E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Generalised Anxiety Disorder (GAD) |
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MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of this study is to evaluate the efficacy of (SEROQUEL SR™ ) quetiapine fumarate sustained-release (SR) compared to placebo in the treatment of anxiety symptoms in patients with generalized anxiety disorder (GAD). |
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E.2.2 | Secondary objectives of the trial |
1.The effect of quetiapine SR on the health-related quality of life in patients with GAD. 2.The early efficacy of quetiapine SR in the treatment of anxiety symptoms in patients with GAD. 3.The efficacy of quetiapine SR in the treatment of anxiety symptoms in patients with GAD. 4.The efficacy of quetiapine SR in the treatment of anxiety symptoms in patients with GAD. 5.The efficacy of quetiapine SR by evaluating the response rate in the treatment of anxiety symptoms in patients with GAD. 6.The efficacy of quetiapine SR by evaluating the remission rate in the treatment of anxiety symptoms in patients with GAD. 7.The efficacy of quetiapine SR in the treatment of depressive symptoms in patients with GAD. 8.The efficacy of quetiapine SR in improving sleep quality in patients with GAD. 9.To evaluate if quetiapine SR improves patient satisfaction in patients with GAD. 10.The safety and tolerability of quetiapine SR in patients with GAD. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1.Provision of informed consent before initiation of any study related procedures. 2.Male or female aged 18 to 65 years, inclusive. 3.A documented clinical diagnosis of generalized anxiety disorder (GAD) according to DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, 4th Edition) criteria 300.02 as assessed by the MINI (Mini-International Neuropsychiatric Interview). 4.HAM-A administered by use of the Structured Interview Guide for the Hamilton Anxiety Rating Scale (SIGH-A) total score ≥20 with Item 1 (anxious mood) and Item 2 (tension) scores ≥2 at both enrollment and randomization. 5.A CGI-S score ≥4 at both enrollment and randomization. 6.Absence of current episode of major depression, documented by a MADRS total score ≤16 at either enrollment or randomization. 7.Female patients must have a negative serum pregnancy test at enrollment and be willing to use a reliable method of birth control. 8.Be able to understand and comply with the requirements of the study. 9.Be able to read and write and be able to understand and use IVRS. 10.Outpatient status at enrollment and randomization, i.e, patient is not hospitalized. |
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E.4 | Principal exclusion criteria |
1.Patients with a current DSM-IV Axis I disorder other than generalized anxiety disorder or simple phobia within 6 months of enrollment. 2.The presence or history of schizophrenia and other psychotic disorders according to DSM-IV. 3.The presence of any DSM-IV Axis II disorder that is likely to interfere with the patient’s ability to participate in the study as judged by the investigator. 4.Patients who, in the investigator’s judgment, pose a current serious suicidal or homicidal risk or have made a suicide attempt or patients who have a MADRS Item 10 score ≥4. 5.Evidence of clinically relevant disease, eg, renal or hepatic impairment, significant coronary artery disease, cerebrovascular disease, viral hepatitis B or C, acquired immunodeficiency syndrome (AIDS) as judged by the investigator. 6.A clinical finding that is unstable (e.g. hypertension, poorly controlled diabetes, unstable angina) or that, in the opinion of the investigator, would be negatively affected by the study medication or that would affect the study medication. 7.Conditions that could affect absorption and metabolism of study medication (e.g. malabsorption syndrome, liver disease) as judged by the investigator. 8.History of seizure disorder, except febrile convulsions. 9.A current diagnosis of cancer (except basal or squamous cell skin carcinoma), unless in remission for at least 5 years. 10.Current or past diagnosis of stroke or Transient Ischemic Attack (TIA). 11.Pregnancy or lactation. 12.Substance or alcohol abuse or dependence. 13.Use of antipsychotic medication within 28 days prior to randomization. 14.Receipt of electroconvulsive therapy (ECT) within 28 days prior to randomization. 15.Patients who in the investigators opinion will require psychotherapy (other than supportive psychotherapy) during the study period, unless psychotherapy has been ongoing for a minimum of 3 months prior to randomization. 16.Use of benzodiazepines, antidepressants, MAO inhibitors and mood stabilizers within 14 days prior to randomization. 17.Use of benzodiazepines, maximum allowable dose of 10 mg equivalent of diazepam per day, more than 3 times per week in the period 14 to 28 days prior to randomization. 18.Use of hypnotics, maximum allowable single dose of 20 mg zolpidem tartrate, 1 gram chloral hydrate, 20 mg zaleplon, or 7.5 mg zolpiclone, at bedtime more than 3 times per week in the 28 days prior to randomization. 19.Administration of a depot antipsychotic medication within 2 dosing intervals prior to randomization. 20.Use of potent cytochrome P450 3A4 inducers (eg, barbiturates, carbamazepine, glucocorticoids, phenytoin, rifampin, rifabutin, thioridazine, and St. John’s Wort) in the 14 days preceding randomization. 21.Use of potent cytochrome P450 3A4 inhibitors in the 14 days preceding randomization. 22.A patient with diabetes mellitus. 23.Clinically significant deviation from the reference range in clinical laboratory test results at enrollment, as judged by the investigator. 24.If the patient’s CBC with WBC differential shows an ANC ≤1.5 x 109/L. 25.A thyroid-stimulating hormone (TSH) concentration more than 10% above the upper limit of the normal range of the laboratory used for sample analysis at enrollment, whether or not the patient is being treated for hypothyroidism. 26.ECG results considered clinically significant as determined by the investigator based on assessment by a centrally located experienced cardiologist interpreting the ECG. 27.AST, ALT levels > 3 times the upper limit of normal. 28.Treatment with quetiapine or paroxetine in the 6 months prior to randomization. 29.Known history of intolerance or hypersensitivity to quetiapine, paroxetine, or to any other component in the tablets. 30.Known lack of response to quetiapine in the treatment of anxiety in a dosage of at least 50 mg for 4 weeks at any time, as judged by the investigator. 31.Known lack of response to paroxetine in the treatment of anxiety in a dosage of at least 20 mg for 4 weeks, as judged by the investigator. 32.Contraindications as detailed in the country-specific prescribing information for quetiapine. 33.Use of any other investigational compound, or participation in another clinical study or compassionate use program within 28 days prior to enrollment. 34.Involvement in the planning and conduct of the study (applies to AZ staff, staff at the investigational site, and third-party vendors). 35.Previous enrollment or randomization to treatment in the following quetiapine GAD studies; D1448C00009;D1448C00011;D1448C00012. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary objective of this study is to evaluate the efficacy of (SEROQUEL SR™ ) quetiapine fumarate sustained-release (SR) compared to placebo in the treatment of anxiety symptoms in patients with generalized anxiety disorder (GAD) by measuring the change from randomization in the Hamilton Anxiety Scale (HAM-A) total score at Day 57. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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End of study is defined as database lock, which is the time point after which no patient will be exposed to study related activities. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 3 |