Clinical Trial Results:
A 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
Summary
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EudraCT number |
2018-003251-37 |
Trial protocol |
GB SK PL FI |
Global end of trial date |
21 Jun 2020
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Results information
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Results version number |
v1(current) |
This version publication date |
07 Jul 2021
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First version publication date |
07 Jul 2021
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
ACP-103-054
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03999918 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Acadia Pharmaceuticals Inc.
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Sponsor organisation address |
12830 El Camino Real, Suite 400, San Diego, United States, 92130
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Public contact |
Sr. Dir. Medical Information and Medical Communications, ACADIA Pharmaceuticals Inc., 001 858 2612897, medicalinformation@acadia-pharm.com
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Scientific contact |
Sr. Dir. Medical Information and Medical Communications, ACADIA Pharmaceuticals Inc., 001 858 2612897, medicalinformation@acadia-pharm.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
30 Jun 2020
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
27 Apr 2020
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Global end of trial reached? |
Yes
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Global end of trial date |
21 Jun 2020
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
To evaluate the efficacy of adjunctive pimavanserin compared to placebo in subjects with major depressive disorder who have an inadequate response to antidepressant therapy
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Protection of trial subjects |
Not applicable
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
08 Jul 2019
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Poland: 18
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Country: Number of subjects enrolled |
Slovakia: 7
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Country: Number of subjects enrolled |
United Kingdom: 34
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Country: Number of subjects enrolled |
Finland: 12
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Country: Number of subjects enrolled |
Ukraine: 30
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Country: Number of subjects enrolled |
South Africa: 2
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Country: Number of subjects enrolled |
Serbia: 17
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Country: Number of subjects enrolled |
Russian Federation: 30
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Worldwide total number of subjects |
150
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EEA total number of subjects |
37
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
137
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From 65 to 84 years |
13
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85 years and over |
0
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Recruitment
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Recruitment details |
The study was performed in patients with with major depressive disorder who had an inadequate response to antidepressant treatment | |||||||||||||||||||||||||||
Pre-assignment
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Screening details |
During the screening period, patients were assessed for study eligibility, and prohibited medications were discontinued when medically appropriate. | |||||||||||||||||||||||||||
Period 1
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Period 1 title |
Overall trial (overall period)
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Is this the baseline period? |
Yes | |||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||||||||||||||||||||
Roles blinded |
Subject, Investigator, Monitor, Data analyst, Assessor | |||||||||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Pimavanserin | |||||||||||||||||||||||||||
Arm description |
Pimavanserin 34 mg administered orally as a single dose once daily | |||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||
Investigational medicinal product name |
Pimavanserin
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Pimavanserin 34 mg administered as 2×17 mg tablets, given as a single dose once daily.
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Arm title
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Placebo | |||||||||||||||||||||||||||
Arm description |
Placebo tablets administered orally as a single oral dose once daily | |||||||||||||||||||||||||||
Arm type |
Placebo | |||||||||||||||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Placebo was given as two tablets (size- and colour-matched to pimavanserin tablets) as a single dose once daily
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Baseline characteristics reporting groups
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Reporting group title |
Pimavanserin
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Reporting group description |
Pimavanserin 34 mg administered orally as a single dose once daily | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
Placebo tablets administered orally as a single oral dose once daily | ||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Pimavanserin
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Reporting group description |
Pimavanserin 34 mg administered orally as a single dose once daily | ||
Reporting group title |
Placebo
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Reporting group description |
Placebo tablets administered orally as a single oral dose once daily |
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End point title |
Change From Baseline in the Hamilton Depression Scale (17 Items) (HAMD-17) Total Score [1] | |||||||||||||||
End point description |
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.
Prespecified inferential testing was not conducted as this trial was prematurely terminated due to business reasons as a result of COVID-19. Therefore, the number of patients with HAMD-17 assessments at BL and Week 5 is given.
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End point type |
Primary
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End point timeframe |
Week 5
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Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Prespecified inferential testing was not conducted as this trial was prematurely terminated due to business reasons as a results of COVID-19. |
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No statistical analyses for this end point |
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Adverse events information
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Timeframe for reporting adverse events |
Adverse Events (AEs) were to be documented through 30 days after the last dose in the study.
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
23.0
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Reporting groups
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Reporting group title |
Pimavanserin
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Reporting group description |
Pimavanserin 34 mg administered orally as a single dose once daily | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
Placebo tablets administered orally as a single oral dose once daily | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? Yes | |||||||
Date |
Amendment |
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05 Dec 2018 |
- Expanded study from elderly to adult population
- Changed timeframe of assessment for primary endpoint (HAMD-17) to change from BL to Week 5
- Revised secondary endpoints to include SDS, CGI-I, CSFQ-14, KSS, HAMD-17, and BIS-11; revised secondary endpoint analyses
- Removed PK, PK/PD, exploratory objectives, endpoints, and analyses
- Removed MMSE score as assessment, changed assessment timeframe for ESRS-A to Week 5 from Baseline
- Decreased number of planned study sites to 40 sites
- Revised timeframes for screening and double-blind periods; deleted stratification by region
- Changed safety follow-up period to at least 30 days; removed DSMB
- Updated duration of patient participation to 14 weeks
- Removed allowance of patients with comorbid neurodegenerative disorders from inclusion criteria
- Revised list of acceptable SSRI/SNRI antidepressants in inclusion criteria
- Clarified procedure and inclusion criteria for repeat screening test for SSRI/SNRI
- Removed exclusion criterion on Huntington’s disease or motor neuron disease; revised assessment for exclusion of active suicidality
- Clarified that bradycardia explained by exercise would not lead to exclusion; explained procedure for positive test for illicit drugs or cannabis and retesting criteria
- Revised sample size to 266 evaluable patients
- Revised statistical methods for efficacy, descriptive statistical analyses
- Removed rescue medication procedures
- Revised randomization methodology; removed stratified randomization by region
- Eliminated collection of dementia history and neurological history
- Revised timeframes for concomitant SSRI/SNRI antidepressant blood sampling
- Clarified interview guides for MADRS, HAMD-17, CGI-S
- Provided description for CSFQ-14 assessment, BIS-11 questionnaire
- Clarified safety laboratory evaluations
- Revised procedure for following a pregnancy to outcome
- Updated information on prohibited, unrestricted medications |
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18 Mar 2019 |
- Removed the option of abstinence as an acceptable method of contraception
- Implemented a less restrictive definition of suicidality in the exclusion criteria |
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29 Oct 2019 |
- Added new safety and tolerability endpoint (sexual dysfunction)
- Extended screening period to 3-28 days
- Clarified procedure for confirming subject eligibility
- Clarified dosing requirements for the background antidepressant prior to SAFER interview for inclusion criteria
- Clarified barrier methods of contraception for inclusion criteria
- Clarified several exclusion criteria (medical conditions; cardiovascular history; viral serology; heart rate)
- Added sexual dysfunction summary and shift tables to the safety analyses
- Added a definition of “inadequate response” to current SSRI/SNRI antidepressant therapy
- Added review of background antidepressant adherence
- Added text on benefits and risks of the study
- Clarified follow-up procedures for discontinued patients
- Clarified prior, concomitant, and prohibited therapy and restrictions on controlled substances
- Clarified major protocol deviations |
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21 Jun 2020 |
- Included description of changes necessitated by the COVID-19 pandemic
- Added description of Study ACP-103-059
- Described impact of the COVID-19 pandemic on Studies ACP-103-054 and ACP-103-059, the study conduct during the time when screening and randomization was suspended, and the decision to combine the 2 studies for the purpose of analysis
- Added COVID-19 relatedness of AEs and concomitant medications
- Described the impact of the COVID-19 pandemic on efficacy and safety assessments; unscheduled visits
- Added description of protocol deviation review and described handling of protocol deviations with respect to relationship to COVID-19
- Updated the statistical methods section to align with statistical Analysis plan
- Changed the statistical comparison method used for both the response and remission rates |
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Interruptions (globally) |
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Were there any global interruptions to the trial? Yes | |||||||
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Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||||||
None reported |