Anxiety Disorders
Conditions
Keywords
Generalized Anxiety Disorder, GAD, Anxiety
Brief summary
The purpose of this research study is to determine whether AstraZeneca's drug AZD7325 is safe and effective in the treatment of generalized anxiety disorder.
Interventions
DRUGAZD7325
2 tablets taken twice a day for 28 days
DRUGPlacebo
2 tablets taken twice a day for 28 days
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Signed informed consent before any study-related procedures start. * The patient is previously diagnosed with Generalized Anxiety Disorder. * The patient has a HADS-A (anxiety) score ≥10 at both screening and randomization.
Exclusion criteria
* Patient has a lifetime history of schizophrenia or other psychotic disorders * Patient has a history of seizures or seizure disorder. * Patient is pregnant or breast feeding. * Patient has received electroconvulsive treatment (ECT) in the past.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Hamilton Rating Scale for Anxiety (HAM-A) Total Score | From randomization (baseline) to week 4 | The HAM -A is a 14-item clinician administered scale for the evaluation of anxiety symptoms. Each HAM-A item is rated on a 0 (not present) to 4 (very severe) scale, higher score indicates high level of anxiety. The HAM-A total score is calculated as the sum of 14 individual scores, with 56 as the maximum. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Hospital Anxiety and Depression Scale for Anxiety (HADS-A) Total Score | From randomization (baseline) to week 4 | The HADS-A is a 7 item, self administered instrument to measure level of anxiety. Each item is a score rate from 0 (happens rarely ) to 3 (happens frequently), and the items are totaled for a maximum score of 21. The mimimum score 0 indicates that the patient rarely suffered from anxiety symptoms. |
| Change in Psychic Anxiety Symptoms as Measured by HAM-A Psychic Anxiety Factor Score | From baseline (randomization) to week 4 | The HAM-A psychic anxiety factor score is calculated as the sum of 7 HAM-A individual items related with psychic anxiety ( each rated from 0 to 4, 0 is the best). The minimum score for HAM-A psychic anxiety factor is 0 and maximum score is 28, higher score indicates severe psychic anxiety symptoms. |
| Change in Somatic Symptoms as Measured by HAM-A Somatic Factor Score | From baseline ( randomization) to week 4 | The HAM-A somatic factor score is calculated as the sum of 7 individual HAM-A items (each is rated from 0 to 4, 0 is the best) related with somatic anxiety symptoms. The minimum score for HAM-A somatic factor is 0 and maximum score is 28, higher score indicates severe somatic anxiety symptoms |
| Change in Sheehan Disability Scale (SDS) Global Total Score | From baseline ( randomization) to week 4 | The Sheehan Disability Scale is a patient-rated measure of functional disability in 3 subscales: work, social, and family life. Each subscale is rated from 0 to 10, with 0 as the best. SDS global total score is calculated as the sum of 3 subscales and ranges from 0(unimpaired) to 30 (highly impaired) |
Countries
United States
Participant flow
Recruitment details
International multi-center study, 44 sites recruited between Dec 2008 and May 2009
Pre-assignment details
Screening for eligibility and wash-out of restriced medications. 725 subjects enrolled but 424 subjects were randomized. Number of participants analyzed is the number of subjects in MITT (modified intent to treat) population, it is different with any of population listed in the participant flow chart.
Participants by arm
| Arm | Count |
|---|---|
| A-AZD7325 2 mg AZD7325 2 mg BID | 107 |
| B-AZD7325 5 mg AZD7325 5 mg BID | 106 |
| C-AZD7325 10 mg AZD7325 10 mg QD | 105 |
| D-Placebo Placebo | 106 |
| Total | 424 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 4 | 7 | 10 | 6 |
| Overall Study | All other reasons | 2 | 1 | 3 | 1 |
| Overall Study | Lack of Efficacy | 1 | 1 | 0 | 0 |
| Overall Study | Lost to Follow-up | 2 | 3 | 3 | 5 |
| Overall Study | Protocol Violation | 3 | 3 | 3 | 0 |
| Overall Study | study specific discontinuation criteria | 1 | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 4 | 0 | 2 | 4 |
Baseline characteristics
| Characteristic | A-AZD7325 2 mg | B-AZD7325 5 mg | C-AZD7325 10 mg | D-Placebo | Total |
|---|---|---|---|---|---|
| Age, Customized 18-39 | 44 Participants | 43 Participants | 48 Participants | 53 Participants | 188 Participants |
| Age, Customized 40-65 | 63 Participants | 63 Participants | 57 Participants | 53 Participants | 236 Participants |
| Sex: Female, Male Female | 62 Participants | 62 Participants | 61 Participants | 62 Participants | 247 Participants |
| Sex: Female, Male Male | 45 Participants | 44 Participants | 44 Participants | 44 Participants | 177 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 13 / — | 18 / — | 32 / — | 14 / — |
| serious Total, serious adverse events | 1 / — | 1 / — | 0 / — | 0 / — |
Outcome results
Primary
Change From Baseline in the Hamilton Rating Scale for Anxiety (HAM-A) Total Score
The HAM -A is a 14-item clinician administered scale for the evaluation of anxiety symptoms. Each HAM-A item is rated on a 0 (not present) to 4 (very severe) scale, higher score indicates high level of anxiety. The HAM-A total score is calculated as the sum of 14 individual scores, with 56 as the maximum.
Time frame: From randomization (baseline) to week 4
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| A-AZD7325 2 mg | Change From Baseline in the Hamilton Rating Scale for Anxiety (HAM-A) Total Score | -10.9 Units on scale | Standard Error 0.87 |
| B-AZD7325 5 mg | Change From Baseline in the Hamilton Rating Scale for Anxiety (HAM-A) Total Score | -11.1 Units on scale | Standard Error 0.86 |
| C-AZD7325 10 mg | Change From Baseline in the Hamilton Rating Scale for Anxiety (HAM-A) Total Score | -11.5 Units on scale | Standard Error 0.87 |
| D-Placebo | Change From Baseline in the Hamilton Rating Scale for Anxiety (HAM-A) Total Score | -10.9 Units on scale | Standard Error 0.88 |
Secondary
Change in Hospital Anxiety and Depression Scale for Anxiety (HADS-A) Total Score
The HADS-A is a 7 item, self administered instrument to measure level of anxiety. Each item is a score rate from 0 (happens rarely ) to 3 (happens frequently), and the items are totaled for a maximum score of 21. The mimimum score 0 indicates that the patient rarely suffered from anxiety symptoms.
Time frame: From randomization (baseline) to week 4
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| A-AZD7325 2 mg | Change in Hospital Anxiety and Depression Scale for Anxiety (HADS-A) Total Score | -4.5 Units on scale | Standard Error 0.49 |
| B-AZD7325 5 mg | Change in Hospital Anxiety and Depression Scale for Anxiety (HADS-A) Total Score | -4.2 Units on scale | Standard Error 0.49 |
| C-AZD7325 10 mg | Change in Hospital Anxiety and Depression Scale for Anxiety (HADS-A) Total Score | -5.2 Units on scale | Standard Error 0.5 |
| D-Placebo | Change in Hospital Anxiety and Depression Scale for Anxiety (HADS-A) Total Score | -4.6 Units on scale | Standard Error 0.5 |
Secondary
Change in Psychic Anxiety Symptoms as Measured by HAM-A Psychic Anxiety Factor Score
The HAM-A psychic anxiety factor score is calculated as the sum of 7 HAM-A individual items related with psychic anxiety ( each rated from 0 to 4, 0 is the best). The minimum score for HAM-A psychic anxiety factor is 0 and maximum score is 28, higher score indicates severe psychic anxiety symptoms.
Time frame: From baseline (randomization) to week 4
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| A-AZD7325 2 mg | Change in Psychic Anxiety Symptoms as Measured by HAM-A Psychic Anxiety Factor Score | -5.9 Unit on scale | Standard Error 0.51 |
| B-AZD7325 5 mg | Change in Psychic Anxiety Symptoms as Measured by HAM-A Psychic Anxiety Factor Score | -5.8 Unit on scale | Standard Error 0.51 |
| C-AZD7325 10 mg | Change in Psychic Anxiety Symptoms as Measured by HAM-A Psychic Anxiety Factor Score | -6.5 Unit on scale | Standard Error 0.52 |
| D-Placebo | Change in Psychic Anxiety Symptoms as Measured by HAM-A Psychic Anxiety Factor Score | -5.8 Unit on scale | Standard Error 0.52 |
Secondary
Change in Sheehan Disability Scale (SDS) Global Total Score
The Sheehan Disability Scale is a patient-rated measure of functional disability in 3 subscales: work, social, and family life. Each subscale is rated from 0 to 10, with 0 as the best. SDS global total score is calculated as the sum of 3 subscales and ranges from 0(unimpaired) to 30 (highly impaired)
Time frame: From baseline ( randomization) to week 4
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| A-AZD7325 2 mg | Change in Sheehan Disability Scale (SDS) Global Total Score | -4.7 Units on scale | Standard Error 0.79 |
| B-AZD7325 5 mg | Change in Sheehan Disability Scale (SDS) Global Total Score | -5.7 Units on scale | Standard Error 0.8 |
| C-AZD7325 10 mg | Change in Sheehan Disability Scale (SDS) Global Total Score | -6.8 Units on scale | Standard Error 0.82 |
| D-Placebo | Change in Sheehan Disability Scale (SDS) Global Total Score | -6.8 Units on scale | Standard Error 0.79 |
Secondary
Change in Somatic Symptoms as Measured by HAM-A Somatic Factor Score
The HAM-A somatic factor score is calculated as the sum of 7 individual HAM-A items (each is rated from 0 to 4, 0 is the best) related with somatic anxiety symptoms. The minimum score for HAM-A somatic factor is 0 and maximum score is 28, higher score indicates severe somatic anxiety symptoms
Time frame: From baseline ( randomization) to week 4
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| A-AZD7325 2 mg | Change in Somatic Symptoms as Measured by HAM-A Somatic Factor Score | -5.0 Units on scale | Standard Error 0.41 |
| B-AZD7325 5 mg | Change in Somatic Symptoms as Measured by HAM-A Somatic Factor Score | -5.3 Units on scale | Standard Error 0.41 |
| C-AZD7325 10 mg | Change in Somatic Symptoms as Measured by HAM-A Somatic Factor Score | -5.1 Units on scale | Standard Error 0.42 |
| D-Placebo | Change in Somatic Symptoms as Measured by HAM-A Somatic Factor Score | -5.2 Units on scale | Standard Error 0.42 |