Brexpiprazole as an Adjunctive Treatment to Paroxetine or Sertraline in Adult Patients Suffering From Post-traumatic Stress Disorder (PTSD)

• Sponsor: H. Lundbeck A/S (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT01987960
• Collaborator: Otsuka Pharmaceutical Co., Ltd. (Industry)
• Enrollment: 417
• Locations: 59
• Arms: 2
• Duration (Months): 22
• Patients Per Site: 7.1
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

To evaluate the efficacy of brexpiprazole as adjunctive treatment to paroxetine (PAR) or sertraline (SER) on PTSD symptoms.

Condition or Disease	Intervention/Treatment	Phase
Post-traumatic Stress Disorder; PTSD	Drug: Placebo; Drug: Brexpiprazole	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 417 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Interventional, Randomised, Double-blind, Parallel-group, Placebo-controlled, Flexible-dose Study of Brexpiprazole as Adjunctive Treatment to Paroxetine or Sertraline in Adult Patients Suffering From Post-traumatic Stress Disorder (PTSD)
• Study Start Date: Dec 1, 2013
• Actual Primary Completion Date: Oct 1, 2015
• Actual Study Completion Date: Oct 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Placebo adjunct to open-label treatment with a commercially available approved treatment for PTSD (PAR/SER)	Drug: Placebo; Once daily, tablets, orally
Experimental: Brexpiprazole Brexpiprazole adjunct to open-label treatment with a commercially available approved treatment for PTSD (PAR/SER). Brexpiprazole dosing was 1mg/day for one week, followed by 2mg/day for 3 weeks. Thereafter the dose was flexible and could be adjusted from 1 to 3 mg/day.	Drug: Brexpiprazole; 1 to 3 mg/day, once daily dose, tablets, orally

Outcome Measures

Primary Outcome Measures

1. PTSD Symptoms Using CAPS-2 Total Score [Period 2: Baseline to Week 12 (of randomized period)]

   Clinician-Administered PTSD Scale Part 2 (CAPS-2): 17 items in criteria B, C and D (Corresponding to CAPS-2) will be administered to provide a total score. They are rated on a 5 point scale for frequency from 0 (never or none) to 4 (daily or almost every day), and intensity from 0 (none) to 4 (extreme). The sum of the 17 items gives a toal score ranging from 0 to 136, with a higher score indicating greater symptom severity.

Secondary Outcome Measures

1. Global Clinical Impression Severity of Illness (CGI-S) Score [Period 2: Baseline to Week 12 (of randomized period)]

   Clinical Global Impression - Severity of Illness (CGI-S) The CGI-S provides the clinician's impression of the patient's current state of mental illness. The clinician uses his or her clinical experience of this patient population to rate the severity of the patient's current mental illness on a 7-point scale ranging from 1 (Normal - not at all ill) to 7 (among the most extremely ill patients).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• The patient has PTSD, diagnosed according to DSM-IV-TR™ and confirmed by the Mini International Neuropsychiatric Interview (MINI).

• The patient has a Clinician-Administered PTSD Scale Part 2 (CAPS-2) total score ≥70 at Screening and Baseline Visits.

• The reported duration of the PTSD is at least 3 months.

Exclusion Criteria:

• The index traumatic event that led to development of PTSD took place more than 15 years before screening.

• The patient has a severe personality disorder that in the investigator's opinion may interfere with the conduct of the study.

• The patient is at significant suicidal risk.

Other inclusion and exclusion criteria may apply.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	US004	Los Angeles	California	United States	90024
2	US025	Los Angeles	California	United States	90102
3	US024	Riverside	California	United States	92504
4	US015	San Diego	California	United States	90103
5	US008	San Diego	California	United States	92123
6	US002	Bradenton	Florida	United States	34201
7	US006	Gainesville	Florida	United States	32607
8	US016	Jacksonville	Florida	United States	32256
9	US020	North Miami	Florida	United States	33161
10	US017	Tampa	Florida	United States	33609
11	US012	Indianapolis	Indiana	United States	46260
12	US021	Roslindale	Massachusetts	United States	02131
13	US019	Las Vegas	Nevada	United States	89102
14	US007	Nashua	New Hampshire	United States	03060
15	US001	Bronx	New York	United States	10467
16	US009	Cincinnati	Ohio	United States	45219
17	US005	Dayton	Ohio	United States	45417
18	US010	Portland	Oregon	United States	97210
19	US014	Norristown	Pennsylvania	United States	19403
20	US011	Memphis	Tennessee	United States	38119
21	US003	Austin	Texas	United States	78731
22	US026	Seattle	Washington	United States	98104
23	EE001	Tallinn		Estonia
24	FI002	Helsinki		Finland
25	FI003	Helsinki		Finland
26	FI001	Kuopio		Finland
27	FI006	Oulu		Finland
28	FI005	Tampere		Finland
29	FI004	Turku		Finland
30	FR002	Fort de France		France
31	FR003	Laxou		France
32	FR004	Nimes Cedex 9		France
33	FR005	Thuir Cedex		France
34	FR001	Tours Cedex 9		France
35	IT005	Andria		Italy
36	IT004	Catania		Italy
37	IT003	Lecce		Italy
38	IT001	Pisa		Italy
39	IT002	Siena		Italy
40	PL003	Bialystok		Poland
41	PL004	Gdansk		Poland
42	PL005	Gdansk		Poland
43	PL001	Leszno		Poland
44	PL002	Lublin		Poland
45	RS006	Belgrade		Serbia
46	RS004	Nis		Serbia
47	RS005	Novi Knezevac		Serbia
48	ZA006	Bloemfontein		South Africa
49	ZA002	Cape Town		South Africa
50	ZA003	Cape Town		South Africa
51	ZA004	Cape Town		South Africa
52	ZA005	Cape Town		South Africa
53	ZA008	Durban		South Africa
54	ZA007	Port Elizabeth		South Africa
55	ZA001	Pretoria		South Africa
56	ZA009	Pretoria		South Africa
57	SE001	Falun		Sweden
58	SE002	Stockholm		Sweden
59	SE003	Uppsala		Sweden

Sponsors and Collaborators

• H. Lundbeck A/S
• Otsuka Pharmaceutical Co., Ltd.

Investigators

• Study Director: Email contact via H. Lundbeck A/S, [e-mail]

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: H. Lundbeck A/S
• ClinicalTrials.gov Identifier: NCT01987960
• Other Study ID Numbers: 14865A; 2012-004982-41
• First Posted: Nov 20, 2013
• Last Update Posted: Mar 13, 2017
• Last Verified: Jan 1, 2017

• Additional relevant MeSH terms: Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic; Brexpiprazole

Study Results

Participant Flow

Recruitment Details	417 patients were enrolled to the study and 413 patients received open-label treatment with a commercially available treatment for PTSD (PAR/SER) in Period 1. Only 40 patients were randomized to Period 2, the randomized period, before the study was terminated; 190 patients entered Period 3. Data are only reported for the randomized period.

Arm/Group Title	Period 1 Placebo and PAR/SER	Period 2 Placebo and PAR/SER (Randomized Period)	Period 2 Brexpiprazole and PAR/SER (Randomized Period)	Period 3 Placebo and PAR/SER
Arm/Group Description	Placebo adjunct to open-label treatment with a commercially available approved treatment for PTSD (PAR/SER). Placebo: Once daily, tablets, orally	Randomized placebo adjunct to open-label treatment with a commercially available approved treatment for PTSD (PAR/SER); randomized period. Placebo: Once daily, tablets, orally	Randomized brexpiprazole adjunct to open-label treatment with a commercially available approved treatment for PTSD (PAR/SER). Brexpiprazole dosing was 1mg/day for one week, followed by 2mg/day for 3 weeks. Thereafter the dose was flexible and could be adjusted from 1 to 3 mg/day; randomized period Brexpiprazole: 1 to 3 mg/day, once daily dose, tablets, orally	Continuation of treatment with placebo adjunct to open-label treatment with a commercially available approved treatment for PTSD (PAR/SER) from Period 1. Placebo: Once daily, tablets, orally
Period Title: Period 1
STARTED	417	0	0	0
COMPLETED	231	0	0	0
NOT COMPLETED	186	0	0	0
Period Title: Period 1
STARTED	0	17	23	0
COMPLETED	0	12	14	0
NOT COMPLETED	0	5	9	0
Period Title: Period 1
STARTED	0	0	0	190
COMPLETED	0	0	0	119
NOT COMPLETED	0	0	0	71

Baseline Characteristics

Arm/Group Title	Period 2 Placebo and PAR/SER (Randomized Period)	Period 2 Brexpiprazole and PAR/SER (Randomized Period)	Total
Arm/Group Description	Randomized placebo adjunct to open-label treatment with a commercially available approved treatment for PTSD (PAR/SER); randomized period. Placebo: Once daily, tablets, orally	Randomized brexpiprazole adjunct to open-label treatment with a commercially available approved treatment for PTSD (PAR/SER). Brexpiprazole dosing was 1mg/day for one week, followed by 2mg/day for 3 weeks. Thereafter the dose was flexible and could be adjusted from 1 to 3 mg/day; randomized period. Brexpiprazole: 1 to 3 mg/day, once daily dose, tablets, orally	Total of all reporting groups
Overall Participants	17	23	40
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	42.9 (11.8)	47.6 (10.4)	45.6 (11.1)
Sex: Female, Male (Count of Participants)
Female	10 58.8%	11 47.8%	21 52.5%
Male	7 41.2%	12 52.2%	19 47.5%

Outcome Measures

1. Primary Outcome

Title	PTSD Symptoms Using CAPS-2 Total Score
Description	Clinician-Administered PTSD Scale Part 2 (CAPS-2): 17 items in criteria B, C and D (Corresponding to CAPS-2) will be administered to provide a total score. They are rated on a 5 point scale for frequency from 0 (never or none) to 4 (daily or almost every day), and intensity from 0 (none) to 4 (extreme). The sum of the 17 items gives a toal score ranging from 0 to 136, with a higher score indicating greater symptom severity.
Time Frame	Period 2: Baseline to Week 12 (of randomized period)

Outcome Measure Data

Analysis Population Description

Due to the low number of enrolled patients eligible for randomization and the sponsor's early termination of the study, the data presented are descriptive i.e. the primary and key secondary efficacy analyses were not done

Arm/Group Title	Period 2 Absolute Mean at Baseline; Placebo and PAR/SER	Period 2 Absolute Mean at Baseline; Brexpiprazole and PAR/SER	Period 2 Absolute Mean at Week 12; Placebo and PAR/SER	Period 2 Absolute Mean at Week 12; Brexpiprazole and PAR/SER
Arm/Group Description	Period 2 absolute mean value at Baseline; Randomized placebo adjunct to open-label treatment with a commercially available approved treatment for PTSD (PAR/SER); randomized period. Placebo: Once daily, tablets, orally	Period 2 absolute mean value at Baseline; Randomized brexpiprazole adjunct to open-label treatment with a commercially available approved treatment for PTSD (PAR/SER). Brexpiprazole dosing was 1mg/day for one week, followed by 2mg/day for 3 weeks. Thereafter the dose was flexible and could be adjusted from 1 to 3 mg/day; randomized period. Brexpiprazole: 1 to 3 mg/day, once daily dose, tablets, orally	Period 2 absolute mean value at Week 12; Randomized placebo adjunct to open-label treatment with a commercially available approved treatment for PTSD (PAR/SER); randomized period. Placebo: Once daily, tablets, orally Absolute values at Week 12 in Period 2 (Study Week 24)	Period 2 absolute mean value at Week 12; Randomized brexpiprazole adjunct to open-label treatment with a commercially available approved treatment for PTSD (PAR/SER). Brexpiprazole dosing was 1mg/day for one week, followed by 2mg/day for 3 weeks. Thereafter the dose was flexible and could be adjusted from 1 to 3 mg/day; randomized period. Brexpiprazole: 1 to 3 mg/day, once daily dose, tablets, orally Absolute values at Week 12 in Period 2 (Study Week 24)
Measure Participants	17	23	15	17
Mean (Standard Deviation) [Score]	82.82 (12.94)	83.43 (13.12)	69.67 (20.26)	69.18 (18.17)

2. Secondary Outcome

Title	Global Clinical Impression Severity of Illness (CGI-S) Score
Description	Clinical Global Impression - Severity of Illness (CGI-S) The CGI-S provides the clinician's impression of the patient's current state of mental illness. The clinician uses his or her clinical experience of this patient population to rate the severity of the patient's current mental illness on a 7-point scale ranging from 1 (Normal - not at all ill) to 7 (among the most extremely ill patients).
Time Frame	Period 2: Baseline to Week 12 (of randomized period)

Outcome Measure Data

Analysis Population Description

Due to the low number of enrolled patients eligible for randomization and the sponsor's early termination of the study, the data presented are descriptive i.e. the primary and key secondary efficacy analyses were not done.

Arm/Group Title	Period 2 Absolute Mean at Baseline; Placebo and PAR/SER	Period 2 Absolute Mean at Baseline; Brexpiprazole and PAR/SER	Period 2 Absolute Mean at Week 12; Placebo and PAR/SER	Period 2 Absolute Mean at Week 12; Brexpiprazole and PAR/SER
Arm/Group Description	Period 2 absolute mean value at Baseline; Randomized placebo adjunct to open-label treatment with a commercially available approved treatment for PTSD (PAR/SER); randomized period. Placebo: Once daily, tablets, orally	Period 2 absolute mean value at Baseline; Randomized brexpiprazole adjunct to open-label treatment with a commercially available approved treatment for PTSD (PAR/SER). Brexpiprazole dosing was 1mg/day for one week, followed by 2mg/day for 3 weeks. Thereafter the dose was flexible and could be adjusted from 1 to 3 mg/day; randomized period. Brexpiprazole: 1 to 3 mg/day, once daily dose, tablets, orally	Period 2 absolute mean value at Week 12; Randomized placebo adjunct to open-label treatment with a commercially available approved treatment for PTSD (PAR/SER) Placebo: Once daily, tablets, orally Absolute values at Week 12 in Period 2 (Study Week 24); randomized period.	Period 2 absolute mean value at Week 12; Randomized brexpiprazole adjunct to open-label treatment with a commercially available approved treatment for PTSD (PAR/SER); randomized period. Brexpiprazole dosing was 1mg/day for one week, followed by 2mg/day for 3 weeks. Thereafter the dose was flexible and could be adjusted from 1 to 3 mg/day. Brexpiprazole: 1 to 3 mg/day, once daily dose, tablets, orally Absolute values at Week 12 in Period 2 (Study Week 24).
Measure Participants	17	23	15	17
Mean (Standard Deviation) [Score]	4.24 (0.83)	4.54 (0.73)	3.73 (1.10)	3.94 (0.83)

Adverse Events

Time Frame	Period 2: Baseline to Week 16 (randomized period)
Arm/Group Title	Brexpiprazole + PAR/SER (Randomized Period)		Placebo + PAR/SER (Randomized Period)
Arm/Group Description
All Cause Mortality
	Brexpiprazole + PAR/SER (Randomized Period)		Placebo + PAR/SER (Randomized Period)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Brexpiprazole + PAR/SER (Randomized Period)		Placebo + PAR/SER (Randomized Period)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/23 (0%)		0/17 (0%)
Other (Not Including Serious) Adverse Events
	Brexpiprazole + PAR/SER (Randomized Period)		Placebo + PAR/SER (Randomized Period)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/23 (13%)		8/17 (47.1%)
Eye disorders
Conjunctivitis	0/23 (0%)		1/17 (5.9%)
Infections and infestations
Gastroenteritis	0/23 (0%)		1/17 (5.9%)
Pharyngitis	0/23 (0%)		1/17 (5.9%)
Upper respiratory tract infection	0/23 (0%)		1/17 (5.9%)
Injury, poisoning and procedural complications
Accidental overdose	2/23 (8.7%)		1/17 (5.9%)
Tendon rupture	0/23 (0%)		1/17 (5.9%)
Metabolism and nutrition disorders
Hypercholesterolaemia	0/23 (0%)		1/17 (5.9%)
Musculoskeletal and connective tissue disorders
Back pain	1/23 (4.3%)		1/17 (5.9%)
Nervous system disorders
Disturbance in attention	0/23 (0%)		1/17 (5.9%)
Reproductive system and breast disorders
Galactorrhoea	0/23 (0%)		1/17 (5.9%)
Skin and subcutaneous tissue disorders
Hyperhidrosis	0/23 (0%)		1/17 (5.9%)

Limitations/Caveats

As the study was terminated limited efficacy and safety data were collected from the randomized patients. The data are descriptive and the primary and key secondary efficacy analyses were not done.

More Information

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.