Trial Outcomes & Findings for Long-term Study of Asenapine in Participants With Residual Subtype, Receiving Multiple or/and High Dose Drugs, or Treatment Refractory Schizophrenia (P06238) (NCT NCT01244828)
NCT ID: NCT01244828
Last Updated: 2024-05-28
Results Overview
For each participant, change from baseline in weight was calculated as the Week 52 value minus the baseline value.
COMPLETED
PHASE3
157 participants
Baseline and Week 52
2024-05-28
Participant Flow
Participant milestones
| Measure |
Asenapine
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.
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|---|---|
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Overall Study
STARTED
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157
|
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Overall Study
COMPLETED
|
79
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Overall Study
NOT COMPLETED
|
78
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Reasons for withdrawal
| Measure |
Asenapine
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.
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|---|---|
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Overall Study
Adverse Event
|
37
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Overall Study
Withdrawal by Subject
|
31
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Overall Study
Lack of Efficacy
|
7
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Overall Study
Lost to Follow-up
|
2
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Overall Study
Other reason (not specified)
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1
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Baseline Characteristics
Long-term Study of Asenapine in Participants With Residual Subtype, Receiving Multiple or/and High Dose Drugs, or Treatment Refractory Schizophrenia (P06238)
Baseline characteristics by cohort
| Measure |
Asenapine
n=157 Participants
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.
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|---|---|
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Age, Continuous
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56.37 years
STANDARD_DEVIATION 14.17 • n=5 Participants
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|
Sex: Female, Male
Female
|
76 Participants
n=5 Participants
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Sex: Female, Male
Male
|
81 Participants
n=5 Participants
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Weight
|
59.45 kg
STANDARD_DEVIATION 13.76 • n=5 Participants
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Body Mass index (BMI)
|
23.04 kg/m^2
STANDARD_DEVIATION 4.37 • n=5 Participants
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Hemoglobin A1c (HbA1c)
|
5.28 percent
STANDARD_DEVIATION 0.47 • n=5 Participants
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Fasting glucose
|
5.14 mmol/L
STANDARD_DEVIATION 0.74 • n=5 Participants
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Insulin
|
6.35 µIU/mL
STANDARD_DEVIATION 4.73 • n=5 Participants
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|
Prolactin
|
43.92 µg/L
STANDARD_DEVIATION 41.66 • n=5 Participants
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|
Positive and Negative Syndrome Scale (PANSS) total score
|
89.99 score on a scale
STANDARD_DEVIATION 18.31 • n=5 Participants
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PRIMARY outcome
Timeframe: Baseline and Week 52Population: Participants who received at least one dose of study drug and had both a baseline and a Week 52 value of the measure.
For each participant, change from baseline in weight was calculated as the Week 52 value minus the baseline value.
Outcome measures
| Measure |
Asenapine
n=79 Participants
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.
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|---|---|
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Change From Baseline in Weight at Week 52
|
0.25 kg
Standard Deviation 5.23
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PRIMARY outcome
Timeframe: Baseline and Week 52Population: Participants who received at least one dose of study drug and had both a baseline and a Week 52 value of the measure.
For each participant, change from baseline in BMI was calculated as the Week 52 value minus the baseline value.
Outcome measures
| Measure |
Asenapine
n=79 Participants
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.
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|---|---|
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Change From Baseline in BMI at Week 52
|
0.07 kg/m^2
Standard Deviation 1.93
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PRIMARY outcome
Timeframe: Up to 30 days after last dose of study drug (Up to approximately 56 weeks)Population: Participants who received at least one dose of study drug.
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.
Outcome measures
| Measure |
Asenapine
n=157 Participants
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.
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|---|---|
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Number of Participants With Extrapyramidal Symptoms
Any extrapyramidal symptom
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24 participants
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Number of Participants With Extrapyramidal Symptoms
Restlessness
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3 participants
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Number of Participants With Extrapyramidal Symptoms
Akathisia
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3 participants
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Number of Participants With Extrapyramidal Symptoms
Dystonia
|
2 participants
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Number of Participants With Extrapyramidal Symptoms
Extrapyramidal disorder
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10 participants
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|
Number of Participants With Extrapyramidal Symptoms
Parkinsonism
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1 participants
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Number of Participants With Extrapyramidal Symptoms
Tremor
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5 participants
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Number of Participants With Extrapyramidal Symptoms
Oculogyric crisis
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2 participants
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Number of Participants With Extrapyramidal Symptoms
Gait disturbance
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1 participants
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PRIMARY outcome
Timeframe: Baseline and Week 52Population: Participants who received at least one dose of study drug and had both a baseline and a Week 52 value of the measure.
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.
Outcome measures
| Measure |
Asenapine
n=79 Participants
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.
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|---|---|
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Change From Baseline in HbA1c at Week 52
|
0.00 percent
Standard Deviation 0.26
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PRIMARY outcome
Timeframe: Baseline and Week 52Population: Participants who received at least one dose of study drug and had both a baseline and a Week 52 value of the measure.
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.
Outcome measures
| Measure |
Asenapine
n=75 Participants
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.
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|---|---|
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Change From Baseline in Fasting Glucose at Week 52
|
0.11 mmol/L
Standard Deviation 0.63
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PRIMARY outcome
Timeframe: Baseline and Week 52Population: Participants who received at least one dose of study drug and had both a baseline and a Week 52 value of the measure.
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.
Outcome measures
| Measure |
Asenapine
n=79 Participants
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.
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|---|---|
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Change From Baseline in Insulin at Week 52
|
2.31 µIU/mL
Standard Deviation 11.93
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PRIMARY outcome
Timeframe: Baseline and Week 52Population: Participants who received at least one dose of study drug and had both a baseline and a Week 52 value of the measure.
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.
Outcome measures
| Measure |
Asenapine
n=79 Participants
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.
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|---|---|
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Change From Baseline in Prolactin at Week 52
|
0.66 µg/L
Standard Deviation 24.20
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PRIMARY outcome
Timeframe: Baseline and Week 52Population: Participants who received at least one dose of study drug and had both a baseline and a Week 52 PANSS measurement.
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.
Outcome measures
| Measure |
Asenapine
n=79 Participants
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.
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|---|---|
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Change From Baseline in PANSS Total Score at Week 52
|
-11.08 score on a scale
Standard Error 1.36
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PRIMARY outcome
Timeframe: Baseline up to Week 52Population: Participants who received at least one dose of study drug and had a baseline and at least one post-baseline PANSS measurement.
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.
Outcome measures
| Measure |
Asenapine
n=153 Participants
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.
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|---|---|
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Change From Baseline in PANSS Total Score at Final Assessment
|
-5.48 score on a scale
Standard Error 1.08
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Adverse Events
Asenapine
Serious adverse events
| Measure |
Asenapine
n=157 participants at risk
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.
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|---|---|
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Infections and infestations
Pneumonia
|
1.3%
2/157 • Number of events 2 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)
Analysis population is participants who received at least one dose of study drug.
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|
Infections and infestations
Abdominal abscess
|
0.64%
1/157 • Number of events 1 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)
Analysis population is participants who received at least one dose of study drug.
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|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder neoplasm
|
0.64%
1/157 • Number of events 1 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)
Analysis population is participants who received at least one dose of study drug.
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|
Psychiatric disorders
Completed suicide
|
0.64%
1/157 • Number of events 1 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)
Analysis population is participants who received at least one dose of study drug.
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Psychiatric disorders
Schizophrenia
|
2.5%
4/157 • Number of events 4 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)
Analysis population is participants who received at least one dose of study drug.
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Nervous system disorders
Postresuscitation encephalopathy
|
0.64%
1/157 • Number of events 1 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)
Analysis population is participants who received at least one dose of study drug.
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|
Cardiac disorders
Cardio-respiratory arrest
|
0.64%
1/157 • Number of events 1 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)
Analysis population is participants who received at least one dose of study drug.
|
|
Respiratory, thoracic and mediastinal disorders
Asphyxia
|
0.64%
1/157 • Number of events 1 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)
Analysis population is participants who received at least one dose of study drug.
|
|
Respiratory, thoracic and mediastinal disorders
Choking
|
0.64%
1/157 • Number of events 1 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)
Analysis population is participants who received at least one dose of study drug.
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia aspiration
|
1.3%
2/157 • Number of events 2 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)
Analysis population is participants who received at least one dose of study drug.
|
|
Gastrointestinal disorders
Ileus
|
0.64%
1/157 • Number of events 1 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)
Analysis population is participants who received at least one dose of study drug.
|
|
Gastrointestinal disorders
Intestinal obstruction
|
0.64%
1/157 • Number of events 1 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)
Analysis population is participants who received at least one dose of study drug.
|
|
Gastrointestinal disorders
Upper gastrointestinal haemorrhage
|
0.64%
1/157 • Number of events 1 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)
Analysis population is participants who received at least one dose of study drug.
|
|
General disorders
Asthenia
|
0.64%
1/157 • Number of events 1 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)
Analysis population is participants who received at least one dose of study drug.
|
|
General disorders
Death
|
0.64%
1/157 • Number of events 1 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)
Analysis population is participants who received at least one dose of study drug.
|
|
Investigations
Blood creatine phosphokinase increased
|
0.64%
1/157 • Number of events 1 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)
Analysis population is participants who received at least one dose of study drug.
|
Other adverse events
| Measure |
Asenapine
n=157 participants at risk
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.
|
|---|---|
|
Gastrointestinal disorders
Constipation
|
6.4%
10/157 • Number of events 11 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)
Analysis population is participants who received at least one dose of study drug.
|
|
Gastrointestinal disorders
Hypoaesthesia oral
|
10.8%
17/157 • Number of events 17 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)
Analysis population is participants who received at least one dose of study drug.
|
|
Gastrointestinal disorders
Salivary hypersecretion
|
5.1%
8/157 • Number of events 9 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)
Analysis population is participants who received at least one dose of study drug.
|
|
Gastrointestinal disorders
Vomiting
|
5.7%
9/157 • Number of events 9 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)
Analysis population is participants who received at least one dose of study drug.
|
|
General disorders
Pyrexia
|
8.9%
14/157 • Number of events 17 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)
Analysis population is participants who received at least one dose of study drug.
|
|
Infections and infestations
Nasopharyngitis
|
21.0%
33/157 • Number of events 63 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)
Analysis population is participants who received at least one dose of study drug.
|
|
Injury, poisoning and procedural complications
Contusion
|
6.4%
10/157 • Number of events 12 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)
Analysis population is participants who received at least one dose of study drug.
|
|
Injury, poisoning and procedural complications
Fall
|
6.4%
10/157 • Number of events 10 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)
Analysis population is participants who received at least one dose of study drug.
|
|
Investigations
Alanine aminotransferase increased
|
5.1%
8/157 • Number of events 8 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)
Analysis population is participants who received at least one dose of study drug.
|
|
Investigations
Aspartate aminotransferase increased
|
7.0%
11/157 • Number of events 11 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)
Analysis population is participants who received at least one dose of study drug.
|
|
Investigations
Blood creatine phosphokinase increased
|
6.4%
10/157 • Number of events 10 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)
Analysis population is participants who received at least one dose of study drug.
|
|
Investigations
Blood prolactin increased
|
5.1%
8/157 • Number of events 8 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)
Analysis population is participants who received at least one dose of study drug.
|
|
Investigations
Weight decreased
|
7.6%
12/157 • Number of events 12 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)
Analysis population is participants who received at least one dose of study drug.
|
|
Investigations
Weight increased
|
12.7%
20/157 • Number of events 20 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)
Analysis population is participants who received at least one dose of study drug.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
7.0%
11/157 • Number of events 11 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)
Analysis population is participants who received at least one dose of study drug.
|
|
Nervous system disorders
Extrapyramidal disorder
|
6.4%
10/157 • Number of events 10 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)
Analysis population is participants who received at least one dose of study drug.
|
|
Nervous system disorders
Headache
|
5.1%
8/157 • Number of events 9 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)
Analysis population is participants who received at least one dose of study drug.
|
|
Nervous system disorders
Somnolence
|
12.7%
20/157 • Number of events 21 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)
Analysis population is participants who received at least one dose of study drug.
|
|
Psychiatric disorders
Insomnia
|
5.1%
8/157 • Number of events 9 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)
Analysis population is participants who received at least one dose of study drug.
|
|
Psychiatric disorders
Schizophrenia
|
10.8%
17/157 • Number of events 17 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)
Analysis population is participants who received at least one dose of study drug.
|
|
Skin and subcutaneous tissue disorders
Eczema
|
5.7%
9/157 • Number of events 9 • Up to 30 days after last dose of study drug (Up to approximately 56 weeks)
Analysis population is participants who received at least one dose of study drug.
|
Additional Information
Senior Vice President, Global Clinical Development
Merck Sharp & Dohme Corp.
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER