Anxiety Disorders
Conditions
Keywords
Generalised Anxiety Disorder, GAD
Brief summary
The primary purpose of this study is to evaluate whether treatment with (SEROQUEL SR) quetiapine fumarate sustained release (SR) for 9 weeks compared to placebo will improve elderly patients with generalised anxiety disorder. PLEASE NOTE: Seroquel SR and Seroquel extended release(XR) refer to the same formulation. The SR designation was changed to XR after consultation with FDA.
Interventions
DRUGQuetiapine XR
Quetiapine XR 50 mg tablets orally administered in flexible doses of 50 to 300 mg quetiapine XR once daily, in the evening for a 9-week treatment period.
DRUGPlacebo
Matching placebo tablets orally administered in flexible doses of 50 to 300 mg once daily, in the evening for a 9-week treatment period.
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
66 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female patients, 66 years or older, with a documented clinical diagnosis of Generalised Anxiety Disorder (GAD). * Absence of current episode of major depression.
Exclusion criteria
* The presence of dementia or other mental disorder than GAD. * Serious suicidal risk, uncontrolled hypertension, substance or alcohol abuse. * A current diagnosis of cancer or current or past diagnosis of stroke.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in the Hamilton Rating Scale for Anxiety (HAM-A) Total Score | Randomization to Week 9 | HAM-A total score ( 0-56 units), 0 is the best, Change : score at week 9 minus score at randomization |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in the Clinical Global Impression - Severity of Illness (CGI-S) Score | Randomization to Week 9 | CGI-S score is accessed on a seven-graded scale ranging from most extremely ill/ very much worse (7) to normal/very much improved (1) , 1 is best Change : score at week 9 minus score at randomization |
| Change in Psychic Anxiety Factor as Measured by HAM-A Psychic Cluster Score | Randomization to Week 9 | HAM-A psychic cluster score ( 0-28), 0 is the best Change : score at week 9 minus score at randomization |
| Change in Somatic Symptoms as Measured by HAM-A Somatic Cluster Score | Randomization to Week 9 | HAM-A somatic cluster score (0-28), 0 is the best Change : score at week 9 minus score at randomization |
| Hamilton Rating Scale for Anxiety (HAM-A) Response. | Week 9 | HAM-A response, defined as 50% or greater reduction from randomization in HAM-A total score. |
| Change in Health-related Quality of Life as Measured by Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) Percent Maximum Total Score | Randomization to Week 9 | Q-LES-Q total score is the sum of the first 14 items of Q-LES-Q, and this total score is converted to a % maximum total score by : (Q-LES-Q total score -14) /56 x 100%, Larger values indicate a higher perceived quality of life enjoyment and satisfaction. Change : percentage at week 9 minus percentage at randomization |
| Change in Montgomery-Asberg Depression Rating Scale (MADRS) | Randomization to week 9 | MADRS total score (0-60), 0 is best Change : score at week 9 minus score at randomization |
| Change in the Visual Analogue Scale (VAS) Measuring Pain | Randomization to week 9 | Visual Analogue Scale (VAS) measuring pain (0-100 mm), 0 is best Change : scale at week 9 minus scale at randomization |
| Safety and Well Tolerated as Measured in Adverse Event | From the start of treatment to last dose plus 30 days | Number of patients have at least one adverse event |
| Safety and Well Tolerated as Measured by Extra Pyramidal Symptoms (EPS) | From start of the study teatment to last dose plus 30 days | Number of patients have adverse events associated with EPS |
| Number of Patients Reaching Hamilton Rating Scale for Anxiety (HAM-A) Remission | Week 9 | HAM-A remission, defined as HAM-A total score less or equal to 7. An indicator of HAM-A remission is calculated as: * If HAM-A total score≤7, THEN indicator=1 * If HAM-A total score \>7, THEN indicator=0 |
Countries
Estonia, Poland, Russia, Ukraine, United States
Participant flow
Recruitment details
International multi-center study, 47 sites recruited between Sept 2006 and Apr 2008
Pre-assignment details
Screening for eligibility and wash-out of restriced medications
Participants by arm
| Arm | Count |
|---|---|
| Quetiapine XR Quetiapine fumerate XR - flexibly dosed (50 - 300 mg) | 223 |
| Placebo | 227 |
| Total | 450 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 11 | 3 |
| Overall Study | Lack of Efficacy | 3 | 14 |
| Overall Study | Lost to Follow-up | 1 | 2 |
| Overall Study | Multiple Reasons | 9 | 11 |
| Overall Study | Physician Decision | 2 | 2 |
| Overall Study | Protocol Violation | 2 | 0 |
| Overall Study | Withdrawal by Subject | 17 | 27 |
Baseline characteristics
| Characteristic | Quetiapine XR | Placebo | Total |
|---|---|---|---|
| Age, Customized 66 to 75 years | 197 Participants | 195 Participants | 392 Participants |
| Age, Customized > 75 years | 26 Participants | 32 Participants | 58 Participants |
| Sex: Female, Male Female | 161 Participants | 157 Participants | 318 Participants |
| Sex: Female, Male Male | 62 Participants | 70 Participants | 132 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 171 / 223 | 89 / 227 |
| serious Total, serious adverse events | 1 / 223 | 3 / 227 |
Outcome results
Primary
Change in the Hamilton Rating Scale for Anxiety (HAM-A) Total Score
HAM-A total score ( 0-56 units), 0 is the best, Change : score at week 9 minus score at randomization
Time frame: Randomization to Week 9
Population: Modified Intent to Treat (MITT) population.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Quetiapine XR | Change in the Hamilton Rating Scale for Anxiety (HAM-A) Total Score | -14.97 units on scale | Standard Deviation 7.4 |
| Placebo | Change in the Hamilton Rating Scale for Anxiety (HAM-A) Total Score | -7.21 units on scale | Standard Deviation 7.8 |
Secondary
Change in Health-related Quality of Life as Measured by Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) Percent Maximum Total Score
Q-LES-Q total score is the sum of the first 14 items of Q-LES-Q, and this total score is converted to a % maximum total score by : (Q-LES-Q total score -14) /56 x 100%, Larger values indicate a higher perceived quality of life enjoyment and satisfaction. Change : percentage at week 9 minus percentage at randomization
Time frame: Randomization to Week 9
Population: In reporting Q-LES-Q there was missing data even with last observation carried forward (LOCF), so the total number of patients analyzed is 428 ( 211 Quetiapine XR and 217 Placebo).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Quetiapine XR | Change in Health-related Quality of Life as Measured by Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) Percent Maximum Total Score | 14.82 Percentage of Maximum Total Score | Standard Deviation 12.4 |
| Placebo | Change in Health-related Quality of Life as Measured by Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) Percent Maximum Total Score | 4.94 Percentage of Maximum Total Score | Standard Deviation 11.6 |
Secondary
Change in Montgomery-Asberg Depression Rating Scale (MADRS)
MADRS total score (0-60), 0 is best Change : score at week 9 minus score at randomization
Time frame: Randomization to week 9
Population: Modified Intent to Treat (MITT) population.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Quetiapine XR | Change in Montgomery-Asberg Depression Rating Scale (MADRS) | -6.94 units on scale | Standard Deviation 4.7 |
| Placebo | Change in Montgomery-Asberg Depression Rating Scale (MADRS) | -2.22 units on scale | Standard Deviation 4.7 |
Secondary
Change in Psychic Anxiety Factor as Measured by HAM-A Psychic Cluster Score
HAM-A psychic cluster score ( 0-28), 0 is the best Change : score at week 9 minus score at randomization
Time frame: Randomization to Week 9
Population: Modified Intent to Treat (MITT) population.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Quetiapine XR | Change in Psychic Anxiety Factor as Measured by HAM-A Psychic Cluster Score | -8.88 units on scale | Standard Deviation 4.2 |
| Placebo | Change in Psychic Anxiety Factor as Measured by HAM-A Psychic Cluster Score | -3.81 units on scale | Standard Deviation 4.6 |
Secondary
Change in Somatic Symptoms as Measured by HAM-A Somatic Cluster Score
HAM-A somatic cluster score (0-28), 0 is the best Change : score at week 9 minus score at randomization
Time frame: Randomization to Week 9
Population: Modified Intent to Treat (MITT) population.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Quetiapine XR | Change in Somatic Symptoms as Measured by HAM-A Somatic Cluster Score | -6.05 units on scale | Standard Deviation 4 |
| Placebo | Change in Somatic Symptoms as Measured by HAM-A Somatic Cluster Score | -3.37 units on scale | Standard Deviation 3.9 |
Secondary
Change in the Clinical Global Impression - Severity of Illness (CGI-S) Score
CGI-S score is accessed on a seven-graded scale ranging from most extremely ill/ very much worse (7) to normal/very much improved (1) , 1 is best Change : score at week 9 minus score at randomization
Time frame: Randomization to Week 9
Population: Modified Intent to Treat (MITT) population.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Quetiapine XR | Change in the Clinical Global Impression - Severity of Illness (CGI-S) Score | -1.76 units on scale | Standard Deviation 1.1 |
| Placebo | Change in the Clinical Global Impression - Severity of Illness (CGI-S) Score | -0.59 units on scale | Standard Deviation 1 |
Secondary
Change in the Visual Analogue Scale (VAS) Measuring Pain
Visual Analogue Scale (VAS) measuring pain (0-100 mm), 0 is best Change : scale at week 9 minus scale at randomization
Time frame: Randomization to week 9
Population: Modified Intent to Treat (MITT) population.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Quetiapine XR | Change in the Visual Analogue Scale (VAS) Measuring Pain | -17.95 mm | Standard Deviation 21.8 |
| Placebo | Change in the Visual Analogue Scale (VAS) Measuring Pain | -6.18 mm | Standard Deviation 19.8 |
Secondary
Hamilton Rating Scale for Anxiety (HAM-A) Response.
HAM-A response, defined as 50% or greater reduction from randomization in HAM-A total score.
Time frame: Week 9
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Quetiapine XR | Hamilton Rating Scale for Anxiety (HAM-A) Response. | 152 Number of participants. |
| Placebo | Hamilton Rating Scale for Anxiety (HAM-A) Response. | 54 Number of participants. |
Secondary
Number of Patients Reaching Hamilton Rating Scale for Anxiety (HAM-A) Remission
HAM-A remission, defined as HAM-A total score less or equal to 7. An indicator of HAM-A remission is calculated as: * If HAM-A total score≤7, THEN indicator=1 * If HAM-A total score \>7, THEN indicator=0
Time frame: Week 9
Population: Modified Intent to Treat (MITT) population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Quetiapine XR | Number of Patients Reaching Hamilton Rating Scale for Anxiety (HAM-A) Remission | 89 Number of participants. |
| Placebo | Number of Patients Reaching Hamilton Rating Scale for Anxiety (HAM-A) Remission | 29 Number of participants. |
Secondary
Safety and Well Tolerated as Measured by Extra Pyramidal Symptoms (EPS)
Number of patients have adverse events associated with EPS
Time frame: From start of the study teatment to last dose plus 30 days
Population: Safety population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Quetiapine XR | Safety and Well Tolerated as Measured by Extra Pyramidal Symptoms (EPS) | 12.00 Patients |
| Placebo | Safety and Well Tolerated as Measured by Extra Pyramidal Symptoms (EPS) | 5.00 Patients |
Secondary
Safety and Well Tolerated as Measured in Adverse Event
Number of patients have at least one adverse event
Time frame: From the start of treatment to last dose plus 30 days
Population: Safety population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Quetiapine XR | Safety and Well Tolerated as Measured in Adverse Event | 145.00 Participants |
| Placebo | Safety and Well Tolerated as Measured in Adverse Event | 114.00 Participants |