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

Adjunctive Treatment of Major Depressive Disorder Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03968159
• Other study ID #: ACP-103-054/059
• Secondary ID: 2018-003251-37
• Status: Completed
• Phase: Phase 3
• Start date: April 25, 2019
• Est. completion date: May 29, 2020

Study information

• Verified date: October 2021
• Source: ACADIA Pharmaceuticals Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Other known NCT identifiers

• NCT03999918

Recruitment information / eligibility

• Status: Completed
• Enrollment: 298
• Est. completion date: May 29, 2020
• Est. primary completion date: April 30, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Adjunctive Treatment of Major Depressive Disorder
• Depression
• Depressive Disorder
• Depressive Disorder, Major

Intervention

Drug:
• Pimavanserin
Pimavanserin 34 mg (provided as 2×17 mg tablets) administered orally as a single dose once daily
• Placebo
Placebo (2×placebo tablets [size- and color-matched to pimavanserin]) administered orally as a single dose once daily

Locations

Country	Name	City	State
Finland	ARTES Psykiatrinen Palvelukeskus Oy (Mederon Ltd.)	Helsinki
Finland	Savon Psykiatripalvelu Oy	Kuopio
Finland	Oulu Mentalcare Oy	Oulu
Finland	Satakunnan Psykiatripalvelu Oy at Mehiläinen Pori	Pori
Finland	Psykiatri- ja psykologikeskus Mentoria	Tampere
Poland	Gabinet Lekarski Psychiatryczny Ireneusz Kaczorowski	Belchatów
Poland	Przychodnia Sródmiescie Sp. z o.o.	Bydgoszcz
Poland	Indywidualna Specijalistyczna Praktyka Lekarska Wieslaw Jerzy Cubala	Gdansk
Poland	Nzop Mentis	Leszno
Poland	Neurologiczny NZOZ im. dr n. med. Hanki	Plewiska
Poland	Zachodniopomorski Instytut Psychoterapii	Szczecin
Russian Federation	Mental Health Research Center, Department #6	Moscow
Russian Federation	City Narcology Hospital	Saint Petersburg
Russian Federation	Psychoneurological Dispensary # 5	Saint Petersburg
Russian Federation	St. Nicholas the Wonder Worker Psychiatric Hospital	Saint Petersburg
Russian Federation	Samara Psychiatric Hospital	Samara
Russian Federation	Regional Clinical Psychiatric Hospital of St. Sofia	Saratov
Russian Federation	Saratov City Clinical Hospital # 2 n.a. V.I. Razumovsky	Saratov
Russian Federation	LION-MED	Voronezh
Serbia	Clinical Center of Serbia, Clinic for psychiatry	Belgrade
Serbia	Clinical Hospital Center Dr Dragisa Misovic	Belgrade
Serbia	Special hospital for psychiatric diseases "Kovin"	Kovin
Serbia	Clinical Center Kragujevac	Kragujevac
Serbia	Clinical Center Kragujevac , Clinic for Psychiatry	Kragujevac
Serbia	Centre for Mental Health Protection, Clinical Center Nis	Niš
Serbia	Clinical Centre Nis, Clinic for Psychiatry Gornja	Toponica
Slovakia	EPAMED s r.o.	Košice
Slovakia	Liptovska nemocnice s poliklinikou MUDr. Ivana Stodolu, Psychiatricke oddelenie	Liptovský Mikuláš
Slovakia	Centrum Zdravia R.B.K., s.r.o.	Svidník
South Africa	Cape Trial Centre	Cape Town
South Africa	Dr DG Dennis Incorporated Knighton Surgery	Cape Town
South Africa	Flexivest Fourteen Research Centre, Unit 1, Durbanville Health Center	Durbanville
South Africa	Dr GP Bosch Clinical Research	Pretoria
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	Odesa Regional Medical Centre of Mental Health	Odesa
Ukraine	Kherson Regional Psychiatric Hospital Department # 3 and # 10 Kherson region	Stepanivka
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	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	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
United Kingdom	MAC Clinical Research - Blackpool	Blackpool
United Kingdom	MAC Clinical Research Ltd - Liverpool	Liverpool
United Kingdom	MAC Clinical Research - Manchester	Manchester
United States	Emory University School of Medicine	Atlanta	Georgia
United States	Synexus Clinical Research	Atlanta	Georgia
United States	University of Alabama at Birmingham (UAB)	Birmingham	Alabama
United States	Integrative Clinical Trials	Brooklyn	New York
United States	Social Psychiatry Research Institute (SPRI)	Brooklyn	New York
United States	Great Lakes Clinical Trials	Chicago	Illinois
United States	MCB Clinical Research Centers, LLC	Colorado Springs	Colorado
United States	CT Clinical Research	Cromwell	Connecticut
United States	Future Search Trials of Dallas	Dallas	Texas
United States	Mountain View Clinical Research, Inc.	Denver	Colorado
United States	Psychiatric Consultants, PC	Franklin	Tennessee
United States	CNS Network	Garden Grove	California
United States	Charak Clinical Research Center	Garfield Heights	Ohio
United States	Behavioral Research Specialists	Glendale	California
United States	Clinical Trial of America, LLC	Hickory	North Carolina
United States	Baylor College of Medicine	Houston	Texas
United States	Sun Valley Research Center	Imperial	California
United States	Irvine Clinical Research	Irvine	California
United States	Clinical Neuroscience Solutions ( CNS Healthcare)-Jacksonville	Jacksonville	Florida
United States	Synergy San Diego	Lemon Grove	California
United States	Capstone Clinical Research	Libertyville	Illinois
United States	Meridien Research	Maitland	Florida
United States	Clinical Neuroscience Solutions CNS Healthcare	Memphis	Tennessee
United States	Research Strategies of Memphis, LLC	Memphis	Tennessee
United States	Florida Research Center, Inc.	Miami	Florida
United States	Clinical Trials of America (Monroe, LA)	Monroe	Louisiana
United States	Coastal Carolina Research Center	Mount Pleasant	South Carolina
United States	Mount Sinai Hospital	New York	New York
United States	The Medical Research Network, LLC	New York	New York
United States	Pacific Research Partners, LLC	Oakland	California
United States	NRC Research Institute	Orange	California
United States	CNS Health Care (Orlando)	Orlando	Florida
United States	University Of Pennsylvania	Philadelphia	Pennsylvania
United States	Summit Research Network (Oregon) Inc.	Portland	Oregon
United States	Collective Medical Research, LLC	Prairie Village	Kansas
United States	Finger Lake Clinical Research	Rochester	New York
United States	St. Charles Psychiatric Associates-Midwest Research Group	Saint Charles	Missouri
United States	Clinical Trials of Texas, Inc.	San Antonio	Texas
United States	Adams Clinical	Watertown	Massachusetts
United States	IPC Research	Waukesha	Wisconsin
United States	Grayline Research Center	Wichita Falls	Texas

Sponsors (1)

Lead Sponsor	Collaborator
ACADIA Pharmaceuticals Inc.

Countries where clinical trial is conducted

United States,  Finland,  Poland,  Russian Federation,  Serbia,  Slovakia,  South Africa,  Ukraine,  United Kingdom, 

Outcome

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