A Trial to Evaluate the Safety and Tolerability of Brexpiprazole in the Treatment of Participants With Bipolar I Disorder.
Study Details
Study Description
Brief Summary
This study evaluated the safety and evaluate the safety and tolerability of open-label brexpiprazole (2 - 4 mg/day, with a starting dose of 2 mg/day) for the treatment of adult subjects with bipolar I disorder. All participants received a starting dose of brexpiprazole.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
Phase 3 |
Detailed Description
While the availability of atypical antipsychotics had increased the therapeutic options available, there remains a need for safer and more effective therapies in the treatment of manic and depressive episodes of bipolar I disorder. Brexpiprazole's specific receptor activity profile likely correlates with its established efficacy in schizophrenia and major depressive disorder, and may prove to be an effective target for the treatment of acute mania of bipolar I disorder.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Brexpiprazole Brexpiprazole was administered in participants orally with flexible dosing from 2 mg/day from Days 1 to 3 regardless of treatment assignment in the previous double-blind trial, followed by titration to 3 mg/day on Day 4. Participants may have been titrated (or re-titrated) to a higher dose of brexpiprazole, up to a maximum of 4 mg/day, based on treatment response and at the investigator's discretion anytime at Day 7 or thereafter. Participants who were unable to tolerate their current dose could have been titrated down to a minimum of 2 mg/day any time after Day 4. |
Drug: Brexpiprazole
Brexpiprazole tablets
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Number of Participants With at Least One Treatment Emergent Adverse Event (TEAE) by Severity [From Day 1 (after dosing) through 29 weeks (26 weeks treatment, 3 weeks safety follow-up)]
An adverse event (AE) was defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A TEAE is defined as an adverse event with an onset that occurs after receiving study drug. AEs severity were graded on a 3-point scale as: 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.
Eligibility Criteria
Criteria
Inclusion Criteria (rollover participants from 331-201-00080 & 331-201-00081 trials)
-
Participants remaining in hospital at the Day 21 visit of trial 331-201-00080 or 331-201-00081 were permitted to enroll in the 331-201-00083 trial at the week 3 visit of the double-blind trial if they were planned to be discharged from the hospital before the week 1 visit of trial 331-201-0083. Participants not discharged by the week 1 visit of trial 331-201-0083 were withdrawn.
-
Participants who, in the opinion of the investigator, could potentially benefit from administration of oral brexpiprazole for the treatment of bipolar I disorder and who completed 3 weeks of post-randomization treatment in Trial 331-201-00080 & Trial 331-201-00081.
Exclusion Criteria (rollover participants from 331-201-00080 & 331-201-00081 trials)
- Participants with a major protocol violation during the course of their participation in the double-blind phase 3 trials (331-201-00080 or 331-201-00081).
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Woodland International Research Group | Little Rock | Arkansas | United States | 72211 |
2 | Woodland Research Northwest, LLC | Rogers | Arkansas | United States | 72758 |
3 | Citrials Inc. | Bellflower | California | United States | 90706 |
4 | Radiant Research | Cerritos | California | United States | 90703 |
5 | ProScience Research Group | Culver City | California | United States | 90230 |
6 | Collaborative Neuroscience Network, LLC | Garden Grove | California | United States | 92845 |
7 | Behavioral Research Specialists, LLC | Glendale | California | United States | 91206 |
8 | Apostle Clinical Trials | Long Beach | California | United States | 90813 |
9 | Pacific Research Partners, LLC | Oakland | California | United States | 94607 |
10 | NRC Research Institute | Orange | California | United States | 92868 |
11 | Asclepes Research Centers, PC | Panorama City | California | United States | 91402 |
12 | CI Trials | Riverside | California | United States | 92705 |
13 | CNRI-San Diego | San Diego | California | United States | 92102 |
14 | Artemis Institute for Clinical Research | San Diego | California | United States | 92103 |
15 | Sharp Mesa Vista Hospital | San Diego | California | United States | 92123 |
16 | CI Trials | Santa Ana | California | United States | 92705 |
17 | Collaborative Neuroscience Network, LLC | Torrance | California | United States | 90502 |
18 | Shreenath Clinical Service | Yorba Linda | California | United States | 92886 |
19 | Optimus U Corp | Coral Gables | Florida | United States | 33134 |
20 | Segal Trials | Fort Lauderdale | Florida | United States | 33308 |
21 | Galiz Research | Hialeah | Florida | United States | 33016 |
22 | Research Centers of America, LLC | Hollywood | Florida | United States | 33024 |
23 | Florida Behavioral Medicine | Largo | Florida | United States | 33770 |
24 | University of South Florida Board of Trustees | Tampa | Florida | United States | 33613 |
25 | iResearch Atlanta, LLC | Decatur | Georgia | United States | 30030 |
26 | Alexian Brothers Center for Psychiatric Research | Hoffman Estates | Illinois | United States | 60169 |
27 | NeuroPsychiatric Research | Winfield | Illinois | United States | 60190 |
28 | Louisiana Clinical Research | Shreveport | Louisiana | United States | 71101 |
29 | CBH Health | Gaithersburg | Maryland | United States | 20877 |
30 | St. Charles Psychiatric Associates | Saint Charles | Missouri | United States | 63304 |
31 | Arch Clinical Trials, LLC | Saint Louis | Missouri | United States | 63118 |
32 | St. Louis Clinical Trials | Saint Louis | Missouri | United States | 63141 |
33 | Hassman Research Institute, LLC | Berlin | New Jersey | United States | 08009 |
34 | Clinical Trials of America-NC, LLC | Hickory | North Carolina | United States | 28601 |
35 | Richard H Weisler, MD PA Associates | Raleigh | North Carolina | United States | 27609 |
36 | SP Research PLLC | Oklahoma City | Oklahoma | United States | 73112 |
37 | Cutting Edge Research Group | Oklahoma City | Oklahoma | United States | 73116 |
38 | Community Clinical Research, Inc. | Austin | Texas | United States | 78754 |
39 | InSite Clinical Research | DeSoto | Texas | United States | 75115 |
40 | North Texas Clinical Trials | Fort Worth | Texas | United States | 76104 |
41 | Pillar Clinical Research LLC | Garland | Texas | United States | 75042 |
42 | Pillar Clinical Research, LLC | Richardson | Texas | United States | 75080 |
43 | Core Clinical Research | Everett | Washington | United States | 98201 |
44 | Mid Columbia Research | Richland | Washington | United States | 99352 |
45 | Mental Health Center Prof. Dr. Ivan Temkov - Burgas EOOD, Department for Treatment of Emergency Psychiatric Condition | Burgas | Bulgaria | 8000 | |
46 | State Psychiatry Hospital - Kardzhali,Third Male Department, First Female Department | Kardzhali | Bulgaria | 6600 | |
47 | State Psychiatry Hospital Sv. Ivan Rilski, First Male department, First Female Department | Novi Iskar | Bulgaria | 1282 | |
48 | University Multiprofile Hospital for Active Treatment Sveti Georgi EAD, Clinic of Psychiatry | Plovdiv | Bulgaria | 4002 | |
49 | "Mental Health Centre-Ruse" EOOD, Male department for persons with severe mental disorders, Female department for persons with severe mental disorders | Ruse | Bulgaria | 7003 | |
50 | University Multiprofile Hospital for Active Treatment -Alexandrovska EAD, Clinic of Psychiatry, First Department of Psychiatry | Sofia | Bulgaria | 1431 | |
51 | Multiprofile Hospital for Active Treatment - Targovishte AD, Department of Psychiatry | Targovishte | Bulgaria | 7700 | |
52 | Mental Health Center - Veliko Tarnovo EOOD, Department of Psychiatry for Active Treatment of Persons with Severe Mental Disorders | Veliko Tarnovo | Bulgaria | 5000 | |
53 | Mental Health Center - Vratsa EOOD, Department of Psychiatry | Vratsa | Bulgaria | 3000 | |
54 | CHC Rijeka-Clinic for Psychiatrics | Rijeka | Croatia | 51000 | |
55 | Poliklinika Neuron /Polyclinic Neuron | Zagreb | Croatia | 10000 | |
56 | Indywidualna Specjalistyczna Praktyka Lekarska Wieslaw Jerzy Cubala | GdaĆsk | Poland | 80-438 | |
57 | NZOZ Prywatna Klinika Psychiatryczna Inventiva | Tuszyn | Poland | 95-080 | |
58 | CHC Dr Dragisa Misovic | Belgrade | Serbia | 11000 | |
59 | Clinic for Psychiatric Disorders, Dr Laza Lazarevic | Belgrade | Serbia | 11000 | |
60 | Clinic for Psychiatry | Belgrade | Serbia | 11000 | |
61 | Specialized Hospital for Psychiatry Diseases Kovin | Kovin | Serbia | 26220 | |
62 | Clinical Center Kragujevac, Clinic of Psychiatry | Kragujevac | Serbia | 34000 | |
63 | Klinika za psihijariju, Klinicki Centar Vojvodine | Novi Sad | Serbia | 21000 | |
64 | Regional Clinical Hospital n.a I.I. Mechnicov | Dnipro | Ukraine | 49005 | |
65 | SI of Neurology Psychiatry and Narcology NAMS | Kharkiv | Ukraine | 61068 | |
66 | Kherson Regional Psychiatric Hospital | Kherson | Ukraine | 73488 | |
67 | Kyiv Regional Medical Incorporation Psychiatry | Kyiv | Ukraine | 04080 | |
68 | CI of LOR Lviv Regional Clinical Psychiatric Hospital, Department #25 | Lviv | Ukraine | 79021 | |
69 | Communal Institution of Lviv Regional Council "Lviv Regional Clinical Psychiatric Hospital", department #20 | Lviv | Ukraine | 79021 | |
70 | Odesa Regional Psychiatric Hospital 2 | Odesa | Ukraine | 67513 | |
71 | Maltsev Regional Clinical Psychiatric Hospital | Poltava | Ukraine | 36013 | |
72 | Ternopil Regional Municipal Clinical Psychoneurological Hospital | Ternopil' | Ukraine | 46027 | |
73 | O.I. Yushenko Vinnitsa Regional Clinic | Vinnitsa | Ukraine | 21018 |
Sponsors and Collaborators
- Otsuka Pharmaceutical Development & Commercialization, Inc.
- H. Lundbeck A/S
Investigators
None specified.Study Documents (Full-Text)
More Information
Publications
None provided.- 331-201-00083
- 2017-002225-38
Study Results
Participant Flow
Recruitment Details | |
---|---|
Pre-assignment Detail | The study included participants who completed 3-week double-blind treatment in studies 331-201-00080 (NCT03259555)/331-201-00081 (NCT03257865) and, who in the investigator's judgment, could potentially benefit to receive brexpiprazole in this study. Data was summarized as per the treatment received in the previous studies. |
Arm/Group Title | Prior Brexpiprazole | Prior Placebo |
---|---|---|
Arm/Group Description | Brexpiprazole was administered in participants orally with flexible dosing from 2 mg/day from Days 1 to 3 regardless of treatment assignment in the previous double-blind trial, followed by titration to 3 mg/day on Day 4. Participants may have been titrated (or re-titrated) to a higher dose of brexpiprazole, up to a maximum of 4 mg/day, based on treatment response and at the investigator's discretion anytime at Day 7 or thereafter. Participants who were unable to tolerate their current dose could have been titrated down to a minimum of 2 mg/day any time after Day 4. Participants who received brexpiprazole in the double-blind treatment period in previous studies were included in this group. | Brexpiprazole was administered in participants orally with flexible dosing from 2 mg/day from Days 1 to 3 regardless of treatment assignment in the previous double-blind trial, followed by titration to 3 mg/day on Day 4. Participants may have been titrated (or re-titrated) to a higher dose of brexpiprazole, up to a maximum of 4 mg/day, based on treatment response and at the investigator's discretion anytime at Day 7 or thereafter. Participants who were unable to tolerate their current dose could have been titrated down to a minimum of 2 mg/day any time after Day 4. Participants who received placebo in the double-blind treatment period in previous studies were included in this group. |
Period Title: Overall Study | ||
STARTED | 188 | 193 |
Analyzed For Safety (Safety Sample) | 184 | 184 |
COMPLETED | 105 | 100 |
NOT COMPLETED | 83 | 93 |
Baseline Characteristics
Arm/Group Title | Prior Brexpiprazole | Prior Placebo | Total |
---|---|---|---|
Arm/Group Description | Brexpiprazole was administered in participants orally with flexible dosing from 2 mg/day from Days 1 to 3 regardless of treatment assignment in the previous double-blind trial, followed by titration to 3 mg/day on Day 4. Participants may have been titrated (or re-titrated) to a higher dose of brexpiprazole, up to a maximum of 4 mg/day, based on treatment response and at the investigator's discretion anytime at Day 7 or thereafter. Participants who were unable to tolerate their current dose could have been titrated down to a minimum of 2 mg/day any time after Day 4. Participants who received brexpiprazole in the double-blind treatment period in previous studies were included in this group. | Brexpiprazole was administered in participants orally with flexible dosing from 2 mg/day from Days 1 to 3 regardless of treatment assignment in the previous double-blind trial, followed by titration to 3 mg/day on Day 4. Participants may have been titrated (or re-titrated) to a higher dose of brexpiprazole, up to a maximum of 4 mg/day, based on treatment response and at the investigator's discretion anytime at Day 7 or thereafter. Participants who were unable to tolerate their current dose could have been titrated down to a minimum of 2 mg/day any time after Day 4. Participants who received placebo in the double-blind treatment period in previous studies were included in this group. | Total of all reporting groups |
Overall Participants | 188 | 193 | 381 |
Age (years) [Mean (Standard Deviation) ] | |||
Mean (Standard Deviation) [years] |
45.6
(11.0)
|
46.1
(11.5)
|
45.8
(11.2)
|
Sex: Female, Male (Count of Participants) | |||
Female |
97
51.6%
|
92
47.7%
|
189
49.6%
|
Male |
91
48.4%
|
101
52.3%
|
192
50.4%
|
Race/Ethnicity, Customized (Count of Participants) | |||
White |
129
68.6%
|
146
75.6%
|
275
72.2%
|
Black or African American |
52
27.7%
|
47
24.4%
|
99
26%
|
American Indian or Alaska Native |
3
1.6%
|
0
0%
|
3
0.8%
|
Asian |
2
1.1%
|
0
0%
|
2
0.5%
|
Race-Other |
2
1.1%
|
0
0%
|
2
0.5%
|
Race/Ethnicity, Customized (Count of Participants) | |||
Hispanic or Latino |
21
11.2%
|
24
12.4%
|
45
11.8%
|
Not Hispanic or Latino |
165
87.8%
|
169
87.6%
|
334
87.7%
|
Ethnicity-Other |
2
1.1%
|
0
0%
|
2
0.5%
|
Outcome Measures
Title | Number of Participants With at Least One Treatment Emergent Adverse Event (TEAE) by Severity |
---|---|
Description | An adverse event (AE) was defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A TEAE is defined as an adverse event with an onset that occurs after receiving study drug. AEs severity were graded on a 3-point scale as: 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. |
Time Frame | From Day 1 (after dosing) through 29 weeks (26 weeks treatment, 3 weeks safety follow-up) |
Outcome Measure Data
Analysis Population Description |
---|
Safety Sample included all participants who received at least 1 dose of IMP (brexpiprazole). |
Arm/Group Title | Prior Brexpiprazole | Prior Placebo |
---|---|---|
Arm/Group Description | Brexpiprazole was administered in participants orally with flexible dosing from 2 mg/day from Days 1 to 3 regardless of treatment assignment in the previous double-blind trial, followed by titration to 3 mg/day on Day 4. Participants may have been titrated (or re-titrated) to a higher dose of brexpiprazole, up to a maximum of 4 mg/day, based on treatment response and at the investigator's discretion anytime at Day 7 or thereafter. Participants who were unable to tolerate their current dose could have been titrated down to a minimum of 2 mg/day any time after Day 4. Participants who received brexpiprazole in the double-blind treatment period in previous studies were included in this group. | Brexpiprazole was administered in participants orally with flexible dosing from 2 mg/day from Days 1 to 3 regardless of treatment assignment in the previous double-blind trial, followed by titration to 3 mg/day on Day 4. Participants may have been titrated (or re-titrated) to a higher dose of brexpiprazole, up to a maximum of 4 mg/day, based on treatment response and at the investigator's discretion anytime at Day 7 or thereafter. Participants who were unable to tolerate their current dose could have been titrated down to a minimum of 2 mg/day any time after Day 4. Participants who received placebo in the double-blind treatment period in previous studies were included in this group. |
Measure Participants | 184 | 184 |
TEAE, Any grade |
79
42%
|
86
44.6%
|
TEAE, Mild |
60
31.9%
|
68
35.2%
|
TEAE, Moderate |
31
16.5%
|
29
15%
|
TEAE, Severe |
8
4.3%
|
5
2.6%
|
Adverse Events
Time Frame | From Day 1 (after dosing) through 29 weeks (26 weeks treatment, 3 weeks safety follow-up) | |||
---|---|---|---|---|
Adverse Event Reporting Description | Safety Sample included all participants who received at least 1 dose of IMP. | |||
Arm/Group Title | Prior Brexpiprazole | Prior Placebo | ||
Arm/Group Description | Brexpiprazole was administered in participants orally with flexible dosing from 2 mg/day from Days 1 to 3 regardless of treatment assignment in the previous double-blind trial, followed by titration to 3 mg/day on Day 4. Participants may have been titrated (or re-titrated) to a higher dose of brexpiprazole, up to a maximum of 4 mg/day, based on treatment response and at the investigator's discretion anytime at Day 7 or thereafter. Participants who were unable to tolerate their current dose could have been titrated down to a minimum of 2 mg/day any time after Day 4. Participants who received brexpiprazole in the double-blind treatment period in previous studies were included in this group. | Brexpiprazole was administered in participants orally with flexible dosing from 2 mg/day from Days 1 to 3 regardless of treatment assignment in the previous double-blind trial, followed by titration to 3 mg/day on Day 4. Participants may have been titrated (or re-titrated) to a higher dose of brexpiprazole, up to a maximum of 4 mg/day, based on treatment response and at the investigator's discretion anytime at Day 7 or thereafter. Participants who were unable to tolerate their current dose could have been titrated down to a minimum of 2 mg/day any time after Day 4. Participants who received placebo in the double-blind treatment period in previous studies were included in this group. | ||
All Cause Mortality |
||||
Prior Brexpiprazole | Prior Placebo | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/184 (0%) | 0/184 (0%) | ||
Serious Adverse Events |
||||
Prior Brexpiprazole | Prior Placebo | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 11/184 (6%) | 8/184 (4.3%) | ||
Cardiac disorders | ||||
Acute Myocardial Infarction | 0/184 (0%) | 0 | 1/184 (0.5%) | 1 |
Ear and labyrinth disorders | ||||
Vertigo Positional | 0/184 (0%) | 0 | 1/184 (0.5%) | 1 |
Gastrointestinal disorders | ||||
Upper Gastrointestinal Haemorrhage | 1/184 (0.5%) | 1 | 0/184 (0%) | 0 |
General disorders | ||||
Chest Pain | 0/184 (0%) | 0 | 1/184 (0.5%) | 1 |
Infections and infestations | ||||
Cellulitis | 1/184 (0.5%) | 1 | 0/184 (0%) | 0 |
Nervous system disorders | ||||
Migraine | 0/184 (0%) | 0 | 1/184 (0.5%) | 1 |
Psychiatric disorders | ||||
Bipolar Disorder | 0/184 (0%) | 0 | 1/184 (0.5%) | 1 |
Depression | 3/184 (1.6%) | 3 | 2/184 (1.1%) | 2 |
Mania | 5/184 (2.7%) | 5 | 1/184 (0.5%) | 1 |
Suicidal Behaviour | 1/184 (0.5%) | 1 | 0/184 (0%) | 0 |
Suicidal Ideation | 0/184 (0%) | 0 | 1/184 (0.5%) | 1 |
Other (Not Including Serious) Adverse Events |
||||
Prior Brexpiprazole | Prior Placebo | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 13/184 (7.1%) | 26/184 (14.1%) | ||
Nervous system disorders | ||||
Akathisia | 8/184 (4.3%) | 9 | 17/184 (9.2%) | 17 |
Headache | 5/184 (2.7%) | 5 | 10/184 (5.4%) | 12 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
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.
Results Point of Contact
Name/Title | Global Clinical Development |
---|---|
Organization | Otsuka Pharmaceutical Development & Commercialization, Inc. |
Phone | 1-609-524-6788 |
clinicaltransparency@otsuka-us.com |
- 331-201-00083
- 2017-002225-38