Schizophrenia
Conditions
Brief summary
This study will evaluate the safety and durability of effect of ALKS 9072 (also known as ALKS 9070) during long-term treatment of subjects with stable schizophrenia.
Interventions
DRUGALKS 9072, Low
IM injection, given monthly
DRUGALKS 9072, High
IM injection, given monthly
Sponsors
Alkermes, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
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
(Subjects who participated in ALK9072-003) * Completed the ALK9072-003 Day 85 visit * Continues to require treatment with an antipsychotic medication (New Subjects) * On a stable dose of oral antipsychotic medication * Diagnosis of chronic schizophrenia based on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria that is clinically stable * Has been able to achieve outpatient status for more than 3 months prior to screening * Body Mass Index (BMI) of 18.5 to 40.0 kg/m2 (inclusive) * Resides in a stable living situation
Exclusion criteria
(Subjects who participated in ALK9072-003) * Abnormal clinical laboratory, vital sign, or electrocardiogram (ECG) finding during participation in study ALK9072-003 that was clinically relevant and related to study drug * Missed more than 1 scheduled study visit during participation in study ALK9072-003 * Has a significant or unstable medical condition that would preclude safe completion of the current study * Subject is pregnant or breastfeeding * Subject expects to be incarcerated in the next 12 months, or has pending legal action which may impact compliance with study participation or procedures (New Subjects) * History of poor or inadequate clinical response to treatment with aripiprazole * History of treatment resistance * Diagnosis of current substance dependence (including alcohol) * Pregnant, lactating, or breastfeeding * Has received any long-acting intramuscular antipsychotic medication within 60 days prior to screening * Currently under involuntary hospitalization * Current or expected incarceration Additional inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Treatment-emergent Adverse Events (TEAEs) | 52 weeks | This measure includes incidences \>5%. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline to Endpoint in Clinical Global Impression Scale for Severity (CGI-S) | 52 weeks | The CGI-S is a 7-point scale that requires the clinician to assess how mentally ill the patient is in a specific point in time. Results indicate participants evaluated at one of the following categories: 1: normal, not at all ill; 2: borderline mentally ill; 3: mildly ill; 4: moderately ill; 5: markedly ill; 6: severely ill; and 7: among the most extremely ill patients. Results indicate a change in CGI-S score from baseline to Day 365 based on the observed data. |
| Discontinuation From Study Due to Adverse Events (AEs) | 52 weeks | Number of subjects who discontinued the study due to AE. |
| Suicidal Ideation and Behavior Using the Columbia Suicide Severity Rating Scale (C-SSRS) | 52 weeks | The C-SSRS is a questionnaire used for suicide assessment. Subjects are asked a series of questions that determine whether or not the patient demonstrates any suicidal ideation or behavior. The C-SSRS was administered to subjects at each study visit. |
| Incidence of Clinically Significant Changes Will be Calculated for Movement Disorders, Vital Signs and Routine Laboratory Tests | 52 weeks | Includes incidence \>2% but \<5%. |
| Mean Change From Baseline to Endpoint Using the Positive and Negative Symptom Scale (PANSS) Total Score and Subscale Scores | 52 weeks | This scale consists of symptom constructs (7 positive, 7 negative, 16 general psychopathology), each to be rated on a 7-point Likert-type scale of severity with 1 being absent to 7 being extreme. Minimum scores (best outcome) equals 30 (total scale), 7 (positive/negative subscales), and 16 (general subscale); maximum scores (worst outcome) equals 210 (total scale), 49 (positive/negative subscales), and 112 (general subscale). |
Countries
Bulgaria, Malaysia, Philippines, Romania, Russia, South Korea, Ukraine, United States
Participant flow
Recruitment details
Subjects who successfully completed the Day 85 visit in Study ALK9072-003 and continued to meet eligibility criteria were eligible to enroll in this extension study. In addition, adults with chronic stable schizophrenia on a stable oral antipsychotic medication not previously enrolled in Study ALK9072-003 were also eligible to enroll.
Pre-assignment details
While there were only 2 treatment groups in this extension study (low dose and high dose), data for several outcome measures is presented by lead-in study groups, and separated into 5 categories: PBO-441 mg, 441-441 mg, PBO-882 mg, 882-882 mg, and de novo.
Participants by arm
| Arm | Count |
|---|---|
| ALKS 9072, Low ALKS 9072, Low: IM injection, given monthly | 110 |
| ALKS 9072, High ALKS 9072, High: IM injection, given monthly | 368 |
| Total | 478 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 27 |
| Overall Study | Incarceration | 0 | 2 |
| Overall Study | Lack of Efficacy | 6 | 7 |
| Overall Study | Lost to Follow-up | 2 | 27 |
| Overall Study | Physician Decision | 1 | 4 |
| Overall Study | Protocol Violation | 1 | 1 |
| Overall Study | Site Closure | 2 | 3 |
| Overall Study | Withdrawal by Subject | 21 | 46 |
Baseline characteristics
| Characteristic | ALKS 9072, Low | ALKS 9072, High | Total |
|---|---|---|---|
| Age, Continuous | 38.1 years STANDARD_DEVIATION 10.88 | 39.8 years STANDARD_DEVIATION 11.76 | 39.4 years STANDARD_DEVIATION 11.57 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 20 Participants | 59 Participants | 79 Participants |
| Race (NIH/OMB) Black or African American | 13 Participants | 79 Participants | 92 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 77 Participants | 228 Participants | 305 Participants |
| Region of Enrollment Bulgaria | 19 participants | 43 participants | 62 participants |
| Region of Enrollment Korea, Republic of | 0 participants | 6 participants | 6 participants |
| Region of Enrollment Malaysia | 3 participants | 21 participants | 24 participants |
| Region of Enrollment Philippines | 17 participants | 32 participants | 49 participants |
| Region of Enrollment Romania | 3 participants | 2 participants | 5 participants |
| Region of Enrollment Russian Federation | 20 participants | 60 participants | 80 participants |
| Region of Enrollment Ukraine | 29 participants | 93 participants | 122 participants |
| Region of Enrollment United States | 19 participants | 111 participants | 130 participants |
| Sex: Female, Male Female | 45 Participants | 158 Participants | 203 Participants |
| Sex: Female, Male Male | 65 Participants | 210 Participants | 275 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 16 / 110 | 59 / 368 |
| serious Total, serious adverse events | 0 / 110 | 15 / 368 |
Outcome results
Primary
Number of Subjects With Treatment-emergent Adverse Events (TEAEs)
This measure includes incidences \>5%.
Time frame: 52 weeks
Population: Safety population includes all subjects who receive at least 1 dose of ALKS 9072 in the current study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ALKS 9072, Low | Number of Subjects With Treatment-emergent Adverse Events (TEAEs) | 51 participants |
| ALKS 9072, High | Number of Subjects With Treatment-emergent Adverse Events (TEAEs) | 190 participants |
Secondary
Discontinuation From Study Due to Adverse Events (AEs)
Number of subjects who discontinued the study due to AE.
Time frame: 52 weeks
Population: Safety population includes all subjects who received at least 1 dose of ALKS 9072 in the current study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ALKS 9072, Low | Discontinuation From Study Due to Adverse Events (AEs) | 2 participants |
| ALKS 9072, High | Discontinuation From Study Due to Adverse Events (AEs) | 27 participants |
Secondary
Incidence of Clinically Significant Changes Will be Calculated for Movement Disorders, Vital Signs and Routine Laboratory Tests
Includes incidence \>2% but \<5%.
Time frame: 52 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ALKS 9072, Low | Incidence of Clinically Significant Changes Will be Calculated for Movement Disorders, Vital Signs and Routine Laboratory Tests | Akathisia | 1 participants |
| ALKS 9072, Low | Incidence of Clinically Significant Changes Will be Calculated for Movement Disorders, Vital Signs and Routine Laboratory Tests | Tremor | 1 participants |
| ALKS 9072, Low | Incidence of Clinically Significant Changes Will be Calculated for Movement Disorders, Vital Signs and Routine Laboratory Tests | Glycosylated haemoglobin increased | 0 participants |
| ALKS 9072, Low | Incidence of Clinically Significant Changes Will be Calculated for Movement Disorders, Vital Signs and Routine Laboratory Tests | Hypertension | 1 participants |
| ALKS 9072, High | Incidence of Clinically Significant Changes Will be Calculated for Movement Disorders, Vital Signs and Routine Laboratory Tests | Akathisia | 0 participants |
| ALKS 9072, High | Incidence of Clinically Significant Changes Will be Calculated for Movement Disorders, Vital Signs and Routine Laboratory Tests | Hypertension | 0 participants |
| ALKS 9072, High | Incidence of Clinically Significant Changes Will be Calculated for Movement Disorders, Vital Signs and Routine Laboratory Tests | Tremor | 0 participants |
| ALKS 9072, High | Incidence of Clinically Significant Changes Will be Calculated for Movement Disorders, Vital Signs and Routine Laboratory Tests | Glycosylated haemoglobin increased | 3 participants |
| PBO-882 mg | Incidence of Clinically Significant Changes Will be Calculated for Movement Disorders, Vital Signs and Routine Laboratory Tests | Hypertension | 1 participants |
| PBO-882 mg | Incidence of Clinically Significant Changes Will be Calculated for Movement Disorders, Vital Signs and Routine Laboratory Tests | Tremor | 0 participants |
| PBO-882 mg | Incidence of Clinically Significant Changes Will be Calculated for Movement Disorders, Vital Signs and Routine Laboratory Tests | Glycosylated haemoglobin increased | 0 participants |
| PBO-882 mg | Incidence of Clinically Significant Changes Will be Calculated for Movement Disorders, Vital Signs and Routine Laboratory Tests | Akathisia | 2 participants |
| 882-882 mg | Incidence of Clinically Significant Changes Will be Calculated for Movement Disorders, Vital Signs and Routine Laboratory Tests | Akathisia | 3 participants |
| 882-882 mg | Incidence of Clinically Significant Changes Will be Calculated for Movement Disorders, Vital Signs and Routine Laboratory Tests | Tremor | 4 participants |
| 882-882 mg | Incidence of Clinically Significant Changes Will be Calculated for Movement Disorders, Vital Signs and Routine Laboratory Tests | Hypertension | 3 participants |
| 882-882 mg | Incidence of Clinically Significant Changes Will be Calculated for Movement Disorders, Vital Signs and Routine Laboratory Tests | Glycosylated haemoglobin increased | 0 participants |
| De Novo | Incidence of Clinically Significant Changes Will be Calculated for Movement Disorders, Vital Signs and Routine Laboratory Tests | Hypertension | 4 participants |
| De Novo | Incidence of Clinically Significant Changes Will be Calculated for Movement Disorders, Vital Signs and Routine Laboratory Tests | Glycosylated haemoglobin increased | 3 participants |
| De Novo | Incidence of Clinically Significant Changes Will be Calculated for Movement Disorders, Vital Signs and Routine Laboratory Tests | Tremor | 7 participants |
| De Novo | Incidence of Clinically Significant Changes Will be Calculated for Movement Disorders, Vital Signs and Routine Laboratory Tests | Akathisia | 12 participants |
Secondary
Mean Change From Baseline to Endpoint in Clinical Global Impression Scale for Severity (CGI-S)
The CGI-S is a 7-point scale that requires the clinician to assess how mentally ill the patient is in a specific point in time. Results indicate participants evaluated at one of the following categories: 1: normal, not at all ill; 2: borderline mentally ill; 3: mildly ill; 4: moderately ill; 5: markedly ill; 6: severely ill; and 7: among the most extremely ill patients. Results indicate a change in CGI-S score from baseline to Day 365 based on the observed data.
Time frame: 52 weeks
Population: The full analysis set consists of all subjects who received at least 1 dose of ALKS 9072 and had at least 1 postbaseline assessment of PANSS score after administration of ALKS 9072.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ALKS 9072, Low | Mean Change From Baseline to Endpoint in Clinical Global Impression Scale for Severity (CGI-S) | -0.9 units on a scale | Standard Deviation 0.68 |
| ALKS 9072, High | Mean Change From Baseline to Endpoint in Clinical Global Impression Scale for Severity (CGI-S) | -0.5 units on a scale | Standard Deviation 0.71 |
| PBO-882 mg | Mean Change From Baseline to Endpoint in Clinical Global Impression Scale for Severity (CGI-S) | -0.8 units on a scale | Standard Deviation 0.85 |
| 882-882 mg | Mean Change From Baseline to Endpoint in Clinical Global Impression Scale for Severity (CGI-S) | -0.3 units on a scale | Standard Deviation 0.61 |
| De Novo | Mean Change From Baseline to Endpoint in Clinical Global Impression Scale for Severity (CGI-S) | -0.2 units on a scale | Standard Deviation 0.61 |
Secondary
Mean Change From Baseline to Endpoint Using the Positive and Negative Symptom Scale (PANSS) Total Score and Subscale Scores
This scale consists of symptom constructs (7 positive, 7 negative, 16 general psychopathology), each to be rated on a 7-point Likert-type scale of severity with 1 being absent to 7 being extreme. Minimum scores (best outcome) equals 30 (total scale), 7 (positive/negative subscales), and 16 (general subscale); maximum scores (worst outcome) equals 210 (total scale), 49 (positive/negative subscales), and 112 (general subscale).
Time frame: 52 weeks
Population: The full analysis set consisted of all subjects who received at least 1 dose of ALKS 9072 and had at least 1 postbaseline assessment of PANSS total score after administration of ALKS 9072.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ALKS 9072, Low | Mean Change From Baseline to Endpoint Using the Positive and Negative Symptom Scale (PANSS) Total Score and Subscale Scores | Total Score | -19.1 units on a scale | Standard Deviation 15.5 |
| ALKS 9072, Low | Mean Change From Baseline to Endpoint Using the Positive and Negative Symptom Scale (PANSS) Total Score and Subscale Scores | Positive Subscale Score | -5.8 units on a scale | Standard Deviation 6 |
| ALKS 9072, Low | Mean Change From Baseline to Endpoint Using the Positive and Negative Symptom Scale (PANSS) Total Score and Subscale Scores | Negative Subscale Score | -4.1 units on a scale | Standard Deviation 4.2 |
| ALKS 9072, Low | Mean Change From Baseline to Endpoint Using the Positive and Negative Symptom Scale (PANSS) Total Score and Subscale Scores | General Psychopathology Subscale Score | -9.2 units on a scale | Standard Deviation 7.6 |
| ALKS 9072, High | Mean Change From Baseline to Endpoint Using the Positive and Negative Symptom Scale (PANSS) Total Score and Subscale Scores | Total Score | -10.0 units on a scale | Standard Deviation 10.2 |
| ALKS 9072, High | Mean Change From Baseline to Endpoint Using the Positive and Negative Symptom Scale (PANSS) Total Score and Subscale Scores | General Psychopathology Subscale Score | -5.1 units on a scale | Standard Deviation 5.6 |
| ALKS 9072, High | Mean Change From Baseline to Endpoint Using the Positive and Negative Symptom Scale (PANSS) Total Score and Subscale Scores | Positive Subscale Score | -3.4 units on a scale | Standard Deviation 3.4 |
| ALKS 9072, High | Mean Change From Baseline to Endpoint Using the Positive and Negative Symptom Scale (PANSS) Total Score and Subscale Scores | Negative Subscale Score | -1.5 units on a scale | Standard Deviation 3.5 |
| PBO-882 mg | Mean Change From Baseline to Endpoint Using the Positive and Negative Symptom Scale (PANSS) Total Score and Subscale Scores | General Psychopathology Subscale Score | -5.9 units on a scale | Standard Deviation 6.1 |
| PBO-882 mg | Mean Change From Baseline to Endpoint Using the Positive and Negative Symptom Scale (PANSS) Total Score and Subscale Scores | Positive Subscale Score | -4.1 units on a scale | Standard Deviation 4.1 |
| PBO-882 mg | Mean Change From Baseline to Endpoint Using the Positive and Negative Symptom Scale (PANSS) Total Score and Subscale Scores | Negative Subscale Score | -1.6 units on a scale | Standard Deviation 3.8 |
| PBO-882 mg | Mean Change From Baseline to Endpoint Using the Positive and Negative Symptom Scale (PANSS) Total Score and Subscale Scores | Total Score | -11.6 units on a scale | Standard Deviation 11.7 |
| 882-882 mg | Mean Change From Baseline to Endpoint Using the Positive and Negative Symptom Scale (PANSS) Total Score and Subscale Scores | Total Score | -8.3 units on a scale | Standard Deviation 8.2 |
| 882-882 mg | Mean Change From Baseline to Endpoint Using the Positive and Negative Symptom Scale (PANSS) Total Score and Subscale Scores | Positive Subscale Score | -2.3 units on a scale | Standard Deviation 3.1 |
| 882-882 mg | Mean Change From Baseline to Endpoint Using the Positive and Negative Symptom Scale (PANSS) Total Score and Subscale Scores | General Psychopathology Subscale Score | -4.0 units on a scale | Standard Deviation 4.7 |
| 882-882 mg | Mean Change From Baseline to Endpoint Using the Positive and Negative Symptom Scale (PANSS) Total Score and Subscale Scores | Negative Subscale Score | -2.1 units on a scale | Standard Deviation 3 |
| De Novo | Mean Change From Baseline to Endpoint Using the Positive and Negative Symptom Scale (PANSS) Total Score and Subscale Scores | General Psychopathology Subscale Score | -2.9 units on a scale | Standard Deviation 4.7 |
| De Novo | Mean Change From Baseline to Endpoint Using the Positive and Negative Symptom Scale (PANSS) Total Score and Subscale Scores | Negative Subscale Score | -1.2 units on a scale | Standard Deviation 3.3 |
| De Novo | Mean Change From Baseline to Endpoint Using the Positive and Negative Symptom Scale (PANSS) Total Score and Subscale Scores | Positive Subscale Score | -1.8 units on a scale | Standard Deviation 2.8 |
| De Novo | Mean Change From Baseline to Endpoint Using the Positive and Negative Symptom Scale (PANSS) Total Score and Subscale Scores | Total Score | -5.9 units on a scale | Standard Deviation 8.3 |
Secondary
Suicidal Ideation and Behavior Using the Columbia Suicide Severity Rating Scale (C-SSRS)
The C-SSRS is a questionnaire used for suicide assessment. Subjects are asked a series of questions that determine whether or not the patient demonstrates any suicidal ideation or behavior. The C-SSRS was administered to subjects at each study visit.
Time frame: 52 weeks
Population: Safety population includes all subjects who received at least 1 dose of ALKS 9072 in the current study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ALKS 9072, Low | Suicidal Ideation and Behavior Using the Columbia Suicide Severity Rating Scale (C-SSRS) | Any suicidal ideation | 0 participants |
| ALKS 9072, Low | Suicidal Ideation and Behavior Using the Columbia Suicide Severity Rating Scale (C-SSRS) | Any suicidal behavior | 0 participants |
| ALKS 9072, High | Suicidal Ideation and Behavior Using the Columbia Suicide Severity Rating Scale (C-SSRS) | Any suicidal ideation | 1 participants |
| ALKS 9072, High | Suicidal Ideation and Behavior Using the Columbia Suicide Severity Rating Scale (C-SSRS) | Any suicidal behavior | 0 participants |
| PBO-882 mg | Suicidal Ideation and Behavior Using the Columbia Suicide Severity Rating Scale (C-SSRS) | Any suicidal ideation | 1 participants |
| PBO-882 mg | Suicidal Ideation and Behavior Using the Columbia Suicide Severity Rating Scale (C-SSRS) | Any suicidal behavior | 0 participants |
| 882-882 mg | Suicidal Ideation and Behavior Using the Columbia Suicide Severity Rating Scale (C-SSRS) | Any suicidal behavior | 0 participants |
| 882-882 mg | Suicidal Ideation and Behavior Using the Columbia Suicide Severity Rating Scale (C-SSRS) | Any suicidal ideation | 1 participants |
| De Novo | Suicidal Ideation and Behavior Using the Columbia Suicide Severity Rating Scale (C-SSRS) | Any suicidal ideation | 4 participants |
| De Novo | Suicidal Ideation and Behavior Using the Columbia Suicide Severity Rating Scale (C-SSRS) | Any suicidal behavior | 0 participants |