Clinical Trial Results:
A 2-month, Observational, Rollover Trial to Evaluate the Safety of Subjects with Agitation Associated with Dementia of the Alzheimer’s Type who were Previously Treated with Brexpiprazole (OPC-34712) or Placebo in a Phase 3, Double-blind Trial
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Summary
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EudraCT number |
2014-000424-23 |
Trial protocol |
ES DE SI FR GB HR BG |
Global end of trial date |
30 May 2017
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Results information
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Results version number |
v1(current) |
This version publication date |
02 Apr 2021
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First version publication date |
02 Apr 2021
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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 |
331-13-211
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02192554 | ||
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 |
Otsuka Transparency Department, Otsuka Pharmaceutical Development & Commercialization,
Inc., DT-inquiry@otsuka.jp
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Scientific contact |
Otsuka Transparency Department, Otsuka Pharmaceutical Development & Commercialization,
Inc., DT-inquiry@otsuka.jp
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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 May 2017
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
30 May 2017
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Global end of trial reached? |
Yes
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Global end of trial date |
30 May 2017
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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 evaluate the safety of subjects with agitation associated with dementia of the Alzheimer's type who were previously treated with brexpiprazole (0.5, 1, or 2 mg/day) or placebo during Trial 331-12-283 or Trial 331-12-284.
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Protection of trial subjects |
This trial was conducted in compliance with Good Clinical Practice guidelines for conducting, recording, and reporting trials, as well as for archiving essential documents. Consistent with ethical principles for the protection of human research subjects, no trial procedures were performed on trial candidates until written consent had been obtained from them. The informed consent form, protocol, and amendments for this trial were submitted to and approved by the institutional review board or ethics committee at each respective trial center. During the phase 3 trials, subjects were treated for a period of 12 weeks with a 30-day safety follow-up period. Trial 331-13-211 was designed to extend the duration of the safety follow-up period for the aforementioned Phase 3 trials from 30 days to 3 months (ie, 30 days from the previous phase 3 trials [331-12-283 or 331-12-284] plus 2 months from Trial 331-13-211).
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Background therapy |
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Evidence for comparator |
- | ||
Actual start date of recruitment |
05 Jul 2014
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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 |
Slovenia: 4
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Country: Number of subjects enrolled |
Spain: 17
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Country: Number of subjects enrolled |
Ukraine: 92
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Country: Number of subjects enrolled |
United States: 111
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Country: Number of subjects enrolled |
Bulgaria: 42
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Country: Number of subjects enrolled |
Canada: 7
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Country: Number of subjects enrolled |
Croatia: 16
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Country: Number of subjects enrolled |
France: 7
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Country: Number of subjects enrolled |
Germany: 9
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Country: Number of subjects enrolled |
Russian Federation: 108
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Country: Number of subjects enrolled |
Serbia: 37
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Worldwide total number of subjects |
450
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EEA total number of subjects |
95
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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) |
66
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From 65 to 84 years |
339
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85 years and over |
45
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Recruitment
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Recruitment details |
This trial was conducted at 87 sites in 12 countries: Bulgaria, Canada, Croatia, France, Germany, Great Britain, Russia, Serbia, Slovenia, Spain, Ukraine, and United States. Subjects with agitation associated with dementia of the Alzheimer's type were involved in this study. | |||||||||||||||||||||
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Pre-assignment
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Screening details |
This was an observational trial without study drug to characterize the long-term safety of subjects after the investigational trials (Trials 331-12-283 & Trial 331-12-284). Subjects were allowed to take any medications to treat agitation or other symptoms of illness without limitation. Informed consent signed, eligibility criteria checked. | |||||||||||||||||||||
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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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Are arms mutually exclusive |
Yes
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Arm title
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Prior Brexpiprazole | |||||||||||||||||||||
Arm description |
This arm comprised of subjects with agitation associated with dementia of the Alzheimer's type who previously received brexpiprazole (0.5, 1, or 2 mg/day) during a phase 3 brexpiprazole trial (Trial 331-12-283 and Trial 331-12-284). This study comprised of 2 months of continued observation following a subject's completion of participation in the previous phase 3 brexpiprazole trials and included 3 visits: at baseline, Month 1 (± 5 days), and Month 2 (±5 days)/ Early termination (ET). No Investigational medicinal product (IMP) was provided during this 2-month observational rollover trial. | |||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||
Investigational medicinal product name |
Brexpiprazole
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Investigational medicinal product code |
OPC-34712
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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 |
Brexpiprazole (0.5, 1, or 2 mg/day) was administered during a phase 3 brexpiprazole trial (Trial 331-12-283 and Trial 331-12-284).
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Arm title
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Prior Placebo | |||||||||||||||||||||
Arm description |
This arm comprised of subjects with agitation associated with dementia of the Alzheimer's type, who previously received brexpiprazole matching placebo during a phase 3 brexpiprazole trial (Trial 331-12-283 and Trial 331-12-284). In this rollover study no placebo was administered. | |||||||||||||||||||||
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 |
Brexpiprazole matching placebo was administered during a phase 3 brexpiprazole trial (Trial 331-12-283 and Trial 331-12-284).
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Baseline characteristics reporting groups
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Reporting group title |
Prior Brexpiprazole
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Reporting group description |
This arm comprised of subjects with agitation associated with dementia of the Alzheimer's type who previously received brexpiprazole (0.5, 1, or 2 mg/day) during a phase 3 brexpiprazole trial (Trial 331-12-283 and Trial 331-12-284). This study comprised of 2 months of continued observation following a subject's completion of participation in the previous phase 3 brexpiprazole trials and included 3 visits: at baseline, Month 1 (± 5 days), and Month 2 (±5 days)/ Early termination (ET). No Investigational medicinal product (IMP) was provided during this 2-month observational rollover trial. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Prior Placebo
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Reporting group description |
This arm comprised of subjects with agitation associated with dementia of the Alzheimer's type, who previously received brexpiprazole matching placebo during a phase 3 brexpiprazole trial (Trial 331-12-283 and Trial 331-12-284). In this rollover study no placebo was administered. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Prior Brexpiprazole
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Reporting group description |
This arm comprised of subjects with agitation associated with dementia of the Alzheimer's type who previously received brexpiprazole (0.5, 1, or 2 mg/day) during a phase 3 brexpiprazole trial (Trial 331-12-283 and Trial 331-12-284). This study comprised of 2 months of continued observation following a subject's completion of participation in the previous phase 3 brexpiprazole trials and included 3 visits: at baseline, Month 1 (± 5 days), and Month 2 (±5 days)/ Early termination (ET). No Investigational medicinal product (IMP) was provided during this 2-month observational rollover trial. | ||
Reporting group title |
Prior Placebo
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Reporting group description |
This arm comprised of subjects with agitation associated with dementia of the Alzheimer's type, who previously received brexpiprazole matching placebo during a phase 3 brexpiprazole trial (Trial 331-12-283 and Trial 331-12-284). In this rollover study no placebo was administered. | ||
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End point title |
Number of participants with Adverse Events (AEs) [1] | |||||||||||||||||||||||||||
End point description |
An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. A SAE included any event that resulted in death, life-threatening event, persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, in-patient hospitalization or prolonged hospitalization, congenital anomaly/birth defect, and other medically significant events that, based upon appropriate medical judgment, jeopardized the subject and required medical or surgical intervention. Safety endpoints related to AEs that were evaluated during this trial were: frequency and severity of AEs, SAEs, and discontinuations from the trial due to AEs, frequency and severity of AEs related to the worsening of agitation and cognition associated with Alzheimer's disease. Subjects had no limitations to take any medication to treat agitation or other symptoms during this study.
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End point type |
Primary
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End point timeframe |
From baseline to Month 2/ET
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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: Safety results were summarized and presented and no formal statistical analysis was performed. |
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End point title |
Mean Change in Mini-Mental State Examination (MMSE) Score [2] | ||||||||||||||||||
End point description |
The MMSE was a brief practical test used for assessing cognitive dysfunction. The test consisted of 5 sections (orientation,registration, attention and calculation, recall, and language) and had a total possible score of 30. Higher scores indicate better cognitive functioning.
MMSE safety scale was used as one of the safety variable. The MMSE was performed at the Month 2/ET visit.
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End point type |
Primary
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End point timeframe |
From baseline to Month 2/ET
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| Notes [2] - 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 non-comparative, observational study. The mean change in the MMSE score from baseline to Month 2/ET was summarized by descriptive statistics, eg, mean and standard deviation. |
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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 baseline to Month 2/ET
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Adverse event reporting additional description |
An AE was defined as any untoward medical occurrence associated with the use of a drug in human. An serious adverse event (SAE) included events that resulted in death, life threatening event, persistent incapacity of the ability to conduct normal life functions, in-patient hospitalization, congenital anomaly, and other medically events.
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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 |
20.0
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Reporting groups
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Reporting group title |
Prior Brexpiprazole
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Reporting group description |
This arm comprised of subjects with agitation associated with dementia of the Alzheimer's type who previously received brexpiprazole (0.5, 1, or 2 mg/day)during a phase 3 brexpiprazole trial (Trial 331-12-283 and Trial 331-12-284). This study comprised of 2 months of continued observation following a participant's completion of participation in the previous phase 3 brexpiprazole trials and included 3 visits: at baseline, Month 1 (± 5 days), and Month 2 (± 5 days)/ Early termination (ET). No Investigational medicinal product (IMP) was provided during this 2-month observational rollover trial.months of continued observation following a subject's completion of participation in the previous phase 3 brexpiprazole trials and included 3 visits: at baseline, Month 1 (± 5 days), and Month 2 (± 5 days)/ Early termination (ET). No Investigational medicinal product (IMP) was provided during this 2-month observational rollover trial. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Prior Placebo
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Reporting group description |
This arm comprised of subjects with agitation associated with dementia of the Alzheimer's type, who previously received brexpiprazole matching placebo during a phase 3 brexpiprazole trial (Trial 331-12-283 and Trial 331-12-284). In this rollover study no placebo was administered. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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20 Oct 2014 |
This first amendment served to reflect clarifications and additions to study procedures intended to enhance participant safety and accuracy of data. In addition, administrative clarifications were made, including changes to text to enhance readability and consistency and to correct typographical, punctuation, and formatting errors. These changes were minor and did not change the design or content of the protocol. |
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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 | |||
