Trial Outcomes & Findings for Quetiapine Fumarate (SEROQUEL) in the Treatment of Adolescent Patients With Schizophrenia and Bipolar I Disorder (NCT NCT00227305)

NCT ID: NCT00227305

Last Updated: 2013-01-08

Results Overview

Number of participants that had AE which occurred from first dose date to last dose date + 30 days.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 381 participants
• Primary outcome timeframe: from open label to week 26+ 30 days
• Results posted on: 2013-01-08

Participant Flow

Enrollment was contingent on completing one of 2 short term efficacy studies, recruitment period August 2004 through July 2007 at 59 international clinical research sites

Required to have completed one feeder study, either bipolar mania study D1441C00149 or schizophrenia study D1441C00112 and be willing to participate in a 26 week open label study and be between the ages of 10 and 18 years at the time of consent for this study, initial titration to maintain blind in feeder study

Participant milestones

Measure	Quetiapine Quetiapine 400mg/day to 800mg/day
Overall Study STARTED	381
Overall Study Drug Received	380
Overall Study COMPLETED	237
Overall Study NOT COMPLETED	144

Reasons for withdrawal

Measure	Quetiapine Quetiapine 400mg/day to 800mg/day
Overall Study Adverse Event	40
Overall Study Withdrawal by Subject	42
Overall Study Lost to Follow-up	33
Overall Study Study specific discontinuation	13
Overall Study MOVED OUT OF AREA	3
Overall Study Lack of Efficacy	7
Overall Study Physician Decision	3
Overall Study PERIOD SHORTENED FROM 6 wks to 4 wks	1
Overall Study LEAVING TOWN FOR 6 WEEKS	1
Overall Study NECESSITY OF USING ANTI DEPRESSANT	1

Baseline Characteristics

Quetiapine Fumarate (SEROQUEL) in the Treatment of Adolescent Patients With Schizophrenia and Bipolar I Disorder

Baseline characteristics by cohort

Measure	Quetiapine n=380 Participants Quetiapine 400mg/day to 800mg/day
Age, Customized 10 - 12 years	87 Participants n=5 Participants
Age, Customized 13 - 18 years	293 Participants n=5 Participants
Sex: Female, Male Female	154 Participants n=5 Participants
Sex: Female, Male Male	226 Participants n=5 Participants
Diagnosis Bipolar	205 participant from feeder studies n=5 Participants
Diagnosis Schizophrenia	175 participant from feeder studies n=5 Participants

PRIMARY outcome

Timeframe: from open label to week 26+ 30 days

Number of participants that had AE which occurred from first dose date to last dose date + 30 days.

Outcome measures

Measure	Quetiapine n=380 Participants Quetiapine 400mg/day to 800mg/day
Incidence and Nature of Adverse Events (AEs)	321 Participants

PRIMARY outcome

Timeframe: during 26 weeks of treatment

Number of subjects who withdrew from the study due to AEs.

Outcome measures

Measure	Quetiapine n=380 Participants Quetiapine 400mg/day to 800mg/day
Number of Patients Withdrawn Due to AEs.	37 Participants

PRIMARY outcome

Timeframe: Duration of study participation

Clinical important shift to high prolactin from open-label (OL) baseline to week 26.

High Prolactin is defined as value >26 ug/L for female and value >20 ug/L for male.

Outcome measures

Measure	Quetiapine n=380 Participants Quetiapine 400mg/day to 800mg/day
Changes in Laboratory Test Results (Prolactin)	19 Participants

PRIMARY outcome

Timeframe: OL baseline to week 26

Population: Number of patients with SAS score at OL baseline and week 26.

Number of patients for who the total score is estimated as worse. The Simpson Angus Scale (SAS)is used to assess Parkinsonian symptoms (a type of movement disorders). The score was calculated as the sum of the 10 individual item scores. Total Score ranges from 0-40 (normal to worse). Individual item scale range from 0 to 4 (normal to worse).

Improved define as those with a <= -1 change in SAS total score. Worsened defined as those with a >=1 change in SAS total score.

Outcome measures

Measure	Quetiapine n=373 Participants Quetiapine 400mg/day to 800mg/day
Categorical Change From OL Baseline to Week 26 in Simpson-Angus Scale (SAS)Total Score	34 Participants

PRIMARY outcome

Timeframe: 26 weeks of treatment

Population: Number of patients with BARS score at OL baseline and week 26.

Number of patients for who the total score is estimated as worse. The Barnes Akathisia Rating Scale (BARS) global score is used to measure Akathisia (a type of movement disorders). BARS is the item 4 score from the BARS assessment. The scale is from a range 0-5 (normal to worse). Change from baseline in BARS global score increase means worse.

Improved defined as those with a <= -1 change in BARS global score. Worsened defined as those with a >= 1 change in BARS global score.

Outcome measures

Measure	Quetiapine n=373 Participants Quetiapine 400mg/day to 800mg/day
Categorical Change From Baseline in Barnes Akathisia Rating Scale (BARS) Global Score	11 Participants

PRIMARY outcome

Timeframe: 26 weeks of treatment

Population: Number of participants is based on patients with both baseline values and post-baseline values.

Number with 7% or more increase (without adjustment for normal growth)

Outcome measures

Measure	Quetiapine n=373 Participants Quetiapine 400mg/day to 800mg/day
Change From Baseline in Weight	134 Participants

PRIMARY outcome

Timeframe: OL baseline to week 26

Population: Number of participants with OL baseline and post treatment visits

Change from OL baseline to week 26 in supine pulse (bpm)

Outcome measures

Measure	Quetiapine n=375 Participants Quetiapine 400mg/day to 800mg/day
Change From Baseline in Supine Pulse	0.8 bpm Standard Deviation 14.75

PRIMARY outcome

Timeframe: OL baseline to Week 26

Population: Number of participants with OL baseline and post treatment visits

Changes from OL baseline to the final visits in Supine systolic BP (mmHg)

Outcome measures

Measure	Quetiapine n=375 Participants Quetiapine 400mg/day to 800mg/day
Change From OL Baseline in Supine Systolic BP.	1.7 mmHg Standard Deviation 11.52

PRIMARY outcome

Timeframe: OL baseline to Week 26

Population: Number of participants with OL baseline and post treatment visits

Changes from OL baseline to the final visits in Supine diastolic BP (mmHg)

Outcome measures

Measure	Quetiapine n=375 Participants Quetiapine 400mg/day to 800mg/day
Change From OL Baseline in Supine Diastolic BP.	1.3 mmHg Standard Deviation 9.22

SECONDARY outcome

Timeframe: Change from OL baseline to week 26 in the Tanner stage

Population: Number of patients with Tanner stagging data at OL baseline and week 26 (final visit)

Category shift in Tanner stage. Number of subjects who experienced the change is presented.

Tanner stages (I-V) was used to characterize physical development in children, adolescents, and adults. The stages was based on external primary and secondary sex characteristics, such as the size of the breasts, genitalia, and development of pubic hair. Tanner stage is considered going up when the organs grow bigger.

Outcome measures

Measure	Quetiapine n=373 Participants Quetiapine 400mg/day to 800mg/day
Changes in Tanner Stage	70 Participants

SECONDARY outcome

Timeframe: OL Baseline to Week 26

Population: Number of patients with CGAS score at OL baseline and week 26.

Children's Global Assessment Scale (CGAS) is used to rate the general functioning of children under the age of 18. It is the 100-point single-item score that was collected in the Clinical Report Form (CRF), scored from 0-100 (worse to normal).

Outcome measures

Measure	Quetiapine n=320 Participants Quetiapine 400mg/day to 800mg/day
Change From Baseline in Children's Global Assessment Scale (CGAS) Score	7 units on a scale Standard Deviation 13.9

Adverse Events

Quetiapine

Serious events: 46 serious events

Other events: 340 other events

Deaths: 0 deaths

Serious adverse events

Measure	Quetiapine n=380 participants at risk Quetiapine 400mg/day to 800mg/day
Psychiatric disorders Abnormal Behaviour	0.26% 1/380 • Other AE module includes adverse events which occurred before first dose date to last dose date + 30 days.
Psychiatric disorders Aggression	1.1% 4/380 • Other AE module includes adverse events which occurred before first dose date to last dose date + 30 days.
Psychiatric disorders Agitation	0.26% 1/380 • Other AE module includes adverse events which occurred before first dose date to last dose date + 30 days.
Infections and infestations Amoebiasis	0.26% 1/380 • Other AE module includes adverse events which occurred before first dose date to last dose date + 30 days.
Infections and infestations Appendicitis	0.53% 2/380 • Other AE module includes adverse events which occurred before first dose date to last dose date + 30 days.
Infections and infestations Bacterial Infection	0.26% 1/380 • Other AE module includes adverse events which occurred before first dose date to last dose date + 30 days.
Psychiatric disorders Bipola Disorder	3.2% 12/380 • Other AE module includes adverse events which occurred before first dose date to last dose date + 30 days.
Infections and infestations Cellulitis Staphylococcal	0.26% 1/380 • Other AE module includes adverse events which occurred before first dose date to last dose date + 30 days.
Gastrointestinal disorders Constipation	0.26% 1/380 • Other AE module includes adverse events which occurred before first dose date to last dose date + 30 days.
Metabolism and nutrition disorders Decreased Appetite	0.26% 1/380 • Other AE module includes adverse events which occurred before first dose date to last dose date + 30 days.
Psychiatric disorders Delusion	0.26% 1/380 • Other AE module includes adverse events which occurred before first dose date to last dose date + 30 days.
Psychiatric disorders Disinhibition	0.26% 1/380 • Other AE module includes adverse events which occurred before first dose date to last dose date + 30 days.
Injury, poisoning and procedural complications Drug Toxicity	0.26% 1/380 • Other AE module includes adverse events which occurred before first dose date to last dose date + 30 days.
Psychiatric disorders Hallucitnation Auditory	0.26% 1/380 • Other AE module includes adverse events which occurred before first dose date to last dose date + 30 days.
Psychiatric disorders Hostility	0.26% 1/380 • Other AE module includes adverse events which occurred before first dose date to last dose date + 30 days.
Metabolism and nutrition disorders Hyperglycaemia	0.26% 1/380 • Other AE module includes adverse events which occurred before first dose date to last dose date + 30 days.
Vascular disorders Hypertensive Crisis	0.26% 1/380 • Other AE module includes adverse events which occurred before first dose date to last dose date + 30 days.
General disorders Irritability	0.26% 1/380 • Other AE module includes adverse events which occurred before first dose date to last dose date + 30 days.
Psychiatric disorders Mania	0.26% 1/380 • Other AE module includes adverse events which occurred before first dose date to last dose date + 30 days.
Cardiac disorders Myocarditis Post Infection	0.26% 1/380 • Other AE module includes adverse events which occurred before first dose date to last dose date + 30 days.
Blood and lymphatic system disorders Neutropenia	0.26% 1/380 • Other AE module includes adverse events which occurred before first dose date to last dose date + 30 days.
Injury, poisoning and procedural complications Overdose	0.53% 2/380 • Other AE module includes adverse events which occurred before first dose date to last dose date + 30 days.
Psychiatric disorders Perceptual Alteration Paroxysmal	0.26% 1/380 • Other AE module includes adverse events which occurred before first dose date to last dose date + 30 days.
Vascular disorders Physical Assault	0.26% 1/380 • Other AE module includes adverse events which occurred before first dose date to last dose date + 30 days.
Psychiatric disorders Pyschotic Disorder	0.53% 2/380 • Other AE module includes adverse events which occurred before first dose date to last dose date + 30 days.
Respiratory, thoracic and mediastinal disorders Pulmonary Hypertension	0.26% 1/380 • Other AE module includes adverse events which occurred before first dose date to last dose date + 30 days.
Respiratory, thoracic and mediastinal disorders Pyrexia	0.26% 1/380 • Other AE module includes adverse events which occurred before first dose date to last dose date + 30 days.
Psychiatric disorders Restlessness	0.26% 1/380 • Other AE module includes adverse events which occurred before first dose date to last dose date + 30 days.
Psychiatric disorders Schizophrenia	2.1% 8/380 • Other AE module includes adverse events which occurred before first dose date to last dose date + 30 days.
Psychiatric disorders Schizophrenia, Paraniod Type	0.26% 1/380 • Other AE module includes adverse events which occurred before first dose date to last dose date + 30 days.
Infections and infestations Staphylococcal Infection	0.26% 1/380 • Other AE module includes adverse events which occurred before first dose date to last dose date + 30 days.
Psychiatric disorders Suicide Attempt	0.26% 1/380 • Other AE module includes adverse events which occurred before first dose date to last dose date + 30 days.
Nervous system disorders Syncope	0.26% 1/380 • Other AE module includes adverse events which occurred before first dose date to last dose date + 30 days.
Infections and infestations Typhoid Fever	0.26% 1/380 • Other AE module includes adverse events which occurred before first dose date to last dose date + 30 days.
Infections and infestations Upper Respiratory Tract Infection	0.26% 1/380 • Other AE module includes adverse events which occurred before first dose date to last dose date + 30 days.
Infections and infestations Urinary Tract Infection	0.26% 1/380 • Other AE module includes adverse events which occurred before first dose date to last dose date + 30 days.

Other adverse events

Measure	Quetiapine n=380 participants at risk Quetiapine 400mg/day to 800mg/day
Psychiatric disorders AGITATION	6.8% 26/380 • Other AE module includes adverse events which occurred before first dose date to last dose date + 30 days.
Nervous system disorders DIZZINESS	6.8% 26/380 • Other AE module includes adverse events which occurred before first dose date to last dose date + 30 days.
Gastrointestinal disorders DRY MOUTH	9.2% 35/380 • Other AE module includes adverse events which occurred before first dose date to last dose date + 30 days.
Gastrointestinal disorders FATIGUE	5.3% 20/380 • Other AE module includes adverse events which occurred before first dose date to last dose date + 30 days.
Nervous system disorders HEADACHE	11.3% 43/380 • Other AE module includes adverse events which occurred before first dose date to last dose date + 30 days.
Metabolism and nutrition disorders INCREASED APPETITE	20.0% 76/380 • Other AE module includes adverse events which occurred before first dose date to last dose date + 30 days.
Psychiatric disorders INSOMNIA	11.3% 43/380 • Other AE module includes adverse events which occurred before first dose date to last dose date + 30 days.
Psychiatric disorders IRRITABILITY	6.1% 23/380 • Other AE module includes adverse events which occurred before first dose date to last dose date + 30 days.
Respiratory, thoracic and mediastinal disorders NASAL CONGESTION	5.3% 20/380 • Other AE module includes adverse events which occurred before first dose date to last dose date + 30 days.
Gastrointestinal disorders NAUSEA	10.3% 39/380 • Other AE module includes adverse events which occurred before first dose date to last dose date + 30 days.
Nervous system disorders SEDATION	18.9% 72/380 • Other AE module includes adverse events which occurred before first dose date to last dose date + 30 days.
Nervous system disorders SOMNOLENCE	30.3% 115/380 • Other AE module includes adverse events which occurred before first dose date to last dose date + 30 days.
Cardiac disorders TACHYCARDIA	6.6% 25/380 • Other AE module includes adverse events which occurred before first dose date to last dose date + 30 days.
Infections and infestations UPPER RESPIRATORY TRACT INFECTION	7.1% 27/380 • Other AE module includes adverse events which occurred before first dose date to last dose date + 30 days.
Gastrointestinal disorders VOMITING	11.3% 43/380 • Other AE module includes adverse events which occurred before first dose date to last dose date + 30 days.
Gastrointestinal disorders WEIGHT INCREASED	17.1% 65/380 • Other AE module includes adverse events which occurred before first dose date to last dose date + 30 days.

Additional Information

Seroquel Medical Science Director, MD

AstraZeneca

Email: AZTrial_Results_Posting@astrazeneca.com

Results disclosure agreements

• Principal investigator is a sponsor employee AstraZeneca as sponsor will first publish results for the multicenter study
• Publication restrictions are in place

Restriction type: OTHER