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Trial record 48 of 64 for:    brexpiprazole

Phase 1 Study to Assess the Safety/Tolerability of Brexpiprazole as Adjunctive Therapy in Elderly Subjects With Major Depressive Disorder

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ClinicalTrials.gov Identifier: NCT01670279
Recruitment Status : Completed
First Posted : August 22, 2012
Results First Posted : February 4, 2016
Last Update Posted : February 4, 2016
Sponsor:
Collaborator:
H. Lundbeck A/S
Information provided by (Responsible Party):
Otsuka Pharmaceutical Development & Commercialization, Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Major Depressive Disorder
Interventions Drug: Brexpiprazole
Drug: Placebo
Enrollment 18
Recruitment Details This was a phase 1, multicenter, randomized, double-blind, placebo-controlled, multiple ascending dose trial planned in 3 sequential cohorts of elderly participants (70 to 85 years old) with major depressive disorder (MDD). Brexpiprazole was administered as an adjunct treatment to the current antidepressant therapy that the participant received.
Pre-assignment Details The study included a 30-day screening period, a 14-day washout period, up to 45-day inpatient treatment period (titration: received brexpiprazole or placebo once daily [QD] for 14 or 21 days and fixed dose phase: received assigned fixed dose for 14 or 28 days), and a 30-day follow-up after the last dose of study drug.
Arm/Group Title Brexpiprazole-Cohort 1 Brexpiprazole-Cohort 2 Brexpiprazole-Cohort 3 Placebo
Hide Arm/Group Description In the titration phase, participants received 0.5 mg brexpiprazole QD for 7 days, followed by 1 mg brexpiprazole QD for 7 days. In the fixed dose phase, participants received 2 mg brexpiprazole QD for 14 days, followed by 3 mg brexpiprazole QD for 14 days. In the titration phase, participants received 0.5 mg brexpiprazole QD for 7 days, followed by 1 mg brexpiprazole QD for 7 days. In the fixed dose phase, participants received 3 mg brexpiprazole QD for 14 days. In the titration phase, participants were to receive 0.5 mg brexpiprazole or placebo QD for 7 days, followed by 1 mg brexpiprazole or placebo QD for 7 days, and then 2 mg brexpiprazole or placebo QD for 7 days. In the fixed dose phase, participants were to receive 3 mg brexpiprazole or placebo QD for 14 days. However, Cohort 3 was not conducted due to safety and tolerability results from Cohorts 1 and 2. In the titration phase, participants received 0.5 mg placebo QD for 7 days, followed by 1 mg placebo QD for 7 days. In the fixed dose phase, Cohort 1: participants received 2 mg placebo QD for 14 days, followed by 3 mg placebo QD for 14 days. Cohort 2: participants received 3 mg placebo QD for 14 days.
Period Title: Overall Study
Started 6 7 0 5
Completed 6 5 0 4
Not Completed 0 2 0 1
Reason Not Completed
Adverse Event             0             1             0             0
Physician Decision             0             1             0             0
Participant met withdrawal criteria             0             0             0             1
Arm/Group Title Brexpiprazole-Cohort 1 Brexpiprazole-Cohort 2 Placebo Total
Hide Arm/Group Description In the titration phase, participants received 0.5 mg brexpiprazole QD for 7 days, followed by 1 mg brexpiprazole QD for 7 days. In the fixed dose phase, participants received 2 mg brexpiprazole QD for 14 days, followed by 3 mg brexpiprazole QD for 14 days. In the titration phase, participants received 0.5 mg brexpiprazole QD for 7 days, followed by 1 mg brexpiprazole QD for 7 days. In the fixed dose phase, participants received 3 mg brexpiprazole QD for 14 days. In the titration phase, participants received 0.5 mg placebo QD for 7 days, followed by 1 mg placebo QD for 7 days. In the fixed dose phase, Cohort 1: participants received 2 mg placebo QD for 14 days, followed by 3 mg placebo QD for 14 days. Cohort 2: participants received 3 mg placebo QD for 14 days. Total of all reporting groups
Overall Number of Baseline Participants 6 7 5 18
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 6 participants 7 participants 5 participants 18 participants
73.2  (4.0) 76.0  (5.3) 72.6  (1.5) 74.1  (4.2)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 7 participants 5 participants 18 participants
Female
4
  66.7%
5
  71.4%
4
  80.0%
13
  72.2%
Male
2
  33.3%
2
  28.6%
1
  20.0%
5
  27.8%
1.Primary Outcome
Title Number of Participants Who Tolerated Brexpiprazole
Hide Description Safety and tolerability of brexpiprazole was noted to be primary outcome measure. Brexpiprazole was judged to be tolerated if at least 6 out of 8 (75%) of the participants in a test cohort tolerated the dose after 14 days of QD dosing at the end of the fixed dose phase based on the blinded data. Dose toleration was defined as follows: during the course of the trial, the participants did not experience any moderate or severe adverse events (AEs) or potentially clinically relevant changes from Baseline in laboratory values, vital signs, electrocardiogram (ECG) tracings, Columbia-Suicide Severity Rating Scale (C-SSRS), or extrapyramidal symptom (EPS) ratings, which were assessed as possibly related to the study drug, and would have warranted a dose decrease or discontinuation of the study drug. The safety and tolerability of brexpiprazole was defined by parameters: AEs, laboratory values, vital signs, ECG, C-SSRS, or EPS ratings, the results of each of the parameters reported separately.
Time Frame 45 Days
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Hide Analysis Population Description
Tolerability assessed in phase 1 trial in healthy participants (18-45 years) with MDD as adjunct therapy to ADTs; the efficacy assessed in phase 3 trials in participants (18-65 years) with MDD as adjunct therapy to ADTs. Thus, safety/tolerability of brexpiprazole in participants (>65 years) with MDD as adjunct therapy to ADTs was not characterized.
Arm/Group Title Brexpiprazole-Cohort 1 Brexpiprazole-Cohort 2 Placebo
Hide Arm/Group Description:
In the titration phase, participants received 0.5 mg brexpiprazole QD for 7 days, followed by 1 mg brexpiprazole QD for 7 days. In the fixed dose phase, participants received 2 mg brexpiprazole QD for 14 days, followed by 3 mg brexpiprazole QD for 14 days.
In the titration phase, participants received 0.5 mg brexpiprazole QD for 7 days, followed by 1 mg brexpiprazole QD for 7 days. In the fixed dose phase, participants received 3 mg brexpiprazole QD for 14 days.
In the titration phase, participants received 0.5 mg placebo QD for 7 days, followed by 1 mg placebo QD for 7 days. In the fixed dose phase, Cohort 1: participants received 2 mg placebo QD for 14 days, followed by 3 mg placebo QD for 14 days. Cohort 2: participants received 3 mg placebo QD for 14 days.
Overall Number of Participants Analyzed 6 7 5
Measure Type: Number
Unit of Measure: participants
6 7 5
2.Primary Outcome
Title Number of AEs Reported.
Hide Description The AEs were one of the primary parameters to measure the safety and tolerability of individual participants. The AEs were captured for all participants from the time the ICF was signed until the end of the trial. AEs were measured throughout the 14-day titration and 28-day fixed dose phase until follow-up (30 [±2] days after last dose of study medication).
Time Frame Throughout the study, up to 119 days
Hide Outcome Measure Data
Hide Analysis Population Description
The safety dataset included all randomized participants who received at least one dose of study medication.
Arm/Group Title Brexpiprazole-Cohort 1 Brexpiprazole-Cohort 2 Placebo
Hide Arm/Group Description:
In the titration phase, participants received 0.5 mg brexpiprazole QD for 7 days, followed by 1 mg brexpiprazole QD for 7 days. In the fixed dose phase, participants received 2 mg brexpiprazole QD for 14 days, followed by 3 mg brexpiprazole QD for 14 days.
In the titration phase, participants received 0.5 mg brexpiprazole QD for 7 days, followed by 1 mg brexpiprazole QD for 7 days. In the fixed dose phase, participants received 3 mg brexpiprazole QD for 14 days.
In the titration phase, participants received 0.5 mg placebo QD for 7 days, followed by 1 mg placebo QD for 7 days. In the fixed dose phase, Cohort 1: participants received 2 mg placebo QD for 14 days, followed by 3 mg placebo QD for 14 days. Cohort 2: participants received 3 mg placebo QD for 14 days.
Overall Number of Participants Analyzed 6 6 5
Measure Type: Number
Unit of Measure: Events
Adverse events 12 33 5
Treatment emergent adverse events (TEAEs) 6 6 3
Serious adverse events 0 0 0
3.Primary Outcome
Title Incidence of Laboratory Values of Potential Clinical Significance
Hide Description The laboratory values were one of the primary parameters to measure the safety and tolerability of individual participants. Incidence of TEAEs of potential clinical relevance include abnormal values in serum chemistry, hematology, urinalyses and prolactin tests that were identified based on pre-defined criteria.
Time Frame Titration Day 7, Fixed dose Day 14 and 28 and Last Visit
Hide Outcome Measure Data
Hide Analysis Population Description
The safety dataset included all randomized participants who received at least one dose of study medication.
Arm/Group Title Brexpiprazole-Cohort 1 Brexpiprazole-Cohort 2 Placebo
Hide Arm/Group Description:
In the titration phase, participants received 0.5 mg brexpiprazole QD for 7 days, followed by 1 mg brexpiprazole QD for 7 days. In the fixed dose phase, participants received 2 mg brexpiprazole QD for 14 days, followed by 3 mg brexpiprazole QD for 14 days.
In the titration phase, participants received 0.5 mg brexpiprazole QD for 7 days, followed by 1 mg brexpiprazole QD for 7 days. In the fixed dose phase, participants received 3 mg brexpiprazole QD for 14 days.
In the titration phase, participants received 0.5 mg placebo QD for 7 days, followed by 1 mg placebo QD for 7 days. In the fixed dose phase, Cohort 1: participants received 2 mg placebo QD for 14 days, followed by 3 mg placebo QD for 14 days. Cohort 2: participants received 3 mg placebo QD for 14 days.
Overall Number of Participants Analyzed 6 6 5
Measure Type: Number
Unit of Measure: Participants
Cholesterol, fasting 0 1 1
Glucose 0 0 1
LDL direct, fasting 0 0 1
Triglycerides, fasting 2 1 3
Uric acid 0 0 1
Hematocrit 0 2 1
Prolactin 2 0 0
4.Primary Outcome
Title Incidence of Vital Signs of Potential Clinical Significance
Hide Description The vital signs were one of the primary parameters to measure the safety and tolerability of individual participants. Incidence of TEAEs of potential clinical relevance included abnormal values in heart rate, systolic and diastolic blood pressure, respiratory rate and weight that were identified based on pre-defined criteria.
Time Frame Baseline, Titration Day 1, 2, 7, 8, Fixed Days 1, 2, 14, 15, 28, 29, Early Termination and Last Visit.
Hide Outcome Measure Data
Hide Analysis Population Description
The safety dataset included all randomized participants who received at least one dose of study medication.
Arm/Group Title Brexpiprazole-Cohort 1 Brexpiprazole-Cohort 2 Placebo
Hide Arm/Group Description:
In the titration phase, participants received 0.5 mg brexpiprazole QD for 7 days, followed by 1 mg brexpiprazole QD for 7 days. In the fixed dose phase, participants received 2 mg brexpiprazole QD for 14 days, followed by 3 mg brexpiprazole QD for 14 days.
In the titration phase, participants received 0.5 mg brexpiprazole QD for 7 days, followed by 1 mg brexpiprazole QD for 7 days. In the fixed dose phase, participants received 3 mg brexpiprazole QD for 14 days.
In the titration phase, participants received 0.5 mg placebo QD for 7 days, followed by 1 mg placebo QD for 7 days. In the fixed dose phase, Cohort 1: participants received 2 mg placebo QD for 14 days, followed by 3 mg placebo QD for 14 days. Cohort 2: participants received 3 mg placebo QD for 14 days.
Overall Number of Participants Analyzed 6 6 5
Measure Type: Number
Unit of Measure: Participants
Weight increase 2 0 0
Supine hypotension, decrease 1 0 0
5.Primary Outcome
Title Incidence of ECG Evaluations of Potential Clinical Significance
Hide Description The measurement of ECG was one of the primary parameters to measure the safety and tolerability of individual participants. Incidence of TEAEs of potential clinical relevance include abnormal changes in heart rate and ECG intervals of PR, QRS, QT, QTcB, and QTcF that were identified based on pre-defined criteria.
Time Frame Titratrion Day 1 and 7, Fixed dose Day 1, 14, 28, Early Termination
Hide Outcome Measure Data
Hide Analysis Population Description
The safety dataset included all randomized participants who received at least one dose of study medication.
Arm/Group Title Brexpiprazole-Cohort 1 Brexpiprazole-Cohort 2 Placebo
Hide Arm/Group Description:
In the titration phase, participants received 0.5 mg brexpiprazole QD for 7 days, followed by 1 mg brexpiprazole QD for 7 days. In the fixed dose phase, participants received 2 mg brexpiprazole QD for 14 days, followed by 3 mg brexpiprazole QD for 14 days.
In the titration phase, participants received 0.5 mg brexpiprazole QD for 7 days, followed by 1 mg brexpiprazole QD for 7 days. In the fixed dose phase, participants received 3 mg brexpiprazole QD for 14 days.
In the titration phase, participants received 0.5 mg placebo QD for 7 days, followed by 1 mg placebo QD for 7 days. In the fixed dose phase, Cohort 1: participants received 2 mg placebo QD for 14 days, followed by 3 mg placebo QD for 14 days. Cohort 2: participants received 3 mg placebo QD for 14 days.
Overall Number of Participants Analyzed 6 6 5
Measure Type: Number
Unit of Measure: Participants
Supraventricular premature beat 0 2 1
Ventricular premature beat 3 0 1
Left bundle-branch block 0 0 1
Myocardial ischemia 1 0 0
Symmetrical T-wave inversions 1 1 0
Increase in QTcB 1 3 2
Increase in QTcF 1 2 2
6.Primary Outcome
Title Incidence of Physical Examination Evaluation of Potential Clinical Significance
Hide Description The physical examination evaluation was one of the primary parameters to measure the safety and tolerability of individual participants. Incidence of TEAEs of potential clinical relevance include abnormal changes in the following body systems: head, ears, eyes, nose, and throat; thorax; abdomen; urogenital; extremities; neurological; and skin and mucosae.
Time Frame Physical examination was performed at Screening, check-in, and discharge
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Hide Analysis Population Description
Safety Sample was analyzed. Any clinically significant condition present at the post-treatment physical examination that was not present at the baseline examination was documented as an adverse event and followed to a satisfactory conclusion. There were no clinically significant physical examination findings reported in this study.
Arm/Group Title Brexpiprazole-Cohort 1 Brexpiprazole-Cohort 2 Placebo
Hide Arm/Group Description:
In the titration phase, participants received 0.5 mg brexpiprazole QD for 7 days, followed by 1 mg brexpiprazole QD for 7 days. In the fixed dose phase, participants received 2 mg brexpiprazole QD for 14 days, followed by 3 mg brexpiprazole QD for 14 days.
In the titration phase, participants received 0.5 mg brexpiprazole QD for 7 days, followed by 1 mg brexpiprazole QD for 7 days. In the fixed dose phase, participants received 3 mg brexpiprazole QD for 14 days.
In the titration phase, participants received 0.5 mg placebo QD for 7 days, followed by 1 mg placebo QD for 7 days. In the fixed dose phase, Cohort 1: participants received 2 mg placebo QD for 14 days, followed by 3 mg placebo QD for 14 days. Cohort 2: participants received 3 mg placebo QD for 14 days.
Overall Number of Participants Analyzed 6 6 4
Measure Type: Number
Unit of Measure: Participants
0 0 0
7.Primary Outcome
Title Mean Change From Baseline to Study Completion in Simpson-Angus Scale (SAS) Total Score
Hide Description EPS was one of the primary parameters to measure the safety and tolerability of individual participants. The SAS is a rating scale used to measure EPS. The SAS scale consists of a list of 10 symptoms of parkinsonism (gait, arm dropping, shoulder shaking, elbow rigidity, wrist rigidity, head rotation, glabella tap, tremor, salivation, and akathisia), with each item rated from 0 to 4, with 0 being normal and 4 being the worst. The SAS Total score is sum of ratings for all 10 items, with possible Total scores from 0 to 40.
Time Frame End of Titration, Day 15, Day 29, Early Termination and Last visit
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Sample includes all randomized participants who receive at least one dose of study medication.
Arm/Group Title Brexpiprazole-Cohort 1 Brexpiprazole-Cohort 2 Placebo
Hide Arm/Group Description:
In the titration phase, participants received 0.5 mg brexpiprazole QD for 7 days, followed by 1 mg brexpiprazole QD for 7 days. In the fixed dose phase, participants received 2 mg brexpiprazole QD for 14 days, followed by 3 mg brexpiprazole QD for 14 days.
In the titration phase, participants received 0.5 mg brexpiprazole QD for 7 days, followed by 1 mg brexpiprazole QD for 7 days. In the fixed dose phase, participants received 3 mg brexpiprazole QD for 14 days.
In the titration phase, participants received 0.5 mg placebo QD for 7 days, followed by 1 mg placebo QD for 7 days. In the fixed dose phase, Cohort 1: participants received 2 mg placebo QD for 14 days, followed by 3 mg placebo QD for 14 days. Cohort 2: participants received 3 mg placebo QD for 14 days.
Overall Number of Participants Analyzed 6 6 5
Mean (Standard Deviation)
Unit of Measure: Units on a scale
End of Titration (N= 6, 6, 4) -0.3  (0.5) -0.5  (0.8) -1.0  (0.8)
Day 15 (N= 0, 5, 2) NA [1]   (NA) 0.2  (0.4) -1.5  (0.7)
Day 29 (N=6, 0, 2) -0.3  (0.4) NA [1]   (NA) 0.0  (0.0)
Early Termination (N= 0, 1, 1) NA [1]   (NA) -1.0 [2]   (NA) 0.0 [2]   (NA)
Last visit (N= 6, 6, 5) -0.2  (0.4) 0.0  (0.6) -0.6  (0.9)
[1]
N=0, data not collected.
[2]
N=1, standard deviation is not applicable.
8.Primary Outcome
Title Mean Change From Baseline to Study Completion in Barnes Akathisia Global Score
Hide Description EPS was one of the primary parameters to measure the safety and tolerability of individual participants. The Barnes Akathisia Rating Scale was an EPS rating scale. The Barnes Akathisia Rating Scale was used to assess the presence and severity of akathisia. This scale consists of 4 items. Only the 4th item, the Global Clinical Assessment of Akathisia, was evaluated in this trial. This item is rated on a 6 point scale, with 0 being best (absent) and 5 being worst (severe akathisia).
Time Frame End of Titration, Day 15, Day 29, Early Termination and Last visit
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Sample includes all randomized participants who receive at least one dose of study medication.
Arm/Group Title Brexpiprazole-Cohort 1 Brexpiprazole-Cohort 2 Placebo
Hide Arm/Group Description:
In the titration phase, participants received 0.5 mg brexpiprazole QD for 7 days, followed by 1 mg brexpiprazole QD for 7 days. In the fixed dose phase, participants received 2 mg brexpiprazole QD for 14 days, followed by 3 mg brexpiprazole QD for 14 days.
In the titration phase, participants received 0.5 mg brexpiprazole QD for 7 days, followed by 1 mg brexpiprazole QD for 7 days. In the fixed dose phase, participants received 3 mg brexpiprazole QD for 14 days.
In the titration phase, participants received 0.5 mg placebo QD for 7 days, followed by 1 mg placebo QD for 7 days. In the fixed dose phase, Cohort 1: participants received 2 mg placebo QD for 14 days, followed by 3 mg placebo QD for 14 days. Cohort 2: participants received 3 mg placebo QD for 14 days.
Overall Number of Participants Analyzed 6 6 5
Mean (Standard Deviation)
Unit of Measure: Units on a scale
End of Titration (N= 6, 6, 4) -0.2  (0.4) 0.0  (0.0) -0.5  (0.6)
Day 15 (N= 0, 5, 2) NA [1]   (NA) 0.0  (0.0) -0.5  (0.7)
Day 29 (N= 6, 0, 2) 0.0  (0.0) NA [1]   (NA) -0.5  (0.7)
Early Termination (N= 0, 1, 1) NA [1]   (NA) 0.0 [2]   (NA) 0.0 [2]   (NA)
Last visit (N= 6, 6, 5) 0.0  (0.0) 0.0  (0.0) -0.4  (0.5)
[1]
N=0, data not collected.
[2]
N=1, standard deviation is not applicable.
9.Primary Outcome
Title Mean Change From Baseline to Study Completion in Abnormal Involuntary Movement Scale (AIMS) Rating Score.
Hide Description EPS was one of the primary parameters to measure the safety and tolerability of individual participants. The AIMS Scale was an EPS rating scale. The AIMS is a 12 item scale. The first 10 items are rated from 0 to 4 (0=best, 4=worst). Items 11 and 12, related to dental status, have dichotomous responses, 0=no and 1=yes. The AIMS Total Score is the sum of the ratings for the first seven items. The possible total scores are from 0 to 28.
Time Frame End of Titration, Day 15, Day 29, Early Termination and Last visit
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Sample includes all randomized participants who receive at least one dose of study medication.
Arm/Group Title Brexpiprazole-Cohort 1 Brexpiprazole-Cohort 2 Placebo
Hide Arm/Group Description:
In the titration phase, participants received 0.5 mg brexpiprazole QD for 7 days, followed by 1 mg brexpiprazole QD for 7 days. In the fixed dose phase, participants received 2 mg brexpiprazole QD for 14 days, followed by 3 mg brexpiprazole QD for 14 days.
In the titration phase, participants received 0.5 mg brexpiprazole QD for 7 days, followed by 1 mg brexpiprazole QD for 7 days. In the fixed dose phase, participants received 3 mg brexpiprazole QD for 14 days.
In the titration phase, participants received 0.5 mg placebo QD for 7 days, followed by 1 mg placebo QD for 7 days. In the fixed dose phase, Cohort 1: participants received 2 mg placebo QD for 14 days, followed by 3 mg placebo QD for 14 days. Cohort 2: participants received 3 mg placebo QD for 14 days.
Overall Number of Participants Analyzed 6 6 5
Mean (Standard Deviation)
Unit of Measure: Units on a scale
End of Titration (N= 6, 6, 4) 0.0  (0.0) 0.2  (0.4) 0.0  (0.0)
Day 15 (N= 0, 5, 2) NA [1]   (NA) 0.0  (0.0) 0.0  (0.0)
Day 29 (N= 6, 0, 2) 0.0  (0.0) NA [1]   (NA) 0.0  (0.0)
Early Termination (N= 0, 1, 1) NA [1]   (NA) 0.0 [2]   (NA) 0.0 [2]   (NA)
Last Visit (N= 6, 6, 5) 0.0  (0.0) 0.0  (0.0) 0.0  (0.0)
[1]
N=0, data not collected.
[2]
N=1, standard deviation is not applicable.
10.Primary Outcome
Title Change From Baseline to Study Completion in C-SSRS Score.
Hide Description The C-SSRS was one of the primary parameters to measure the safety and tolerability of individual participants. Suicidality was monitored during the trial using the C-SSRS. This scale consists of a baseline evaluation that assesses the lifetime experience of the participant with suicide events and suicidal ideation and a post-baseline evaluation that focuses on suicidality since the last trial visit.
Time Frame Baseline, End of Titration, Fixed dose Day 14 and 28, Day 15 and 29, Early Termination, Last Visit
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Sample includes all randomized participants who receive at least one dose of study medication.
Arm/Group Title Brexpiprazole-Cohort 1 Brexpiprazole-Cohort 2 Placebo
Hide Arm/Group Description:
In the titration phase, participants received 0.5 mg brexpiprazole QD for 7 days, followed by 1 mg brexpiprazole QD for 7 days. In the fixed dose phase, participants received 2 mg brexpiprazole QD for 14 days, followed by 3 mg brexpiprazole QD for 14 days.
In the titration phase, participants received 0.5 mg brexpiprazole QD for 7 days, followed by 1 mg brexpiprazole QD for 7 days. In the fixed dose phase, participants received 3 mg brexpiprazole QD for 14 days.
In the titration phase, participants received 0.5 mg placebo QD for 7 days, followed by 1 mg placebo QD for 7 days. In the fixed dose phase, Cohort 1: participants received 2 mg placebo QD for 14 days, followed by 3 mg placebo QD for 14 days. Cohort 2: participants received 3 mg placebo QD for 14 days.
Overall Number of Participants Analyzed 6 6 5
Measure Type: Number
Unit of Measure: Participants
Suicidality 0 0 0
Suicidal behaviour 0 0 0
Suicidal ideation 0 0 0
Time Frame AEs were captured for all participants from the signing of the informed consent and were measured throughout the 14-day titration period, 28-day fixed dose period until follow-up (30 [±2] days after last dose of study medication).
Adverse Event Reporting Description Participants who had received at least one dose of study medication were included in safety analysis.
 
Arm/Group Title Brexpiprazole-Cohort 1 Brexpiprazole-Cohort 2 Placebo
Hide Arm/Group Description In the titration phase, participants received 0.5 mg brexpiprazole QD for 7 days, followed by 1 mg brexpiprazole QD for 7 days. In the fixed dose phase, participants received 2 mg brexpiprazole QD for 14 days, followed by 3 mg brexpiprazole QD for 14 days. In the titration phase, participants received 0.5 mg brexpiprazole QD for 7 days, followed by 1 mg brexpiprazole QD for 7 days. In the fixed dose phase, participants received 3 mg brexpiprazole QD for 14 days. In the titration phase, participants received 0.5 mg placebo QD for 7 days, followed by 1 mg placebo QD for 7 days. In the fixed dose phase, Cohort 1: participants received 2 mg placebo QD for 14 days, followed by 3 mg placebo QD for 14 days. Cohort 2: participants received 3 mg placebo QD for 14 days.
All-Cause Mortality
Brexpiprazole-Cohort 1 Brexpiprazole-Cohort 2 Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Brexpiprazole-Cohort 1 Brexpiprazole-Cohort 2 Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/6 (0.00%)   0/6 (0.00%)   0/5 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Brexpiprazole-Cohort 1 Brexpiprazole-Cohort 2 Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   6/6 (100.00%)   6/6 (100.00%)   1/5 (20.00%) 
Cardiac disorders       
Atrioventricular block first degree * 1  1/6 (16.67%)  1/6 (16.67%)  0/5 (0.00%) 
Endocrine disorders       
Hyperprolactinaemia * 1  1/6 (16.67%)  0/6 (0.00%)  0/5 (0.00%) 
Eye disorders       
Eye pruritis * 1  0/6 (0.00%)  0/6 (0.00%)  1/5 (20.00%) 
Dry eye * 1  0/6 (0.00%)  0/6 (0.00%)  1/5 (20.00%) 
Gastrointestinal disorders       
Diarrhoea * 1  0/6 (0.00%)  1/6 (16.67%)  0/5 (0.00%) 
Dyspepsia * 1  0/6 (0.00%)  2/6 (33.33%)  0/5 (0.00%) 
Nausea * 1  0/6 (0.00%)  2/6 (33.33%)  0/5 (0.00%) 
Constipation * 1  0/6 (0.00%)  1/6 (16.67%)  0/5 (0.00%) 
Dental caries * 1  1/6 (16.67%)  0/6 (0.00%)  0/5 (0.00%) 
Gastrooesophageal reflux disease * 1  0/6 (0.00%)  1/6 (16.67%)  0/5 (0.00%) 
Vomiting * 1  0/6 (0.00%)  1/6 (16.67%)  0/5 (0.00%) 
General disorders       
Oedema peripheral * 1  1/6 (16.67%)  0/6 (0.00%)  0/5 (0.00%) 
Infections and infestations       
Upper respiratory tract infection * 1  1/6 (16.67%)  0/6 (0.00%)  0/5 (0.00%) 
Investigations       
Cardiac murmur * 1  0/6 (0.00%)  1/6 (16.67%)  0/5 (0.00%) 
Electrocardiogram QT prolonged * 1  0/6 (0.00%)  1/6 (16.67%)  0/5 (0.00%) 
Weight increased * 1  2/6 (33.33%)  0/6 (0.00%)  0/5 (0.00%) 
Blood pressure * 1  1/6 (16.67%)  0/6 (0.00%)  0/5 (0.00%) 
Musculoskeletal and connective tissue disorders       
Arthritis * 1  0/6 (0.00%)  1/6 (16.67%)  0/5 (0.00%) 
Back pain * 1  0/6 (0.00%)  1/6 (16.67%)  0/5 (0.00%) 
Pain in extremity * 1  0/6 (0.00%)  1/6 (16.67%)  0/5 (0.00%) 
Nervous system disorders       
Dizziness * 1  0/6 (0.00%)  3/6 (50.00%)  0/5 (0.00%) 
Headache * 1  1/6 (16.67%)  0/6 (0.00%)  1/5 (20.00%) 
Tremor * 1  1/6 (16.67%)  0/6 (0.00%)  0/5 (0.00%) 
Psychiatric disorders       
Insomnia * 1  1/6 (16.67%)  1/6 (16.67%)  0/5 (0.00%) 
Renal and urinary disorders       
Pollakiuria * 1  2/6 (33.33%)  0/6 (0.00%)  0/5 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Oropharyngeal pain * 1  1/6 (16.67%)  0/6 (0.00%)  1/5 (20.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 15.0
Cohort 3 was not initiated based on the safety/tolerability results from Cohorts 1 and 2.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Global Medical Affairs
Organization: Otsuka Pharmaceutical Development and Commercialization, Inc.
Phone: 800 562-3974
Responsible Party: Otsuka Pharmaceutical Development & Commercialization, Inc.
ClinicalTrials.gov Identifier: NCT01670279     History of Changes
Other Study ID Numbers: 331-12-291
First Submitted: August 7, 2012
First Posted: August 22, 2012
Results First Submitted: August 4, 2015
Results First Posted: February 4, 2016
Last Update Posted: February 4, 2016