Schizophrenia
Conditions
Keywords
Alkermes, ALKS 3831, Samidorphan, Schizophrenia, Acute Exacerbation of Schizophrenia
Brief summary
This study will evaluate the efficacy of ALKS 3831 in adult subjects with acute exacerbation of schizophrenia.
Interventions
DRUGOlanzapine
Daily dosing
DRUGPlacebo
Daily dosing
DRUGALK3831
Daily dosing
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
* Has a body mass index (BMI) of 18.0 - 40.0 kg/m\^2 * Meets criteria for the diagnosis of schizophrenia * Resides in a stable living situation when not hospitalized * Is willing and able to provide government-issued identification * Additional criteria may apply
Exclusion criteria
* Has had a psychiatric hospitalization for more than 30 days during the 90 days before screening * Subject initiated first antipsychotic treatment within the past 12 months, or \<1 year has elapsed since the initial onset of active-phase of schizophrenia symptoms * Subject poses a current suicide risk * Subject has a history of treatment resistance * Subject has a history of poor or inadequate response to treatment with olanzapine * Subject requires or has had electroconvulsive therapy (ECT) treatment in the 2-month period prior to screening * Subject has a diagnosis of moderate or severe alcohol or drug use disorder * Subject has a positive urine drug screen for opioids, amphetamine/methamphetamine, phencyclidine, or cocaine at screening * Additional criteria may apply
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 4 | 4 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); maximum scores (worst outcome) equals 210 (total scale). Change is calculated between the baseline visit and Week 4. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Clinical Global Impressions-Severity (CGIS) Score at Week 4 | 4 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 Week 4 based on the observed data. Change is calculated between the baseline visit and Week 4. |
| Incidence of Adverse Events | Approximately 4 weeks | — |
Countries
Bulgaria, Serbia, Ukraine, United States
Participant flow
Pre-assignment details
Disposition is shown for the safety population - subjects who were randomized and received at least 1 dose of study drug. 1 subject in the placebo group and 1 subject in the olanzapine-only group were randomized but not treated, and thus were not included in the safety population.
Participants by arm
| Arm | Count |
|---|---|
| ALKS 3831 Administered as a coated bilayer tablet
ALK3831: Daily dosing | 134 |
| Olanzapine Administered as a coated bilayer tablet
Olanzapine: Daily dosing | 133 |
| Placebo Administered as a coated bilayer tablet
Placebo: Daily dosing | 134 |
| Total | 401 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 2 | 7 |
| Overall Study | Lack of Efficacy | 1 | 2 | 8 |
| Overall Study | Lost to Follow-up | 1 | 0 | 0 |
| Overall Study | Protocol Violation | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 8 | 9 | 8 |
Baseline characteristics
| Characteristic | Olanzapine | Placebo | ALKS 3831 | Total |
|---|---|---|---|---|
| Age, Continuous | 41.5 years STANDARD_DEVIATION 10.89 | 41.1 years STANDARD_DEVIATION 10.59 | 40.8 years STANDARD_DEVIATION 12.55 | 41.1 years STANDARD_DEVIATION 11.35 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants | 4 Participants | 2 Participants | 13 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 126 Participants | 130 Participants | 132 Participants | 388 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 3 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 33 Participants | 38 Participants | 42 Participants | 113 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 | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 3 Participants | 5 Participants |
| Race (NIH/OMB) White | 99 Participants | 91 Participants | 87 Participants | 277 Participants |
| Region of Enrollment Bulgaria | 38 participants | 45 participants | 44 participants | 127 participants |
| Region of Enrollment Serbia | 19 participants | 11 participants | 11 participants | 41 participants |
| Region of Enrollment Ukraine | 26 participants | 29 participants | 24 participants | 79 participants |
| Region of Enrollment United States | 50 participants | 49 participants | 55 participants | 154 participants |
| Sex: Female, Male Female | 52 Participants | 56 Participants | 49 Participants | 157 Participants |
| Sex: Female, Male Male | 81 Participants | 78 Participants | 85 Participants | 244 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 134 | 1 / 133 | 0 / 134 |
| other Total, other adverse events | 50 / 134 | 45 / 133 | 24 / 134 |
| serious Total, serious adverse events | 1 / 134 | 1 / 133 | 0 / 134 |
Outcome results
Primary
Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 4
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); maximum scores (worst outcome) equals 210 (total scale). Change is calculated between the baseline visit and Week 4.
Time frame: 4 weeks
Population: Subjects that received at least 1 dose of study drug and had at least 1 post-baseline PANSS assessment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| ALKS 3831 | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 4 | -23.9 units on a scale | Standard Error 1.28 |
| Olanzapine | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 4 | -22.8 units on a scale | Standard Error 1.29 |
| Placebo | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 4 | -17.5 units on a scale | Standard Error 1.32 |
p-value: <0.00195% CI: [-10, -2.8]Mixed Models Analysis
p-value: 0.00495% CI: [-8.9, -1.7]Mixed Models Analysis
Secondary
Change From Baseline in Clinical Global Impressions-Severity (CGIS) Score at Week 4
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 Week 4 based on the observed data. Change is calculated between the baseline visit and Week 4.
Time frame: 4 weeks
Population: Subjects who received at least 1 dose of study drug and had at least 1 post-baseline PANSS assessment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| ALKS 3831 | Change From Baseline in Clinical Global Impressions-Severity (CGIS) Score at Week 4 | -1.21 units on a scale | Standard Error 0.082 |
| Olanzapine | Change From Baseline in Clinical Global Impressions-Severity (CGIS) Score at Week 4 | -1.27 units on a scale | Standard Error 0.083 |
| Placebo | Change From Baseline in Clinical Global Impressions-Severity (CGIS) Score at Week 4 | -0.84 units on a scale | Standard Error 0.085 |
p-value: 0.00295% CI: [-0.61, -0.14]Mixed Models Analysis
p-value: <0.00195% CI: [-0.67, -0.2]Mixed Models Analysis
Secondary
Incidence of Adverse Events
Time frame: Approximately 4 weeks
Population: Number of subjects who received study drug and had a treatment-emergent adverse event
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ALKS 3831 | Incidence of Adverse Events | 73 Participants |
| Olanzapine | Incidence of Adverse Events | 73 Participants |
| Placebo | Incidence of Adverse Events | 60 Participants |