Clinical Trial Results:
A 12-week, Multicenter, Active-treatment Extension Trial to Evaluate the Safety and Tolerability of Brexpiprazole in the Treatment of Subjects With Agitation Associated With Dementia of the Alzheimer’s Type
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Summary
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EudraCT number |
2018-002783-88 |
Trial protocol |
BG ES HU SK |
Global end of trial date |
19 Sep 2022
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Results information
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Results version number |
v1 |
This version publication date |
05 Oct 2023
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First version publication date |
05 Oct 2023
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Other versions |
v2 |
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 |
331-201-00182
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03594123 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Otsuka Pharmaceutical Development & Commercialization, Inc.
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Sponsor organisation address |
2440 Research Boulevard , Rockville, United States, MD 20850
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Public contact |
Global Clinical Development, Otsuka Pharmaceutical Development & Commercialization, Inc, clinicaltransparency@otsuka-us.com
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Scientific contact |
Global Clinical Development, Otsuka Pharmaceutical Development & Commercialization, Inc, clinicaltransparency@otsuka-us.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 |
19 Sep 2022
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
19 Sep 2022
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To assess the long-term safety and tolerability of oral brexpiprazole as treatment in adult subjects with agitation associated with dementia of Alzheimer’s type (AAD).
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Protection of trial subjects |
Informed consent was obtained from all subjects participating in the study.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
11 Oct 2018
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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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 |
Slovakia: 8
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Country: Number of subjects enrolled |
Spain: 8
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Country: Number of subjects enrolled |
Bulgaria: 26
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Country: Number of subjects enrolled |
Hungary: 5
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Country: Number of subjects enrolled |
Serbia: 17
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Country: Number of subjects enrolled |
United States: 109
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Country: Number of subjects enrolled |
Ukraine: 86
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Worldwide total number of subjects |
259
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EEA total number of subjects |
47
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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) |
29
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From 65 to 84 years |
208
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85 years and over |
22
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Recruitment
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Recruitment details |
This study was conducted at 66 sites from 11 October 2018 to 19 September 2022 in the following countries: Bulgaria, Hungary, Serbia, Slovakia, Spain, Ukraine, and the United States. | ||||||||||||||||||||||||||||||
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Pre-assignment
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Screening details |
Of the 259 subjects who enrolled in the study, there were 163 subjects who received brexpiprazole, and 96 subjects who received placebo in the parent study (331-14-213). All 259 subjects received brexpiprazole during this study. | ||||||||||||||||||||||||||||||
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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 |
Non-randomised - controlled
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Blinding used |
Double blind | ||||||||||||||||||||||||||||||
Roles blinded |
Subject, Investigator, Carer, Assessor | ||||||||||||||||||||||||||||||
Blinding implementation details |
Although this was an active-treatment extension trial, dose assignment was handled in a blinded fashion to maintain blinding of subjects’ previous treatment in Trial 331-14-213 (2017-003940-19).
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Prior Brexpiprazole | ||||||||||||||||||||||||||||||
Arm description |
Subjects who received brexpiprazole in a previous double-blind phase 3 study (Trial 331-14-213 {2017-003940-19}), received the same dose of brexpiprazole [2 or 3 milligrams (mg)] once daily (QD), orally, as they received during the previous study, for up to 12 weeks with dose adjustment. | ||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||
Investigational medicinal product name |
Brexpiprazole
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Investigational medicinal product code |
OPC-34712
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Other name |
Rexulti®
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Brexpiprazole tablets, administered orally, 2-3 mg QD up to Week 12 during the treatment phase. Adjustments could be made to dosing.
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Arm title
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Prior Placebo | ||||||||||||||||||||||||||||||
Arm description |
Subjects who received placebo in a previous double-blind phase 3 study (Trial 331-14-213 {2017-003940-19}), received brexpiprazole following a titration schedule, to gradually increase their dose from 0.5 mg QD, in the starting to 2 or 3 mg QD, orally, for up to 12 weeks with dose adjustment. | ||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||
Investigational medicinal product name |
Brexpiprazole
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Investigational medicinal product code |
OPC-34712
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Other name |
Rexulti®
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Brexpiprazole tablets, administered orally, in a titration manner starting from 0.5 mg up to 2-3 mg QD, up to Week 12 during the treatment phase. Adjustments could be made to dosing.
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Baseline characteristics reporting groups
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Reporting group title |
Prior Brexpiprazole
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Reporting group description |
Subjects who received brexpiprazole in a previous double-blind phase 3 study (Trial 331-14-213 {2017-003940-19}), received the same dose of brexpiprazole [2 or 3 milligrams (mg)] once daily (QD), orally, as they received during the previous study, for up to 12 weeks with dose adjustment. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Prior Placebo
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Reporting group description |
Subjects who received placebo in a previous double-blind phase 3 study (Trial 331-14-213 {2017-003940-19}), received brexpiprazole following a titration schedule, to gradually increase their dose from 0.5 mg QD, in the starting to 2 or 3 mg QD, orally, for up to 12 weeks with dose adjustment. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Prior Brexpiprazole
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Reporting group description |
Subjects who received brexpiprazole in a previous double-blind phase 3 study (Trial 331-14-213 {2017-003940-19}), received the same dose of brexpiprazole [2 or 3 milligrams (mg)] once daily (QD), orally, as they received during the previous study, for up to 12 weeks with dose adjustment. | ||
Reporting group title |
Prior Placebo
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Reporting group description |
Subjects who received placebo in a previous double-blind phase 3 study (Trial 331-14-213 {2017-003940-19}), received brexpiprazole following a titration schedule, to gradually increase their dose from 0.5 mg QD, in the starting to 2 or 3 mg QD, orally, for up to 12 weeks with dose adjustment. | ||
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End point title |
Percentage of Subjects With Treatment-Emergent Adverse Events (TEAEs) by Severity [1] | |||||||||||||||||||||
End point description |
An adverse event (AE) was defined as any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment. TEAEs were defined as AEs with an onset date on or after the first dose of brexpiprazole. They are all adverse events that started after start of brexpiprazole; or if the event was continuous from baseline and was worsening, serious, study drug-related, or resulted in death, discontinuation, interruption, or reduction of study therapy. AEs were graded on a 3-point scale: 1= Mild: Discomfort noticed, but no disruption to daily activity. 2= Moderate: Discomfort sufficient to reduce or affect normal daily activity. 3= Severe: Inability to work or perform normal daily activity. Safety Sample comprised of those subjects who signed an informed consent form (ICF) for the trial and received at least one dose of brexpiprazole in Trial 331-201-00182.
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End point type |
Primary
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End point timeframe |
From first dose through 30 days after last dose of study drug (Up to approximately Week 16)
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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: Inferential statistical analysis was not performed for the safety endpoint. Descriptive statistics are included (percentage of participants). |
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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 |
From first dose through 30 days after last dose of study drug (Up to approximately Week 16)
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Adverse event reporting additional description |
Safety Sample comprised of those subjects who signed an ICF for the trial and received at least one dose of brexpiprazole in Trial 331-201-00182.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
25.1
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Reporting groups
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Reporting group title |
Prior Brexpiprazole
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Reporting group description |
Subjects who received brexpiprazole in a previous double-blind phase 3 study (Trial 331-14-213 {2017-003940-19}), received the same dose of brexpiprazole [2 or 3 mg], QD, orally, as they received during the previous study, for up to 12 weeks with dose adjustment. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Prior Placebo
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Reporting group description |
Subjects who received placebo in a previous double-blind phase 3 study (Trial 331-14-213 {2017-003940-19}), received brexpiprazole following a titration schedule, to gradually increase their dose from 0.5 mg QD, in the starting to 2 or 3 mg QD, orally, for up to 12 weeks with dose adjustment. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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26 Jun 2020 |
•Addendum for any protocol-specified activities that are not able to be performed or cannot be performed due to COVID-19 considerations.
•Added that subjects who are early terminated from Trial 331-14-213, if the trial is terminated due to overwhelming efficacy from the interim analysis, may be offered entry into this trial.
•The changes from amendment 1 of protocol 331-201-00182 did not go into effect and the amendment was not distributed to sites or Institutional review boards.
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06 Aug 2020 |
• Deleted language stating that subjects who are early terminated from Trial 331-14-213, if the trial is terminated due to overwhelming efficacy from the interim analysis, may be offered entry into this trial. |
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22 Sep 2020 |
• Added that subjects who are early terminated from Trial 331-14-213, if the trial is terminated due to overwhelming efficacy from the interim analysis, may be offered entry into this trial. |
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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. | |||
| None reported | |||
