Clinical Trial Results:
A Multicenter, Open-label Trial to Evaluate the Safety and Tolerability of Brexpiprazole in the Treatment of Adult Subjects With Borderline Personality Disorder
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Summary
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EudraCT number |
2019-002897-30 |
Trial protocol |
ES |
Global end of trial date |
22 Sep 2021
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Results information
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Results version number |
v1(current) |
This version publication date |
11 Oct 2022
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First version publication date |
11 Oct 2022
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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 |
331-201-00195
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT04186403 | ||
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, 20850
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Public contact |
Clinical Transparency, 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 |
22 Sep 2021
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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 |
22 Sep 2021
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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 and tolerability of brexpiprazole in the treatment of subjects with a diagnosis of borderline personality disorder (BPD).
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Protection of trial subjects |
All study subjects were required to read and sign an informed consent form (ICF).
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
13 Jan 2020
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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 |
Spain: 6
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Country: Number of subjects enrolled |
Ukraine: 10
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Country: Number of subjects enrolled |
United States: 185
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Worldwide total number of subjects |
201
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EEA total number of subjects |
6
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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) |
201
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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 |
Subjects were enrolled at 55 investigational sites in Spain, Ukraine, and the United States (US) from 13 January 2020 to 22 September 2021. | ||||||||||||||||||||||||||||||
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Pre-assignment
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Screening details |
A total of 203 subjects with borderline personality disorder (BPD), who completed the previous double-blind trial (2019-002813-20) were screened, out of which 201 subjects were enrolled in this study. Of enrolled subjects, 90 received 2 to 3 mg/day brexpiprazole and 111 received brexpiprazole matching placebo in previous double-blind trial. | ||||||||||||||||||||||||||||||
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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 2-3 Milligrams Per Day | ||||||||||||||||||||||||||||||
Arm description |
Subjects who received blinded brexpiprazole 2 to 3 milligrams per day (mg/day) in the previous double-blind trial (2019-002813-20), received open-label brexpiprazole 2 to 3 mg/day tablets, orally for up to 12 weeks. | ||||||||||||||||||||||||||||||
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, 1 or 2 or 3 mg/day administered orally up to Week 12.
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Arm title
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Prior Placebo | ||||||||||||||||||||||||||||||
Arm description |
Subjects who received blinded brexpiprazole matching placebo in the previous double-blind trial (2019-002813-20), received open-label brexpiprazole 2 to 3 mg/day tablets, orally for up to 12 weeks. | ||||||||||||||||||||||||||||||
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, 1 or 2 or 3 mg/day administered orally up to Week 12.
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Baseline characteristics reporting groups
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Reporting group title |
Prior Brexpiprazole 2-3 Milligrams Per Day
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Reporting group description |
Subjects who received blinded brexpiprazole 2 to 3 milligrams per day (mg/day) in the previous double-blind trial (2019-002813-20), received open-label brexpiprazole 2 to 3 mg/day tablets, orally for up to 12 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Prior Placebo
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Reporting group description |
Subjects who received blinded brexpiprazole matching placebo in the previous double-blind trial (2019-002813-20), received open-label brexpiprazole 2 to 3 mg/day tablets, orally for up to 12 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Prior Brexpiprazole 2-3 Milligrams Per Day
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Reporting group description |
Subjects who received blinded brexpiprazole 2 to 3 milligrams per day (mg/day) in the previous double-blind trial (2019-002813-20), received open-label brexpiprazole 2 to 3 mg/day tablets, orally for up to 12 weeks. | ||
Reporting group title |
Prior Placebo
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Reporting group description |
Subjects who received blinded brexpiprazole matching placebo in the previous double-blind trial (2019-002813-20), received open-label brexpiprazole 2 to 3 mg/day tablets, orally for up to 12 weeks. | ||
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End point title |
Number of Subjects With Treatment-Emergent Adverse Events (TEAEs) and as per Severity [1] | |||||||||||||||||||||
End point description |
An adverse event (AE) is defined as any untoward medical occurrence in a clinical trial subject administered an investigational medicinal product (IMP) and which does not necessarily have a causal relationship with this treatment. TEAEs are defined as AEs with an onset date on or after the start of open-label treatment. Safety sample included all subjects who received at least 1 dose of IMP. The severity of AEs was 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), and 3=Severe (Inability to work or perform normal daily activity).
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End point type |
Primary
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End point timeframe |
Signing of ICF up to 30 days post last dose of study drug (up to approximately 16 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: Only descriptive statistical analysis was planned to be reported for this endpoint. |
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| No statistical analyses for this end point | ||||||||||||||||||||||
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End point title |
Number of Subjects With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities | |||||||||||||||||||||
End point description |
Potentially clinically significant ECG abnormalities included rate: Bradycardia (vent <=50 beats per minute [bpm] and decrease >=15 bpm); Rhythm: Sinus bradycardia (<=50 bpm and decrease >=15 bpm), absence during baseline and presence of ventricular premature beat post baseline; ST/T morphology: Absence at baseline and presence of symmetrical T-wave inversion post baseline. Safety sample included all subjects who received at least 1 dose of IMP. ‘Number analysed (n)’ signifies number of subjects with available data for the specified measurement.
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End point type |
Secondary
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End point timeframe |
Screening up to Week 12
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| No statistical analyses for this end point | ||||||||||||||||||||||
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End point title |
Number of Subjects With Potentially Clinically Significant Vital Sign Abnormalities | ||||||||||||||||||
End point description |
Potentially clinically significant vital sign abnormalities included: Heart rate standing in bpm (<50 bpm and decrease >=15 bpm, >120 bpm and increase >=15 bpm); Weight in kilograms (kgs) (decrease >=7%, increase >=7%). Safety sample included all subjects who received at least 1 dose of IMP.
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End point type |
Secondary
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End point timeframe |
Screening up to Week 12
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Number of Subjects With Potentially Clinically Significant Laboratory Abnormalities | |||||||||||||||||||||||||||
End point description |
Potentially clinically significant laboratory abnormalities included serum chemistry: Prolactin >upper limit of normal (ULN) (nanograms per millilitre [ng/ml] in males and females), fasting glucose ≥100 (milligrams per decilitre [mg/dl]), fasting high-density lipoprotein (HDL) cholesterol <40 (men)/ <50 (women) (mg/dl), fasting low-density lipoprotein (LDL) cholesterol ≥160 (mg/dl), fasting cholesterol ≥240 (mg/dl), fasting triglycerides ≥150 (mg/dl); Creatine phosphokinase (CPK)/renal: Creatine kinase >3xULN (units per litre [U/l]), creatinine ≥2.0 (mg/dl), urea nitrogen ≥30 (mg/dl). Safety sample included all subjects who received at least 1 dose of IMP. ‘Number analysed (n)’ signifies number of subjects with available data for the specified measurement.
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End point type |
Secondary
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End point timeframe |
Screening up to Week 12
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| No statistical analyses for this end point | ||||||||||||||||||||||||||||
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End point title |
Change From Baseline in Simpson-Angus Scale (SAS) Total Score | ||||||||||||||||||
End point description |
The SAS scale is used to evaluate extrapyramidal symptoms (EPS) and 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). Each item is rated on a 5-point scale, with a score range of 0 (absence of symptoms) to 4 (severe condition). The SAS total score is the sum of the scores for all 10 items, possible total score is 0 to 40. Negative change from baseline indicates less symptoms. Safety sample included all subjects who received at least 1 dose of IMP. Number of subjects analysed is the number of subjects with data available for analyses. ‘Number analysed (n)’ signifies number of subjects with available data for this outcome measure at the specified timepoint.
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End point type |
Secondary
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End point timeframe |
Baseline and Week 12
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Total Score | ||||||||||||||||||
End point description |
The AIMS scale consists of 10 items describing symptoms of dyskinesia: Facial and oral movements (items 1-4), extremity movements (items 5 and 6), and trunk movements (item 7), dyskinesias (items 8-10). Each item is rated on a 5-point scale, with a score range of 0 (absence of symptoms) (for item 10, no awareness) to 4 (severe condition) (for item 10, awareness, severe distress). AIMS total score is the sum of the ratings for the first seven items with the possible total scores of 0 to 28. Negative change from baseline indicates less symptoms. Safety sample included all subjects who received at least 1 dose of IMP. Number of subjects analysed is the number of subjects with data available for analyses. ‘Number analysed (n)’ signifies number of subjects with available data for this outcome measure at the specified timepoint.
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End point type |
Secondary
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End point timeframe |
Baseline and Week 12
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Change From Baseline in Barnes Akathisia Rating Scale (BARS): Global Clinical Assessment of Akathisia Score | ||||||||||||||||||
End point description |
The BARS consists of 4 items related to akathisia: Objective observation of akathisia by the investigator, subjective feelings of restlessness by the subject, subjective distress due to akathisia, and global clinical assessment of akathisia. The fourth item, global clinical evaluation was rated on a 6-point scale, with a score range of 0 (absence of symptoms) to 5 (severe akathisia). Lower scores indicate less symptoms and negative change from baseline indicate less symptoms. Safety sample included all subjects who received at least 1 dose of IMP. Number of subjects analysed is the number of subjects with data available for analyses. ‘Number analysed (n)’ signifies number of subjects with available data for this outcome measure at the specified timepoint.
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End point type |
Secondary
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End point timeframe |
Baseline and Week 12
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Number of Subjects With Suicidal Ideation and Behavior as Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) | |||||||||||||||
End point description |
C-SSRS was used to assess the suicidality of subjects during the study. The assessment included “yes” or “no” responses for 5 questions, each related to suicidal ideation (wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with any methods, active suicidal ideation with some intent, active suicidal ideation with specific plan) and suicidal behavior (preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, suicide). Numeric ratings were provided for suicidal ideation: Score range of 1 (wish to be dead) to 5 (active suicidal ideation with specific plan and intent), higher total scores indicate more suicidal ideation; Suicidal behavior: Score range of 0 (no suicidal behavior) to 4 (actual suicide attempt), higher total scores indicate more suicidal behavior. Safety sample included all subjects who received at least 1 dose of IMP.
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End point type |
Secondary
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End point timeframe |
Baseline up to Week 12
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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 |
Signing of ICF up to 30 days post last dose of study drug (up to approximately 16 weeks)
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Adverse event reporting additional description |
All-cause mortality: Enrolled sample included all subjects who signed an ICF and were enrolled into the trial (N=90, 111);
Adverse events: Safety sample included all subjects who received at least 1 dose of IMP.
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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 |
24.0
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Reporting groups
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Reporting group title |
Prior Brexpiprazole 2-3 Milligrams Per Day
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Reporting group description |
Subjects who received blinded brexpiprazole 2 to 3 mg/day in the previous double-blind trial (2019-002813-20), received open-label brexpiprazole 2 to 3 mg/day tablets, orally for up to 12 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Prior Placebo
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Reporting group description |
Subjects who received blinded brexpiprazole matching placebo in the previous double-blind trial (2019-002813-20), received open-label brexpiprazole 2 to 3 mg/day tablets, orally for up to 12 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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01 Jul 2020 |
The purpose of this protocol amendment was to introduce a COVID-19 Addendum for any protocol-specified activities that were not able to be performed per protocol or could not be performed due to COVID-19 considerations. |
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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 | |||
