Schizophrenia
Conditions
Keywords
Alkermes, schizophrenia, ALKS 9072, ALKS 9070, aripiprazole lauroxil
Brief summary
The study will determine the efficacy of ALKS 9072 (also known as aripiprazole lauroxil or ALKS 9070) for the treatment of schizophrenia in subjects experiencing an acute exacerbation.
Interventions
DRUGALKS 9072
Intramuscular (IM) injection, 441 mg or 882 mg given monthly
DRUGPlacebo
Placebo for IM injection, given monthly
Sponsors
Alkermes, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of schizophrenia according to DSM-IV-TR criteria * Has been able to achieve outpatient status for more than 3 months in the past year * Body mass index (BMI) of 18.5 to 40.0 kg/m2 (inclusive) * Resides in a stable living situation * Willing and able to be confined to an inpatient study unit for 2 weeks or longer
Exclusion criteria
* History of poor or inadequate clinical response to treatment with aripiprazole * History of treatment resistance * Known or suspected intolerance of, allergy, or hypersensitivity to aripiprazole, its ingredients, other antipsychotic agent, or INTRALIPID (including peanuts, soy, egg, or glycerol) * Diagnosis of current substance dependence (including alcohol) * Pregnant, lactating, or breastfeeding * Receipt of any antipsychotic medication by IM injection within 60 days before Screening * Current involuntary hospitalization or incarceration * Hospitalized for more than 30 days during the 90 days before Screening Additional inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Change From Baseline at Day 85 in Positive and Negative Syndrome Scale (PANSS) Total Score | Data collected from baseline to day 85 | The PANSS scale contains 30 questions, each containing an answer range of 1-7. A total PANSS score can range from between 30 to 210; a higher score indicates a worse disease condition. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Global Impression - Improvement (CGI-I) Scores at Day 85 | 85 Days | The CGI-I is a 7-point scale that requires the clinician to assess how much the participant's illness has improved or worsened relative to a baseline state at the beginning of the study. Results indicate participants evaluated at one of the following categories: 1: very much improved; 2: much improved; 3: minimally improved; 4: no change; 5: minimally worse; 6: much worse; or 7: very much worse. |
Countries
Bulgaria, Malaysia, Philippines, Romania, Russia, South Korea, Ukraine, United States
Participant flow
Recruitment details
Included subjects with schizophrenia experiencing an acute exacerbation episode.
Pre-assignment details
Subjects were admitted to an inpatient study unit. Currently prescribed antipsychotics were discontinued prior to administration of study drug. One randomized subject was discontinued for a protocol violation prior to receiving investigational treatment.
Participants by arm
| Arm | Count |
|---|---|
| Aripiprazole Lauroxil 441 mg Intramuscular injection, given monthly | 207 |
| Aripiprazole Lauroxil 882 mg Intramuscular injection, given monthly | 208 |
| Placebo Intramuscular injection, given monthly | 208 |
| Total | 623 |
Baseline characteristics
| Characteristic | Aripiprazole Lauroxil 441 mg | Aripiprazole Lauroxil 882 mg | Total | Placebo |
|---|---|---|---|---|
| Age, Categorical <=18 years | 2 Participants | 0 Participants | 3 Participants | 1 Participants |
| Age, Categorical >=65 years | 0 Participants | 1 Participants | 2 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 205 Participants | 207 Participants | 618 Participants | 206 Participants |
| Age, Continuous | 39.9 Years STANDARD_DEVIATION 10.13 | 39.7 Years STANDARD_DEVIATION 11.06 | 39.7 Years STANDARD_DEVIATION 11.02 | 39.5 Years STANDARD_DEVIATION 11.85 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 24 Participants | 28 Participants | 81 Participants | 29 Participants |
| Race (NIH/OMB) Black or African American | 83 Participants | 81 Participants | 248 Participants | 84 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 99 Participants | 98 Participants | 291 Participants | 94 Participants |
| Region of Enrollment Bulgaria | 23 participants | 19 participants | 59 participants | 17 participants |
| Region of Enrollment Malaysia | 7 participants | 7 participants | 24 participants | 10 participants |
| Region of Enrollment Philippines | 16 participants | 21 participants | 53 participants | 16 participants |
| Region of Enrollment Romania | 5 participants | 6 participants | 17 participants | 6 participants |
| Region of Enrollment Russian Federation | 24 participants | 24 participants | 73 participants | 25 participants |
| Region of Enrollment Ukraine | 29 participants | 29 participants | 90 participants | 32 participants |
| Region of Enrollment United States | 103 participants | 102 participants | 307 participants | 102 participants |
| Sex: Female, Male Female | 66 Participants | 65 Participants | 200 Participants | 69 Participants |
| Sex: Female, Male Male | 141 Participants | 143 Participants | 423 Participants | 139 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 66 / 207 | 68 / 208 | 76 / 207 |
| serious Total, serious adverse events | 3 / 207 | 4 / 208 | 4 / 207 |
Outcome results
Primary
The Change From Baseline at Day 85 in Positive and Negative Syndrome Scale (PANSS) Total Score
The PANSS scale contains 30 questions, each containing an answer range of 1-7. A total PANSS score can range from between 30 to 210; a higher score indicates a worse disease condition.
Time frame: Data collected from baseline to day 85
Population: Full Analysis Set (FAS) defined as all randomized subjects who received at least 1 dose of IM study drug and had at least 1 primary efficacy assessment after administration of IM study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Aripiprazole Lauroxil 441 mg | The Change From Baseline at Day 85 in Positive and Negative Syndrome Scale (PANSS) Total Score | -20.9 units on a scale | Standard Error 1.39 |
| Aripiprazole Lauroxil 882 mg | The Change From Baseline at Day 85 in Positive and Negative Syndrome Scale (PANSS) Total Score | -21.8 units on a scale | Standard Error 1.35 |
| Placebo | The Change From Baseline at Day 85 in Positive and Negative Syndrome Scale (PANSS) Total Score | -9.8 units on a scale | Standard Error 1.39 |
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
Secondary
Clinical Global Impression - Improvement (CGI-I) Scores at Day 85
The CGI-I is a 7-point scale that requires the clinician to assess how much the participant's illness has improved or worsened relative to a baseline state at the beginning of the study. Results indicate participants evaluated at one of the following categories: 1: very much improved; 2: much improved; 3: minimally improved; 4: no change; 5: minimally worse; 6: much worse; or 7: very much worse.
Time frame: 85 Days
Population: FAS, defined as all randomized subjects who received at least 1 IM dose of study drug and had at least 1 primary efficacy assessment after administration of IM study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Aripiprazole Lauroxil 441 mg | Clinical Global Impression - Improvement (CGI-I) Scores at Day 85 | CGI Score: Much improved | 68 participants in category |
| Aripiprazole Lauroxil 441 mg | Clinical Global Impression - Improvement (CGI-I) Scores at Day 85 | CGI Score: Minimally worse | 11 participants in category |
| Aripiprazole Lauroxil 441 mg | Clinical Global Impression - Improvement (CGI-I) Scores at Day 85 | CGI Score: No change | 32 participants in category |
| Aripiprazole Lauroxil 441 mg | Clinical Global Impression - Improvement (CGI-I) Scores at Day 85 | CGI Score: Very much improved | 27 participants in category |
| Aripiprazole Lauroxil 441 mg | Clinical Global Impression - Improvement (CGI-I) Scores at Day 85 | CGI Score: Very much worse | 1 participants in category |
| Aripiprazole Lauroxil 441 mg | Clinical Global Impression - Improvement (CGI-I) Scores at Day 85 | CGI Score: Much worse | 12 participants in category |
| Aripiprazole Lauroxil 441 mg | Clinical Global Impression - Improvement (CGI-I) Scores at Day 85 | GCI Score: Minimally improved | 45 participants in category |
| Aripiprazole Lauroxil 882 mg | Clinical Global Impression - Improvement (CGI-I) Scores at Day 85 | CGI Score: No change | 24 participants in category |
| Aripiprazole Lauroxil 882 mg | Clinical Global Impression - Improvement (CGI-I) Scores at Day 85 | CGI Score: Very much improved | 25 participants in category |
| Aripiprazole Lauroxil 882 mg | Clinical Global Impression - Improvement (CGI-I) Scores at Day 85 | CGI Score: Much improved | 81 participants in category |
| Aripiprazole Lauroxil 882 mg | Clinical Global Impression - Improvement (CGI-I) Scores at Day 85 | GCI Score: Minimally improved | 52 participants in category |
| Aripiprazole Lauroxil 882 mg | Clinical Global Impression - Improvement (CGI-I) Scores at Day 85 | CGI Score: Minimally worse | 16 participants in category |
| Aripiprazole Lauroxil 882 mg | Clinical Global Impression - Improvement (CGI-I) Scores at Day 85 | CGI Score: Much worse | 5 participants in category |
| Aripiprazole Lauroxil 882 mg | Clinical Global Impression - Improvement (CGI-I) Scores at Day 85 | CGI Score: Very much worse | 1 participants in category |
| Placebo | Clinical Global Impression - Improvement (CGI-I) Scores at Day 85 | CGI Score: Minimally worse | 37 participants in category |
| Placebo | Clinical Global Impression - Improvement (CGI-I) Scores at Day 85 | CGI Score: Much improved | 33 participants in category |
| Placebo | Clinical Global Impression - Improvement (CGI-I) Scores at Day 85 | CGI Score: Very much worse | 3 participants in category |
| Placebo | Clinical Global Impression - Improvement (CGI-I) Scores at Day 85 | CGI Score: Much worse | 23 participants in category |
| Placebo | Clinical Global Impression - Improvement (CGI-I) Scores at Day 85 | CGI Score: No change | 42 participants in category |
| Placebo | Clinical Global Impression - Improvement (CGI-I) Scores at Day 85 | GCI Score: Minimally improved | 43 participants in category |
| Placebo | Clinical Global Impression - Improvement (CGI-I) Scores at Day 85 | CGI Score: Very much improved | 15 participants in category |
p-value: <0.001Wilcoxon rank sum test based on LOCF
p-value: <0.001Wilcoxon rank sum test based on LOCF