6-Month Extension Trial of Asenapine With Olanzapine in Negative Symptoms Patients Who Completed the First 6- Month Trial (A7501014)(COMPLETED)(P05772)

• Sponsor: Organon and Co (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00174265
• Collaborator: (none)
• Enrollment: 196
• Arms: 2
• Duration (Months): 46

Study Details

Study Description

Brief Summary

This is an extension study of A7501013 (P05771/NCT00145496) to further test

the efficacy and safety of Asenapine compared with a

marketed agent (olanzapine) in the treatment of patients with

persistent negative symptoms of schizophrenia.

Condition or Disease	Intervention/Treatment	Phase
Schizophrenia	Drug: asenapine; Drug: olanzapine	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 196 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Double-Blind, Flexible-Dose, 6-Month Extension Trial Comparing the Safety and Efficacy of Asenapine With Olanzapine in Subjects Who Completed Protocol A7501013
• Study Start Date: Jul 1, 2005
• Actual Primary Completion Date: Apr 1, 2009
• Actual Study Completion Date: May 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: asenapine	Drug: asenapine; 5-10 mg sublingually twice daily for 26 weeks
Active Comparator: olanzapine	Drug: olanzapine; 5-20 mg by mouth once daily for 26 weeks; Other Names: Zyprexa

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Negative Symptoms of Schizophrenia Measured by the Negative Symptom Assessment (NSA) Scale Total Score [Baseline of A7501013 to Day 365]

   The NSA Scale is a 16-item clinician-rated instrument for rating the negative symptomatology of schizophrenia. Total score ranges from 16 (best) to 96 (worst), with greater scores indicating greater severity of symptoms.

Secondary Outcome Measures

1. Change From Baseline in Quality of Life Measured by the Quality of Life Scale (QLS) Total Score [Baseline of A7501013 to Day 365]

   The QLS is a 21-item clinician-rated scale for rating psychosocial functioning (Interpersonal Relations, Instrumental Role, Intrapsychic Foundations, and Common Objects and Activities). The score ranges from 0 (worst) to 126 (best), with greater values indicating better quality of life.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Continue to meet all demographic and procedural

inclusion criteria of the A7501013 trial to enter into

this extension trial.

• Have demonstrated an acceptable degree of compliance

and completed the A7501013 trial, and would benefit

from continued treatment according to the investigator.

Exclusion Criteria:

• Have an uncontrolled, unstable clinically significant

medical condition.

• Have been judged to be medically noncompliant in the

management of their disease.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Organon and Co

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Organon and Co
• ClinicalTrials.gov Identifier: NCT00174265
• Other Study ID Numbers: P05772; Aphrodite; A7501014
• First Posted: Sep 15, 2005
• Last Update Posted: Feb 9, 2022
• Last Verified: Feb 1, 2022

• Additional relevant MeSH terms: Schizophrenia; Olanzapine; Asenapine

Study Results

Participant Flow

Arm/Group Title	Asenapine	Olanzapine
Arm/Group Description	5-10 mg sublingually twice daily for 26 weeks	5-20 mg by mouth once daily for 26 weeks
Period Title: Overall Study
STARTED	86	110
COMPLETED	57	89
NOT COMPLETED	29	21

Baseline Characteristics

Arm/Group Title	Asenapine	Olanzapine	Total
Arm/Group Description	5-10 mg sublingually twice daily for 26 weeks	5-20 mg by mouth once daily for 26 weeks	Total of all reporting groups
Overall Participants	85	110	195
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	84 98.8%	108 98.2%	192 98.5%
>=65 years	1 1.2%	2 1.8%	3 1.5%
Sex: Female, Male (Count of Participants)
Female	18 21.2%	27 24.5%	45 23.1%
Male	67 78.8%	83 75.5%	150 76.9%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Negative Symptoms of Schizophrenia Measured by the Negative Symptom Assessment (NSA) Scale Total Score
Description	The NSA Scale is a 16-item clinician-rated instrument for rating the negative symptomatology of schizophrenia. Total score ranges from 16 (best) to 96 (worst), with greater scores indicating greater severity of symptoms.
Time Frame	Baseline of A7501013 to Day 365

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) population. In-treatment change from baseline scores by visit and baseline scores from the ITT population are included in the Mixed Model for Repeated Measurements (MMRM) model.

Arm/Group Title	Asenapine	Olanzapine
Arm/Group Description	5-10 mg sublingually twice daily for 26 weeks	5-20 mg by mouth once daily for 26 weeks
Measure Participants	83	110
Baseline	61.5 (1.37)	60.3 (1.20)
Change from Baseline at Day 365	-15.8 (1.48)	-11.0 (1.27)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Asenapine, Olanzapine
	Comments	The null hypothesis was that there was no difference in change from Baseline in NSA Scale total score between asenapine and olanzapine at Day 365.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0148
	Comments	The test of hypothesis was a 2-tailed test with alpha=0.05 (0.049 to adjust for one interim analysis).
	Method	Mixed Model for Repeated Measurements
	Comments

2. Secondary Outcome

Title	Change From Baseline in Quality of Life Measured by the Quality of Life Scale (QLS) Total Score
Description	The QLS is a 21-item clinician-rated scale for rating psychosocial functioning (Interpersonal Relations, Instrumental Role, Intrapsychic Foundations, and Common Objects and Activities). The score ranges from 0 (worst) to 126 (best), with greater values indicating better quality of life.
Time Frame	Baseline of A7501013 to Day 365

Outcome Measure Data

Analysis Population Description

ITT population. In-treatment change from baseline scores by visit and baseline scores from the ITT population are included in the MMRM model.

Arm/Group Title	Asenapine	Olanzapine
Arm/Group Description	5-10 mg sublingually twice daily for 26 weeks	5-20 mg by mouth once daily for 26 weeks
Measure Participants	83	110
Baseline	45.3 (2.27)	42.3 (1.99)
Change from Baseline at Day 365	12.4 (2.05)	11.7 (1.73)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Asenapine, Olanzapine
	Comments	The null hypothesis was that there was no difference in change from Baseline in QLS total score between asenapine and olanzapine at Week 52.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.8100
	Comments	Significant level adjusted for one interim analysis was set as 0.049 two-sided.
	Method	Mixed Model for Repeated Measurements
	Comments

Adverse Events

Arm/Group Title	Asenapine		Olanzapine
Arm/Group Description	5-10 mg sublingually twice daily for 26 weeks		5-20 mg by mouth once daily for 26 weeks
All Cause Mortality
	Asenapine		Olanzapine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Asenapine		Olanzapine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/85 (4.7%)		4/110 (3.6%)
Gastrointestinal disorders
Gastritis	0/85 (0%)	0	1/110 (0.9%)	1
Metabolism and nutrition disorders
Hyponatraemia	1/85 (1.2%)	1	0/110 (0%)	0
Psychiatric disorders
Alcohol Abuse	1/85 (1.2%)	1	0/110 (0%)	0
Psychotic Disorder	1/85 (1.2%)	1	0/110 (0%)	0
Schizophrenia	0/85 (0%)	0	3/110 (2.7%)	3
Schizophrenia, Paranoid Type	1/85 (1.2%)	1	0/110 (0%)	0
Other (Not Including Serious) Adverse Events
	Asenapine		Olanzapine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	14/85 (16.5%)		31/110 (28.2%)
Infections and infestations
Nasopharyngitis	2/85 (2.4%)	2	8/110 (7.3%)	10
Investigations
Weight Increased	5/85 (5.9%)	5	13/110 (11.8%)	13
Nervous system disorders
Headache	2/85 (2.4%)	2	8/110 (7.3%)	12
Psychiatric disorders
Insomnia	9/85 (10.6%)	9	6/110 (5.5%)	7

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Except for compelling legal reasons, neither the sponsor nor the investigator will communicate to third parties any result of the clinical trial before the clinical trial report has been released by the sponsor.