E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Generalised Anxiety Disorder |
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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 the study is to evaluate the efficacy of quetiapine fumarate sustained release (hereafter referred to as quetiapine SR) versus placebo in the treatment of anxiety symptoms in patients with Generalised Anxiety Disorder (GAD), as assessed by the change from randomisation in the HAM A total score at Day 64. |
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E.2.2 | Secondary objectives of the trial |
1.The efficacy of quetiapine SR versus placebo by evaluating the response rate in the treatment of anxiety symptoms in patients with GAD. 2.The efficacy of quetiapine SR versus placebo on the health-related quality of life of patients with GAD. 3.The efficacy of quetiapine SR versus placebo in the treatment of anxiety symptoms in patients with GAD. 4.The efficacy of quetiapine SR versus placebo by evaluating the remission rate in the treatment of anxiety symptoms in patients with GAD. 5.The efficacy of quetiapine SR versus placebo in the treatment of depressive symptom in patients with GAD. 6.The efficacy of quetiapine SR versus placebo in improving somatic symptoms in the treatment of patients with GAD. 7.The efficacy of quetiapine SR versus placebo in improving sleep quality in patients with GAD. 8.If quetiapine SR improves satisfaction with medication in patients with GAD, compared with placebo. 9.The safety and tolerability of quetiapine SR in patients with GAD.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Provision of written informed consent before initiation of any study related procedures 2.Men and women aged 66 years or older 3.A documented clinical diagnosis of GAD according to DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) criteria 300.02 as assessed by M.I.N.I. 4.A HAM-A total score ≥20 with Item 1 (anxious mood) and Item 2 (tension) scores ≥2 at both enrolment and randomisation 5.A CGI-S score ≥4 at both enrolment and randomisation 6.Absence of current episode of major depression, defined as having a MADRS total score of ≤16 at both enrolment and randomisation 7.Be able to understand and comply with the requirements of the study, as judged by the investigator 8.Outpatient status and living in home environment at enrolment and randomisation
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E.4 | Principal exclusion criteria |
1.A Mini Mental State Examination (MMSE) score ≤25 2.Patients meeting the DSM-IV Diagnostic Criteria for Dementia of the Alzheimer’s type; Diagnostic Criteria for Vascular Dementia; DSM-IV Diagnostic Criteria for Dementia Due to Other General Medical Conditions (e.g., head trauma, intracranial structural abnormality, etc); Practice Parameter for Mild Cognitive Impairment (Neurology 2001;56: 1133-1142); Diagnostic Criteria of The Consortium for Dementia with Lewy Bodies; and the Consensus Diagnostic Criteria for Frontotemporal Dementia 3.Patients with a DSM-IV Axis I disorder other than GAD or simple phobia within 6 months of enrolment, which is considered clinically relevant as judged by the investigator. 4.Patients with a DSM-IV Axis II disorder having a major impact on the current psychiatric status. 5.Patients who, in the investigator’s judgement, pose a current serious suicidal or homicidal risk or have made a suicide attempt within 6 months prior to randomization or patients who have a MADRS Item 10 score ≥4. 6.Patients treated with antihypertensive medications must be on a stable dose for at least 30 days prior to Visit 1. 7.Substance or alcohol abuse or dependence,. 8.Use of drugs that induce or inhibit the hepatic metabolising cytochrome P450 3A4 enzymes within 2 weeks prior to randomisation. 9.Evidence of clinically relevant disease, e.g., renal or hepatic impairment, significant coronary artery disease, cerebrovascular disease, viral hepatitis B or C, acquired immunodeficiency syndrome (AIDS) as judged by the investigator. 10.A clinical finding that is unstable or that, in the opinion of the investigator, would be negatively affected by the study medication or that would affect the study medication. 11.Conditions that could affect absorption and metabolism of study medication (e.g., malabsorption syndrome, liver disease) as judged by the investigator. 12.Significant hearing dysfunction, visual impairment, or communication disabilities that would interfere with the accurate assessment of the patient or impact the conduct of the study. 13.A current diagnosis of cancer (except basal or squamous cell skin carcinoma), unless in remission for at least 5 years. 14.Current or past diagnosis of stroke. 15.History of seizure disorder, except febrile convulsions. 16.Prior history of Neuroleptic Malignant Syndrome. 17.Receipt of electroconvulsive therapy (ECT) or transcranial magnetic stimulation (TMS) fo treatment of depression within 90 days prior to randomisation, or the presence of a vagal nerve sti,ulator (VNS) device. 18.Use of antipsychotic, mood stabiliser, or antidepressant drugs within 7 days before randomisation, or use of fluoxetine within 28 days before randomisation, or use of monamine oxidase inhibitors (MAO inhibitors), anxiolytics or hypnotics within 14 days before randomisation (with the exception of those allowed with restriction per protocol), or use of a depot antipsychotic injection within 2 dosing interval before randomisation. 19.Patients unable to swallow oral medications whole or have difficulty swallowing. 20.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 randomisation. 21.Patients with any diagnosis of a neurological condition, such as Parkinson’s disease, Huntington’s disease, essential tremor, multiple sclerosis, prior brain injury, space-occupying lesions, etc. 22.A patient with diabetes mellitus 23.Clinically significant deviation from the reference range in clinical laboratory test results as judged by the investigator. 24.An absolute neutrophil count (ANC) of ≤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 enrolment, whether or not the patient is being treated for hypothyroidism. 26.ECG results considered being clinically significant as determined by the investigator based on assessment by a centrally located experienced cardiologist interpreting the ECG. 27.An ECG with a QTcF of ≥500 msec at enrolment. 28.Known history of intolerance or hypersensitivity to quetiapine or to any other component in the tablets. 29.Known lack of response to quetiapine in the treatment of anxiety in a dosage of at least 50 mg per day for 4 weeks (at any time before study start), as judged by the investigator. 30.Contraindications as detailed in the country-specific prescribing information for quetiapine. 31.Involvement in the planning and conduct of the study (applies to all AZ staff, the investigational site staff and third-party vendors). 32.Previous randomisation in the present study or any AZ-sponsored GAD study on quetiapine. 33.Participation in another clinical study or compassionate use programme within 4 weeks of randomisation or longer in accordance with local requirements.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary objective of the study is to evaluate the efficacy of quetiapine fumarate sustained release (hereafter referred to as quetiapine SR) versus placebo in the treatment of anxiety symptoms in patients with Generalised Anxiety Disorder (GAD), as assessed by the change from randomisation in the HAM A total score at Day 64. |
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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) | 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.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 14 |
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 | Yes |
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 | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |