Trial Outcomes & Findings for A 12-week 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 (NCT NCT03594123)
NCT ID: NCT03594123
Last Updated: 2023-11-14
Results Overview
An adverse event (AE) was defined as any untoward medical occurrence in a patient or clinical trial participant 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. Adverse events were graded on a 3-point scale. The intensity of an adverse experience was defined as follows: 1 = Mild: Discomfort noticed, but no disruption to daily activity, 2 = Moderate: Discomfort sufficient to reduce or affect normal daily activity, and 3 = Severe: Inability to work or perform normal daily activity.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
259 participants
Primary outcome timeframe
From first dose through 30 days after last dose of study drug (Up to approximately Week 16)
Results posted on
2023-11-14
Participant Flow
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.
Of the 259 participants,163 participants received brexpiprazole and 96 participants received placebo in the parent study 331-14-213. All 259 participants received brexpiprazole in this study. As prespecified in the SAP,data was analyzed based on the treatments (Brexpiprazole or Placebo) received in parent study 331-14-213. Participants received brexpiprazole 2 or 3 mg or placebo in the parent study, data for this study was analyzed and reported in a combined way for brexpiprazole 2 and 3 mg.
Participant milestones
| Measure |
Prior Brexpiprazole
Participants who received brexpiprazole in a previous double-blind phase 3 study (Trial 331-14-213 {NCT03548584}), 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.
|
Prior Placebo
Participants who received placebo in a previous double-blind phase 3 study (Trial 331-14-213 {NCT03548584}), 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.
|
|---|---|---|
|
Overall Study
STARTED
|
163
|
96
|
|
Overall Study
Efficacy Sample:
|
159
|
95
|
|
Overall Study
COMPLETED
|
142
|
87
|
|
Overall Study
NOT COMPLETED
|
21
|
9
|
Reasons for withdrawal
| Measure |
Prior Brexpiprazole
Participants who received brexpiprazole in a previous double-blind phase 3 study (Trial 331-14-213 {NCT03548584}), 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.
|
Prior Placebo
Participants who received placebo in a previous double-blind phase 3 study (Trial 331-14-213 {NCT03548584}), 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.
|
|---|---|---|
|
Overall Study
Lost to Follow-up
|
0
|
1
|
|
Overall Study
Adverse Event
|
8
|
5
|
|
Overall Study
Site Terminated by Sponsor
|
4
|
1
|
|
Overall Study
Subject Withdrew Consent to Participate
|
7
|
1
|
|
Overall Study
Lack of Efficacy
|
1
|
0
|
|
Overall Study
Other (Not Related to COVID-19)
|
1
|
1
|
Baseline Characteristics
A 12-week 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
Baseline characteristics by cohort
| Measure |
Prior Brexpiprazole
n=163 Participants
Participants who received brexpiprazole in a previous double-blind phase 3 study (Trial 331-14-213 {NCT03548584}), 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.
|
Prior Placebo
n=96 Participants
Participants who received placebo in a previous double-blind phase 3 study (Trial 331-14-213 {NCT03548584}), 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.
|
Total
n=259 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
74.8 years
STANDARD_DEVIATION 7.9 • n=5 Participants
|
73.4 years
STANDARD_DEVIATION 73.0 • n=7 Participants
|
74.3 years
STANDARD_DEVIATION 75.0 • n=5 Participants
|
|
Sex: Female, Male
Female
|
99 Participants
n=5 Participants
|
46 Participants
n=7 Participants
|
145 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
64 Participants
n=5 Participants
|
50 Participants
n=7 Participants
|
114 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
52 Participants
n=5 Participants
|
30 Participants
n=7 Participants
|
82 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
111 Participants
n=5 Participants
|
66 Participants
n=7 Participants
|
177 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
7 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
154 Participants
n=5 Participants
|
94 Participants
n=7 Participants
|
248 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
Bulgaria
|
15 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
26 Participants
n=5 Participants
|
|
Region of Enrollment
Hungary
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Region of Enrollment
Serbia
|
9 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
17 Participants
n=5 Participants
|
|
Region of Enrollment
Slovakia
|
5 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
|
Region of Enrollment
Spain
|
5 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
|
Region of Enrollment
Ukraine
|
55 Participants
n=5 Participants
|
31 Participants
n=7 Participants
|
86 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
71 Participants
n=5 Participants
|
38 Participants
n=7 Participants
|
109 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: From first dose through 30 days after last dose of study drug (Up to approximately Week 16)Population: Safety Sample comprised of those participants who signed an informed consent form (ICF) for the trial and received at least one dose of brexpiprazole in Trial 331-201-00182. As prespecified in the SAP, data was analyzed based on the treatments (Brexpiprazole or Placebo) received in parent study 331-14-213. Participants received brexpiprazole 2 or 3 mg or placebo in the parent study, data for this study was analyzed and reported in a combined way for brexpiprazole 2 and 3 mg.
An adverse event (AE) was defined as any untoward medical occurrence in a patient or clinical trial participant 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. Adverse events were graded on a 3-point scale. The intensity of an adverse experience was defined as follows: 1 = Mild: Discomfort noticed, but no disruption to daily activity, 2 = Moderate: Discomfort sufficient to reduce or affect normal daily activity, and 3 = Severe: Inability to work or perform normal daily activity.
Outcome measures
| Measure |
Prior Brexpiprazole
n=163 Participants
Participants who received brexpiprazole in a previous double-blind phase 3 study (Trial 331-14-213 {NCT03548584}), 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.
|
Prior Placebo
n=96 Participants
Participants who received placebo in a previous double-blind phase 3 study (Trial 331-14-213 {NCT03548584}), 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.
|
|---|---|---|
|
Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) by Severity
Mild
|
20.9 percentage of participants
|
13.5 percentage of participants
|
|
Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) by Severity
Moderate
|
9.2 percentage of participants
|
19.8 percentage of participants
|
|
Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) by Severity
Severe
|
3.1 percentage of participants
|
0 percentage of participants
|
Adverse Events
Prior Brexpiprazole
Serious events: 6 serious events
Other events: 0 other events
Deaths: 0 deaths
Prior Placebo
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Prior Brexpiprazole
n=163 participants at risk
Participants who received brexpiprazole in a previous double-blind phase 3 study (Trial 331-14-213 {NCT03548584}), 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.
|
Prior Placebo
n=96 participants at risk
Participants who received placebo in a previous double-blind phase 3 study (Trial 331-14-213 {NCT03548584}), 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.
|
|---|---|---|
|
Blood and lymphatic system disorders
Blood Loss Anaemia
|
0.61%
1/163 • From first dose through 30 days after last dose of study drug (Up to approximately Week 16)
Safety Sample comprised of those participants who signed an ICF for the trial and received at least one dose of brexpiprazole in Trial 331-201-00182. As prespecified in the SAP, data was analyzed based on the treatments (Brexpiprazole or Placebo) received in parent study 331-14-213. Participants received brexpiprazole 2 or 3 mg or placebo in the parent study, adverse events were analyzed and reported irrespective of the dose, in a combined way for brexpiprazole 2 and 3 mg.
|
0.00%
0/96 • From first dose through 30 days after last dose of study drug (Up to approximately Week 16)
Safety Sample comprised of those participants who signed an ICF for the trial and received at least one dose of brexpiprazole in Trial 331-201-00182. As prespecified in the SAP, data was analyzed based on the treatments (Brexpiprazole or Placebo) received in parent study 331-14-213. Participants received brexpiprazole 2 or 3 mg or placebo in the parent study, adverse events were analyzed and reported irrespective of the dose, in a combined way for brexpiprazole 2 and 3 mg.
|
|
Gastrointestinal disorders
Haemorrhoids
|
0.61%
1/163 • From first dose through 30 days after last dose of study drug (Up to approximately Week 16)
Safety Sample comprised of those participants who signed an ICF for the trial and received at least one dose of brexpiprazole in Trial 331-201-00182. As prespecified in the SAP, data was analyzed based on the treatments (Brexpiprazole or Placebo) received in parent study 331-14-213. Participants received brexpiprazole 2 or 3 mg or placebo in the parent study, adverse events were analyzed and reported irrespective of the dose, in a combined way for brexpiprazole 2 and 3 mg.
|
0.00%
0/96 • From first dose through 30 days after last dose of study drug (Up to approximately Week 16)
Safety Sample comprised of those participants who signed an ICF for the trial and received at least one dose of brexpiprazole in Trial 331-201-00182. As prespecified in the SAP, data was analyzed based on the treatments (Brexpiprazole or Placebo) received in parent study 331-14-213. Participants received brexpiprazole 2 or 3 mg or placebo in the parent study, adverse events were analyzed and reported irrespective of the dose, in a combined way for brexpiprazole 2 and 3 mg.
|
|
Injury, poisoning and procedural complications
Fall
|
1.8%
3/163 • From first dose through 30 days after last dose of study drug (Up to approximately Week 16)
Safety Sample comprised of those participants who signed an ICF for the trial and received at least one dose of brexpiprazole in Trial 331-201-00182. As prespecified in the SAP, data was analyzed based on the treatments (Brexpiprazole or Placebo) received in parent study 331-14-213. Participants received brexpiprazole 2 or 3 mg or placebo in the parent study, adverse events were analyzed and reported irrespective of the dose, in a combined way for brexpiprazole 2 and 3 mg.
|
0.00%
0/96 • From first dose through 30 days after last dose of study drug (Up to approximately Week 16)
Safety Sample comprised of those participants who signed an ICF for the trial and received at least one dose of brexpiprazole in Trial 331-201-00182. As prespecified in the SAP, data was analyzed based on the treatments (Brexpiprazole or Placebo) received in parent study 331-14-213. Participants received brexpiprazole 2 or 3 mg or placebo in the parent study, adverse events were analyzed and reported irrespective of the dose, in a combined way for brexpiprazole 2 and 3 mg.
|
|
Injury, poisoning and procedural complications
Femur Fracture
|
0.61%
1/163 • From first dose through 30 days after last dose of study drug (Up to approximately Week 16)
Safety Sample comprised of those participants who signed an ICF for the trial and received at least one dose of brexpiprazole in Trial 331-201-00182. As prespecified in the SAP, data was analyzed based on the treatments (Brexpiprazole or Placebo) received in parent study 331-14-213. Participants received brexpiprazole 2 or 3 mg or placebo in the parent study, adverse events were analyzed and reported irrespective of the dose, in a combined way for brexpiprazole 2 and 3 mg.
|
0.00%
0/96 • From first dose through 30 days after last dose of study drug (Up to approximately Week 16)
Safety Sample comprised of those participants who signed an ICF for the trial and received at least one dose of brexpiprazole in Trial 331-201-00182. As prespecified in the SAP, data was analyzed based on the treatments (Brexpiprazole or Placebo) received in parent study 331-14-213. Participants received brexpiprazole 2 or 3 mg or placebo in the parent study, adverse events were analyzed and reported irrespective of the dose, in a combined way for brexpiprazole 2 and 3 mg.
|
|
Injury, poisoning and procedural complications
Hip Fracture
|
0.61%
1/163 • From first dose through 30 days after last dose of study drug (Up to approximately Week 16)
Safety Sample comprised of those participants who signed an ICF for the trial and received at least one dose of brexpiprazole in Trial 331-201-00182. As prespecified in the SAP, data was analyzed based on the treatments (Brexpiprazole or Placebo) received in parent study 331-14-213. Participants received brexpiprazole 2 or 3 mg or placebo in the parent study, adverse events were analyzed and reported irrespective of the dose, in a combined way for brexpiprazole 2 and 3 mg.
|
0.00%
0/96 • From first dose through 30 days after last dose of study drug (Up to approximately Week 16)
Safety Sample comprised of those participants who signed an ICF for the trial and received at least one dose of brexpiprazole in Trial 331-201-00182. As prespecified in the SAP, data was analyzed based on the treatments (Brexpiprazole or Placebo) received in parent study 331-14-213. Participants received brexpiprazole 2 or 3 mg or placebo in the parent study, adverse events were analyzed and reported irrespective of the dose, in a combined way for brexpiprazole 2 and 3 mg.
|
|
Investigations
Hepatic Enzyme Increased
|
0.61%
1/163 • From first dose through 30 days after last dose of study drug (Up to approximately Week 16)
Safety Sample comprised of those participants who signed an ICF for the trial and received at least one dose of brexpiprazole in Trial 331-201-00182. As prespecified in the SAP, data was analyzed based on the treatments (Brexpiprazole or Placebo) received in parent study 331-14-213. Participants received brexpiprazole 2 or 3 mg or placebo in the parent study, adverse events were analyzed and reported irrespective of the dose, in a combined way for brexpiprazole 2 and 3 mg.
|
0.00%
0/96 • From first dose through 30 days after last dose of study drug (Up to approximately Week 16)
Safety Sample comprised of those participants who signed an ICF for the trial and received at least one dose of brexpiprazole in Trial 331-201-00182. As prespecified in the SAP, data was analyzed based on the treatments (Brexpiprazole or Placebo) received in parent study 331-14-213. Participants received brexpiprazole 2 or 3 mg or placebo in the parent study, adverse events were analyzed and reported irrespective of the dose, in a combined way for brexpiprazole 2 and 3 mg.
|
|
Nervous system disorders
Syncope
|
0.61%
1/163 • From first dose through 30 days after last dose of study drug (Up to approximately Week 16)
Safety Sample comprised of those participants who signed an ICF for the trial and received at least one dose of brexpiprazole in Trial 331-201-00182. As prespecified in the SAP, data was analyzed based on the treatments (Brexpiprazole or Placebo) received in parent study 331-14-213. Participants received brexpiprazole 2 or 3 mg or placebo in the parent study, adverse events were analyzed and reported irrespective of the dose, in a combined way for brexpiprazole 2 and 3 mg.
|
0.00%
0/96 • From first dose through 30 days after last dose of study drug (Up to approximately Week 16)
Safety Sample comprised of those participants who signed an ICF for the trial and received at least one dose of brexpiprazole in Trial 331-201-00182. As prespecified in the SAP, data was analyzed based on the treatments (Brexpiprazole or Placebo) received in parent study 331-14-213. Participants received brexpiprazole 2 or 3 mg or placebo in the parent study, adverse events were analyzed and reported irrespective of the dose, in a combined way for brexpiprazole 2 and 3 mg.
|
Other adverse events
| Measure |
Prior Brexpiprazole
n=163 participants at risk
Participants who received brexpiprazole in a previous double-blind phase 3 study (Trial 331-14-213 {NCT03548584}), 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.
|
Prior Placebo
n=96 participants at risk
Participants who received placebo in a previous double-blind phase 3 study (Trial 331-14-213 {NCT03548584}), 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.
|
|---|---|---|
|
Infections and infestations
Nasopharyngitis
|
0.00%
0/163 • From first dose through 30 days after last dose of study drug (Up to approximately Week 16)
Safety Sample comprised of those participants who signed an ICF for the trial and received at least one dose of brexpiprazole in Trial 331-201-00182. As prespecified in the SAP, data was analyzed based on the treatments (Brexpiprazole or Placebo) received in parent study 331-14-213. Participants received brexpiprazole 2 or 3 mg or placebo in the parent study, adverse events were analyzed and reported irrespective of the dose, in a combined way for brexpiprazole 2 and 3 mg.
|
5.2%
5/96 • From first dose through 30 days after last dose of study drug (Up to approximately Week 16)
Safety Sample comprised of those participants who signed an ICF for the trial and received at least one dose of brexpiprazole in Trial 331-201-00182. As prespecified in the SAP, data was analyzed based on the treatments (Brexpiprazole or Placebo) received in parent study 331-14-213. Participants received brexpiprazole 2 or 3 mg or placebo in the parent study, adverse events were analyzed and reported irrespective of the dose, in a combined way for brexpiprazole 2 and 3 mg.
|
Additional Information
Global Clinical Development
Otsuka Pharmaceutical Development & Commercialization, Inc.
Phone: 1-609-524-6788
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee Sponsor reserves the right to review results publications prior to public release and can delay such publications for a period greater than 60 days but no more than 120 days from the date that the publication is submitted to the Sponsor for review. Sponsor can require changes to the publication to protect Sponsor's intellectual property rights and/or confidential information and reserves the right to limit publication timing and scope of data published based on the number of study locations.
- Publication restrictions are in place
Restriction type: OTHER