Clinical Trial Results:
A 52-Week Open-Label Extension Study of Pimavanserin in Subjects With Major Depressive Disorder and Inadequate Response to Antidepressant Treatment
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Summary
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EudraCT number |
2018-003252-20 |
Trial protocol |
GB SK PL FI |
Global end of trial date |
22 Feb 2021
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Results information
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Results version number |
v1(current) |
This version publication date |
08 Mar 2022
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First version publication date |
08 Mar 2022
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Other versions |
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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-103-055
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT04000009 | ||
WHO universal trial number (UTN) |
- | ||
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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, +1 858 261 2897, medicalinformation@acadia-pharm.com
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Scientific contact |
Sr. Dir. Medical Information and Medical Communications, ACADIA Pharmaceuticals Inc, +1 858 261 2897, 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 |
22 Feb 2021
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
22 Feb 2021
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Global end of trial reached? |
Yes
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Global end of trial date |
22 Feb 2021
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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 assess the safety and tolerability of long-term pimavanserin treatment in subjects with major depressive disorder and inadequate response to antidepressant treatment
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Protection of trial subjects |
Not applicable
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
06 Jun 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: 16
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Country: Number of subjects enrolled |
Slovakia: 5
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Country: Number of subjects enrolled |
United Kingdom: 27
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Country: Number of subjects enrolled |
Finland: 10
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Country: Number of subjects enrolled |
Russian Federation: 26
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Country: Number of subjects enrolled |
Serbia: 13
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Country: Number of subjects enrolled |
South Africa: 1
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Country: Number of subjects enrolled |
Ukraine: 26
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Country: Number of subjects enrolled |
United States: 111
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Worldwide total number of subjects |
235
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EEA total number of subjects |
31
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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) |
218
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From 65 to 84 years |
17
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85 years and over |
0
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Recruitment
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Recruitment details |
The study recruited patients that had completed a previous study of pimavanserin, i.e. study ACP-103-054 or ACP-103-059. It was planned to enroll about 420 patients. The study was terminated early by the Sponsor for business reasons due to the COVID-19 pandemic; there were no safety concerns contributing to study termination. | ||||||||||||||||||||||||||||
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Pre-assignment
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Screening details |
During the screening period, subjects were assessed for study eligibility and prohibited medications were discontinued when medically appropriate. | ||||||||||||||||||||||||||||
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Period 1
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Period 1 title |
Overall study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||||||||||||||
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Arms
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Arm title
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Pimavanserin | ||||||||||||||||||||||||||||
Arm description |
Pimavanserin 34 mg (administered as 2 x 17 mg pimavanserin tablets) once daily, for 52 weeks | ||||||||||||||||||||||||||||
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 x 17 mg pimavanserin tablets) taken once daily, for 52 weeks
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Baseline characteristics reporting groups
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Reporting group title |
Overall study
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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 as 2 x 17 mg pimavanserin tablets) once daily, for 52 weeks | ||
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End point title |
Treatment-emergent Adverse Events (TEAEs) [1] | ||||||
End point description |
Number of patients with treatment emergent AEs
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End point type |
Primary
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End point timeframe |
52 weeks
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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: This was a single-arm study. Inferential testing was neither planned nor performed. |
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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 |
52 weeks
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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 as 2 x 17 mg pimavanserin tablets) once daily, for 52 weeks | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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 |
Key changes included:
- Allowed inclusion of patients beyond elderly population
- Removed cognition and replaced quality of life with functional impairment and sexual functioning as exploratory assessments
- Removed Mini-Mental Sate Examination score as exploratory safety endpoint
- Removed EQ-5D as exploratory efficacy endpoint; added CSFQ-14 and KSS score as exploratory efficacy endpoints
- Increased planned patient number from 290 to 420 by adding rollover patients from study ACP-103-059 in addition to -054
- Revised dosing to pimavanserin 34 mg only; removed dose adjustment between 20 and 34 mg pimavanserin
- Excluded patients with comorbid neurodegenerative disorders
- Adapted several study procedures/timelines to align with procedures/timelines in the rollover studies 054/059
- Removed rescue medication procedures |
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18 Mar 2019 |
- Removed abstinence as acceptable contraception method
- Implemented less restrictive definition of suicidality |
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12 Nov 2019 |
Key changes included:
- Added sexual dysfunction as safety endpoint
- Clarified use of background antidepressants in the study
- Clarified barrier methods of contraception
- Clarified the assessment of heart rate for patient eligibility
- Replaced BMI upper bound criterion for patient eligibility with weight increase of ≥7% as criterion
- Clarified assessment of background antidepressant adherence
- Clarified follow-up procedures for discontinued patients
- Tightened restrictions on controlled substances
- Specified randomisation in error as major protocol deviation
- Added ketamine and esketamine to the list of prohibited antidepressants and clarified timeframe for stable dosing of these drugs |
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11 Aug 2020 |
Key changes included:
- Added specifications for changes due to COVID-19 pandemic: visits performed remotely; use of a 6-lead ECG device at home; home delivery of study drug; study conduct, exploratory efficacy assessments, safety assessments, and unscheduled visits; COVID-19 relatedness of concomitant medications; relationship of selected AEs to COVID-19; protocol deviations related to COVID-19; remote monitoring of study sites due to travel/ visiting restrictions caused by COVID-19 pandemic; return of unused study drug and packaging when site staff visited patient’s home
- Allowed for interim analyses, if required for regulatory reporting |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
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. | |||
| This study was terminated early by the Sponsor for business reasons due to the COVID-19 pandemic; there were no safety concerns contributing to study termination. Patients were discontinued from the study and completed safety follow-up procedures. | |||
