Long-term Study of Asenapine in Participants With Residual Subtype, Receiving Multiple or/and High Dose Drugs, or Treatment Refractory Schizophrenia (P06238)

• Sponsor: Organon and Co (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01244828
• Collaborator: (none)
• Enrollment: 157
• Arm: 1
• Actual Duration (Months): 40.5

Study Details

Study Description

Brief Summary

This is a multi-site, open-label fixed-flexible dose long-term study of asenapine in participants with schizophrenia. Participants in this study consist of schizophrenia with residual subtype or receiving high dose/multiple antipsychotic drugs, treatment refractory, or elderly participants with schizophrenia. The treatment period is up to 52 weeks.

Condition or Disease	Intervention/Treatment	Phase
Schizophrenia	Drug: Asenapine	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 157 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Long-term Study of Asenapine in Subjects With Residual Subtype, Receiving Multiple or/and High Dose Drugs, or Treatment Refractory Schizophrenia (Protocol P06238)
• Actual Study Start Date: Apr 5, 2011
• Actual Primary Completion Date: Aug 21, 2014
• Actual Study Completion Date: Aug 21, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Asenapine Asenapine 5 mg twice daily (BID) for the first week of treatment, then either 5 mg or 10 mg BID.	Drug: Asenapine; 5 mg or 10 mg fast-dissolving sublingual tablets BID for up to 52 weeks

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Weight at Week 52 [Baseline and Week 52]

   For each participant, change from baseline in weight was calculated as the Week 52 value minus the baseline value.

2. Change From Baseline in BMI at Week 52 [Baseline and Week 52]

   For each participant, change from baseline in BMI was calculated as the Week 52 value minus the baseline value.

3. Number of Participants With Extrapyramidal Symptoms [Up to 30 days after last dose of study drug (Up to approximately 56 weeks)]

   This measure reports the overall number of participants with any of a group of adverse events that were defined to represent extrapyramidal symptoms. The number of participants with each of the individual adverse events within this definition is also presented, for terms that occurred in at least one participant. For this measure, all adverse event terms within the Medical Dictionary for Regulatory Activities (MedDRA) Standardized MedDRA Query (SMQ) for "extrapyramidal syndrome" were treated as extrapyramidal symptoms.

4. Change From Baseline in HbA1c at Week 52 [Baseline and Week 52]

   Blood samples for determination of HbA1c were obtained at baseline and during the study. For each participant, change from baseline in HbA1c at Week 52 was calculated as the Week 52 value minus the baseline value.

5. Change From Baseline in Fasting Glucose at Week 52 [Baseline and Week 52]

   Blood samples for determination of fasting glucose level were obtained at baseline and during the study. For each participant, change from baseline in fasting glucose at Week 52 was calculated as the Week 52 level minus the baseline level.

6. Change From Baseline in Insulin at Week 52 [Baseline and Week 52]

   Blood samples for determination of insulin level were obtained at baseline and during the study. For each participant, change from baseline in insulin at Week 52 was calculated as the Week 52 level minus the baseline level.

7. Change From Baseline in Prolactin at Week 52 [Baseline and Week 52]

   Blood samples for determination of prolactin level were obtained at baseline and during the study. For each participant, change from baseline in prolactin at Week 52 was calculated as the Week 52 level minus the baseline level.

8. Change From Baseline in PANSS Total Score at Week 52 [Baseline and Week 52]

   The PANSS is a 30-item clinician-rated instrument for assessing the symptoms of schizophrenia. It consists of 3 subscales: positive subscale (7 items), negative subscale (7 items), and general psychopathology subscale (16 items). Positive symptoms refer to an excess or distortion of normal mental status (e.g., delusions). Negative symptoms represent a diminution or loss of normal functions (e.g., emotional withdrawal). For each item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. The PANSS total score for each participant was calculated as the sum of the rating assigned to each of the 30 PANSS items, and ranged from 30 to 210 with a higher score indicating greater severity of symptoms. The reported measure is the change from baseline at Week 52 (calculated for a participant as Week 52 value minus baseline value); improvement in symptoms is represented by negative values.

9. Change From Baseline in PANSS Total Score at Final Assessment [Baseline up to Week 52]

   The PANSS is a 30-item clinician-rated instrument for assessing the symptoms of schizophrenia. It consists of 3 subscales: positive subscale (7 items), negative subscale (7 items), and general psychopathology subscale (16 items). Positive symptoms refer to an excess or distortion of normal mental status (e.g., delusions). Negative symptoms represent a diminution or loss of normal functions (e.g., emotional withdrawal). For each item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. The PANSS total score for each participant was calculated as the sum of the rating assigned to each of the 30 PANSS items, and ranged from 30 to 210 with a higher score indicating greater severity of symptoms. The reported measure is the change from baseline at the final assessment for a participant (calculated for a participant as final assessment value minus baseline value); improvement in symptoms is represented by negative values.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Minimum age of 20 years

• Participants who meet at least one of the following:

• current diagnosis of schizophrenia of residual subtype

• received treatment with 3 or more antipsychotic drugs

• treatment-refractory participants with schizophrenia

• 65 years old and over with positive schizophrenia symptoms with score of 3 (mild) or more in 1 or more items in the positive subscale of the Positive and Negative Syndrome Scale (PANSS) at the baseline

• Participants who have a Clinical Global Impressions-Severity (CGI-S) score of at least 4 (moderately ill) at the baseline

Exclusion Criteria:

• Uncontrolled, unstable clinically significant medical condition

• Clinically significant abnormal laboratory, vital sign, physical examination, or electrocardiogram (ECG) findings at Screening

• Positive pregnancy test at Screening, or the intention to become pregnant during the course of the study

• Seizure disorder beyond childhood (12 years old or younger)

• History of neuroleptic malignant syndrome

• Allergy or sensitivity to drugs such as psychotropics and antipsychotics

• Known history of or currently treated for narrow angle glaucoma

• Parkinson's disease

• Diagnosis of schizoaffective disorder; schizophreniform disorder

• Concurrent psychiatric disorder other than schizophrenia coded on Axis I; a primary diagnosis other than schizophrenia

• Diagnosis of borderline personality disorder

• Diagnosis of mental retardation or organic brain disorder

• Current (past 6 months) substance abuse or dependence according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria (excluding nicotine)

• Positive drug/alcohol tests at the Screening visit

• Imminent risk of self-harm or harm to others, in the Investigator's opinion

• Substance induced psychotic disorder or a behavioral disturbance thought to be due to substance abuse

• Currently under involuntary inpatient confinement

• Use of a non-approved drug in Japan within 12 weeks prior to informed consent

• Previously treated in an asenapine study

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Organon and Co

Investigators

• Study Director: Medical Director, Merck Sharp & Dohme LLC

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Organon and Co
• ClinicalTrials.gov Identifier: NCT01244828
• Other Study ID Numbers: P06238; 132325; MK-8274-042
• First Posted: Nov 19, 2010
• Last Update Posted: Feb 4, 2022
• Last Verified: Feb 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Additional relevant MeSH terms: Schizophrenia; Asenapine

Study Results

Participant Flow

Arm/Group Title	Asenapine
Arm/Group Description	All participants receive asenapine 5 mg twice daily (BID) for the first 7 days of treatment. After the initial 7-day period, the asenapine dose may be increased to 10 mg BID based on observed response to and toleration of the treatment. Asenapine dosing is flexible throughout the remainder of the study and may be adjusted, using the dose options of 5 and 10 mg BID, based on response and tolerability. The total duration of treatment is up to 52 weeks.
Period Title: Overall Study
STARTED	157
COMPLETED	79
NOT COMPLETED	78

Baseline Characteristics

Arm/Group Title	Asenapine
Arm/Group Description	All participants receive asenapine 5 mg BID for the first 7 days of treatment. After the initial 7-day period, the asenapine dose may be increased to 10 mg BID based on observed response to and toleration of the treatment. Asenapine dosing is flexible throughout the remainder of the study and may be adjusted, using the dose options of 5 and 10 mg BID, based on response and tolerability. The total duration of treatment is up to 52 weeks.
Overall Participants	157
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	56.37 (14.17)
Sex: Female, Male (Count of Participants)
Female	76 48.4%
Male	81 51.6%
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	59.45 (13.76)
Body Mass index (BMI) (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	23.04 (4.37)
Hemoglobin A1c (HbA1c) (percent) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percent]	5.28 (0.47)
Fasting glucose (mmol/L) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmol/L]	5.14 (0.74)
Insulin (µIU/mL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [µIU/mL]	6.35 (4.73)
Prolactin (µg/L) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [µg/L]	43.92 (41.66)
Positive and Negative Syndrome Scale (PANSS) total score (score on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [score on a scale]	89.99 (18.31)

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Weight at Week 52
Description	For each participant, change from baseline in weight was calculated as the Week 52 value minus the baseline value.
Time Frame	Baseline and Week 52

Outcome Measure Data

Analysis Population Description

Participants who received at least one dose of study drug and had both a baseline and a Week 52 value of the measure.

Arm/Group Title	Asenapine
Arm/Group Description	All participants receive asenapine 5 mg BID for the first 7 days of treatment. After the initial 7-day period, the asenapine dose may be increased to 10 mg BID based on observed response to and toleration of the treatment. Asenapine dosing is flexible throughout the remainder of the study and may be adjusted, using the dose options of 5 and 10 mg BID, based on response and tolerability. The total duration of treatment is up to 52 weeks.
Measure Participants	79
Mean (Standard Deviation) [kg]	0.25 (5.23)

2. Primary Outcome

Title	Change From Baseline in BMI at Week 52
Description	For each participant, change from baseline in BMI was calculated as the Week 52 value minus the baseline value.
Time Frame	Baseline and Week 52

Outcome Measure Data

Analysis Population Description

Participants who received at least one dose of study drug and had both a baseline and a Week 52 value of the measure.

Arm/Group Title	Asenapine
Arm/Group Description	All participants receive asenapine 5 mg BID for the first 7 days of treatment. After the initial 7-day period, the asenapine dose may be increased to 10 mg BID based on observed response to and toleration of the treatment. Asenapine dosing is flexible throughout the remainder of the study and may be adjusted, using the dose options of 5 and 10 mg BID, based on response and tolerability. The total duration of treatment is up to 52 weeks.
Measure Participants	79
Mean (Standard Deviation) [kg/m^2]	0.07 (1.93)

3. Primary Outcome

Title	Number of Participants With Extrapyramidal Symptoms
Description	This measure reports the overall number of participants with any of a group of adverse events that were defined to represent extrapyramidal symptoms. The number of participants with each of the individual adverse events within this definition is also presented, for terms that occurred in at least one participant. For this measure, all adverse event terms within the Medical Dictionary for Regulatory Activities (MedDRA) Standardized MedDRA Query (SMQ) for "extrapyramidal syndrome" were treated as extrapyramidal symptoms.
Time Frame	Up to 30 days after last dose of study drug (Up to approximately 56 weeks)

Outcome Measure Data

Analysis Population Description

Participants who received at least one dose of study drug.

Arm/Group Title	Asenapine
Arm/Group Description	All participants receive asenapine 5 mg BID for the first 7 days of treatment. After the initial 7-day period, the asenapine dose may be increased to 10 mg BID based on observed response to and toleration of the treatment. Asenapine dosing is flexible throughout the remainder of the study and may be adjusted, using the dose options of 5 and 10 mg BID, based on response and tolerability. The total duration of treatment is up to 52 weeks.
Measure Participants	157
Any extrapyramidal symptom	24 15.3%
Restlessness	3 1.9%
Akathisia	3 1.9%
Dystonia	2 1.3%
Extrapyramidal disorder	10 6.4%
Parkinsonism	1 0.6%
Tremor	5 3.2%
Oculogyric crisis	2 1.3%
Gait disturbance	1 0.6%

4. Primary Outcome

Title	Change From Baseline in HbA1c at Week 52
Description	Blood samples for determination of HbA1c were obtained at baseline and during the study. For each participant, change from baseline in HbA1c at Week 52 was calculated as the Week 52 value minus the baseline value.
Time Frame	Baseline and Week 52

Outcome Measure Data

Analysis Population Description

Participants who received at least one dose of study drug and had both a baseline and a Week 52 value of the measure.

Arm/Group Title	Asenapine
Arm/Group Description	All participants receive asenapine 5 mg BID for the first 7 days of treatment. After the initial 7-day period, the asenapine dose may be increased to 10 mg BID based on observed response to and toleration of the treatment. Asenapine dosing is flexible throughout the remainder of the study and may be adjusted, using the dose options of 5 and 10 mg BID, based on response and tolerability. The total duration of treatment is up to 52 weeks.
Measure Participants	79
Mean (Standard Deviation) [percent]	0.00 (0.26)

5. Primary Outcome

Title	Change From Baseline in Fasting Glucose at Week 52
Description	Blood samples for determination of fasting glucose level were obtained at baseline and during the study. For each participant, change from baseline in fasting glucose at Week 52 was calculated as the Week 52 level minus the baseline level.
Time Frame	Baseline and Week 52

Outcome Measure Data

Analysis Population Description

Participants who received at least one dose of study drug and had both a baseline and a Week 52 value of the measure.

Arm/Group Title	Asenapine
Arm/Group Description	All participants receive asenapine 5 mg BID for the first 7 days of treatment. After the initial 7-day period, the asenapine dose may be increased to 10 mg BID based on observed response to and toleration of the treatment. Asenapine dosing is flexible throughout the remainder of the study and may be adjusted, using the dose options of 5 and 10 mg BID, based on response and tolerability. The total duration of treatment is up to 52 weeks.
Measure Participants	75
Mean (Standard Deviation) [mmol/L]	0.11 (0.63)

6. Primary Outcome

Title	Change From Baseline in Insulin at Week 52
Description	Blood samples for determination of insulin level were obtained at baseline and during the study. For each participant, change from baseline in insulin at Week 52 was calculated as the Week 52 level minus the baseline level.
Time Frame	Baseline and Week 52

Outcome Measure Data

Analysis Population Description

Participants who received at least one dose of study drug and had both a baseline and a Week 52 value of the measure.

Arm/Group Title	Asenapine
Arm/Group Description	All participants receive asenapine 5 mg BID for the first 7 days of treatment. After the initial 7-day period, the asenapine dose may be increased to 10 mg BID based on observed response to and toleration of the treatment. Asenapine dosing is flexible throughout the remainder of the study and may be adjusted, using the dose options of 5 and 10 mg BID, based on response and tolerability. The total duration of treatment is up to 52 weeks.
Measure Participants	79
Mean (Standard Deviation) [µIU/mL]	2.31 (11.93)

7. Primary Outcome

Title	Change From Baseline in Prolactin at Week 52
Description	Blood samples for determination of prolactin level were obtained at baseline and during the study. For each participant, change from baseline in prolactin at Week 52 was calculated as the Week 52 level minus the baseline level.
Time Frame	Baseline and Week 52

Outcome Measure Data

Analysis Population Description

Participants who received at least one dose of study drug and had both a baseline and a Week 52 value of the measure.

Arm/Group Title	Asenapine
Arm/Group Description	All participants receive asenapine 5 mg BID for the first 7 days of treatment. After the initial 7-day period, the asenapine dose may be increased to 10 mg BID based on observed response to and toleration of the treatment. Asenapine dosing is flexible throughout the remainder of the study and may be adjusted, using the dose options of 5 and 10 mg BID, based on response and tolerability. The total duration of treatment is up to 52 weeks.
Measure Participants	79
Mean (Standard Deviation) [µg/L]	0.66 (24.20)

8. Primary Outcome

Title	Change From Baseline in PANSS Total Score at Week 52
Description	The PANSS is a 30-item clinician-rated instrument for assessing the symptoms of schizophrenia. It consists of 3 subscales: positive subscale (7 items), negative subscale (7 items), and general psychopathology subscale (16 items). Positive symptoms refer to an excess or distortion of normal mental status (e.g., delusions). Negative symptoms represent a diminution or loss of normal functions (e.g., emotional withdrawal). For each item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. The PANSS total score for each participant was calculated as the sum of the rating assigned to each of the 30 PANSS items, and ranged from 30 to 210 with a higher score indicating greater severity of symptoms. The reported measure is the change from baseline at Week 52 (calculated for a participant as Week 52 value minus baseline value); improvement in symptoms is represented by negative values.
Time Frame	Baseline and Week 52

Outcome Measure Data

Analysis Population Description

Participants who received at least one dose of study drug and had both a baseline and a Week 52 PANSS measurement.

Arm/Group Title	Asenapine
Arm/Group Description	All participants receive asenapine 5 mg BID for the first 7 days of treatment. After the initial 7-day period, the asenapine dose may be increased to 10 mg BID based on observed response to and toleration of the treatment. Asenapine dosing is flexible throughout the remainder of the study and may be adjusted, using the dose options of 5 and 10 mg BID, based on response and tolerability. The total duration of treatment is up to 52 weeks.
Measure Participants	79
Mean (Standard Error) [score on a scale]	-11.08 (1.36)

9. Primary Outcome

Title	Change From Baseline in PANSS Total Score at Final Assessment
Description	The PANSS is a 30-item clinician-rated instrument for assessing the symptoms of schizophrenia. It consists of 3 subscales: positive subscale (7 items), negative subscale (7 items), and general psychopathology subscale (16 items). Positive symptoms refer to an excess or distortion of normal mental status (e.g., delusions). Negative symptoms represent a diminution or loss of normal functions (e.g., emotional withdrawal). For each item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. The PANSS total score for each participant was calculated as the sum of the rating assigned to each of the 30 PANSS items, and ranged from 30 to 210 with a higher score indicating greater severity of symptoms. The reported measure is the change from baseline at the final assessment for a participant (calculated for a participant as final assessment value minus baseline value); improvement in symptoms is represented by negative values.
Time Frame	Baseline up to Week 52

Outcome Measure Data

Analysis Population Description

Participants who received at least one dose of study drug and had a baseline and at least one post-baseline PANSS measurement.

Arm/Group Title	Asenapine
Arm/Group Description	All participants receive asenapine 5 mg BID for the first 7 days of treatment. After the initial 7-day period, the asenapine dose may be increased to 10 mg BID based on observed response to and toleration of the treatment. Asenapine dosing is flexible throughout the remainder of the study and may be adjusted, using the dose options of 5 and 10 mg BID, based on response and tolerability. The total duration of treatment is up to 52 weeks.
Measure Participants	153
Mean (Standard Error) [score on a scale]	-5.48 (1.08)

Adverse Events

Time Frame	Up to 30 days after last dose of study drug (Up to approximately 56 weeks)
Adverse Event Reporting Description	Analysis population is participants who received at least one dose of study drug.
Arm/Group Title	Asenapine
Arm/Group Description	All participants receive asenapine 5 mg BID for the first 7 days of treatment. After the initial 7-day period, the asenapine dose may be increased to 10 mg BID based on observed response to and toleration of the treatment. Asenapine dosing is flexible throughout the remainder of the study and may be adjusted, using the dose options of 5 and 10 mg BID, based on response and tolerability. The total duration of treatment is up to 52 weeks.
All Cause Mortality
	Asenapine
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Asenapine
	Affected / at Risk (%)	# Events
Total	14/157 (8.9%)
Cardiac disorders
Cardio-respiratory arrest	1/157 (0.6%)	1
Gastrointestinal disorders
Ileus	1/157 (0.6%)	1
Intestinal obstruction	1/157 (0.6%)	1
Upper gastrointestinal haemorrhage	1/157 (0.6%)	1
General disorders
Asthenia	1/157 (0.6%)	1
Death	1/157 (0.6%)	1
Infections and infestations
Pneumonia	2/157 (1.3%)	2
Abdominal abscess	1/157 (0.6%)	1
Investigations
Blood creatine phosphokinase increased	1/157 (0.6%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder neoplasm	1/157 (0.6%)	1
Nervous system disorders
Postresuscitation encephalopathy	1/157 (0.6%)	1
Psychiatric disorders
Completed suicide	1/157 (0.6%)	1
Schizophrenia	4/157 (2.5%)	4
Respiratory, thoracic and mediastinal disorders
Asphyxia	1/157 (0.6%)	1
Choking	1/157 (0.6%)	1
Pneumonia aspiration	2/157 (1.3%)	2
Other (Not Including Serious) Adverse Events
	Asenapine
	Affected / at Risk (%)	# Events
Total	111/157 (70.7%)
Gastrointestinal disorders
Constipation	10/157 (6.4%)	11
Hypoaesthesia oral	17/157 (10.8%)	17
Salivary hypersecretion	8/157 (5.1%)	9
Vomiting	9/157 (5.7%)	9
General disorders
Pyrexia	14/157 (8.9%)	17
Infections and infestations
Nasopharyngitis	33/157 (21%)	63
Injury, poisoning and procedural complications
Contusion	10/157 (6.4%)	12
Fall	10/157 (6.4%)	10
Investigations
Alanine aminotransferase increased	8/157 (5.1%)	8
Aspartate aminotransferase increased	11/157 (7%)	11
Blood creatine phosphokinase increased	10/157 (6.4%)	10
Blood prolactin increased	8/157 (5.1%)	8
Weight decreased	12/157 (7.6%)	12
Weight increased	20/157 (12.7%)	20
Musculoskeletal and connective tissue disorders
Back pain	11/157 (7%)	11
Nervous system disorders
Extrapyramidal disorder	10/157 (6.4%)	10
Headache	8/157 (5.1%)	9
Somnolence	20/157 (12.7%)	21
Psychiatric disorders
Insomnia	8/157 (5.1%)	9
Schizophrenia	17/157 (10.8%)	17
Skin and subcutaneous tissue disorders
Eczema	9/157 (5.7%)	9

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Initial public presentation of the Investigator's results will occur only together with the other sites unless permission is obtained from Sponsor. Sponsor must be able to review all proposed results communications regarding study 45 days prior to submission for publication/presentation. In case of disagreement concerning appropriateness of materials, Investigator and Sponsor must meet to make a good faith effort to discuss/resolve the issues, prior to submission for publication/presentation.