E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Maintenance treatment of patients with Generalised Anxiety Disorder. |
|
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 the study is to evaluate the efficacy of quetiapine SR compared to placebo in increasing time from randomisation to a depressed event in patients with Generalised Anxiety Disorder (GAD). |
|
E.2.2 | Secondary objectives of the trial |
1.To evaluate the effect of quetiapine SR compared to placebo on health-related quality of life in patients with GAD during long-term treatment. 2.To evaluate the efficacy of quetiapine SR compared to placebo in maintaining improvement of anxiety symptoms in patients with GAD during long-term treatment. 3.To evaluate the effect of quetiapine SR compared to placebo on depressive symptoms in patients with GAD during long-term treatment. 4.To evaluate the effect of quetiapine SR compared to placebo on quality of sleep in patients with GAD during long-term treatment. 5.To evaluate the effect of quetiapine SR compared to placebo on suicidal ideation in patients with GAD during long-term treatment. 6.To evaluate the effect of quetiapine SR compared to placebo on functional disability in patients with GAD during long-term treatment. 7.To evaluate if quetiapine SR compared to placebo is safe and well-tolerated in patients with GAD during long-term treatment.
|
|
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 GAD according to DSM-IV criteria 300.02 as assessed by the MINI. 4.A 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 enrolment. 5.A CGI-S score ≥4 at enrolment. 6.Female patients of childbearing potential must have a negative serum pregnancy test at enrolment and be willing to use a reliable method of birth control (i.e., double-barrier method, oral contraceptive, implant, dermal contraception, long-term injectable contraceptive, intrauterine device, or tubal ligation) during the study, as judged by the investigator. 7.Be able to understand and comply with the requirements of the study, as judged by the investigator. 8.Outpatient status at enrolment.
|
|
E.4 | Principal exclusion criteria |
1.Patients with a current DSM-IV Axis I disorder other than GAD (with or without simple phobia) within 6 months of enrolment. 2.The presence or history of schizophrenia and other psychotic disorders according to DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, 4th Edition), including: Schizophrenia 295.xx;Schizophreniform Disorder 295.xx;Schizoaffective Disorder 295.x;Delusional Disorder 297.1; Brief Psychotic Disorder 298.8;Shared Psychotic Disorder 297.3;Substance-Induced Psychotic Disorder 291.xx, 292.xx;Psychotic Disorder Not Otherwise Specified 298.9;Mood disorder with Psychotic Features: x4 specifier (eg, 296.24 = Major Depressive Disorder, Single Episode, Severe, with Psychotic Features). 3.Patients with a diagnosis of 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 suffering from depressive symptoms, defined as having a MADRS total score ³17 at enrolment. 5.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. 6.Evidence of clinically relevant disease, eg, renal or hepatic impairment, significant coronary artery disease, cerebrovascular disease, viral hepatitis B or C, HIV positive or acquired immunodeficiency syndrome (AIDS). 7.A clinical finding that is unstable. 8.Conditions that could affect absorption and metabolism of study medication (e.g. malabsorption syndrome, liver disease). 9.Laboratory values for alanine aminotransferase (ALT) or aspartate aminotransferase (AST) that are 3 times the upper limit of normal. 10.History of seizure disorder, except febrile convulsions. 11.A current diagnosis of cancer, (except basal or squamous cell skin carcinoma), unless in remission for at least 5 years. 12.Current or past diagnosis of stroke or Transient Ischemic Attack (TIA). 13.Substance or alcohol abuse or dependence. 14.Use of the following medications prior to start of Open-label Run-in Treatment Period (Visit 2): antipsychotic, mood stabiliser, anticonvulsant (except carbamazepine; see Exclusion 19) or antidepressant drugs within 7 days before Visit 2;fluoxetine within 28 days before Visit 2;MAO inhibitors within 14 days before Visit 2;anxiolytics (including benzodiazepines) or hypnotics within 14 days before Visit 2;depot antipsychotic injection within two dosing intervals before Visit 2. 15.Receipt of electro convulsive therapy (ECT) within 90 days prior to enrolment. 16.Patients who in the investigators opinion will require psychotherapy (other than supportive psychotherapy) during the study, unless psychotherapy has been ongoing for a minimum of 3 months prior to enrolment. 17.Use of potent cytochrome P450 (CYP) 3A4 inducers (e.g., barbiturates, carbamazepine, glucocorticoids [except for topical use or inhalation], phenytoin, rifampin, rifabutin, thioridazine, and St John’s Wort) within 14 days prior to the OLRT (Visit 2). 18.Use of potent CYP 3A4 inhibitors. 19.A patient with Diabetes Mellitus (DM). 20.Clinically significant deviation from the reference range in clinical laboratory test results at enrolment, as judged by the investigator. 21.If the patient’s CBC with WBC differential shows an ANC ≤ 1.5 x 109/L. 22.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 enrolment, whether or not the patient is being treated for hypothyroidism 23.ECG results considered clinically significant as determined by the investigator based on assessment by a centrally located experienced cardiologist interpreting the ECG. 24.Treatment with quetiapine in the 6 months prior to enrolment. 25.Known history of intolerance or hypersensitivity to quetiapine, or to any other component in the tablets. 26.Known lack of response to quetiapine in the treatment of GAD in a dosage of at least 50 mg/day for 4 continuous weeks (at any time before study start), as judged by the investigator. 27.Contraindications as detailed in the country-specific prescribing information for quetiapine. 28.Participation in another clinical study or compassionate use program within 4 weeks of enrolment or longer in accordance with local requirements. 29.Involvement in the planning and conduct of the study. 30.Previous randomisation in any AstraZeneca- sponsored GAD study with quetiapine. 31.Previous enrolment in the present study. 32.Pregnancy or lactation.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary objective of this study is to evaluate the efficacy of quetiapine SR compared to placebo in increasing time from randomisation to an anxiety event in patients with generalised anxiety disorder (GAD).
|
|
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) | No |
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 |
|
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
|
End of study is defined as database lock, which is the time point after which no patient will be exposed to study related activities. |
|
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 | 6 |
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 | 6 |