Evaluation of Effectiveness of Risperdal® Consta® Compared to Abilify® Over a Two-year Period in Patients With Schizophrenia

• Sponsor: Johnson & Johnson Pharmaceutical Research & Development, L.L.C. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00299702
• Collaborator: Janssen, LP (Industry)
• Enrollment: 355
• Arms: 2
• Duration (Months): 35

Study Details

Study Description

Brief Summary

The purpose of this study is to compare the effectiveness of two antipsychotic medications, Risperdal® Consta® versus Abilify®, over a 2-year treatment period in the long-term maintenance of patients with schizophrenia.

Condition or Disease	Intervention/Treatment	Phase
Schizophrenia; Psychotic Disorders	Drug: Abilify; Drug: Risperidal Consta	Phase 4

Detailed Description

Although many patients with schizophrenia currently take oral antipsychotic medications, it is estimated that up to 75% of them have difficulty adhering to the daily oral regimen. Long-acting injectable formulations of antipsychotics may eliminate the need for daily medication and enhance patient compliance with the treatment regimen. The purpose of this trial is to evaluate the long-term effectiveness of Risperdal® Consta®, a long-acting injectable antipsychotic medication, versus Abilify®, an oral antipsychotic medication in patients with schizophrenia. The study will include patients, who in the investigator's opinion may benefit from a change in their current antipsychotic medication due to insufficient effectiveness, side effects or difficulty in adhering to a daily dose regimen. This is an open-label, randomized study in which patients will have an equal chance of receiving treatment for up to 2 years with Risperdal® Consta®, administered in the muscles near the hip every 2 weeks, or Abilify®, taken orally once daily. The initial dose and subsequent dose of study drug will be determined by the investigator. The patient's current oral antipsychotic medication will be decreased over the first four weeks of the study and discontinued. During the study, investigators may adjust the dose of study drug or add new antipsychotic medications to treat worsening psychotic symptoms. Patients may continue on or have added, antidepressants, mood stabilizers (except carbamazepine), sedative hypnotics, or anxiolytic medications during the study. Patients will return to the doctor's office every two weeks to receive an injection of Risperdal® Consta® or another supply of Abilify®. During certain visits, patients will be asked questions which will help the investigator determine the severity of the patient's illness, how well the study drug is working, quality of life, reasoning, memory, judgement and perception and side effects that may be associated with schizophrenia or treatment. Safety evaluations include the incidence of adverse events during the study, vital signs and clinical laboratory tests (both blood and urine). The study hypothesis is that Risperdal® Consta® is superior to Abilify® in the long-term treatment of subjects with schizophrenia as measured by time to relapse and time in remission. Treatment with Risperdal® Consta® (administered in the muscle every 2 weeks) at a dose of 25, 37.5 or 50 mg or Abilify® (administered orally daily) at a dose of 10-30 mg for 2 years. Investigators will determine the starting dose and may adjust the dosage of study drug during the study according to symptoms and treatment response.

Study Design

• Study Type: Interventional
• Actual Enrollment: 355 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A 2-year, Prospective, Blinded-rater, Open-label, Active-controlled, Multicenter, Randomized Study of Long-term Efficacy and Effectiveness Comparing Risperdal® Consta® and Abilify® (Aripiprazole) in Adults With Schizophrenia
• Study Start Date: Feb 1, 2006
• Actual Primary Completion Date: Jan 1, 2009
• Actual Study Completion Date: Jan 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 002	Drug: Abilify; 10-30 mg once daily for 104 weeks
Experimental: 001	Drug: Risperidal Consta; 25mg, 37.5mg, or 50mg every 2 weeks for 104 weeks

Outcome Measures

Primary Outcome Measures

1. Time to Relapse [Day 1 to relapse]

   Time to relapse was defined as the number of days from the date of first dose to the date of relapse, as determined by the Relapse Monitoring Board.

2. Time in Remission [Day 1 to last PANSS measurement]

   Time in remission for an individual subject was defined as the length of time (in days) that the remission criteria were maintained during the trial. Remission was defined as the simultaneous attainment of a score of 3 (mild), 2 (minimal), or 1 (absent) for all the following individual items from Positive and Negative Syndrome Scale (PANSS): delusions (P1), concept disorganization (P2), hallucinatory behavior (P3), unusual thought content (G9), mannerisms and posturing (G5), blunted affect (N1), passive/apathetic social withdrawal (N4), and lack of spontaneity and flow of conversation (N6).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients with diagnosis of schizophrenia

• Patient has had at least 2 psychotic relapses in the two years prior to study entry

• patient is not adequately benefiting from their current antipsychotic medication

Exclusion Criteria:

• Patients that have been hospitalized or had major medication changes within 2 months of study entry

• Patients currently experiencing, or who have experienced worsening of disease symptoms within 2 months of study entry

• Patients currently using clozapine or carbamazepine

• Patients who have undergone electroconvulsive therapy or depot antipsychotic treatment within 6 months prior to study entry

• pregnant or breast-feeding

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
• Janssen, LP

Investigators

• Study Director: Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial, Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00299702
• Other Study ID Numbers: CR006121; RISSCH4060
• First Posted: Mar 7, 2006
• Last Update Posted: Dec 30, 2011
• Last Verified: Dec 1, 2011

• Keywords provided by , ,: Schizophrenia; Relapse; Remission; Treatment Outcome; long-acting injectable
• Additional relevant MeSH terms: Schizophrenia; Mental Disorders; Psychotic Disorders; Aripiprazole; Risperidone

Study Results

Participant Flow

Recruitment Details	The first patient in was on February 28, 2006; last patient out was on January 26, 2009. Enrollment occurred across multiple sites in the United States, Argentina, Chile, and India and patients were enrolled from outpatient psychiatric clinics associated with private medical practices, private clinical trial sites, and academic medical centers.
Pre-assignment Detail	A Screening Visit (maximum of 14 days) prior to the Treatment Phase. Baseline included psychiatric exam, lab, ECG, and schizophrenia symptom rating scale. Subjects were permitted to remain on previous psychotropic medications (i.e., antipsychotic, antidepressant, mood stabilizer, anxiolytics) up to the first 4 weeks of the Treatment Phase.

Arm/Group Title	Risperdal Consta	Abilify
Arm/Group Description	25mg, 37.5mg, or 50mg every 2 weeks injection for 104 weeks	10-30 mg once daily oral for 104 weeks
Period Title: Overall Study
STARTED	179	176
COMPLETED	126	126
NOT COMPLETED	53	50

Baseline Characteristics

Arm/Group Title	Risperdal Consta	Abilify	Total
Arm/Group Description	25mg, 37.5mg, or 50mg every 2 weeks injection for 104 weeks	10-30 mg once daily oral for 104 weeks	Total of all reporting groups
Overall Participants	179	176	355
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	177 98.9%	173 98.3%	350 98.6%
>=65 years	2 1.1%	3 1.7%	5 1.4%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	38.3 (11.66)	37.8 (11.49)	38 (11.56)
Sex: Female, Male (Count of Participants)
Female	73 40.8%	70 39.8%	143 40.3%
Male	106 59.2%	106 60.2%	212 59.7%
Region of Enrollment (participants) [Number]
India	91 50.8%	91 51.7%	182 51.3%
United States	51 28.5%	52 29.5%	103 29%
South America	37 20.7%	33 18.8%	70 19.7%

Outcome Measures

1. Primary Outcome

Title	Time to Relapse
Description	Time to relapse was defined as the number of days from the date of first dose to the date of relapse, as determined by the Relapse Monitoring Board.
Time Frame	Day 1 to relapse

Outcome Measure Data

Analysis Population Description

explanatory ITT analysis data set (eITT) contains all subjects who had at least one administration of study drug as well as at least one follow-up efficacy measurement; includes assessments while the subject is on study drug.

Arm/Group Title	Risperdal Consta	Abilify
Arm/Group Description	25mg, 37.5mg, or 50mg every 2 weeks injection for 104 weeks	10-30 mg once daily oral for 104 weeks
Measure Participants	177	172
Median (95% Confidence Interval) [days]	131	113

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Risperdal Consta, Abilify
	Comments	Null hypothesis: there is no difference in time to relapse
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.684
	Comments	Hochberg procedure was used for adjusting multiple endpoint comparisons
	Method	Log Rank
	Comments	Insufficient number of subjects who had an event for median estimation.

2. Primary Outcome

Title	Time in Remission
Description	Time in remission for an individual subject was defined as the length of time (in days) that the remission criteria were maintained during the trial. Remission was defined as the simultaneous attainment of a score of 3 (mild), 2 (minimal), or 1 (absent) for all the following individual items from Positive and Negative Syndrome Scale (PANSS): delusions (P1), concept disorganization (P2), hallucinatory behavior (P3), unusual thought content (G9), mannerisms and posturing (G5), blunted affect (N1), passive/apathetic social withdrawal (N4), and lack of spontaneity and flow of conversation (N6).
Time Frame	Day 1 to last PANSS measurement

Outcome Measure Data

Analysis Population Description

explanatory ITT analysis data set (eITT) contains all subjects who had at least one administration of study drug as well as at least one follow-up efficacy measurement; includes assessments while the subject is on study drug.

Arm/Group Title	Risperdal Consta	Abilify
Arm/Group Description	25mg, 37.5mg, or 50mg every 2 weeks injection for 104 weeks	10-30 mg once daily oral for 104 weeks
Measure Participants	179	176
Mean (Standard Deviation) [days]	373.5 (282.6)	356.7 (291.99)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Risperdal Consta, Abilify
	Comments	Null hypothesis: there is no difference in time in remission between the two treatment groups
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.646
	Comments	Hochberg procedure was used for adjusting multiple endpoint comparisons
	Method	Wilcoxon (Mann-Whitney)
	Comments

Adverse Events

Time Frame	Adverse events were reported as treatment emergent if the onset date is before or within 49 days of last dose of RISPERDAL CONSTA or before or within 30 days of last dose of Abilify.
Arm/Group Title	RISPERDAL CONSTA		Abilify
Arm/Group Description	25mg, 37.5mg, or 50mg every 2 weeks injection for 104 weeks		10-30 mg once daily oral for 104 weeks
All Cause Mortality
	RISPERDAL CONSTA		Abilify
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	RISPERDAL CONSTA		Abilify
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	31/179 (17.3%)		35/176 (19.9%)
Blood and lymphatic system disorders
ANAEMIA	0/179 (0%)		1/176 (0.6%)
PANCYTOPENIA	0/179 (0%)		1/176 (0.6%)
Cardiac disorders
CARDIO-RESPIRATORY ARREST	1/179 (0.6%)		0/176 (0%)
Endocrine disorders
GOITRE	0/179 (0%)		1/176 (0.6%)
Gastrointestinal disorders
ANAL FISSURE	0/179 (0%)		1/176 (0.6%)
DIARRHOEA	0/179 (0%)		1/176 (0.6%)
IRRITABLE BOWEL SYNDROME	0/179 (0%)		1/176 (0.6%)
MELAENA	0/179 (0%)		1/176 (0.6%)
VOMITING	0/179 (0%)		1/176 (0.6%)
General disorders
DEATH	1/179 (0.6%)		0/176 (0%)
PYREXIA	0/179 (0%)		1/176 (0.6%)
Infections and infestations
CELLULITIS	1/179 (0.6%)		0/176 (0%)
PNEUMONIA	0/179 (0%)		1/176 (0.6%)
Injury, poisoning and procedural complications
ANKLE FRACTURE	0/179 (0%)		1/176 (0.6%)
JOINT DISLOCATION	0/179 (0%)		1/176 (0.6%)
MULTIPLE DRUG OVERDOSE ACCIDENTAL	1/179 (0.6%)		0/176 (0%)
ROAD TRAFFIC ACCIDENT	1/179 (0.6%)		0/176 (0%)
Metabolism and nutrition disorders
DEHYDRATION	0/179 (0%)		1/176 (0.6%)
DIABETIC KETOACIDOSIS	1/179 (0.6%)		0/176 (0%)
Musculoskeletal and connective tissue disorders
ARTHRITIS	1/179 (0.6%)		0/176 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
LEIOMYOMA	0/179 (0%)		1/176 (0.6%)
Nervous system disorders
AKATHISIA	1/179 (0.6%)		0/176 (0%)
CONVULSION	1/179 (0.6%)		0/176 (0%)
SYNCOPE	0/179 (0%)		1/176 (0.6%)
Psychiatric disorders
PSYCHOTIC DISORDER	12/179 (6.7%)		11/176 (6.3%)
SCHIZOPHRENIA	7/179 (3.9%)		12/176 (6.8%)
SUICIDAL IDEATION	2/179 (1.1%)		1/176 (0.6%)
AGGRESSION	2/179 (1.1%)		0/176 (0%)
DEPRESSION SUICIDAL	2/179 (1.1%)		0/176 (0%)
AFFECT LABILITY	1/179 (0.6%)		0/176 (0%)
ALCOHOLISM	0/179 (0%)		1/176 (0.6%)
ANXIETY	0/179 (0%)		1/176 (0.6%)
COMPLETED SUICIDE	0/179 (0%)		1/176 (0.6%)
DRUG DEPENDENCE	0/179 (0%)		1/176 (0.6%)
HOMICIDAL IDEATION	1/179 (0.6%)		0/176 (0%)
MANIA	0/179 (0%)		1/176 (0.6%)
MENTAL STATUS CHANGES	1/179 (0.6%)		0/176 (0%)
SUICIDE ATTEMPT	1/179 (0.6%)		0/176 (0%)
Respiratory, thoracic and mediastinal disorders
COUGH	0/179 (0%)		1/176 (0.6%)
EPISTAXIS	1/179 (0.6%)		0/176 (0%)
Other (Not Including Serious) Adverse Events
	RISPERDAL CONSTA		Abilify
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	151/179 (84.4%)		141/176 (80.1%)
Endocrine disorders
HYPERPROLACTINAEMIA	9/179 (5%)		0/176 (0%)
Gastrointestinal disorders
DIARRHOEA	12/179 (6.7%)		19/176 (10.8%)
VOMITING	18/179 (10.1%)		13/176 (7.4%)
NAUSEA	16/179 (8.9%)		11/176 (6.3%)
CONSTIPATION	14/179 (7.8%)		12/176 (6.8%)
ABDOMINAL PAIN UPPER	6/179 (3.4%)		11/176 (6.3%)
SALIVARY HYPERSECRETION	7/179 (3.9%)		9/176 (5.1%)
General disorders
PYREXIA	26/179 (14.5%)		21/176 (11.9%)
FATIGUE	10/179 (5.6%)		17/176 (9.7%)
ASTHENIA	7/179 (3.9%)		14/176 (8%)
INJECTION SITE PAIN	9/179 (5%)		1/176 (0.6%)
Infections and infestations
NASOPHARYNGITIS	18/179 (10.1%)		16/176 (9.1%)
UPPER RESPIRATORY TRACT INFECTION	7/179 (3.9%)		18/176 (10.2%)
INFLUENZA	11/179 (6.1%)		7/176 (4%)
Investigations
WEIGHT INCREASED	15/179 (8.4%)		15/176 (8.5%)
Metabolism and nutrition disorders
DECREASED APPETITE	29/179 (16.2%)		16/176 (9.1%)
Musculoskeletal and connective tissue disorders
PAIN IN EXTREMITY	14/179 (7.8%)		14/176 (8%)
BACK PAIN	12/179 (6.7%)		14/176 (8%)
ARTHRALGIA	12/179 (6.7%)		12/176 (6.8%)
Nervous system disorders
TREMOR	39/179 (21.8%)		40/176 (22.7%)
HEADACHE	30/179 (16.8%)		27/176 (15.3%)
AKATHISIA	20/179 (11.2%)		20/176 (11.4%)
DIZZINESS	25/179 (14%)		13/176 (7.4%)
HYPERSOMNIA	11/179 (6.1%)		10/176 (5.7%)
SOMNOLENCE	12/179 (6.7%)		7/176 (4%)
SEDATION	10/179 (5.6%)		6/176 (3.4%)
Psychiatric disorders
INSOMNIA	47/179 (26.3%)		51/176 (29%)
PSYCHOTIC DISORDER	30/179 (16.8%)		30/176 (17%)
ANXIETY	32/179 (17.9%)		26/176 (14.8%)
SCHIZOPHRENIA	25/179 (14%)		21/176 (11.9%)
DEPRESSION	24/179 (13.4%)		15/176 (8.5%)
RESTLESSNESS	11/179 (6.1%)		5/176 (2.8%)
SLEEP DISORDER	7/179 (3.9%)		9/176 (5.1%)
Respiratory, thoracic and mediastinal disorders
COUGH	17/179 (9.5%)		12/176 (6.8%)

Limitations/Caveats

15% of subjects did not meet stability inclusion criteria; many received supplemental antipsychotics post-randomization; biweekly visits may have increased aripiprazole adherence; numerous early dropouts may have led to dependent censoring and bias.

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.