Schizophrenia
Conditions
Keywords
Alkermes, schizophrenia, aripiprazole lauroxil, ARISTADA, ARISTADA INITIO
Brief summary
This study will evaluate the efficacy of initiating treatment of schizophrenia with ARISTADA INITIO plus 30 mg oral aripiprazole followed by a 2-month dose of AL.
Interventions
COMBINATION_PRODUCTAripiprazole Lauroxil
Intramuscular injection; study drug provided using a pre-filled syringe
DRUGPaliperidone Palmitate
Intramuscular injection
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 65 Years
Healthy volunteers
No
Inclusion criteria
* Has a diagnosis of schizophrenia * Requires acute treatment for symptoms of schizophrenia * Willing and able to be confined to an inpatient study unit for up to 3-4 weeks * Has experienced at least one previous hospitalization for schizophrenia * Has been able to achieve outpatient status for more than 3 months in the past year * Has a body mass index (BMI) between 18.0 and 40.0 kg/m\^2 * Resides in a stable living situation when not hospitalized * Has an identified reliable caregiver (for example, family member) * Additional criteria may apply
Exclusion criteria
* Poses a current suicide risk * Pregnant, planning to become pregnant, or breastfeeding * Initiated first antipsychotic treatment within the past 12 months * Has received a long-acting injectable antipsychotic in the past 3 months * Has participated in a clinical study involving any investigational product within the past 3 months, or is currently participating in a clinical study involving an investigational product. * A positive urine drug test for drugs of abuse * Additional criteria may apply
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score at Week 4 | Baseline and 4 weeks | Change within treatment groups of Positive and Negative Syndrome Scale (PANSS) total score between baseline and week 4 based on the observed data without imputation for missing data. 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 |
|---|---|---|
| Change in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 9 | Baseline and 9 weeks | Change within treatment groups from baseline Positive and Negative Syndrome Scale (PANSS) and 9 weeks based on the observed data without imputation for missing data. 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. |
| Change in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 25 | Baseline and 25 weeks | Change within treatment groups at baseline Positive and Negative Syndrome Scale (PANSS) and at 25 weeks based on the observed data without imputation for missing data. 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 |
| Least Squares Mean Change in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 4 | Baseline and 4 weeks | Least squares mean change in Positive and Negative Syndrome Scale (PANSS) between at 4 weeks from Mixed Models Repeated Measures (MMRM). 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 |
| Least Squares Mean Change in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 25 | Baseline and 25 weeks | Least squares mean change in Positive and Negative Syndrome Scale (PANSS) total score at week 25 from Mixed Models Repeated Measures. 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 |
| Number of Participants With Serious and Non-serious Adverse Events (AEs) | Up to 25 weeks | — |
| Least Squares Mean Change in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 9 | Baseline and 9 weeks | Least squares mean change from baseline Positive and Negative Syndrome Scale (PANSS) and 9 weeks from Mixed Models Repeated Measures (MMRM).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 |
Countries
United States
Participant flow
Pre-assignment details
Of the 200 patients enrolled and randomized to treatment, there were 195 patients included in the full analysis set. These were patients who randomized, received 1 dose study drug and had at least one post-baseline Positive and Negative Syndrome Scale (PANSS) assessment.
Participants by arm
| Arm | Count |
|---|---|
| Aripiprazole Lauroxil Aripiprazole lauroxil (AL)1-day initiation regimen (30mg oral aripiprazole + intramuscular injection aripiprazole lauroxil nano-cyrstalline milled dispersion \[AL-NCD\]) on day 1, followed by 1064mg intramuscular injection aripiprazole lauroxil on day 8 and every 2 months thereafter | 99 |
| Paliperidone Palmitate Paliperidone palmitate (PP) initiation dosing (234mg intramuscular injection on day 1 + 156mg intramuscular injection on day 8), followed by 156mg intramuscular injection paliperidone palmitate every month thereafter | 101 |
| Total | 200 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 10 | 11 |
| Overall Study | Lack of Efficacy | 4 | 2 |
| Overall Study | Lost to Follow-up | 8 | 9 |
| Overall Study | Physician Decision | 0 | 2 |
| Overall Study | Protocol Violation | 1 | 3 |
| Overall Study | Withdrawal by Subject | 20 | 31 |
Baseline characteristics
| Characteristic | Aripiprazole Lauroxil | Paliperidone Palmitate | Total |
|---|---|---|---|
| Age, Continuous | 43.5 years STANDARD_DEVIATION 9.67 | 43.4 years STANDARD_DEVIATION 10.83 | 43.4 years STANDARD_DEVIATION 10.25 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 8 Participants | 11 Participants | 19 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 91 Participants | 90 Participants | 181 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Positive and Negative Syndrome Scale (PANSS) Total Score | 94.1 units on a scale STANDARD_DEVIATION 9.04 | 94.6 units on a scale STANDARD_DEVIATION 8.41 | 94.4 units on a scale STANDARD_DEVIATION 8.71 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 4 Participants | 6 Participants |
| Race (NIH/OMB) Black or African American | 72 Participants | 78 Participants | 150 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 25 Participants | 17 Participants | 42 Participants |
| Sex: Female, Male Female | 26 Participants | 25 Participants | 51 Participants |
| Sex: Female, Male Male | 73 Participants | 76 Participants | 149 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 99 | 0 / 101 |
| other Total, other adverse events | 39 / 99 | 50 / 101 |
| serious Total, serious adverse events | 8 / 99 | 7 / 101 |
Outcome results
Primary
Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score at Week 4
Change within treatment groups of Positive and Negative Syndrome Scale (PANSS) total score between baseline and week 4 based on the observed data without imputation for missing data. 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: Baseline and 4 weeks
Population: The analysis is based on the subjects who had both baseline and observed week 4 Positive and Negative Syndrome Scale (PANSS) data (160 participants).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aripiprazole Lauroxil | Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score at Week 4 | -17.4 units on a scale | Standard Deviation 11.57 |
| Paliperidone Palmitate | Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score at Week 4 | -20.1 units on a scale | Standard Deviation 13.72 |
p-value: <0.001t-test, 2 sided
p-value: <0.001t-test, 2 sided
Secondary
Change in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 25
Change within treatment groups at baseline Positive and Negative Syndrome Scale (PANSS) and at 25 weeks based on the observed data without imputation for missing data. 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: Baseline and 25 weeks
Population: The analysis is based on the subjects who had both baseline and observed week 25 Positive and Negative Syndrome Scale (PANSS) data (99 participants).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aripiprazole Lauroxil | Change in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 25 | -23.3 units on a scale | Standard Deviation 11.25 |
| Paliperidone Palmitate | Change in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 25 | -21.7 units on a scale | Standard Deviation 14.37 |
Secondary
Change in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 9
Change within treatment groups from baseline Positive and Negative Syndrome Scale (PANSS) and 9 weeks based on the observed data without imputation for missing data. 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: Baseline and 9 weeks
Population: The analysis is based on the subjects who had both baseline and observed week 9 Positive and Negative Syndrome Scale (PANSS) data (131 participants).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aripiprazole Lauroxil | Change in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 9 | -19.8 units on a scale | Standard Deviation 11.61 |
| Paliperidone Palmitate | Change in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 9 | -22.5 units on a scale | Standard Deviation 13.98 |
Secondary
Least Squares Mean Change in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 25
Least squares mean change in Positive and Negative Syndrome Scale (PANSS) total score at week 25 from Mixed Models Repeated Measures. 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: Baseline and 25 weeks
Population: The analysis is based on the subjects who had both baseline and observed week 25 Positive and Negative Syndrome Scale (PANSS) data (99 participants).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Aripiprazole Lauroxil | Least Squares Mean Change in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 25 | -22.0 units on a scale | Standard Error 1.42 |
| Paliperidone Palmitate | Least Squares Mean Change in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 25 | -21.1 units on a scale | Standard Error 1.53 |
Secondary
Least Squares Mean Change in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 4
Least squares mean change in Positive and Negative Syndrome Scale (PANSS) between at 4 weeks from Mixed Models Repeated Measures (MMRM). 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: Baseline and 4 weeks
Population: The analysis is based on the subjects who had both baseline and observed week 4 Positive and Negative Syndrome Scale (PANSS) data (160 participants).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Aripiprazole Lauroxil | Least Squares Mean Change in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 4 | -17.3 units on a scale | Standard Error 1.28 |
| Paliperidone Palmitate | Least Squares Mean Change in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 4 | -19.3 units on a scale | Standard Error 1.25 |
Secondary
Least Squares Mean Change in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 9
Least squares mean change from baseline Positive and Negative Syndrome Scale (PANSS) and 9 weeks from Mixed Models Repeated Measures (MMRM).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: Baseline and 9 weeks
Population: The analysis is based on the subjects who had both baseline and observed week 9 PANSS data (131 participants).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Aripiprazole Lauroxil | Least Squares Mean Change in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 9 | -18.8 units on a scale | Standard Error 1.33 |
| Paliperidone Palmitate | Least Squares Mean Change in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 9 | -21.5 units on a scale | Standard Error 1.34 |
Secondary
Number of Participants With Serious and Non-serious Adverse Events (AEs)
Time frame: Up to 25 weeks
Population: Participants who received at least one dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Aripiprazole Lauroxil | Number of Participants With Serious and Non-serious Adverse Events (AEs) | 69 Participants |
| Paliperidone Palmitate | Number of Participants With Serious and Non-serious Adverse Events (AEs) | 72 Participants |