A study to evaluate the safety of Pimavanserin therapy in subject with Major Depressive Disorder
- Conditions
- Major Depressive DisorderMedDRA version: 21.1Level: LLTClassification code 10025454Term: Major depressive disorder, recurrent episodeSystem Organ Class: 100000004873Therapeutic area: Psychiatry and Psychology [F] - Mental Disorders [F03]
- Registration Number
- EUCTR2018-003251-37-GB
- Lead Sponsor
- ACADIA Pharmaceuticals Inc
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 280
1. Is a male or female =18 years of age
2. Can understand the nature of the study and protocol requirements and is willing to comply with study drug administration requirements and discontinue prohibited concomitant medications
3. Provides written informed consent to participate in the study
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. Has a clinical diagnosis of major depressive disorder with or without anxious distress by Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria and confirmed by the Mini-International Neuropsychiatric Interview (MINI) during the screening period. Subject may have either recurrent or single episode of major depressive disorder.
6. Is treated during the current major depressive episode with one of the following SSRI/SNRI antidepressants at a minimally effective dose for at least 8 weeks with at least the same stable dose over 4 weeks prior to the SAFER State versus trait, Assessability, Face validity, Ecological validity, and Rule of three Ps (pervasive, persistent, and pathological) (SAFER) remote interview:
a. Citalopram
b. Escitalopram
c. Paroxetine
d. Fluoxetine
e. Sertraline
f. Duloxetine
g. Venlafaxine
h. Desvenlafaxine
I. Venlafaxine XR
The dose level of the antidepressant is expected to remain stable throughout the study. Adherence to the antidepressant should be reviewed throughout the study.
7. Must have a detectable blood level of a prescribed SSRI/SNRI during Screening. A negative screening test may be repeated as assessed by the Medical Monitor when the subject and/or site can provide additional evidence of subject adherence to antidepressant treatment or evidence of sample or laboratory error.
8. During the screening period, the subject’s inadequate response to SSRI/SNRI antidepressant treatment is confirmed by the Massachusetts General Hospital Antidepressant Treatment Response Questionnaire (MGH ATRQ) through the SAFER remote interview and the subject continues to exhibit an inadequate response to treatment at the time of the SAFER interview.
9. Subjects who are currently taking a second antidepressant or antidepressant augmentation agent at a subtherapeutic dose or for inadequate duration at Screening are eligible for inclusion in the study if it is clinically appropriate to discontinue the drug before the Baseline visit (in the opinion of the Investigator); the second antidepressant/augmentation agent must be discontinued and washed out at least 5 half-lives prior to Baseline. This second antidepressant/augmentation agent should not be discontinued solely to make the subject eligible for enrollment in the study.
10. Has a Montgomery-Asberg Depression Rating Scale (MADRS) total score >20 at both Screening and Baseline
11. Has a Clinical Global Impression–Severity (CGI-S) score =4 (moderately ill or worse) for depression at both Screening and Baseline
12.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 for at least 1 month prior to Visit 2 (Baseline), during the study, and 1 month following completion of the study.
Acceptable methods of contraception include the following:
a.
1 Has a history of schizophrenia or other psychotic disorder, major depressive disorder with psychotic features, bipolar I or II disorder. Subjects who are currently being treated or require treatment for post-traumatic stress disorder, acute stress disorder, panic disorder, or obsessive compulsive disorder are also not eligible.
2 Has a current primary diagnosis of borderline, antisocial, paranoid, schizoid, schizotypal, or histrionic personality disorder, according to DSM-5 criteria
3 Has met DSM-5 criteria for substance use disorders within the last 6 months prior to Screening, except for disorders related to the use of caffeine or nicotine
4 Is suicidal at Visit 1 (Screening) or Visit 2 (Baseline) as defined below:
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 (Screening); OR
c.Is actively suicidal in the Investigator’s judgment
5.Has current evidence of delirium or an unstable neurological, cardiovascular, respiratory, gastrointestinal, renal, hepatic, hematologic, or other medical disorder, including cancer or malignancies that, in the judgment of the Investigator or medical monitor, would jeopardize the safe participation of the subject in the study or significantly interfere with the conduct or interpretation of the study
6 Has a history of epilepsy
7 Has atrial fibrillation unless adequately anti-coagulated
8 Has a history of myocardial infarction, unstable angina, acute coronary syndrome, or cerebrovascular accident
9 Has a history of any of the following:
a Greater than New York Heart Association (NYHA) Class II congestive heart failure
b Grade II or greater angina pectoris (by Canadian Cardiovascular Society Angina Grading Scale)
c Sustained ventricular tachycardia
d Ventricular fibrillation
e Torsade de pointes
f Syncope due to an arrhythmia
g An implantable cardiac defibrillator
10 Has laboratory evidence of hypothyroidism at Screening, as measured by thyroid stimulating hormone (TSH) and reflex free thyroxine (T4). If TSH is abnormal and the reflex free T4 is normal, the subject may be enrolled
11 Has current unstable diabetes or glycosylated hemoglobin (HbA1c) >8% at Screening
12 Has a known history of a positive hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV) test
13 Has a history of neuroleptic malignant syndrome or serotonin syndrome
14 Has a known personal or family history of long QT syndrome or family history of sudden cardiac death
15 Has any of the following ECG results at Visit 1 (Screening) or Visit 2 (Baseline):
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
At Screening, if the set of triplicate ECGs has a prolonged QTcF due to an identifiable cause, and it is medically appropriate to address that cause, a repeat set of triplicate ECGs may be performed during Screening at the discretion of the Medical Monitor.
16 Has a heart rate <50 beats per minute as measured by peripheral pulse rate , not explained by regular exercise. or medication in discussion with Medical Monitor . If bradycardia is secondary to iatrogenic or treatable cause
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate the efficacy of adjunctive pimavanserin compared to placebo in subjects with major depressive disorder who have an inadequate response to antidepressant therapy;Secondary Objective: To evaluate the efficacy and benefits of adjunctive pimavanserin compared to placebo in subjects with major depressive disorder who have an inadequate response to antidepressant therapy on the following: <br>• Functional impairment<br>• Clinician’s global impression of severity and improvement of depressive symptoms<br>• Sexual functioning<br>• Sleepiness<br>• Treatment response and remission<br>• Anxiety<br>• Impulsiveness<br>•Early response to treatment<br>;Primary end point(s): Change from Baseline in the Hamilton Depression Scale (17 items) (HAMD 17) total score;Timepoint(s) of evaluation of this end point: After final Database lock
- Secondary Outcome Measures
Name Time Method Secondary end point(s): •Change from Baseline in Sheehan Disability Scale (SDS) score<br>•Change from Baseline in Clinical Global Impression–Severity (CGI-S) score for depressive symptoms<br>•Clinical Global Impression–Improvement (CGI-I) score for depressive symptoms<br>•Change from Baseline in the Changes in Sexual Functioning Questionnaire Short Form (CSFQ-14)<br>•Change from Baseline in Karolinska Sleepiness Scale (KSS) score<br>•Treatment responder rates. Treatment response is defined as a reduction from Baseline in HAMD-17 total score of 50% or more.<br>•Treatment remission rates. Treatment remission is defined as a HAMD-17 total score =7.<br>•Change from Baseline in the Hamilton Depression (HAMD) Anxiety/Somatization factor score<br>•Change from Baseline in the Barratt Impulsiveness Scale (BIS-11)<br>•Change from Baseline to Week 1 in the HAMD-17 total score<br>;Timepoint(s) of evaluation of this end point: After final Database lock