Study Comparing the Tolerability of Seroquel IR With Seroquel XR in Patients With Bipolar Depression

A Phase IV, Multi-center, Double-blind, Double-dummy, Randomized, Parallel-group Study to Compare the Tolerability of Quetiapine Fumarate Immediate Release (Seroquel IR) With Quetiapine Fumarate Extended Release (Seroquel XR) During Initial Dose Escalation in Patients With Bipolar Depression

The purpose of the study is to compare the sedation profile one hour after dose administration between Seroquel IR and Seroquel XR.

Study Overview

• Status: Completed
• Conditions: Bipolar Depression
• Intervention / Treatment: Drug: Quetiapine Immediate Release; Drug: Quetiapine Extended Release

• Study Type: Interventional
• Enrollment (Actual): 139
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Quetiapine Immediate Release (IR); Quetiapine 25, 100, 200 and 300 mg	Drug: Quetiapine Immediate Release; Oral, 3 tablets daily: (2 x 25 mg + 1 x 50 mg) at one time each day; Other Names: Seroquel IR
Active Comparator: Quetiapine Extended Release (XR); Quetiapine 50, 200, 300	Drug: Quetiapine Extended Release; Oral, 3 tablets daily: (2 x 25 mg + 1 x 50 mg) at one time each day; Other Names: Seroquel XR

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	At 1 hour post-dose, Day 2 (50 mg)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	At 1 hour post-dose, Day 3 (100 mg)
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.	At 1 hour post-dose, Day 4 (200 mg)
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.	At 1 hour post-dose, Day 5 (300 mg)
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.	At 1 hour post-dose, Day 6 (300 mg)
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	During Day 2 (50 mg)
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	During Day 2 (50 mg)
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	During Day 2 (50 mg)
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.	Randomization to Day 7
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.	Randomization to Day 7
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.	Randomization to Day 7
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	From start of the study treatment to last dose plus 30 days
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	From start of the study treatment to last dose plus 30 days

Collaborators and Investigators

• Sponsor: AstraZeneca

Publications and helpful links

General Publications

• Riesenberg RA, Baldytcheva I, Datto C. Self-reported sedation profile of quetiapine extended-release and quetiapine immediate-release during 6-day initial dose escalation in bipolar depression: a multicenter, randomized, double-blind, phase IV study. Clin Ther. 2012 Nov;34(11):2202-11. doi: 10.1016/j.clinthera.2012.09.002. Epub 2012 Oct 8.

Study record dates

Study Major Dates

• Study Start: June 1, 2009
• Primary Completion (Actual): August 1, 2009
• Study Completion (Actual): August 1, 2009

Study Registration Dates

• First Submitted: June 19, 2009
• First Submitted That Met QC Criteria: June 22, 2009
• First Posted (Estimate): June 23, 2009

Study Record Updates

• Last Update Posted (Estimate): May 11, 2011
• Last Update Submitted That Met QC Criteria: May 10, 2011
• Last Verified: May 1, 2011

More Information

Terms related to this study

• Keywords: tolerability; safety; quetiapine; Seroquel XR; bipolar depression; inpatient; Seroquel IR
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Bipolar and Related Disorders; Depression; Depressive Disorder; Bipolar Disorder; Physiological Effects of Drugs; Central Nervous System Depressants; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Antidepressive Agents; Quetiapine Fumarate
• Other Study ID Numbers: D1443C00040