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

October 19, 2021 updated by: ACADIA Pharmaceuticals Inc.

Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Adjunctive Pimavanserin in Subjects With Major Depressive Disorder and Inadequate Response to Antidepressant Treatment (ACP-103-054/059)

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

Study Overview

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.

Study Type

Interventional

Enrollment (Actual)

298

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Helsinki, Finland, 00100
        • ARTES Psykiatrinen Palvelukeskus Oy (Mederon Ltd.)
      • Kuopio, Finland, 70110
        • Savon Psykiatripalvelu Oy
      • Oulu, Finland, 90100
        • Oulu Mentalcare Oy
      • Pori, Finland, 28130
        • Satakunnan Psykiatripalvelu Oy at Mehiläinen Pori
      • Tampere, Finland, 33200
        • Psykiatri- ja psykologikeskus Mentoria
      • Bełchatów, Poland, 97-400
        • Gabinet Lekarski Psychiatryczny Ireneusz Kaczorowski
      • Bydgoszcz, Poland, 85-080
        • Przychodnia Srodmiescie Sp. z o.o.
      • Gdańsk, Poland, 80-438
        • Indywidualna Specijalistyczna Praktyka Lekarska Wiesław Jerzy Cubała
      • Leszno, Poland, 64-100
        • Nzop Mentis
      • Plewiska, Poland, 62-064
        • Neurologiczny NZOZ im. dr n. med. Hanki
      • Szczecin, Poland, 70-480
        • Zachodniopomorski Instytut Psychoterapii
      • Moscow, Russian Federation, 115522
        • Mental Health Research Center, Department #6
      • Saint Petersburg, Russian Federation, 190121
        • St. Nicholas the Wonder Worker Psychiatric Hospital
      • Saint Petersburg, Russian Federation, 199004
        • City Narcology Hospital
      • Saint Petersburg, Russian Federation, 195176
        • Psychoneurological Dispensary # 5
      • Samara, Russian Federation, 443016
        • Samara Psychiatric Hospital
      • Saratov, Russian Federation, 410060
        • Regional Clinical Psychiatric Hospital of St. Sofia
      • Saratov, Russian Federation, 410028
        • Saratov City Clinical Hospital # 2 n.a. V.I. Razumovsky
      • Voronezh, Russian Federation, 394052
        • LION-MED
      • Belgrade, Serbia, 11000
        • Clinical Center of Serbia, Clinic for Psychiatry
      • Belgrade, Serbia, 11000
        • Clinical Hospital Center Dr Dragisa Misovic
      • Kovin, Serbia, 26220
        • Special Hospital for Psychiatric Diseases "Kovin"
      • Kragujevac, Serbia, 34000
        • Clinical Center Kragujevac
      • Kragujevac, Serbia, 34000
        • Clinical Center Kragujevac , Clinic for Psychiatry
      • Niš, Serbia, 18000
        • Centre for Mental Health Protection, Clinical Center Nis
      • Toponica, Serbia, 18202
        • Clinical Centre Nis, Clinic for Psychiatry Gornja
      • Košice, Slovakia, 040 17
        • EPAMED s r.o.
      • Liptovský Mikuláš, Slovakia, 031 23
        • Liptovska nemocnice s poliklinikou MUDr. Ivana Stodolu, Psychiatricke oddelenie
      • Svidník, Slovakia, 089 01
        • Centrum Zdravia R.B.K., s.r.o.
      • Cape Town, South Africa, 7530
        • Cape Trial Centre
      • Cape Town, South Africa, 7708
        • Dr DG Dennis Incorporated Knighton Surgery
      • Durbanville, South Africa, 7550
        • Flexivest Fourteen Research Centre, Unit 1, Durbanville Health Center
      • Pretoria, South Africa, 0081
        • Dr GP Bosch Clinical Research
      • Dnipro, Ukraine, 49005
        • Regional Centre of Psychosomatic Disorders based on Psychoneurology Department, Communal Institution "Dnipropetrovsk Regional Clinical Hospital named after I.I. Mechnykov
      • Kharkiv, Ukraine, 61091
        • Institute of neurology, Psychiatry and Narcology of NAMS of Ukraine, MC "Neuron"
      • Kyiv, Ukraine, 01030
        • Kyiv Railway Clinical Hospital № 1 of Branch "Health Center" of the Public joint stock company "Ukrainian Railway"
      • Odesa, Ukraine, 65006
        • Odesa Regional Medical Centre of Mental Health
      • Stepanivka, Ukraine, 73488
        • Kherson Regional Psychiatric Hospital Department # 3 and # 10 Kherson region
      • Ternopil', Ukraine, 46027
        • 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
      • Vinnytsia, Ukraine, 21005
        • 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, 21005
        • 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
      • Blackpool, United Kingdom, FY2 0JH
        • MAC Clinical Research - Blackpool
      • Liverpool, United Kingdom, L34 1BH
        • MAC Clinical Research Ltd - Liverpool
      • Manchester, United Kingdom, M13 9NQ
        • MAC Clinical Research - Manchester
    • Alabama
      • Birmingham, Alabama, United States, 35233
        • University of Alabama at Birmingham (UAB)
    • California
      • Garden Grove, California, United States, 92845
        • CNS Network
      • Glendale, California, United States, 91206
        • Behavioral Research Specialists
      • Imperial, California, United States, 92251
        • Sun Valley Research Center
      • Irvine, California, United States, 92614
        • Irvine Clinical Research
      • Lemon Grove, California, United States, 91945
        • Synergy San Diego
      • Oakland, California, United States, 94607
        • Pacific Research Partners, LLC
      • Orange, California, United States, 92868
        • NRC Research Institute
    • Colorado
      • Colorado Springs, Colorado, United States, 80910
        • MCB Clinical Research Centers, LLC
      • Denver, Colorado, United States, 80209
        • Mountain View Clinical Research, Inc.
    • Connecticut
      • Cromwell, Connecticut, United States, 06416
        • CT Clinical Research
    • Florida
      • Jacksonville, Florida, United States, 32256
        • Clinical Neuroscience Solutions ( CNS Healthcare)-Jacksonville
      • Maitland, Florida, United States, 32751
        • Meridien Research
      • Miami, Florida, United States, 33174
        • Florida Research Center, Inc.
      • Orlando, Florida, United States, 32801
        • CNS Health Care (Orlando)
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Emory University School of Medicine
      • Atlanta, Georgia, United States, 30328
        • Synexus Clinical Research
    • Illinois
      • Chicago, Illinois, United States, 60640
        • Great Lakes Clinical Trials
      • Libertyville, Illinois, United States, 60048
        • Capstone Clinical Research
    • Kansas
      • Prairie Village, Kansas, United States, 66208
        • Collective Medical Research, LLC
    • Louisiana
      • Monroe, Louisiana, United States, 71201
        • Clinical Trials of America (Monroe, LA)
    • Massachusetts
      • Watertown, Massachusetts, United States, 02472
        • Adams Clinical
    • Missouri
      • Saint Charles, Missouri, United States, 63304
        • St. Charles Psychiatric Associates-Midwest Research Group
    • New York
      • Brooklyn, New York, United States, 11229
        • Integrative Clinical Trials
      • Brooklyn, New York, United States, 11235
        • Social Psychiatry Research Institute (SPRI)
      • New York, New York, United States, 10128
        • The Medical Research Network, LLC
      • New York, New York, United States, 10029
        • Mount Sinai Hospital
      • Rochester, New York, United States, 14618
        • Finger Lake Clinical Research
    • North Carolina
      • Hickory, North Carolina, United States, 28601
        • Clinical Trial of America, LLC
    • Ohio
      • Garfield Heights, Ohio, United States, 44125
        • Charak Clinical Research Center
    • Oregon
      • Portland, Oregon, United States, 97210
        • Summit Research Network (Oregon) Inc.
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • University of Pennsylvania
    • South Carolina
      • Mount Pleasant, South Carolina, United States, 26464
        • Coastal Carolina Research Center
    • Tennessee
      • Franklin, Tennessee, United States, 37067
        • Psychiatric Consultants, PC
      • Memphis, Tennessee, United States, 38119
        • Research Strategies of Memphis, LLC
      • Memphis, Tennessee, United States, 38119
        • Clinical Neuroscience Solutions CNS Healthcare
    • Texas
      • Dallas, Texas, United States, 75231
        • Future Search Trials of Dallas
      • Houston, Texas, United States, 77030
        • Baylor College of Medicine
      • San Antonio, Texas, United States, 78229
        • Clinical Trials of Texas, Inc.
      • Wichita Falls, Texas, United States, 76309
        • Grayline Research Center
    • Wisconsin
      • Waukesha, Wisconsin, United States, 53188
        • IPC Research

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
Placebo tablets
Placebo (2×placebo tablets [size- and color-matched to pimavanserin]) administered orally as a single dose once daily
Experimental: Drug - pimavanserin
Pimavanserin 34 mg tablets
Pimavanserin 34 mg (provided as 2×17 mg tablets) administered orally as a single dose once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline to Week 5 in Hamilton Depression Scale (17 Items) (HAMD-17) Total Score
Time Frame: Baseline, 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.
Baseline, Week 5

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline to Week 5 in Clinical Global Impression-Severity (CGI-S) Score for Depressive Symptoms
Time Frame: Baseline, 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.
Baseline, 5 weeks
Change From Baseline to Week 5 in Sheehan Disability Scale (SDS) Score
Time Frame: Baseline, 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.
Baseline, 5 weeks
Change From Baseline to Week 5 in the Changes in Sexual Functioning Questionnaire Short Form
Time Frame: Baseline, 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.
Baseline, 5 weeks
Change From Baseline to Week 5 in Karolinska Sleepiness Scale (KSS) Score
Time Frame: Baseline, 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.
Baseline, 5 weeks
Change From Baseline to Week 1 in the HAMD-17 Total Score
Time Frame: Baseline, 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.
Baseline, 1 week
Treatment Responder and Treatment Remission Rates at Week 5
Time Frame: Baseline, 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.
Baseline, 5 weeks
Change From Baseline to Week 5 in the Hamilton Depression (HAMD) Anxiety/Somatization Factor Score
Time Frame: Baseline, 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.
Baseline, 5 weeks
Change From Baseline to Week 5 in the Barratt Impulsiveness Scale (BIS-11)
Time Frame: 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.
Baseline, 5 weeks
Clinical Global Impression-Improvement (CGI-I) Score for Depressive Symptoms at Week 5
Time Frame: Baseline, 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.
Baseline, 5 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 25, 2019

Primary Completion (Actual)

April 30, 2020

Study Completion (Actual)

May 29, 2020

Study Registration Dates

First Submitted

May 13, 2019

First Submitted That Met QC Criteria

May 29, 2019

First Posted (Actual)

May 30, 2019

Study Record Updates

Last Update Posted (Actual)

November 17, 2021

Last Update Submitted That Met QC Criteria

October 19, 2021

Last Verified

October 1, 2021

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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