MedPath

Adjunctive Pimavanserin in Subjects With Major Depressive Disorder and Inadequate Response to Antidepressant Treatment

Phase 3
Completed
Conditions
Adjunctive Treatment of Major Depressive Disorder
Interventions
Drug: Placebo
Registration Number
NCT03968159
Lead Sponsor
ACADIA Pharmaceuticals Inc.
Brief Summary

To evaluate the efficacy and safety of adjunctive pimavanserin compared to placebo in subjects with major depressive disorder who have an inadequate response to antidepressant therapy

Detailed Description

Two separate studies, idential in design, were planned and initiated under 2 protocol IDs and NCTs, i.e. study ACP-103-54 (NCT03999918) and ACP-103-059 (NCT03968159). In March 2020, recruitment of new patients was paused due to the emerging coronavirus disease 2019 (COVID-19) pandemic. At that point in time, about half of the planned patients had been randomized. The Sponsor decided to combine the 2 identically designed trials, with a prespecified combined statistical analysis plan. As a result, both trials were closed and proceeded with database lock and statistical analysis of the combined data. No further patients were enrolled.

This entry now includes the combined data of studies ACP-103-054 and ACP-103-059.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
298
Inclusion Criteria
  1. Adult patients, aged 18 years and above

  2. A clinical diagnosis of major depressive disorder (MDD)

  3. Is being treated with one of the following SSRI or SNRI antidepressants:

    1. Citalopram
    2. Escitalopram
    3. Paroxetine
    4. Fluoxetine
    5. Sertraline
    6. Duloxetine
    7. Venlafaxine
    8. Desvenlafaxine
    9. Venlafaxine XR
  4. Inadequate response to SSRI/SNRI antidepressant treatment is confirmed

  5. If the subject is female, she must not be pregnant or breastfeeding. She must also be of non-childbearing potential OR must agree to use acceptable methods of contraception

Exclusion Criteria
  1. Has a history of psychotic disorder or is currently being treated or requires treatment for post-traumatic stress disorder, acute stress disorder, panic disorder, or obsessive compulsive disorder
  2. Has current evidence of delirium or an unstable neurological, cardiovascular, respiratory, gastrointestinal, renal, hepatic, hematologic, or other medical disorder, including cancer or malignancies that would affect the patient's ability to participate in the program
  3. Has a known history or symptoms of long QT syndrome
  4. Is determined to be inappropriate for the study for any reason

Additional inclusion/exclusion criteria apply. 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).

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Drug - pimavanserinPimavanserinPimavanserin 34 mg tablets
PlaceboPlaceboPlacebo tablets
Primary Outcome Measures
NameTimeMethod
Change From Baseline to Week 5 in Hamilton Depression Scale (17 Items) (HAMD-17) Total ScoreBaseline, Week 5

The HAMD-17 consists of 8 items with a score on a 3 point scale and 9 items with a score on a 5 point scale. The total score ranging from 0 to 52 will be calculated as the sum of the scores for all 17 items. Higher total scores denote more severe depression.

Secondary Outcome Measures
NameTimeMethod
Change From Baseline to Week 5 in Clinical Global Impression-Severity (CGI-S) Score for Depressive SymptomsBaseline, 5 weeks

The CGI-S rates the severity of a subject's depression over the past 7 days and the score ranges from 1 to 7. Higher CGI-S scores denote more severe depression.

Change From Baseline to Week 5 in Sheehan Disability Scale (SDS) ScoreBaseline, 5 weeks

The SDS is a 3-item subject-facing questionnaire used to evaluate impairments in the domains of work, social life/leisure, and family life/home responsibility. Subjects rate each item using an 11-point scale ranging from 0 (not at all) to 10 (extremely). Higher scores denote greater disability.

Change From Baseline to Week 5 in the Changes in Sexual Functioning Questionnaire Short FormBaseline, 5 weeks

The CSFQ-14 is a 14-item version of the CSFQ. This is a patient-facing questionnaire, with a male version and a female version. The total score ranging from 14 to 70 will be calculated as the sum of the scores for all 14 items. Higher total scores denote better sexual functioning.

Change From Baseline to Week 5 in Karolinska Sleepiness Scale (KSS) ScoreBaseline, 5 weeks

The KSS is a scale that measures the subject's drowsiness and is frequently used in studies measuring subjective sleepiness. Scoring is based on a 9-point verbally anchored scale going from "1 = extremely alert" to "9 = very sleepy, great effort to keep awake, fighting sleep". Higher scores denote more drowsiness.

Change From Baseline to Week 1 in the HAMD-17 Total ScoreBaseline, 1 week

The HAMD-17 consists of 8 items with a score on a 3 point scale and 9 items with a score on a 5 point scale. The total score ranging from 0 to 52 will be calculated as the sum of the scores for all 17 items. Higher total scores denote more severe depression.

Treatment Responder and Treatment Remission Rates at Week 5Baseline, 5 weeks

The HAMD-17 consists of 8 items with a score on a 3 point scale and 9 items with a score on a 5 point scale. The total score ranging from 0 to 52 will be calculated as the sum of the scores for all 17 items. Treatment response is defined as a reduction from Baseline in HAMD-17 total score of 50% or more. Treatment remission is defined as a HAMD-17 total score ≤7.

Change From Baseline to Week 5 in the Hamilton Depression (HAMD) Anxiety/Somatization Factor ScoreBaseline, 5 weeks

The Anxiety/Somatization factor of the HAMD-17 includes 6 items: psychic anxiety, somatic anxiety, gastrointestinal somatic symptoms, general somatic symptoms, hypochondriasis, and insight. The HAMD-17 Anxiety/Somatization factor score ranging from 0 to 18 will be calculated as the sum of the scores for the 6 items. Higher scores denote more severe anxiety/somatization condition.

Change From Baseline to Week 5 in the Barratt Impulsiveness Scale (BIS-11)Baseline, 5 weeks

The BIS-11 is a questionnaire designed to assess the personality/behavioral construct of impulsiveness. It is composed of 30 items describing common impulsive or non-impulsive (reverse scored items: 1, 7, 8, 9, 10, 12, 13, 15, 20, 29, and 30) behaviors and preferences. Items are scored on the following 4-point scale: Rarely/Never = 1; Occasionally = 2; Often = 3; Almost Always/Always = 4. For reverse scored items, a response of 1 is recoded to 4; 2 is recoded to 3; 3 is recoded to 2; and 4 is recoded to 1. The BIS-11 score ranging from 30 to 120 will be calculated as the sum of the scores for all 30 items. Higher scores denote more impulsiveness.

Clinical Global Impression-Improvement (CGI-I) Score for Depressive Symptoms at Week 5Baseline, 5 weeks

The CGI-I rates the change in a subject's depression over the past 7 days relative to the subject's symptoms at Baseline and the score ranges from 1 to 7. Higher CGI-I scores denote less improvement in Depression.

Trial Locations

Locations (85)

IPC Research

🇺🇸

Waukesha, Wisconsin, United States

Collective Medical Research, LLC

🇺🇸

Prairie Village, Kansas, United States

Clinical Neuroscience Solutions CNS Healthcare

🇺🇸

Memphis, Tennessee, United States

Clinical Trial of America, LLC

🇺🇸

Hickory, North Carolina, United States

NRC Research Institute

🇺🇸

Orange, California, United States

University Of Pennsylvania

🇺🇸

Philadelphia, Pennsylvania, United States

Grayline Research Center

🇺🇸

Wichita Falls, Texas, United States

Future Search Trials of Dallas

🇺🇸

Dallas, Texas, United States

Coastal Carolina Research Center

🇺🇸

Mount Pleasant, South Carolina, United States

ARTES Psykiatrinen Palvelukeskus Oy (Mederon Ltd.)

🇫🇮

Helsinki, Finland

Psychiatric Consultants, PC

🇺🇸

Franklin, Tennessee, United States

Charak Clinical Research Center

🇺🇸

Garfield Heights, Ohio, United States

Psychoneurological Dispensary # 5

🇷🇺

Saint Petersburg, Russian Federation

MAC Clinical Research Ltd - Liverpool

🇬🇧

Liverpool, United Kingdom

LION-MED

🇷🇺

Voronezh, Russian Federation

Zachodniopomorski Instytut Psychoterapii

🇵🇱

Szczecin, Poland

Clinical Hospital Center Dr Dragisa Misovic

🇷🇸

Belgrade, Serbia

Mental Health Research Center, Department #6

🇷🇺

Moscow, Russian Federation

EPAMED s r.o.

🇸🇰

Košice, Slovakia

Saratov City Clinical Hospital # 2 n.a. V.I. Razumovsky

🇷🇺

Saratov, Russian Federation

MAC Clinical Research - Manchester

🇬🇧

Manchester, United Kingdom

Clinical Center of Serbia, Clinic for psychiatry

🇷🇸

Belgrade, Serbia

Special hospital for psychiatric diseases "Kovin"

🇷🇸

Kovin, Serbia

City Narcology Hospital

🇷🇺

Saint Petersburg, Russian Federation

Dr GP Bosch Clinical Research

🇿🇦

Pretoria, South Africa

Clinical Center Kragujevac

🇷🇸

Kragujevac, Serbia

Liptovska nemocnice s poliklinikou MUDr. Ivana Stodolu, Psychiatricke oddelenie

🇸🇰

Liptovský Mikuláš, Slovakia

Samara Psychiatric Hospital

🇷🇺

Samara, Russian Federation

MAC Clinical Research - Blackpool

🇬🇧

Blackpool, United Kingdom

Flexivest Fourteen Research Centre, Unit 1, Durbanville Health Center

🇿🇦

Durbanville, South Africa

Cape Trial Centre

🇿🇦

Cape Town, South Africa

MCB Clinical Research Centers, LLC

🇺🇸

Colorado Springs, Colorado, United States

Behavioral Research Specialists

🇺🇸

Glendale, California, United States

Sun Valley Research Center

🇺🇸

Imperial, California, United States

CNS Network

🇺🇸

Garden Grove, California, United States

Irvine Clinical Research

🇺🇸

Irvine, California, United States

Synergy San Diego

🇺🇸

Lemon Grove, California, United States

Pacific Research Partners, LLC

🇺🇸

Oakland, California, United States

CT Clinical Research

🇺🇸

Cromwell, Connecticut, United States

Clinical Neuroscience Solutions ( CNS Healthcare)-Jacksonville

🇺🇸

Jacksonville, Florida, United States

Synexus Clinical Research

🇺🇸

Atlanta, Georgia, United States

Meridien Research

🇺🇸

Maitland, Florida, United States

Emory University School of Medicine

🇺🇸

Atlanta, Georgia, United States

Clinical Trials of America (Monroe, LA)

🇺🇸

Monroe, Louisiana, United States

Capstone Clinical Research

🇺🇸

Libertyville, Illinois, United States

Adams Clinical

🇺🇸

Watertown, Massachusetts, United States

St. Charles Psychiatric Associates-Midwest Research Group

🇺🇸

Saint Charles, Missouri, United States

Integrative Clinical Trials

🇺🇸

Brooklyn, New York, United States

Social Psychiatry Research Institute (SPRI)

🇺🇸

Brooklyn, New York, United States

Mount Sinai Hospital

🇺🇸

New York, New York, United States

The Medical Research Network, LLC

🇺🇸

New York, New York, United States

Finger Lake Clinical Research

🇺🇸

Rochester, New York, United States

Research Strategies of Memphis, LLC

🇺🇸

Memphis, Tennessee, United States

Savon Psykiatripalvelu Oy

🇫🇮

Kuopio, Finland

Przychodnia Śródmieście Sp. z o.o.

🇵🇱

Bydgoszcz, Poland

Nzop Mentis

🇵🇱

Leszno, Poland

St. Nicholas the Wonder Worker Psychiatric Hospital

🇷🇺

Saint Petersburg, Russian Federation

Regional Clinical Psychiatric Hospital of St. Sofia

🇷🇺

Saratov, Russian Federation

Clinical Center Kragujevac , Clinic for Psychiatry

🇷🇸

Kragujevac, Serbia

Dr DG Dennis Incorporated Knighton Surgery

🇿🇦

Cape Town, South Africa

Mountain View Clinical Research, Inc.

🇺🇸

Denver, Colorado, United States

Summit Research Network (Oregon) Inc.

🇺🇸

Portland, Oregon, United States

Florida Research Center, Inc.

🇺🇸

Miami, Florida, United States

University of Alabama at Birmingham (UAB)

🇺🇸

Birmingham, Alabama, United States

CNS Health Care (Orlando)

🇺🇸

Orlando, Florida, United States

Great Lakes Clinical Trials

🇺🇸

Chicago, Illinois, United States

Baylor College of Medicine

🇺🇸

Houston, Texas, United States

Clinical Trials of Texas, Inc.

🇺🇸

San Antonio, Texas, United States

Odesa Regional Medical Centre of Mental Health

🇺🇦

Odesa, Ukraine

Centre for Mental Health Protection, Clinical Center Nis

🇷🇸

Niš, Serbia

Psykiatri- ja psykologikeskus Mentoria

🇫🇮

Tampere, Finland

Indywidualna Specijalistyczna Praktyka Lekarska Wiesław Jerzy Cubała

🇵🇱

Gdańsk, Poland

Neurologiczny NZOZ im. dr n. med. Hanki

🇵🇱

Plewiska, Poland

Centrum Zdravia R.B.K., s.r.o.

🇸🇰

Svidník, Slovakia

Municipal Institution "Vinnytsya Regional Psychoneurological Hospital n.a. Acad. O.I.Yushchenko", Male Department #14, Female Department #15, Vinnytsya National Medical University n.a. M.I.Pyrogov, Department of Psychiatry, Narcology and Psychotherapeutic

🇺🇦

Vinnytsia, Ukraine

Gabinet Lekarski Psychiatryczny Ireneusz Kaczorowski

🇵🇱

Bełchatów, Poland

Oulu Mentalcare Oy

🇫🇮

Oulu, Finland

Satakunnan Psykiatripalvelu Oy at Mehiläinen Pori

🇫🇮

Pori, Finland

Clinical Centre Nis, Clinic for Psychiatry Gornja

🇷🇸

Toponica, Serbia

Kherson Regional Psychiatric Hospital Department # 3 and # 10 Kherson region

🇺🇦

Stepanivka, Ukraine

Communal Institution "Vinnytsia Regional Psychoneurological Hospital n.a. Acad. O.I.Yushchenko", Department #7 (male), Department #10 (female),Vinnytsia National Medical University n.a. M.I.Pyrogov, Department of Psychiatry, Narcology and Psychotherapeuti

🇺🇦

Vinnytsia, Ukraine

Regional Centre of Psychosomatic Disorders based on Psychoneurology Department, Communal Institution "Dnipropetrovsk Regional Clinical Hospital named after I.I. Mechnykov

🇺🇦

Dnipro, Ukraine

Institute of neurology, Psychiatry and Narcology of NAMS of Ukraine, MC "Neuron"

🇺🇦

Kharkiv, Ukraine

Kyiv Railway Clinical Hospital № 1 of Branch "Health Center" of the Public joint stock company "Ukrainian Railway"

🇺🇦

Kyiv, Ukraine

Ternopil Regional Communal Clinical Psychoneurological Hospital, psychiatric department # 2 (men), psychiatric department # 6 (women), Ternopil State Medical University n.a. I.Y. Gorbachevskyy, Chair of Psychiatry, Narcology and Medical Psychology

🇺🇦

Ternopil', Ukraine

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