Clinical Trial Results:
A 52-Week, Open-Label, Extension Study of Pimavanserin for the Adjunctive Treatment of Schizophrenia
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Summary
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EudraCT number |
2016-003435-38 |
Trial protocol |
HU ES BG CZ DE LT PL IT HR |
Global end of trial date |
30 May 2024
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Results information
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Results version number |
v1(current) |
This version publication date |
30 May 2025
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First version publication date |
30 May 2025
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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-103-035
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Additional study identifiers
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ISRCTN number |
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US NCT number |
NCT03121586 | ||
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 58261 2897, medicalinformation@acadia-pharm.com
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Scientific contact |
Sr. Dir. Medical Information and Medical Communications, ACADIA Pharmaceuticals Inc., 1 58261 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 |
30 Apr 2024
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
30 Apr 2024
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Global end of trial reached? |
Yes
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Global end of trial date |
30 May 2024
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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 long-term safety and tolerability of pimavanserin after 52 weeks of adjunctive treatment in subjects with schizophrenia
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Protection of trial subjects |
Not applicable
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
18 Jan 2017
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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: 13
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Country: Number of subjects enrolled |
Spain: 22
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Country: Number of subjects enrolled |
Croatia: 10
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Country: Number of subjects enrolled |
Bulgaria: 281
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Country: Number of subjects enrolled |
Czechia: 25
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Country: Number of subjects enrolled |
Hungary: 27
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Country: Number of subjects enrolled |
Italy: 2
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Country: Number of subjects enrolled |
Lithuania: 9
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Country: Number of subjects enrolled |
Argentina: 63
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Country: Number of subjects enrolled |
Canada: 2
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Country: Number of subjects enrolled |
Russian Federation: 214
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Country: Number of subjects enrolled |
Serbia: 162
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Country: Number of subjects enrolled |
Ukraine: 93
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Country: Number of subjects enrolled |
United States: 72
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Worldwide total number of subjects |
995
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EEA total number of subjects |
389
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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) |
995
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
This was an open-label extension study for patients from studies ACP-103-034, 038, and 064. Patients who had completed any of those studies and had not shown significant worsening of symptoms, or who may have benefited, or were expected to benefit from continued pimavanserin treatment based on the investigator’s judgment were eligible. | ||||||||||||||||||||||||||||
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Pre-assignment
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Screening details |
Informed consent was obtained before the final procedures of each study, performed at Week 6 for study 034 and Week 26 for studies 038 and 064. Procedures performed at the end of study visits of the 3 double-blind studies were carried over to study 035 and were used baseline information; the respective visits were considered as baseline visit. | ||||||||||||||||||||||||||||
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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 |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||||||||||||||
Blinding implementation details |
Not applicable
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Arms
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Arm title
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Pimavanserin | ||||||||||||||||||||||||||||
Arm description |
Pimavanserin once daily administered orally | ||||||||||||||||||||||||||||
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 once daily administered orally.
Patients rolling over from studies ACP-103-034 or ACP-103-038 received pimavanserin 20 mg for the first 2 weeks. Thereafter, the daily dose could be adjusted to 34, 20, or 10 mg throughout the study, based on the investigator’s assessment of clinical response in the individual patient. Dose adjustments were made at scheduled or unscheduled visits.
Patients rolling over from study ACP-103-064 received pimavanserin 34 mg throughout the entire treatment duration.
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Baseline characteristics reporting groups
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Reporting group title |
Overall trial
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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 once daily administered orally | ||
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End point title |
Number of Patients With Treatment Emergent Adverse Events [1] | ||||||
End point description |
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End point type |
Primary
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End point timeframe |
Treatment period (52 weeks) and follow-up period (30 days): planned total of 56 weeks. As the study was prematurely terminated, the reporting period was shortened; AEs were assessed to the end of treatment, at a mean duration of 319 days (or 46 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 an open-label, uncontrolled extension study. The study had no primary efficacy endpoint; the primary endpoint was safety-related. Inferential statistics were neither planned nor performed for this endpoint. |
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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 |
Treatment period (52 weeks) and follow-up period (30 days): planned total of 56 weeks. As the study was prematurely terminated, the reporting period was shortened; AEs were assessed to the end of treatment, at a mean duration of 319 days (or 46 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 |
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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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30 Nov 2016 |
- Added as secondary objective to characterise the pharmacokinetics and pharmacodynamics of pimavanserin in the study population
- Increased the number of study sites from 100 to 160
- Removed abstinence as a clinically acceptable method of contraception
- Revised Exclusion Criterion 11 from “a history of suicide attempt, actively suicidal, at imminent risk of self-harm, or answers yes to 4 or 5 on the C-SSRS in Studies 034, 038, or 039” to “is at a significant risk of suicide or is a danger to self or others in the opinion of the Investigator”
- Revised test product, dose, and administration details from two 10 mg tablets once daily to 10 mg and 17 mg tablets to be provided as one 10 mg tablet, two 10 mg tablets, or two 17 mg tablets
- Added PK sampling for patients who experienced an SAE or AE leading to discontinuation
- Added details for PK and PK/PD analyses
- Added section for reporting on overdose of study drug
- Updated prohibited and concomitant medications |
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31 Mar 2017 |
- Removed PK objectives and assessments for business reasons and to reduce patient burden
- Modified inclusion and exclusion criteria to better reflect the targeted patient population
- Clarified the AE reporting period and related SAE reporting
- Modified exclusion criteria related to urine drug screen and long QT syndrome |
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11 Aug 2020 |
- Replaced study ACP-103-039 with study ACP-103-064 as parent study from which patients could roll over to the present study and implemented protocol changes to align with incorporation of study ACP-103-064 patients (in terms of dosing regimen; secondary and exploratory endpoints; safety related exclusion criteria)
− Prohibited subjects from Study 064 with positive marijuana test from participating
- Revised study indication from “schizophrenia” to “negative symptoms of schizophrenia”
- Added paliperidone extended release and paliperidone palmitate to the list of main antipsychotics
- Aligned with changes from previous local amendment (Amendment 2-CZ) to generate a single global protocol amendment |
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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 | |||||||
