Clinical Trial Results:
Interventional, open-label, flexible-dose, long-term study to evaluate the safety and tolerability of brexpiprazole as adjunctive treatment in elderly patients with major depressive disorder with an inadequate response to antidepressant treatment

Trial information Top of page
Trial identification
Sponsor protocol code	16160A
Additional study identifiers
ISRCTN number	-
US NCT number	NCT02400346
WHO universal trial number (UTN)	-
Sponsors
Sponsor organisation name	H. Lundbeck A/S
Sponsor organisation address	Ottiliavej 9, Valby, Denmark, 2500
Public contact	LundbeckClinicalTrials@lundbeck.com, H. Lundbeck A/S, +45 36301311, LundbeckClinicalTrials@lundbeck.com
Scientific contact	LundbeckClinicalTrials@lundbeck.com, H. Lundbeck A/S, +45 36301311, LundbeckClinicalTrials@lundbeck.com
Paediatric regulatory details
Is trial part of an agreed paediatric investigation plan (PIP)	No
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?	No
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?	No
Results analysis stage
Analysis stage	Final
Date of interim/final analysis	01 Jun 2016
Is this the analysis of the primary completion data?	Yes
Primary completion date	01 Jun 2016
Global end of trial reached?	Yes
Global end of trial date	01 Jun 2016
Was the trial ended prematurely?	No
General information about the trial
Main objective of the trial	To evaluate the long-term safety and tolerability of brexpiprazole (1 to 3 mg/day) as adjunct treatment to antidepressant treatment (ADT) in elderly patients with MDD and inadequate response to ADT.
Protection of trial subjects	The trial was conducted in accordance with the Declaration of Helsinki (2013) and ICH Good Clinical Practice (1996)
Background therapy	-
Evidence for comparator	-
Actual start date of recruitment	16 Mar 2015
Long term follow-up planned	No
Independent data monitoring committee (IDMC) involvement?	No
Population of trial subjects
Number of subjects enrolled per country
Country: Number of subjects enrolled	United States: 52
Country: Number of subjects enrolled	Poland: 17
Country: Number of subjects enrolled	Estonia: 21
Country: Number of subjects enrolled	Finland: 27
Country: Number of subjects enrolled	Germany: 15
Worldwide total number of subjects	132
EEA total number of subjects	80
Number of subjects enrolled per age group
In utero	0
Preterm newborn - gestational age < 37 wk	0
Newborns (0-27 days)	0
Infants and toddlers (28 days-23 months)	0
Children (2-11 years)	0
Adolescents (12-17 years)	0
Adults (18-64 years)	0
From 65 to 84 years	130
85 years and over	2

Trial information Top of page

Subject disposition Top of page
Recruitment
Recruitment details	-
Pre-assignment
Screening details	Subjects who met each of the inclusion and none of the exclusion criteria were eligible to participate in the study
Period 1
Period 1 title	Overall trial (overall period)
Is this the baseline period?	Yes
Allocation method	Not applicable
Blinding used	Not blinded
Arms
Arm title	Adjunct brexpiprazole
Arm description	Weeks 1-4 titration from 0.5 up to 2 mg once daily, in weekly steps. For the rest of the 26 treatment weeks, maintenance with 1-3 mg once daily. Tablets for oral use once daily during 26 weeks. Tablet strengths: 0.5 mg, 1 mg, 2 mg and 3 mg.
Arm type	Experimental
Investigational medicinal product name	Brexpiprazole
Investigational medicinal product code
Other name
Pharmaceutical forms	Tablet
Routes of administration	Oral use
Dosage and administration details	Once daily dosing during 26 weeks. Weeks 1-4 titration from 0.5 up to 2 mg once daily, in weekly steps. For the rest of the 26 treatment weeks, maintenance with 1-3 mg once daily.Tablet strengths: 0.5 mg, 1 mg, 2 mg and 3 mg.
Number of subjects in period 1 Adjunct brexpiprazole Started 132 Completed 88 Not completed 44      Consent withdrawn by subject 7      Non-complianc with IMP 1      Adverse event, non-fatal 24      Lost to follow-up 1      Lack of efficacy 9      Administrative reason 2

Subject disposition Top of page

Baseline characteristics Top of page
Baseline characteristics reporting groups
Reporting group title	Overall trial
Reporting group description	-
Reporting group values Overall trial Total Number of subjects 132 132 Age categorical Units: Subjects     In utero 0 0     Preterm newborn infants (gestational age < 37 wks) 0 0     Newborns (0-27 days) 0 0     Infants and toddlers (28 days-23 months) 0 0     Children (2-11 years) 0 0     Adolescents (12-17 years) 0 0     Adults (18-64 years) 0 0     From 65-84 years 130 130     85 years and over 2 2 Age continuous Units: years     arithmetic mean (standard deviation) 71 ( 5.3 ) - Gender categorical Units: Subjects     Female 107 107     Male 25 25 Race Units: Subjects     White 130 130     Black or African American 2 2

Baseline characteristics Top of page

End points Top of page
End points reporting groups
Reporting group title	Adjunct brexpiprazole
Reporting group description	Weeks 1-4 titration from 0.5 up to 2 mg once daily, in weekly steps. For the rest of the 26 treatment weeks, maintenance with 1-3 mg once daily. Tablets for oral use once daily during 26 weeks. Tablet strengths: 0.5 mg, 1 mg, 2 mg and 3 mg.

End points Top of page

Primary: Number of Patients With Treatment-Emergent Adverse Events [Time Frame: 30 weeks] Top of page
End point title	Number of Patients With Treatment-Emergent Adverse Events [Time Frame: 30 weeks] [1]
End point description
End point type	Primary
End point timeframe	Baseline to 30 weeks
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: No statistical analyses have been done. Only descriptive data.
End point values Adjunct brexpiprazole Number of subjects analysed 132 Units: Count of participants 102
No statistical analyses for this end point

Primary: Number of Patients With Treatment-Emergent Adverse Events [Time Frame: 30 weeks] Top of page

Adverse events Top of page
Adverse events information
Timeframe for reporting adverse events	Baseline to 30 weeks
Assessment type	Systematic
Dictionary used for adverse event reporting
Dictionary name	MedDRA
Dictionary version	19.0
Reporting groups
Reporting group title	Adjunct brexpiprazole
Reporting group description	Weeks 1-4 titration from 0.5 up to 2 mg once daily, in weekly steps. For the rest of the 26 treatment weeks, maintenance with 1-3 mg once daily. Tablets for oral use once daily during 26 weeks. Tablet strengths: 0.5 mg, 1 mg, 2 mg and 3 mg.
Serious adverse events Adjunct brexpiprazole Total subjects affected by serious adverse events      subjects affected / exposed 6 / 132 (4.55%)      number of deaths (all causes) 1      number of deaths resulting from adverse events 0 Injury, poisoning and procedural complications Eye contusion      subjects affected / exposed 1 / 132 (0.76%)      occurrences causally related to treatment / all 1 / 1      deaths causally related to treatment / all 0 / 0 Facial bones fracture      subjects affected / exposed 1 / 132 (0.76%)      occurrences causally related to treatment / all 1 / 1      deaths causally related to treatment / all 0 / 0 Fall      subjects affected / exposed 1 / 132 (0.76%)      occurrences causally related to treatment / all 1 / 1      deaths causally related to treatment / all 0 / 0 Vascular disorders Hypotension      subjects affected / exposed 1 / 132 (0.76%)      occurrences causally related to treatment / all 1 / 1      deaths causally related to treatment / all 0 / 0 Cardiac disorders Acute myocardial infarction      subjects affected / exposed 1 / 132 (0.76%)      occurrences causally related to treatment / all 0 / 1      deaths causally related to treatment / all 0 / 1 Myocardial rupture      subjects affected / exposed 1 / 132 (0.76%)      occurrences causally related to treatment / all 0 / 1      deaths causally related to treatment / all 0 / 1 Nervous system disorders Transient ischaemic attack      subjects affected / exposed 1 / 132 (0.76%)      occurrences causally related to treatment / all 0 / 1      deaths causally related to treatment / all 0 / 0 Psychiatric disorders Depression      subjects affected / exposed 1 / 132 (0.76%)      occurrences causally related to treatment / all 1 / 1      deaths causally related to treatment / all 0 / 0 Major depression      subjects affected / exposed 1 / 132 (0.76%)      occurrences causally related to treatment / all 0 / 1      deaths causally related to treatment / all 0 / 0 Panic attack      subjects affected / exposed 1 / 132 (0.76%)      occurrences causally related to treatment / all 0 / 1      deaths causally related to treatment / all 0 / 0 Infections and infestations Postoperative wound infection      subjects affected / exposed 1 / 132 (0.76%)      occurrences causally related to treatment / all 0 / 1      deaths causally related to treatment / all 0 / 0
Frequency threshold for reporting non-serious adverse events: 5%
Non-serious adverse events Adjunct brexpiprazole Total subjects affected by non serious adverse events      subjects affected / exposed 79 / 132 (59.85%) Investigations Weight increased      subjects affected / exposed 11 / 132 (8.33%)      occurrences all number 12 Nervous system disorders Akathisia      subjects affected / exposed 11 / 132 (8.33%)      occurrences all number 13 Dizziness      subjects affected / exposed 10 / 132 (7.58%)      occurrences all number 10 Headache      subjects affected / exposed 7 / 132 (5.30%)      occurrences all number 7 Tremor      subjects affected / exposed 9 / 132 (6.82%)      occurrences all number 11 General disorders and administration site conditions Fatigue      subjects affected / exposed 20 / 132 (15.15%)      occurrences all number 20 Psychiatric disorders Insomnia      subjects affected / exposed 8 / 132 (6.06%)      occurrences all number 8 Anxiety      subjects affected / exposed 10 / 132 (7.58%)      occurrences all number 10 Restlessness      subjects affected / exposed 17 / 132 (12.88%)      occurrences all number 18 Musculoskeletal and connective tissue disorders Back pain      subjects affected / exposed 7 / 132 (5.30%)      occurrences all number 7 Infections and infestations Nasopharyngitis      subjects affected / exposed 8 / 132 (6.06%)      occurrences all number 8 Metabolism and nutrition disorders Increased appetite      subjects affected / exposed 13 / 132 (9.85%)      occurrences all number 13

Adverse events Top of page

More information Top of page
Substantial protocol amendments (globally)
Were there any global substantial amendments to the protocol? Yes
Date	Amendment
16 Mar 2015	The main reason for this amendment was to follow a request from Competent Authorities to include the MMSE scale at the Completion/Withdrawal Visit in addition to the Baseline Visit to assess the cognitive aspects as part of long-term safety assessment
Interruptions (globally)
Were there any global interruptions to the trial? No
Limitations and caveats
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
None reported

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