Trial Outcomes & Findings for A Study of Aripiprazole Lauroxil or Paliperidone Palmitate for the Treatment of Schizophrenia (NCT NCT03345979)

Last Updated: 2020-08-11

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

200 participants

Primary outcome timeframe

Baseline and 4 weeks

Results posted on

2020-08-11

Participant Flow

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.

Participant milestones

Participant milestones
Measure	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	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
Overall Study STARTED	99	101
Overall Study COMPLETED	56	43
Overall Study NOT COMPLETED	43	58

Reasons for withdrawal

Reasons for withdrawal
Measure	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	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
Overall Study Withdrawal by Subject	20	31
Overall Study Adverse Event	10	11
Overall Study Lost to Follow-up	8	9
Overall Study Lack of Efficacy	4	2
Overall Study Protocol Violation	1	3
Overall Study Physician Decision	0	2

Baseline Characteristics

FAS population includes those who were randomized and received at least one dose of study drug and have at least one post-baseline Positive and Negative Syndrome Scale (PANSS) assessment

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Aripiprazole Lauroxil n=99 Participants 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	Paliperidone Palmitate n=101 Participants 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	Total n=200 Participants Total of all reporting groups
Age, Continuous	43.5 years STANDARD_DEVIATION 9.67 • n=99 Participants	43.4 years STANDARD_DEVIATION 10.83 • n=101 Participants	43.4 years STANDARD_DEVIATION 10.25 • n=200 Participants
Sex: Female, Male Female	26 Participants n=99 Participants	25 Participants n=101 Participants	51 Participants n=200 Participants
Sex: Female, Male Male	73 Participants n=99 Participants	76 Participants n=101 Participants	149 Participants n=200 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	8 Participants n=99 Participants	11 Participants n=101 Participants	19 Participants n=200 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	91 Participants n=99 Participants	90 Participants n=101 Participants	181 Participants n=200 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	0 Participants n=101 Participants	0 Participants n=200 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants	0 Participants n=101 Participants	0 Participants n=200 Participants
Race (NIH/OMB) Asian	2 Participants n=99 Participants	4 Participants n=101 Participants	6 Participants n=200 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants	0 Participants n=101 Participants	0 Participants n=200 Participants
Race (NIH/OMB) Black or African American	72 Participants n=99 Participants	78 Participants n=101 Participants	150 Participants n=200 Participants
Race (NIH/OMB) White	25 Participants n=99 Participants	17 Participants n=101 Participants	42 Participants n=200 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants	2 Participants n=101 Participants	2 Participants n=200 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	0 Participants n=101 Participants	0 Participants n=200 Participants
Positive and Negative Syndrome Scale (PANSS) Total Score	94.1 units on a scale STANDARD_DEVIATION 9.04 • n=96 Participants • FAS population includes those who were randomized and received at least one dose of study drug and have at least one post-baseline Positive and Negative Syndrome Scale (PANSS) assessment	94.6 units on a scale STANDARD_DEVIATION 8.41 • n=99 Participants • FAS population includes those who were randomized and received at least one dose of study drug and have at least one post-baseline Positive and Negative Syndrome Scale (PANSS) assessment	94.4 units on a scale STANDARD_DEVIATION 8.71 • n=195 Participants • FAS population includes those who were randomized and received at least one dose of study drug and have at least one post-baseline Positive and Negative Syndrome Scale (PANSS) assessment

PRIMARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	Aripiprazole Lauroxil n=80 Participants 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	Paliperidone Palmitate n=80 Participants 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
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	-20.1 units on a scale Standard Deviation 13.72

SECONDARY outcome

Timeframe: 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).

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

Outcome measures

Outcome measures
Measure	Aripiprazole Lauroxil n=80 Participants 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	Paliperidone Palmitate n=80 Participants 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
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	-19.3 units on a scale Standard Error 1.25

SECONDARY outcome

Timeframe: 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).

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.

Outcome measures

Outcome measures
Measure	Aripiprazole Lauroxil n=69 Participants 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	Paliperidone Palmitate n=62 Participants 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
Change in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 9	-19.8 units on a scale Standard Deviation 11.61	-22.5 units on a scale Standard Deviation 13.98

SECONDARY outcome

Timeframe: 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).

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

Outcome measures

Outcome measures
Measure	Aripiprazole Lauroxil n=56 Participants 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	Paliperidone Palmitate n=43 Participants 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
Change in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 25	-23.3 units on a scale Standard Deviation 11.25	-21.7 units on a scale Standard Deviation 14.37

SECONDARY outcome

Timeframe: Baseline and 9 weeks

Population: The analysis is based on the subjects who had both baseline and observed week 9 PANSS data (131 participants).

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

Outcome measures

Outcome measures
Measure	Aripiprazole Lauroxil n=69 Participants 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	Paliperidone Palmitate n=62 Participants 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
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	-21.5 units on a scale Standard Error 1.34

SECONDARY outcome

Timeframe: 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).

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

Outcome measures

Outcome measures
Measure	Aripiprazole Lauroxil n=56 Participants 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	Paliperidone Palmitate n=43 Participants 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
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	-21.1 units on a scale Standard Error 1.53

SECONDARY outcome

Timeframe: Up to 25 weeks

Population: Participants who received at least one dose of study drug.

Outcome measures

Outcome measures
Measure	Aripiprazole Lauroxil n=99 Participants 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	Paliperidone Palmitate n=101 Participants 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
Number of Participants With Serious and Non-serious Adverse Events (AEs)	69 Participants	72 Participants

Adverse Events

Aripiprazole Lauroxil

Serious events: 8 serious events

Other events: 39 other events

Deaths: 0 deaths

Paliperidone Palmitate

Serious events: 7 serious events

Other events: 50 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Aripiprazole Lauroxil n=99 participants at risk 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	Paliperidone Palmitate n=101 participants at risk 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
General disorders Injection Site Pain	17.2% 17/99 • Number of events 28 • Adverse event data was collected over 25 weeks. Adverse event collection was based on investigator's observation and reporting from subjects.	24.8% 25/101 • Number of events 40 • Adverse event data was collected over 25 weeks. Adverse event collection was based on investigator's observation and reporting from subjects.
Investigations Weight increased	9.1% 9/99 • Number of events 9 • Adverse event data was collected over 25 weeks. Adverse event collection was based on investigator's observation and reporting from subjects.	16.8% 17/101 • Number of events 17 • Adverse event data was collected over 25 weeks. Adverse event collection was based on investigator's observation and reporting from subjects.
Nervous system disorders Akathisia	9.1% 9/99 • Number of events 9 • Adverse event data was collected over 25 weeks. Adverse event collection was based on investigator's observation and reporting from subjects.	10.9% 11/101 • Number of events 13 • Adverse event data was collected over 25 weeks. Adverse event collection was based on investigator's observation and reporting from subjects.
Nervous system disorders Headache	8.1% 8/99 • Number of events 9 • Adverse event data was collected over 25 weeks. Adverse event collection was based on investigator's observation and reporting from subjects.	7.9% 8/101 • Number of events 8 • Adverse event data was collected over 25 weeks. Adverse event collection was based on investigator's observation and reporting from subjects.
Nervous system disorders Somnolence	4.0% 4/99 • Number of events 4 • Adverse event data was collected over 25 weeks. Adverse event collection was based on investigator's observation and reporting from subjects.	6.9% 7/101 • Number of events 8 • Adverse event data was collected over 25 weeks. Adverse event collection was based on investigator's observation and reporting from subjects.
Nervous system disorders Dystonia	3.0% 3/99 • Number of events 3 • Adverse event data was collected over 25 weeks. Adverse event collection was based on investigator's observation and reporting from subjects.	5.9% 6/101 • Number of events 6 • Adverse event data was collected over 25 weeks. Adverse event collection was based on investigator's observation and reporting from subjects.

Additional Information

Eva Stroynowski

Alkermes, Inc

Phone: 7816097000

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Should an Investigator desire to disclose study results, Sponsor will review the results disclosure prior to public release and can embargo the disclosure for a period of at least 60 days. Revisions to the disclosure will be negotiated in good faith. For a multicenter study the Investigators agree to publish/publicly present the results together with the other sites for the 12 month period after study results are available unless Sponsor grants written permission in advance.
Publication restrictions are in place

Restriction type: OTHER

Measure	Aripiprazole Lauroxil n=99 participants at risk 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	Paliperidone Palmitate n=101 participants at risk 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
Blood and lymphatic system disorders Leukocytosis	1.0% 1/99 • Number of events 1 • Adverse event data was collected over 25 weeks. Adverse event collection was based on investigator's observation and reporting from subjects.	0.00% 0/101 • Adverse event data was collected over 25 weeks. Adverse event collection was based on investigator's observation and reporting from subjects.
Injury, poisoning and procedural complications Alcohol poisoning	0.00% 0/99 • Adverse event data was collected over 25 weeks. Adverse event collection was based on investigator's observation and reporting from subjects.	0.99% 1/101 • Number of events 1 • Adverse event data was collected over 25 weeks. Adverse event collection was based on investigator's observation and reporting from subjects.
Injury, poisoning and procedural complications Overdose	0.00% 0/99 • Adverse event data was collected over 25 weeks. Adverse event collection was based on investigator's observation and reporting from subjects.	0.99% 1/101 • Number of events 1 • Adverse event data was collected over 25 weeks. Adverse event collection was based on investigator's observation and reporting from subjects.
Injury, poisoning and procedural complications Road traffic accident	0.00% 0/99 • Adverse event data was collected over 25 weeks. Adverse event collection was based on investigator's observation and reporting from subjects.	0.99% 1/101 • Number of events 1 • Adverse event data was collected over 25 weeks. Adverse event collection was based on investigator's observation and reporting from subjects.
Metabolism and nutrition disorders Hypercalcaemia	1.0% 1/99 • Number of events 1 • Adverse event data was collected over 25 weeks. Adverse event collection was based on investigator's observation and reporting from subjects.	0.00% 0/101 • Adverse event data was collected over 25 weeks. Adverse event collection was based on investigator's observation and reporting from subjects.
Musculoskeletal and connective tissue disorders Bone deformity	0.00% 0/99 • Adverse event data was collected over 25 weeks. Adverse event collection was based on investigator's observation and reporting from subjects.	0.99% 1/101 • Number of events 1 • Adverse event data was collected over 25 weeks. Adverse event collection was based on investigator's observation and reporting from subjects.
Nervous system disorders Dystonia	0.00% 0/99 • Adverse event data was collected over 25 weeks. Adverse event collection was based on investigator's observation and reporting from subjects.	0.99% 1/101 • Number of events 1 • Adverse event data was collected over 25 weeks. Adverse event collection was based on investigator's observation and reporting from subjects.
Nervous system disorders Generalised tonic-clonic seizure	1.0% 1/99 • Number of events 1 • Adverse event data was collected over 25 weeks. Adverse event collection was based on investigator's observation and reporting from subjects.	0.00% 0/101 • Adverse event data was collected over 25 weeks. Adverse event collection was based on investigator's observation and reporting from subjects.
Psychiatric disorders Schizophrenia	5.1% 5/99 • Number of events 5 • Adverse event data was collected over 25 weeks. Adverse event collection was based on investigator's observation and reporting from subjects.	2.0% 2/101 • Number of events 2 • Adverse event data was collected over 25 weeks. Adverse event collection was based on investigator's observation and reporting from subjects.
Psychiatric disorders Psychotic disorder	2.0% 2/99 • Number of events 2 • Adverse event data was collected over 25 weeks. Adverse event collection was based on investigator's observation and reporting from subjects.	0.00% 0/101 • Adverse event data was collected over 25 weeks. Adverse event collection was based on investigator's observation and reporting from subjects.
Psychiatric disorders Suicide attempt	1.0% 1/99 • Number of events 1 • Adverse event data was collected over 25 weeks. Adverse event collection was based on investigator's observation and reporting from subjects.	0.99% 1/101 • Number of events 1 • Adverse event data was collected over 25 weeks. Adverse event collection was based on investigator's observation and reporting from subjects.
Psychiatric disorders Depression	0.00% 0/99 • Adverse event data was collected over 25 weeks. Adverse event collection was based on investigator's observation and reporting from subjects.	0.99% 1/101 • Number of events 3 • Adverse event data was collected over 25 weeks. Adverse event collection was based on investigator's observation and reporting from subjects.
Psychiatric disorders Psychotic symptom	0.00% 0/99 • Adverse event data was collected over 25 weeks. Adverse event collection was based on investigator's observation and reporting from subjects.	0.99% 1/101 • Number of events 1 • Adverse event data was collected over 25 weeks. Adverse event collection was based on investigator's observation and reporting from subjects.
Psychiatric disorders Suicidal ideation	1.0% 1/99 • Number of events 1 • Adverse event data was collected over 25 weeks. Adverse event collection was based on investigator's observation and reporting from subjects.	0.00% 0/101 • Adverse event data was collected over 25 weeks. Adverse event collection was based on investigator's observation and reporting from subjects.
Renal and urinary disorders Renal failure	1.0% 1/99 • Number of events 1 • Adverse event data was collected over 25 weeks. Adverse event collection was based on investigator's observation and reporting from subjects.	0.00% 0/101 • Adverse event data was collected over 25 weeks. Adverse event collection was based on investigator's observation and reporting from subjects.