An International, Multicenter, Randomized, Double-blind, Parallel-group, Placebo-controlled, Active-controlled Study of the Efficacy and Safety of Sustained-release Quetiapine Fumarate (Seroquel SR™ ) in the Treatment of Generalized Anxiety Disorder (SILVER Study) - Silver Study

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2005-005054-46-SE
• Date of registration: 18/01/2006
• Prospective Registration: Yes
• Primary sponsor: AstraZeneca AB
• Public title: An International, Multicenter, Randomized, Double-blind, Parallel-group, Placebo-controlled, Active-controlled Study of the Efficacy and Safety of Sustained-release Quetiapine Fumarate (Seroquel SR™ ) in the Treatment of Generalized Anxiety Disorder (SILVER Study) - Silver Study
• Scientific title: An International, Multicenter, Randomized, Double-blind, Parallel-group, Placebo-controlled, Active-controlled Study of the Efficacy and Safety of Sustained-release Quetiapine Fumarate (Seroquel SR™ ) in the Treatment of Generalized Anxiety Disorder (SILVER Study) - Silver Study
• Date of first enrolment: 17/03/2006
• Target sample size: 805
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2005-005054-46
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: yes Other: no Other specify the comparator: Paroxetine

Countries of recruitment

Czech Republic, Denmark, Finland, Germany, Spain, Sweden

Key inclusion & exclusion criteria

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 both enrollment and 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
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1.Patients with a current DSM-IV Axis I disorder other than GAD within 6 months of enrollment. Patients with/without comorbid simple phobia or comorbid panic attacks (who do not meet criteria for panic disorder) are eligible to enter the study. 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 patients who have a MADRS Item 10 score =4, or have made a suicide attempt within 6 months before enrollment. 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, or cervical carcinoma in situ), 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 7 days prior to randomization is prohibited. 14.Receipt of electroconvulsive therapy (ECT) within 90 days prior to enrolment. 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 MAO inhibitors, mood stabilizers within 14 days prior to randomization is prohibited. 17.Use of benzodiazepines and antidepressants within 7 days before randomization is prohibited. (See Table 7 for restricted use between 14-7 days prior to randomization.) 18.Use of fluoxetine within 28 days prior to randomization is prohibited. 19.Use of hypnotics within 7 days before randomization is prohibited. (See table 7 for restricted use between 14-7 days prior to randomization.) 20.Administration of a depot antipsychotic medication within 2 dosing intervals prior to randomization. 21.Use of potent cytochrome P450 3A4 inducers (eg, barbiturates, carbamazepine, glucocorticoids [except for topical use or inhalation], phenytoin, rifampin, rifabutin, thioridazine, and St. John’s Wort) in the 14 days preceding randomization. 22.Use of potent cytochrome P450 3A4 inhibitors in the 14 days preceding randomization. 23.A patient with diabetes mellitus. 24.Clinically significant deviation from the reference range in clinical laboratory test results at enrollment, as judged by the investigator. 25.If the patient’s CBC with WBC differential shows an ANC =1.5 x 109/L at V1 or V2. 26.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 hypoth

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Generalised Anxiety Disorder (GAD)

Intervention(s)

Product Name: Seroquel SR
Product Code: ZD5077
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Quetiapine Fumarate Sustained Release
CAS Number: 111974-72-2
Current Sponsor code: ZD5077
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Pharmaceutical Form: Capsule*
INN or Proposed INN: Paroxetine
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 20-
Pharmaceutical form of the placebo: Capsule*
Route of administration of the placebo: Oral use

Primary Outcome(s)

Secondary Objective: 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 versus Paroxetin 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.

Main Objective: 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).

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.

Secondary ID(s)

D1448C00011