Drug Trials Snapshots: REXULTI
HOW TO USE THIS SNAPSHOT
The information provided in Snapshots highlights who participated in the clinical trials that supported the FDA approval of this drug, and whether there were differences among sex, race, and age groups. The “MORE INFO” bar shows more detailed, technical content for each section. The Snapshot is intended as one tool for consumers to use when discussing the risks and benefits of the drugs.
LIMITATIONS OF THIS SNAPSHOT:
Do not rely on Snapshots to make decisions regarding medical care. Always speak to your health provider about the risks and benefits of a drug. Refer to the REXULTI Prescribing Information for complete information.
REXULTI (brexpiprazole)
(REX-ul-TE)
Otsuka America Pharmaceuticals, Inc.
Approval date: July 10, 2015
DRUG TRIALS SNAPSHOT SUMMARY:
What is the drug for?
REXULTI is a drug for the treatment of major depressive disorder (MDD). In a patient who is already taking a medication for depression that is not adequately treating their symptoms, REXULTI can be added on to improve symptoms.
MDD, commonly referred to as depression, is a brain disorder characterized by mood changes and other symptoms that interfere with a person's ability to work, sleep, study, eat and enjoy once-pleasurable activities.
How is this drug used?
REXULTI is a tablet that is taken once a day.
What are the benefits of this drug?
REXULTI improved symptoms of depression.
What are the benefits of this drug?
The table below summarizes the primary efficacy endpoints for both trials. This was based on the mean change in Montgomery-Asberg Depression Rating Scale (MADRS) score after 6 weeks. The population represents Efficacy population which includes all subjects in the Safety population who had at least one post-randomization efficacy evaluation for MADRS Total Score.
Table 2. Summary of Efficacy Results for Trials 1 and 2
| Trial | Treatment Group | N | Primary Efficacy Measure: MADRS | ||
|---|---|---|---|---|---|
| Mean Baseline Score (SD) | LS Mean Change from Baseline (SE) | Placebo –subtracted Difference a (95% CI) | |||
| 1 | REXULTI (2mg/day)+ADT* Placebo +ADT |
175 178 |
26.9 (5.7) 27.3 (5.6) |
-8.4 (0.6) -5.2 (0.6) |
-3.2 (-4.9, -1.5) - |
| 2 | REXULTI (1mg/day)+ADT REXULTI (3mg/day)+ADT Placebo +ADT |
211 213 203 |
26.5 (5.6) 26.5 (5.3) 26.5 (5.2) |
7.6 (0.5) -8.3 (0.5) -6.3 (0.5) |
1.3 (-2.7, 0.13) - 2.0 (-3.4, -0.5) - |
SD: standard deviation; SE: standard error; LS Mean: least-squares mean; CI: unadjusted confidence interval; ADT: antidepressant
* Dosages statistically significantly superior to placebo.
a Difference (drug minus placebo) in least-squares mean change from baseline.
Source: REXULTI Prescribing Information Section 14, Table 11
Were there any differences in how well the drug worked in clinical trials among sex, race and age?
Subgroup analyses were conducted for sex, race, and age.
- Sex: REXULTI worked similarly in men and women.
- Race: REXULTI worked similarly in all races studied.
- Age: REXULTI worked similarly in all age groups studied.
Were there any differences in how well the drug worked in clinical trials among sex, race, and age groups?
The tables below summarize the responses to REXULTI for the populations in pooled trials. The population represents Efficacy population which includes all subjects in the Safety population who had at least one post-randomization efficacy evaluation for MADRS Total Score.
Table 3. Subgroup Analysis of Primary Endpoint, Pivotal Efficacy Trials (pooled data from 2 trials)
| Subgroup | REXULTI 2 and 3 mg | Placebo | LSMD 95% CI (LL,UL) |
|||||
|---|---|---|---|---|---|---|---|---|
| MADRS Total Score at Baseline Mean (SD) |
Change in MADRS Total Score LS Mean (SE) |
N | MADRS Total Score at Baseline Mean (SD) |
Change in MADRS Total Score LS Mean (SE) | N | |||
| Overall Response/All patients | 26.66 (5.48) |
-8.29 (0.42) |
388 | 26.86 (5.42) |
-5.76 (0.41) |
381 | -2.53 (-3.63,1.43) |
|
| Sex | ||||||||
| Male | 26.68 (5.10) |
-8.41 (0.70) |
122 | 26.89 (5.35) |
-5.78 (0.69) |
123 | -2.63 (-4.56,-0.69) |
|
| Female | 26.65 (5.65) |
-7.87 (0.47) | 266 | 26.85 (5.47) |
-5.55 (0.48) |
258 | -2.32 (-3.64,-1.00) |
|
| Age Group | ||||||||
| >=17 - <40> | 27.10 (5.22) |
-8.6 (0.70) | 128 | 26.69 (5.33) |
-5.05 (0.74) |
108 | -3.54 (-5.55,-1.54) |
|
| >=40 - <65 | 26.45 (5.60) |
-7.77 (0.47) |
259 | 26.88 (5.48) |
-5.79 (0.47) |
270 | -1.98 (-3.29,-0.68) |
|
| >=65 years | 24.00 (0) | NA | 1 | 31.33 (1.53) |
NA | 3 | NA | |
| Race | ||||||||
| White | 26.59 (5.46) |
-8.14 (0.42) |
339 | 26.78 (5.37) |
-5.80 (0.42) |
328 | -2.34 (-3.51,-1.17) |
|
| Black or African American | 26.32 (5.67) |
-6.40 (1.18) |
37 | 27.26 (5.96) |
-4.36 (1.05) |
46 | -2.05 (-5.19,1.10) |
|
| Asian | 30.00 (0) | NA | 1 | 27.50 (3.54) |
NA | 2 | NA | |
| American Indian or Alaska Native | 33.00 (4.76) |
NA | 4 | 28.00 (0) | NA | 1 | NA | |
| Other | 27.67 (4.97) |
NA | 6 | 27.00 (6.56) |
NA | 3 | NA | |
SD: standard deviation; SE: standard error; LS Mean: least-squares mean; LSMD: least-squares mean difference; CI: unadjusted confidence interval, NA not analyzed
Source: Company Clinical Trial Data
What are the possible side effects?
The most common side effects were weight gain and an inner sense of restlessness, which patients commonly describe as feeling the need to move.
REXULTI can raise the risk of death in elderly who have lost touch with reality (psychosis) due to confusion and memory loss (dementia).
REXULTI may increase suicidal thoughts or actions in teenagers, or young adults within the first few months of treatment.
What are the possible side effects?
The table below summarizes adverse reactions for the two pooled trials. The population represents Safety population, which includes any patient who received at least one dose of trial drug.
Table 4. Adverse Events during Treatment in the Pooled Trials
| Placebo (N=411) |
REXULTI | ||||||
|---|---|---|---|---|---|---|---|
| 1 mg/day (N=226) |
2 mg/day (N=188) |
3 mg/day (N=229) |
All REXULTI# (N=643) |
||||
| Gastrointestinal Disorders | |||||||
| Constipation | 1% | 3% | 2% | 1% | 2% | ||
| General Disorders and Administration Site Conditions | |||||||
| Fatigue | 2% | 3% | 2% | 5% | 3% | ||
| Infections and Infestations | |||||||
| Nasopharyngitis | 2% | 7% | 1% | 3% | 4% | ||
| Investigations | |||||||
| Weight Increased | 2% | 7% | 8% | 6% | 7% | ||
| Blood Cortisol Decreased | 1% | 4% | 0% | 3% | 2% | ||
| Metabolism and Nutrition | |||||||
| Increased Appetite | 2% | 3% | 3% | 2% | 3% | ||
| Nervous System Disorders | |||||||
| Akathisia | 2% | 4% | 7% | 14% | 9% | ||
| Headache | 6% | 9% | 4% | 6% | 7% | ||
| Somnolence | 0.5% | 4% | 4% | 6% | 5% | ||
| Tremor | 2% | 4% | 2% | 5% | 4% | ||
| Dizziness | 1% | 1% | 5% | 2% | 3% | ||
| Psychiatric Disorders | |||||||
| Anxiety | 1% | 2% | 4% | 4% | 3% | ||
| Restlessness | 0% | 2% | 3% | 4% | 3% | ||
* Adverse reactions that occurred in ≥ 2% of REXULTI-treated patients and at a greater incidence than in placebo-treated patients
# Dose groups included in ALL treatment groups were 1mg, 2mg, and 4 mg
Source: REXULTI Prescribing Information, Section 6 Table 8
Were there any differences in side effects among sex, race and age?
Subgroup analyses were conducted for sex, race, and age.
- Sex: The risk of overall side effects appeared to be similar in men and women.
- Race: The risk of overall side effects appeared to be similar in all races studied.
- Age: The risk of overall side effects appeared to be similar in all age groups studied.
Were there any differences in side effects of the clinical trials among sex, race, and age groups?
The table below summarizes adverse events in the pooled trials by subgroups. The population represents Safety population, which includes any patient who received at least one dose of trial drug.
Table 5. Subgroup Analysis of Adverse Events during Treatment in the Pooled Trials
| Subgroup | ALL REXULTI | Placebo | Relative Risk | 95% CI | |||
|---|---|---|---|---|---|---|---|
| x (%) | Total, n | x (%) | Total, n | LL | UL | ||
| Any TEAEs* | 380 (59) | 643 | 192 (47) | 411 | 1.27 | 1.12 | 1.43 |
| Sex | |||||||
| Male | 103 (52) | 199 | 54 (42) | 129 | 1.24 | 0.97 | 1.58 |
| Female | 277 (62) | 444 | 138 (49) | 282 | 1.27 | 1.11 | 1.47 |
| Age Group | |||||||
| >=17 - <40 years | 118 (61) | 193 | 57 (50) | 113 | 1.21 | 0.98 | 1.50 |
| >=40-<65 years | 261 (58) | 447 | 133 (45) | 294 | 1.29 | 1.11 | 1.50 |
| >=65 | 1 (33) | 3 | 2 (50) | 4 | 0.67 | 0.10 | 4.35 |
| Race | |||||||
| White | 330 (60) | 547 | 160 (45) | 353 | 1.33 | 1.17 | 1.52 |
| Black or African American |
40 (53) | 75 | 28 (55) | 51 | 0.97 | 0.70 | 1.35 |
| Asian | 2 (29) | 7 | 2 (100) | 2 | 0.29 | 0.09 | 0.92 |
| American Indian or Alaska Native |
3 (60) | 5 | 1 (100) | 1 | 0.60 | 0.29 | 1.23 |
| Other | 4 (50) | 8 | 1 (33) | 3 | 1.50 | 0.26 | 8.58 |
*TEAEs=treatment emergent adverse events
Source: Company Clinical Trial Data
WHO WAS IN THE STUDIES?
Who participated in the clinical trials?
The FDA approved REXULTI based on evidence from two clinical trials of 1054 patients with MDD. The trials were conducted in the United States, Canada, and Europe.
The figure below summarizes how many men and women participated in the clinical trials. The population represents the Safety population (1054 patients), which includes any patient who received at least one dose of trial drug.
Figure 1. Baseline Demographics by Sex
Source: Company Clinical Trial Data
The figure and table below summarize how many patients by race participated in the clinical trials. The population represents the Safety population (1054 patients), which includes any patient who received at least one dose of trial drug.
Figure 2. Baseline Demographics by Race
*=defined as any race not included in other categories
Source: Company Clinical Trial Data
Table 1. Baseline Demographics by Race
| Race | Number of Patients | Percentage of Patients |
|---|---|---|
| White | 900 | 85% |
| African American | 126 | 12% |
| Asian | 9 | 1% |
| American Indian or Alaska Native | 6 | 1% |
| Other* | 11 | 1% |
| Unknown | 2 | less than 1% |
*= defined as any race not included in other categories
Source: Company Clinical Trial Data
The figure below summarizes how many patients by age participated in the clinical trials. The population represents the Safety population (1054 patients), which includes any patient who received at least one dose of trial drug.
Figure 3. Baseline Demographics by Age
Source: Company Clinical Trial Data
Who participated in the trials?
The table below summarizes baseline demographics for the population that participated in the two trials. The population represents Safety population (1054 patients), which includes any patient who received at least one dose of trial drug.
Table 6. Baseline Demographics for the Trials
| Demographic Parameters | Treatment Groups | Placebo (N=411) n (%) |
Total (N=1054) n (%) |
||
|---|---|---|---|---|---|
| REXULTI 1 mg (N=226) n (%) |
REXULTI 2 mg (N=188) n (%) |
REXULTI 3 mg (N=229) n (%) |
|||
| Sex | |||||
| Male | 68 (30) | 58 (31) | 73 (32) | 129 (31) | 328 (31) |
| Female | 158 (70) | 130 (69) | 156 (68) | 282 (69) | 726 (69) |
| Age | |||||
| Mean years (SD) | 45.7 (11.6) | 44.1 (11.6) | 44.6 (11.2) | 45.9 (11.2) | 45.3 (11.4) |
| Median (years) | 48 | 44 | 46 | 47 | 46 |
| Min, Max (years) | 19, 65 | 18,65 | 18, 64 | 18, 65 | 18, 65 |
| Age Group | |||||
| >=17 - <40 years | 57 (25) | 66 (35) | 70 (31) | 113 (27) | 306 (29) |
| >=40-<65 years | 168 (74) | 120 (64) | 159 (69) | 294 (72) | 741 (70) |
| >=65 | 1 (<> | 2 (1) | 0 | 4 (1) | 7 (1) |
| Race | |||||
| White | 183 (81) | 163 (87) | 201 (87) | 353 (86) | 900 (85) |
| Black or African American | 34 (15) | 19 (10) | 22 (10) | 51 (12) | 126 (12) |
| Asian | 6 (3) | 1 (<> | 0 | 2 (1) | 9 (1) |
| American Indian or Alaska Native |
1 (<> | 1 (1) | 3 (1) | 1 (<> | 6 (1) |
| Other | 2 (1) | 3 (2) | 3 (1) | 3 (1) | 11 (1) |
| Unknown | 0 | 1 (<> | 0 | 1 (<> | 2 (<> |
| Ethnicity | |||||
| Hispanic or Latino | 13 (6) | 20 (11) | 14 (6) | 34 (8) | 81 (8) |
| Not Hispanic or Latino | 213 (94) | 162 (86) | 213 (93) | 372 (91) | 960 (91) |
| Unknown | 0 (0) | 6 (3) | 2 (1) | 5 (1) | 13 (1) |
| Region | |||||
| United States | 148 (65) | 125 (67) | 148 (64) | 274 (67) | 695 (66) |
| Canada | 4 (2) | 14 (7) | 6 (3) | 19 (5) | 43 (4) |
| Europe | 74 (33) | 49 (26) | 75 (33) | 118 (28) | 316 (30) |
Source: Company Clinical Trial Data
How were the trials designed?
There were two trials that evaluated the benefit and side effects of REXULTI. In each trial, patients were randomly assigned to receive either REXULTI or placebo once daily for 6 weeks in addition to the antidepressant medication that they were already taking. Neither the patients nor the health care providers knew which treatment was being given until after the trials were completed.
The trials measured overall improvement in the symptoms of depression.
How were the trials designed?
Two randomized, placebo-controlled trials were conducted in adults with MDD (with or without symptoms of anxiety) who had an inadequate response to prior antidepressant therapy. Patients were treated with RELUXI or placebo as an adjunctive treatment to the antidepressant for 6 weeks.
The primary endpoint was the change from baseline in the Montgomery-Asberg Depression Rating Scale (MADRS), a 10-item clinician-related scale used to assess the degree of depressive symptomatology.
GLOSSARY
CLINICAL TRIAL: Voluntary research studies conducted in people and designed to answer specific questions about the safety or effectiveness of drugs, vaccines, other therapies, or new ways of using existing treatments.
COMPARATOR: A previously available treatment or placebo used in clinical trials that is compared to the actual drug being tested.
EFFICACY: How well the drug achieves the desired response when it is taken as described in a controlled clinical setting, such as during a clinical trial.
PLACEBO: An inactive substance or “sugar pill” that looks the same as, and is given the same way as, an active drug or treatment being tested. The effects of the active drug or treatment are compared to the effects of the placebo.
SUBGROUP: A subset of the population studied in a clinical trial. Demographic subsets include sex, race, and age groups.