise or medication, in discussion with the Medical Monitor 4.Has a body mass index (BMI) <18.5 kg/m2 or known unintentional clinically significant weight change (i.e., +/- ≥7% of body weight) in Study ACP 103 054 or Study ACP-103-059 as assessed by the Investigator 5.Has clinically significant laboratory abnormalities that, in the judgment of the Investigator or Medical Monitor, would either: a.jeopardize the safe participation of the subject in the study; OR b.would interfere with the conduct or interpretation of safety or efficacy evaluations in the study 6.Is suicidal as defined below at Visit 1 (Baseline) of the present study: a.An answer of “yes” to C SSRS questions 4 or 5 (current or over the last 6 months); OR b.Has attempted suicide within 1 year prior to Visit 1 (Baseline); OR c.Is actively suicidal in the Investigator’s judgment 7.Has developed delirium or a neurologic, cardiovascular, respiratory, gastrointestinal, renal, hepatic, hematologic, or other medical or mental disorder, including cancer or malignancies that, in the judgment of the Investigator or the Medical Monitor, would increase the risk associated with taking study medication or significantly interfere with the conduct or interpretation of the study 8.Requires treatment with a medication or other substance that is prohibited by the protocol 9.Has a significant sensitivity or allergic reaction to pimavanserin or its excipients 10.Is an employee or is a family member of an employee of ACADIA Pharmaceuticals Inc.
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E.5 End points |
E.5.1 | Primary end point(s) |
Treatment-emergent adverse events (TEAEs) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
After final Database lock |
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E.5.2 | Secondary end point(s) |
Exploratory Endpoints Safety and tolerability endpoints: •Columbia–Suicide Severity Rating Scale (C-SSRS) •Extrapyramidal Symptom Rating Scale–Abbreviated (ESRS-A) score •Vital signs •Body weight •Potentially clinically important laboratory values Efficacy endpoints: •Change from Baseline in Hamilton Depression Scale (17 items) (HAMD-17) total score •Treatment responder rates. Treatment response is defined as a reduction from Baseline in HAMD-17 total score of 50% or more. •Treatment remission rates. Treatmentremission is defined as a HAMD-17 total score ≤7. •Change from Baseline in Clinical Global Impression–Severity (CGI-S) score for depressive symptoms •Change from Baseline in Sheehan Disability Scale (SDS) score •Change from Baseline in the Changes in Sexual Functioning Questionnaire Short Form (CSFQ-14) score •Change from Baseline in Karolinska Sleepiness Scale (KSS) score
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
After final Database lock |
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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 | Yes |
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 | No |
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 | 6 |
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 |
Bulgaria |
Czech Republic |
Finland |
Italy |
Poland |
Romania |
Russian Federation |
Serbia |
Slovakia |
South Africa |
Spain |
Sweden |
Ukraine |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | 10 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 11 |
E.8.9.2 | In all countries concerned by the trial days | 10 |