Bipolar Depression
Conditions
Keywords
inpatient, bipolar depression, quetiapine, Seroquel IR, Seroquel XR, safety, tolerability
Brief summary
The purpose of the study is to compare the sedation profile one hour after dose administration between Seroquel IR and Seroquel XR.
Interventions
DRUGQuetiapine Immediate Release
Oral, 3 tablets daily: (2 x 25 mg + 1 x 50 mg) at one time each day
Oral, 3 tablets daily: (2 x 25 mg + 1 x 50 mg) at one time each day
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
* DSM-IV-TR documented bipolar I or bipolar II, most recent episode depressed * Outpatient status as enrollment
Exclusion criteria
* Other than bipolar disorder under study, patients must not have another current, major disorder that is symptomatic or has required treatment within 6 months of enrollment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Modified Bond-Lader Visual Analog Scale Score After 50-mg Dose (Day 2) | At 1 hour post-dose, Day 2 (50 mg) | The Modified Bond-Lader Visual Analog Scale (VAS) uses a 100 mm line, each with a set of opposing adjectives at either end:Alert (=0) - Drowsy (=100); If patient is sleeping the Bond-Lader VAS will be assign a score of 100. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Modified Bond-Lader Visual Analog Scale Score After 200-mg Dose (Day 4) | At 1 hour post-dose, Day 4 (200 mg) | The Modified Bond-Lader Visual Analog Scale (VAS) uses a 100 mm line, each with a set of opposing adjectives at either end:Alert (=0) - Drowsy (=100); If patient is sleeping the Bond-Lader VAS will be assign a score of 100. |
| Modified Bond-Lader Visual Analog Scale Score After 300-mg Dose (Day 5) | At 1 hour post-dose, Day 5 (300 mg) | The Modified Bond-Lader Visual Analog Scale (VAS) uses a 100 mm line, each with a set of opposing adjectives at either end:Alert (=0) - Drowsy (=100); If patient is sleeping the Bond-Lader VAS will be assign a score of 100. |
| Modified Bond-Lader Visual Analog Scale Score After 300-mg Dose (Day 6) | At 1 hour post-dose, Day 6 (300 mg) | The Modified Bond-Lader Visual Analog Scale (VAS) uses a 100 mm line, each with a set of opposing adjectives at either end:Alert (=0) - Drowsy (=100); If patient is sleeping the Bond-Lader VAS will be assign a score of 100. |
| Maximum Intensity Modified Bond-Lader Visual Analog Scale Score | During Day 2 (50 mg) | The Maximum Intensity Modified Bond-Lader VAS after dose (MaxIntVAS) is calculated as maximum possible value of VAS during that day at any from 1, 2, 3, 4, 5, 12, 13, 14 hours post-dose assessments |
| Time to Maximum Intensity Modified Bond-Lader Visual Analog Scale Score | During Day 2 (50 mg) | Time (Tmax) to Maximum Intensity Modified Bond-Lader VAS after dose is corresponding assessment time (one from 1, 2, 3, 4, 5, 12, 13, 14 hours post-dose) of MaxIntVas |
| Modified Bond-Lader Visual Analog Scale Score After 100-mg Dose (Day 3) | At 1 hour post-dose, Day 3 (100 mg) | The Modified Bond-Lader Visual Analog Scale (VAS) uses a 100 mm line, each with a set of opposing adjectives at either end:Alert (=0) - Drowsy (=100); If patient is sleeping the Bond-Lader VAS will be assign a score of 100. |
| Change in Simpson-Angus Scale (SAS) Total Score | Randomization to Day 7 | SAS total score is the sum of the 10 individual-item scores (range:0-40), with the score for each item ranging from 0 to 4, higher scores indicate greater severity of Parkinsonian symptoms. Change : total score at day 7 minus total score at randomization. Increase in Change of total score indicates an increase in extrapyramidal motor symptoms. |
| Change in Barnes Akathisia Rating Scale (BARS) Global Score | Randomization to Day 7 | BARS global score is the 4th individual-item score on the BARS scale,the Global Assessment of Akathisia, with the score ranging from 0 to 5. Change : score at day 7 minus score at randomization. Increase in Change of BARS global score indicates an increase in akathisia. |
| Change in Abnormal Involuntary Movement Scale (AIMS) Total Score | Randomization to Day 7 | AIMS total score is the sum of the 10 individual-item scores (range:0-40), with the score for each item ranging from 0 to 4. Change : total score at day 7 minus total score at randomization. Increase in Change of total score indicates an increase in abnormal voluntary movements. |
| Number of Patients With Potential Extrapyramidal Symptoms (EPS) | From start of the study treatment to last dose plus 30 days | Number of patients with adverse events potentially associated with EPS collected by MedDRA Preferred Terms as akathisia, extrapyramidal disorder, restlessness |
| Number of Patients With Potential Somnolence | From start of the study treatment to last dose plus 30 days | Number of patients with adverse events potentially associated with somnolence collected by MedDRA Preferred Terms as lethargy, sedation, somnolence |
| Area Under the Modified Bond-Lader Visual Analog Scale-time Curve | During Day 2 (50 mg) | Area under the Modified Bond-Lader VAS-time curve is calculated by the linear trapezoidal formula which equals sum of (Ck+Ck+1)/2 multiplied by the time interval between k and k+1 observations, where Ck and Ck+1 are the corresponding the intensity of sedation evaluations measured by the Modified Bond-Lader VAS from 1 to 14 hours post-dose |
Participant flow
Recruitment details
A 7-day, inpatient, multicenter, double-blind, double-dummy, randomized, parallel group, Phase IV study was done to compare the tolerability of quetiapine IR with quetiapine XR during initial dose escalation in patients with bipolar depression. In total 139 patients were randomized in 15 centers in the USA between June and August 2009.
Pre-assignment details
Patients must have DSM-IV-TR documented bipolar I or bipolar II, most recent episode depressed, and outpatient status at enrollment . Patients must not have another current, major disorder that is symptomatic or has required treatment within 6 months of enrollment.
Participants by arm
| Arm | Count |
|---|---|
| Quetiapine IR Quetiapine fumarate Immediate Release | 69 |
| Quetiapine XR Quetiapine fumarate Extended Release | 70 |
| Total | 139 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 2 |
Baseline characteristics
| Characteristic | Quetiapine IR | Quetiapine XR | Total |
|---|---|---|---|
| Age, Customized 18-39 | 28 Participants | 31 Participants | 59 Participants |
| Age, Customized 40-50 | 41 Participants | 39 Participants | 80 Participants |
| Sex: Female, Male Female | 32 Participants | 34 Participants | 66 Participants |
| Sex: Female, Male Male | 37 Participants | 36 Participants | 73 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 33 / 69 | 29 / 70 |
| serious Total, serious adverse events | 0 / 69 | 3 / 70 |
Outcome results
Primary
Modified Bond-Lader Visual Analog Scale Score After 50-mg Dose (Day 2)
The Modified Bond-Lader Visual Analog Scale (VAS) uses a 100 mm line, each with a set of opposing adjectives at either end:Alert (=0) - Drowsy (=100); If patient is sleeping the Bond-Lader VAS will be assign a score of 100.
Time frame: At 1 hour post-dose, Day 2 (50 mg)
Population: The modified intent-to-treat (MITT) analysis data set included all randomized patients who received study treatment, classified according to their randomized treatment and provided the Modified Bond-Lader VAS score at baseline (pre-dose at Day 1 or Day 2) and at least 1 hour after 50 mg dose administration.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Quetiapine IR | Modified Bond-Lader Visual Analog Scale Score After 50-mg Dose (Day 2) | 45.022 units on scale |
| Quetiapine XR | Modified Bond-Lader Visual Analog Scale Score After 50-mg Dose (Day 2) | 32.472 units on scale |
Secondary
Area Under the Modified Bond-Lader Visual Analog Scale-time Curve
Area under the Modified Bond-Lader VAS-time curve is calculated by the linear trapezoidal formula which equals sum of (Ck+Ck+1)/2 multiplied by the time interval between k and k+1 observations, where Ck and Ck+1 are the corresponding the intensity of sedation evaluations measured by the Modified Bond-Lader VAS from 1 to 14 hours post-dose
Time frame: During Day 2 (50 mg)
Population: The randomized safety analysis data set included all patients who received at 1 dose of randomized study treatment during the Randomized treatment Phase, classified according to actual treatment taken.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Quetiapine IR | Area Under the Modified Bond-Lader Visual Analog Scale-time Curve | 1061.12 mm * hour | Standard Error 31.559 |
| Quetiapine XR | Area Under the Modified Bond-Lader Visual Analog Scale-time Curve | 988.842 mm * hour | Standard Error 30.612 |
Secondary
Change in Abnormal Involuntary Movement Scale (AIMS) Total Score
AIMS total score is the sum of the 10 individual-item scores (range:0-40), with the score for each item ranging from 0 to 4. Change : total score at day 7 minus total score at randomization. Increase in Change of total score indicates an increase in abnormal voluntary movements.
Time frame: Randomization to Day 7
Population: The randomized safety analysis data set included all patients who received at 1 dose of randomized study treatment during the Randomized treatment Phase, classified according to actual treatment taken.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Quetiapine IR | Change in Abnormal Involuntary Movement Scale (AIMS) Total Score | -0.01 units on scale | Standard Deviation 0.3 |
| Quetiapine XR | Change in Abnormal Involuntary Movement Scale (AIMS) Total Score | -0.04 units on scale | Standard Deviation 0.4 |
Secondary
Change in Barnes Akathisia Rating Scale (BARS) Global Score
BARS global score is the 4th individual-item score on the BARS scale,the Global Assessment of Akathisia, with the score ranging from 0 to 5. Change : score at day 7 minus score at randomization. Increase in Change of BARS global score indicates an increase in akathisia.
Time frame: Randomization to Day 7
Population: The randomized safety analysis data set included all patients who received at 1 dose of randomized study treatment during the Randomized treatment Phase, classified according to actual treatment taken.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Quetiapine IR | Change in Barnes Akathisia Rating Scale (BARS) Global Score | -0.07 units on scale | Standard Deviation 0.43 |
| Quetiapine XR | Change in Barnes Akathisia Rating Scale (BARS) Global Score | -0.09 units on scale | Standard Deviation 0.45 |
Secondary
Change in Simpson-Angus Scale (SAS) Total Score
SAS total score is the sum of the 10 individual-item scores (range:0-40), with the score for each item ranging from 0 to 4, higher scores indicate greater severity of Parkinsonian symptoms. Change : total score at day 7 minus total score at randomization. Increase in Change of total score indicates an increase in extrapyramidal motor symptoms.
Time frame: Randomization to Day 7
Population: The randomized safety analysis data set included all patients who received at 1 dose of randomized study treatment during the Randomized treatment Phase, classified according to actual treatment taken.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Quetiapine IR | Change in Simpson-Angus Scale (SAS) Total Score | -0.1 units on scale | Standard Deviation 0.8 |
| Quetiapine XR | Change in Simpson-Angus Scale (SAS) Total Score | 0.1 units on scale | Standard Deviation 0.5 |
Secondary
Maximum Intensity Modified Bond-Lader Visual Analog Scale Score
The Maximum Intensity Modified Bond-Lader VAS after dose (MaxIntVAS) is calculated as maximum possible value of VAS during that day at any from 1, 2, 3, 4, 5, 12, 13, 14 hours post-dose assessments
Time frame: During Day 2 (50 mg)
Population: The modified intent-to-treat (MITT) analysis data set included all randomized patients who received study treatment, classified according to their randomized treatment and provided the Modified Bond-Lader VAS score at baseline (pre-dose at Day 1 or Day 2) and at least 1 hour after 50 mg dose administration.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Quetiapine IR | Maximum Intensity Modified Bond-Lader Visual Analog Scale Score | 99.929 units on scale | Standard Error 1.353 |
| Quetiapine XR | Maximum Intensity Modified Bond-Lader Visual Analog Scale Score | 96.937 units on scale | Standard Error 1.313 |
Secondary
Modified Bond-Lader Visual Analog Scale Score After 100-mg Dose (Day 3)
The Modified Bond-Lader Visual Analog Scale (VAS) uses a 100 mm line, each with a set of opposing adjectives at either end:Alert (=0) - Drowsy (=100); If patient is sleeping the Bond-Lader VAS will be assign a score of 100.
Time frame: At 1 hour post-dose, Day 3 (100 mg)
Population: The modified intent-to-treat (MITT) analysis data set included all randomized patients who received study treatment, classified according to their randomized treatment and provided the Modified Bond-Lader VAS score at baseline (pre-dose at Day 1 or Day 2) and at least 1 hour after 50 mg dose administration.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Quetiapine IR | Modified Bond-Lader Visual Analog Scale Score After 100-mg Dose (Day 3) | 51.521 units on scale | Standard Error 3.341 |
| Quetiapine XR | Modified Bond-Lader Visual Analog Scale Score After 100-mg Dose (Day 3) | 29.146 units on scale | Standard Error 3.239 |
Secondary
Modified Bond-Lader Visual Analog Scale Score After 200-mg Dose (Day 4)
The Modified Bond-Lader Visual Analog Scale (VAS) uses a 100 mm line, each with a set of opposing adjectives at either end:Alert (=0) - Drowsy (=100); If patient is sleeping the Bond-Lader VAS will be assign a score of 100.
Time frame: At 1 hour post-dose, Day 4 (200 mg)
Population: The modified intent-to-treat (MITT) analysis data set included all randomized patients who received study treatment, classified according to their randomized treatment and provided the Modified Bond-Lader VAS score at baseline (pre-dose at Day 1 or Day 2) and at least 1 hour after 50 mg dose administration.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Quetiapine IR | Modified Bond-Lader Visual Analog Scale Score After 200-mg Dose (Day 4) | 48.336 units on scale | Standard Error 3.703 |
| Quetiapine XR | Modified Bond-Lader Visual Analog Scale Score After 200-mg Dose (Day 4) | 30.130 units on scale | Standard Error 3.609 |
Secondary
Modified Bond-Lader Visual Analog Scale Score After 300-mg Dose (Day 5)
The Modified Bond-Lader Visual Analog Scale (VAS) uses a 100 mm line, each with a set of opposing adjectives at either end:Alert (=0) - Drowsy (=100); If patient is sleeping the Bond-Lader VAS will be assign a score of 100.
Time frame: At 1 hour post-dose, Day 5 (300 mg)
Population: The modified intent-to-treat (MITT) analysis data set included all randomized patients who received study treatment, classified according to their randomized treatment and provided the Modified Bond-Lader VAS score at baseline (pre-dose at Day 1 or Day 2) and at least 1 hour after 50 mg dose administration.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Quetiapine IR | Modified Bond-Lader Visual Analog Scale Score After 300-mg Dose (Day 5) | 49.414 units on scale | Standard Error 4.347 |
| Quetiapine XR | Modified Bond-Lader Visual Analog Scale Score After 300-mg Dose (Day 5) | 32.626 units on scale | Standard Error 4.258 |
Secondary
Modified Bond-Lader Visual Analog Scale Score After 300-mg Dose (Day 6)
The Modified Bond-Lader Visual Analog Scale (VAS) uses a 100 mm line, each with a set of opposing adjectives at either end:Alert (=0) - Drowsy (=100); If patient is sleeping the Bond-Lader VAS will be assign a score of 100.
Time frame: At 1 hour post-dose, Day 6 (300 mg)
Population: The modified intent-to-treat (MITT) analysis data set included all randomized patients who received study treatment, classified according to their randomized treatment and provided the Modified Bond-Lader VAS score at baseline (pre-dose at Day 1 or Day 2) and at least 1 hour after 50 mg dose administration.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Quetiapine IR | Modified Bond-Lader Visual Analog Scale Score After 300-mg Dose (Day 6) | 48.959 units on scale | Standard Error 4.015 |
| Quetiapine XR | Modified Bond-Lader Visual Analog Scale Score After 300-mg Dose (Day 6) | 30.144 units on scale | Standard Error 3.91 |
Secondary
Number of Patients With Potential Extrapyramidal Symptoms (EPS)
Number of patients with adverse events potentially associated with EPS collected by MedDRA Preferred Terms as akathisia, extrapyramidal disorder, restlessness
Time frame: From start of the study treatment to last dose plus 30 days
Population: The randomized safety analysis data set included all patients who received at 1 dose of randomized study treatment during the Randomized treatment Phase, classified according to actual treatment taken.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Quetiapine IR | Number of Patients With Potential Extrapyramidal Symptoms (EPS) | 8 Patients |
| Quetiapine XR | Number of Patients With Potential Extrapyramidal Symptoms (EPS) | 2 Patients |
Secondary
Number of Patients With Potential Somnolence
Number of patients with adverse events potentially associated with somnolence collected by MedDRA Preferred Terms as lethargy, sedation, somnolence
Time frame: From start of the study treatment to last dose plus 30 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Quetiapine IR | Number of Patients With Potential Somnolence | 11 Patients |
| Quetiapine XR | Number of Patients With Potential Somnolence | 12 Patients |
Secondary
Time to Maximum Intensity Modified Bond-Lader Visual Analog Scale Score
Time (Tmax) to Maximum Intensity Modified Bond-Lader VAS after dose is corresponding assessment time (one from 1, 2, 3, 4, 5, 12, 13, 14 hours post-dose) of MaxIntVas
Time frame: During Day 2 (50 mg)
Population: The modified intent-to-treat (MITT) analysis data set included all randomized patients who received study treatment, classified according to their randomized treatment and provided the Modified Bond-Lader VAS score at baseline (pre-dose at Day 1 or Day 2) and at least 1 hour after 50 mg dose administration.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Quetiapine IR | Time to Maximum Intensity Modified Bond-Lader Visual Analog Scale Score | 3.685 Hours | Standard Error 0.246 |
| Quetiapine XR | Time to Maximum Intensity Modified Bond-Lader Visual Analog Scale Score | 4.254 Hours | Standard Error 0.239 |