A Study of Aripiprazole Lauroxil or Paliperidone Palmitate for the Treatment of Schizophrenia

• Sponsor: Alkermes, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03345979
• Collaborator: (none)
• Enrollment: 200
• Locations: 16
• Arms: 2
• Actual Duration (Months): 15.8
• Patients Per Site: 12.5
• Patients Per Site Per Month: 0.8

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Schizophrenia	Combination Product: Aripiprazole Lauroxil; Drug: Paliperidone Palmitate	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 200 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 3b, Multicenter, Randomized, Double-blind Study to Evaluate the Efficacy and Safety of Aripiprazole Lauroxil or Paliperidone Palmitate for the Treatment of Schizophrenia in Subjects Hospitalized for Acute Exacerbation
• Actual Study Start Date: Nov 15, 2017
• Actual Primary Completion Date: Mar 12, 2019
• Actual Study Completion Date: Mar 12, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment Group 1 Regular injections	Combination Product: Aripiprazole Lauroxil; Intramuscular injection; study drug provided using a pre-filled syringe; Other Names: ARISTADA ARISTADA INITIO
Active Comparator: Treatment Group 2 Regular injections	Drug: Paliperidone Palmitate; Intramuscular injection; Other Names: Invega Sustenna

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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

2. 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.

3. 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

4. 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

5. 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

6. Number of Participants With Serious and Non-serious Adverse Events (AEs) [Up to 25 weeks]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Alkermes Investigational Site	Little Rock	Arkansas	United States	72211
2	Alkermes Investigational Site	Rogers	Arkansas	United States	72758
3	Alkermes Investigational Site	Cerritos	California	United States	90703
4	Alkermes Investigational Site	Culver City	California	United States	90230
5	Alkermes Investigational Site	Garden Grove	California	United States	92845
6	Alkermes Investigational Site	Lemon Grove	California	United States	91945
7	Alkermes Investigational Site	Hialeah	Florida	United States	33012
8	Alkermes Investigational Site	Chicago	Illinois	United States	60640
9	Alkermes Investigational Site	Hoffman Estates	Illinois	United States	60169
10	Alkermes Investigational Site	Flowood	Mississippi	United States	39232
11	Alkermes Investigational Site	Saint Louis	Missouri	United States	63141
12	Alkermes Investigational Site	Las Vegas	Nevada	United States	89102
13	Alkermes Investigational Site	Berlin	New Jersey	United States	08009
14	Alkermes Investigational Site	Austin	Texas	United States	78754
15	Alkermes Investigational Site	Garland	Texas	United States	75042
16	Alkermes Investigational Site	Richardson	Texas	United States	75080

Sponsors and Collaborators

• Alkermes, Inc.

Investigators

• Study Director: Sanjeev Pathak, MD, Alkermes, Inc.

Study Documents (Full-Text)

• Study Protocol - Jan 4, 2018
• Statistical Analysis Plan - Feb 5, 2019

More Information

Publications

None provided.

• Responsible Party: Alkermes, Inc.
• ClinicalTrials.gov Identifier: NCT03345979
• Other Study ID Numbers: ALK9072-A306
• First Posted: Nov 17, 2017
• Last Update Posted: Aug 11, 2020
• Last Verified: Jul 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: Yes
• Keywords provided by Alkermes, Inc.: Alkermes; schizophrenia; aripiprazole lauroxil; ARISTADA; ARISTADA INITIO
• Additional relevant MeSH terms: Schizophrenia; Aripiprazole; Paliperidone Palmitate; Aripiprazole lauroxil

Study Results

Participant Flow

Pre-assignment Detail	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.

Arm/Group Title	Aripiprazole Lauroxil	Paliperidone Palmitate
Arm/Group Description	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 (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
Period Title: Overall Study
STARTED	99	101
COMPLETED	56	43
NOT COMPLETED	43	58

Baseline Characteristics

Arm/Group Title	Aripiprazole Lauroxil	Paliperidone Palmitate	Total
Arm/Group Description	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 (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 of all reporting groups
Overall Participants	99	101	200
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	43.5 (9.67)	43.4 (10.83)	43.4 (10.25)
Sex: Female, Male (Count of Participants)
Female	26 26.3%	25 24.8%	51 25.5%
Male	73 73.7%	76 75.2%	149 74.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	8 8.1%	11 10.9%	19 9.5%
Not Hispanic or Latino	91 91.9%	90 89.1%	181 90.5%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	2 2%	4 4%	6 3%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	72 72.7%	78 77.2%	150 75%
White	25 25.3%	17 16.8%	42 21%
More than one race	0 0%	2 2%	2 1%
Unknown or Not Reported	0 0%	0 0%	0 0%
Positive and Negative Syndrome Scale (PANSS) Total Score (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	94.1 (9.04)	94.6 (8.41)	94.4 (8.71)

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score at Week 4
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Aripiprazole Lauroxil	Paliperidone Palmitate
Arm/Group Description	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 (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
Measure Participants	80	80
Mean (Standard Deviation) [units on a scale]	-17.4 (11.57)	-20.1 (13.72)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Aripiprazole Lauroxil
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<.001
	Comments
	Method	t-test, 2 sided
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Paliperidone Palmitate
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<.001
	Comments
	Method	t-test, 2 sided
	Comments

2. Secondary Outcome

Title	Least Squares Mean Change in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 4
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Aripiprazole Lauroxil	Paliperidone Palmitate
Arm/Group Description	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 (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
Measure Participants	80	80
Least Squares Mean (Standard Error) [units on a scale]	-17.3 (1.28)	-19.3 (1.25)

3. Secondary Outcome

Title	Change in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 9
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Aripiprazole Lauroxil	Paliperidone Palmitate
Arm/Group Description	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 (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
Measure Participants	69	62
Mean (Standard Deviation) [units on a scale]	-19.8 (11.61)	-22.5 (13.98)

4. Secondary Outcome

Title	Change in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 25
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Aripiprazole Lauroxil	Paliperidone Palmitate
Arm/Group Description	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 (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
Measure Participants	56	43
Mean (Standard Deviation) [units on a scale]	-23.3 (11.25)	-21.7 (14.37)

5. Secondary Outcome

Title	Least Squares Mean Change in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 9
Description	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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Aripiprazole Lauroxil	Paliperidone Palmitate
Arm/Group Description	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 (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
Measure Participants	69	62
Least Squares Mean (Standard Error) [units on a scale]	-18.8 (1.33)	-21.5 (1.34)

6. Secondary Outcome

Title	Least Squares Mean Change in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 25
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Aripiprazole Lauroxil	Paliperidone Palmitate
Arm/Group Description	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 (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
Measure Participants	56	43
Least Squares Mean (Standard Error) [units on a scale]	-22.0 (1.42)	-21.1 (1.53)

7. Secondary Outcome

Title	Number of Participants With Serious and Non-serious Adverse Events (AEs)
Time Frame	Up to 25 weeks

Outcome Measure Data

Analysis Population Description

Participants who received at least one dose of study drug.

Arm/Group Title	Aripiprazole Lauroxil	Paliperidone Palmitate
Arm/Group Description	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 (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
Measure Participants	99	101
Count of Participants [Participants]	69 69.7%	72 71.3%

Adverse Events

Time Frame	Adverse event data was collected over 25 weeks.
Adverse Event Reporting Description	Adverse event collection was based on investigator's observation and reporting from subjects.
Arm/Group Title	Aripiprazole Lauroxil		Paliperidone Palmitate
Arm/Group Description	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 (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
All Cause Mortality
	Aripiprazole Lauroxil		Paliperidone Palmitate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/99 (0%)		0/101 (0%)
Serious Adverse Events
	Aripiprazole Lauroxil		Paliperidone Palmitate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/99 (8.1%)		7/101 (6.9%)
Blood and lymphatic system disorders
Leukocytosis	1/99 (1%)	1	0/101 (0%)	0
Injury, poisoning and procedural complications
Alcohol poisoning	0/99 (0%)	0	1/101 (1%)	1
Overdose	0/99 (0%)	0	1/101 (1%)	1
Road traffic accident	0/99 (0%)	0	1/101 (1%)	1
Metabolism and nutrition disorders
Hypercalcaemia	1/99 (1%)	1	0/101 (0%)	0
Musculoskeletal and connective tissue disorders
Bone deformity	0/99 (0%)	0	1/101 (1%)	1
Nervous system disorders
Dystonia	0/99 (0%)	0	1/101 (1%)	1
Generalised tonic-clonic seizure	1/99 (1%)	1	0/101 (0%)	0
Psychiatric disorders
Schizophrenia	5/99 (5.1%)	5	2/101 (2%)	2
Psychotic disorder	2/99 (2%)	2	0/101 (0%)	0
Suicide attempt	1/99 (1%)	1	1/101 (1%)	1
Depression	0/99 (0%)	0	1/101 (1%)	3
Psychotic symptom	0/99 (0%)	0	1/101 (1%)	1
Suicidal ideation	1/99 (1%)	1	0/101 (0%)	0
Renal and urinary disorders
Renal failure	1/99 (1%)	1	0/101 (0%)	0
Other (Not Including Serious) Adverse Events
	Aripiprazole Lauroxil		Paliperidone Palmitate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	39/99 (39.4%)		50/101 (49.5%)
General disorders
Injection Site Pain	17/99 (17.2%)	28	25/101 (24.8%)	40
Investigations
Weight increased	9/99 (9.1%)	9	17/101 (16.8%)	17
Nervous system disorders
Akathisia	9/99 (9.1%)	9	11/101 (10.9%)	13
Headache	8/99 (8.1%)	9	8/101 (7.9%)	8
Somnolence	4/99 (4%)	4	7/101 (6.9%)	8
Dystonia	3/99 (3%)	3	6/101 (5.9%)	6

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.